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    Hypoadiponectinemia plays a crucial role in the development of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus independent of visceral adipose tissue. Yoneda Masato,Iwasaki Tomoyuki,Fujita Koji,Kirikoshi Hiroyuki,Inamori Masahiko,Nozaki Yuichi,Maeyama Shiro,Wada Koichiro,Saito Satoru,Terauchi Yasuo,Nakajima Atsushi Alcoholism, clinical and experimental research BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Insulin resistance has been found to increase the risk of NASH, and obesity, and decreased levels of adiponectin are important factors in determining the severity of insulin resistance. Recent evidence has indicated that hypoadiponectinemia is involved in hepatic steatosis and NASH. METHODS:To investigate whether hypoadiponectinemia causes hepatic steatosis in type 2 diabetes mellitus (DM) patients independently of visceral adipose tissue, we measured the plasma adiponectin concentration, hepatic fat content based on the liver-to-spleen ratio (L/S ratio) according to computed tomography (CT) attenuation values, and the amount of visceral adipose tissue and subcutaneous adipose tissue by CT in 248 type 2 DM patients. We also investigated the relationship between the serum level of adiponectin and hepatic fibrosis. RESULTS:Significant correlations were observed between the L/S ratios and aspartate aminotransferase, alanine aminotransferase, visceral adipose tissue, subcutaneous adipose tissue, and serum adiponectin values (r=0.300, p=0.0007), and there was a highly significant inverse correlation between the visceral adipose tissue values and the serum adiponectin levels (r=-0.327, p<0.0002). The subcutaneous adipose tissue values, however, were not correlated with the serum adiponectin levels. Multiple regression analysis was used to quantify the impact of measured variables on the L/S ratio. After adjustment for age, gender, and visceral adipose tissue, the serum adiponectin levels were still significantly correlated with the L/S ratios (p=0.0064). And there was a stepwise decrease in the serum adiponectin in parallel to the severity of hepatic fibrosis. CONCLUSIONS:Hypoadiponectinemia is concluded to be involved in the etiology of hepatic steatosis independently of visceral adipose tissue content, and is considered to be an important factor in the progression of fibrosis; further studies will be necessary to elucidate the exact physiological role of adiponectin and its contribution to the progression of NASH. 10.1111/j.1530-0277.2006.00281.x
    Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Wu Haiya,Jia Weiping,Bao Yuqian,Lu Junxi,Zhu Jiehua,Wang Ren,Chen Yaqing,Xiang Kunsan Diabetes research and clinical practice Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease. 10.1016/j.diabres.2007.08.016
    Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Smith Briohny W,Adams Leon A Nature reviews. Endocrinology Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist as they share the pathogenic abnormalities of excess adiposity and insulin resistance. Although type 1 diabetes mellitus (T1DM) is due to a relative lack of insulin, an increased prevalence of obesity and insulin resistance in this population means that NAFLD also commonly coexists with this condition. Both T2DM and NAFLD are associated with adverse outcomes of the other; T2DM is a risk factor for progressive liver disease and liver-related death in patients with NAFLD, whereas NAFLD may be a marker of cardiovascular risk and mortality in individuals with T2DM. Nonalcoholic steatohepatitis-a histological subtype of NAFLD characterized by hepatocyte injury and inflammation-is present in approximately 10% of patients with T2DM and is associated with an increased risk for the development of cirrhosis and liver-related death. Current treatment strategies aim to improve insulin resistance via weight loss and exercise, improve insulin sensitivity by the use of insulin-sensitizing agents (for example, pioglitazone) and reduce oxidative stress by the use of antioxidants, such as vitamin E. Pioglitazone and vitamin E supplementation show the most promise in improving hepatic steatosis and inflammation but have not yet been demonstrated to improve fibrosis, and concern remains regarding the toxicity of long-term use of both of these agents. 10.1038/nrendo.2011.72
    Serum FGF21 levels are increased in newly diagnosed type 2 diabetes with nonalcoholic fatty liver disease and associated with hsCRP levels independently. Li Xuesong,Fan Xiaofang,Ren Fengdong,Zhang Yu,Shen Chunfang,Ren Guoguang,Sun Jue,Zhang Ning,Wang Weiqing,Ning Guang,Yang Jialin Diabetes research and clinical practice OBJECTIVE:Fibroblast growth factor (FGF21) has beneficial effects on lipolysis. Highly sensitive C-reactive protein (hs-CRP) is a predictor of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). This study aimed to determine the levels of serum FGF21 and hs-CRP in newly diagnosed type 2 diabetes patients with and without NAFLD, and further explored the correlation between FGF21 with hs-CRP in newly diagnosed type 2 DM. RESEARCH DESIGN AND METHODS:69 patients with newly diagnosed type 2 DM and 30 normal subjects were included in the study. FGF21 and hs-CRP were measured by ELISA kits. The severity of NAFLD was measured by ultrasound. RESULTS:Serum FGF21 in newly diagnosed type 2 DM with NAFLD group were significantly increased (p<0.01). There was no difference for the FGF21 level in normal control group and newly diagnosed type 2 DM without NFALD group. In type 2 DM group, the FGF21 level was positively correlated with hsCRP (r=0.417, p<0.001). In multiple stepwise regression models, only hsCRP was a significantly independent determinant for serum FGF21. CONCLUSIONS:Serum levels of FGF21 are closely related to liver steatosis in newly diagnosed type 2 DM patients. 10.1016/j.diabres.2011.02.034
    Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2 diabetes. Shin Jang Yel,Kim Soo-Ki,Lee Mi Young,Kim Hyun Soo,Ye Byung Il,Shin Young Goo,Baik Soon Koo,Chung Choon Hee Diabetes research and clinical practice AIM:To clarify the association between serum sex hormone-binding globulin (SHBG) levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes. METHODS:Two hundred seventy nine patients with type 2 diabetes were consecutively enrolled and metabolic parameters were checked. High-grade NAFLD was defined as moderate or severe fatty liver disease, measured using liver ultrasound. SHBG, testosterone, and estradiol levels were measured. RESULTS:SHBG levels were lower in patients with high-grade NAFLD than in those with normal ultrasound and decreased significantly based on the severity of fatty liver disease. SHBG levels were negatively correlated with hypertension, body mass index (BMI), waist circumference, high-grade NAFLD, triglycerides, alanine aminotransferase (ALT), γ-glutamyltransferase (γGT), homeostasis model assessment-estimated insulin resistance (HOMA-IR), and C-reactive protein (CRP) and were positively correlated with testosterone and estradiol levels. The odds ratios (ORs) predicting the presence of high-grade NAFLD in men and women decreased significantly with increasing SHBG tertile. The ORs remained significant even after further adjusting for BMI, waist circumference, hypertension, triglycerides, γGT, ALT, CRP, HOMA-IR, testosterone, estradiol, and anti-diabetic medications. CONCLUSIONS:Serum SHBG levels were independently associated with the high-grade NAFLD in patients with type 2 diabetes. 10.1016/j.diabres.2011.07.029
    [Nonalcoholic fatty liver disease as a risk factor of macroangiopahty in patients with type 2 diabetes]. Trojak Aleksandra,Idzior-Waluś Barbara Przeglad lekarski Nonalcoholic fatty liver disease (NAFLD) is recognized in 20-30% of general population but among the people with impaired glucose metabolism is about 70-90%. There is increasing number publications that show strong association between NAFLD, metabolic syndrome and insulin resistance as risk factors of cardiovascular complication. Gens PNPLAL3 NCAN, LYPAL1 and GCKR that have been linked to lipid metabolism disorders or impaired glucose metabolism can also contribute to development of NAFLD. The reduction of body mass and of known risk factors of atherosclerosis and restriction of simple carbohydrates in diet contribute to regression of NAFLD.
    Nonalcoholic fatty liver disease is associated with left ventricular diastolic dysfunction in patients with type 2 diabetes. Bonapace Stefano,Perseghin Gianluca,Molon Giulio,Canali Guido,Bertolini Lorenzo,Zoppini Giacomo,Barbieri Enrico,Targher Giovanni Diabetes care OBJECTIVE:Data on cardiac function in patients with nonalcoholic fatty liver disease (NAFLD) are limited and conflicting. We assessed whether NAFLD is associated with abnormalities in cardiac function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS:We studied 50 consecutive type 2 diabetic individuals without a history of ischemic heart disease, hepatic diseases, or excessive alcohol consumption, in whom NAFLD was diagnosed by ultrasonography. A tissue Doppler echocardiography with myocardial strain measurement was performed in all patients. RESULTS:Thirty-two patients (64%) had NAFLD, and when compared with the other 18 patients, age, sex, BMI, waist circumference, hypertension, smoking, diabetes duration, microvascular complication status, and medication use were not significantly different. In addition, the left ventricular (LV) mass and volumes, ejection fraction, systemic vascular resistance, arterial elasticity, and compliance were also not different. NAFLD patients had lower e' (8.2 ± 1.5 vs. 9.9 ± 1.9 cm/s, P < 0.005) tissue velocity, higher E-to-e' ratio (7.90 ± 1.3 vs. 5.59 ± 1.1, P < 0.0001), a higher time constant of isovolumic relaxation (43.1 ± 10.1 vs. 33.2 ± 12.9 ms, P < 0.01), higher LV-end diastolic pressure (EDP) (16.5 ± 1.1 vs. 15.1 ± 1.0 mmHg, P < 0.0001), and higher LV EDP/end diastolic volume (0.20 ± 0.03 vs. 0.18 ± 0.02 mmHg, P < 0.05) than those without steatosis. Among the measurements of LV global longitudinal strain and strain rate, those with NAFLD also had higher E/global longitudinal diastolic strain rate during the early phase of diastole (E/SR(E)). All of these differences remained significant after adjustment for hypertension and other cardiometabolic risk factors. CONCLUSIONS:Our data show that in patients with type 2 diabetes and NAFLD, even if the LV morphology and systolic function are preserved, early features of LV diastolic dysfunction may be detected. 10.2337/dc11-1820
    Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Ortiz-Lopez Carolina,Lomonaco Romina,Orsak Beverly,Finch Joan,Chang Zhi,Kochunov Valeria G,Hardies Jean,Cusi Kenneth Diabetes care OBJECTIVE:Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population. RESEARCH DESIGN AND METHODS:We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[(3)H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR(i)= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR(i)= fasting FFA × FPI). RESULTS:Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01-0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001). CONCLUSIONS:Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD. 10.2337/dc11-1849
    Effect of nonalcoholic Fatty liver disease on the development of type 2 diabetes in nonobese, nondiabetic korean men. Chon Chang Wook,Kim Bum Soo,Cho Yong Kyun,Sung Ki Chul,Bae Ji Cheol,Kim Tae Wan,Won Hyun Sun,Joo Kwan Joong Gut and liver BACKGROUND/AIMS:We have a limited understanding of the effect of nonalcoholic fatty liver disease (NAFLD) on the development of type 2 diabetes. METHODS:The study subjects included male who had received biennial medical check-ups between 2005 and 2009 and who had been diagnosed with fatty liver disease. The subjects with sustained NAFLD (FL, n=107) and sustained non-NAFLD (NFL, n=1,054) were followed to determine the development of type 2 diabetes. RESULTS:In the FL group, there were more subjects with impaired fasting glucose (IFG), type 2 diabetes and high HOMA-IR than there were in the NFL group during the 5-year follow-up period (32.7 vs. 17.6%, 1.9 vs. 0.3%, 17.9 vs. 5.2% respectively, p<0.05). The FL group showed a higher risk than NFL group for abnormal glucose metabolism as determined using IFG (odds ratio [OR], 2.13; confidence interval [CI], 1.36 to 3.35), type 2 diabetes (OR, 7.63; 95% CI, 1.03 to 56.79) and high HOMA-IR (OR, 3.25; 95% CI, 1.79 to 5.91) and metabolic parameters such as body mass index (OR, 3.35; 95% CI, 1.87 to 6.02), triglyceride (OR, 3.05; 95% CI, 1.92 to 4.86) and fasting blood sugar (OR, 2.18; 95% CI, 1.39 to 3.41). CONCLUSIONS:Sustained NAFLD appears to be associated with an increased risk for the development of type 2 diabetes and deterioration of metabolic parameters in non-obese, non-diabetic Korean men. 10.5009/gnl.2012.6.3.368
    Relationship between ultrasound features of nonalcoholic fatty liver disease and cardiometabolic risk factors in patients with newly diagnosed type 2 diabetes. Kosmalski Marcin,Kasznicki Jacek,Drzewoski Józef Polskie Archiwum Medycyny Wewnetrznej INTRODUCTION: It is suggested that nonalcoholic fatty liver disease (NAFLD) correlates with cardiometabolic risk factors in patients with newly diagnosed type 2 diabetes. OBJECTIVES: The aim of this study was to evaluate the prevalence of ultrasound features of NAFLD in patients with newly diagnosed type 2 diabetes and their relationship with cardiometabolic risk factors. PATIENTS AND METHODS: The study included 100 consecutive patients (mean age, 55.64 ±13.42 years) with newly diagnosed type 2 diabetes, without other causes of hepatosteatosis. In each patient, medical history was taken, physical and abdominal ultrasound examinations were performed, and anthropometric and biochemical parameters were measured. Based on the results of an ultrasound examination, patients were assigned to 2 groups: with (n = 71) and without (n = 29) NAFLD. RESULTS: NAFLD was present in more than 70% of the patients with diabetes. In patients with NAFLD, significantly higher mean values of body weight, waist and hip circumferences, body mass index, liver enzyme activity, serum C‑reactive protein, total cholesterol, and triglycerides and significantly lower levels of high‑density lipoprotein (HDL) cholesterol were observed. There were no significant differences in the parameters of glycemic control between the groups. A correlation was observed between ultrasound features of NAFLD and some cardiovascular risk factors. Increased waist circumference and serum γ‑glutamyltransferase level and decreased HDL‑cholesterol levels were shown to be independent risk factors of NAFLD. CONCLUSIONS: Liver ultrasound should be performed in every patient with newly diagnosed type 2 diabetes. Our findings indicate a relationship between NAFLD and multiple cardiometabolic risk factors. The measurement of selected biochemical and anthropometric parameters may be used to assess the risk of NAFLD in this patient group.
    Clinical Review: Nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. Targher Giovanni,Byrne Christopher D The Journal of clinical endocrinology and metabolism CONTEXT:Nonalcoholic fatty liver disease (NAFLD) is increasingly diagnosed worldwide and is the most common chronic liver disease in Western countries. In this review, we discuss the role of NAFLD as a novel cardiometabolic risk factor for the development of type 2 diabetes (T2DM) and for the development of major chronic complications and poor glycemic control in people with established T2DM. EVIDENCE ACQUISITION:This is a clinical, narrative review and not a systematic review and meta-analysis. PubMed was extensively searched for articles using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "diabetes risk," "cardiovascular risk," "cardiovascular mortality," "chronic kidney disease," or "diabetic nephropathy" between 1990 and 2012. Articles published in languages other than English were excluded from the analysis. EVIDENCE SYNTHESIS:NAFLD exacerbates hepatic insulin resistance and increases the risk of developing T2DM. Growing evidence also indicates that NAFLD may worsen glycemic control in people with T2DM and may contribute to the development and progression of the most important chronic complications of diabetes, such as cardiovascular disease and chronic kidney disease. CONCLUSIONS:The adverse impact of NAFLD on risk for T2DM and its major chronic vascular complications deserves particular attention among endocrinologists/cardiologists/hepatologists, in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD. Clinicians who manage patients with NAFLD should not only focus on liver disease, but should also recognize the increased risk of developing T2DM and its chronic vascular complications and undertake early, aggressive risk factor modification. 10.1210/jc.2012-3093
    Increased risk of type 2 diabetes in subjects with both elevated liver enzymes and ultrasonographically diagnosed nonalcoholic fatty liver disease: a 4-year longitudinal study. Choi Ji Hun,Rhee Eun Jung,Bae Ji Cheol,Park Se Eun,Park Cheol Young,Cho Yong Kyun,Oh Ki Won,Park Sung Woo,Lee Won Young Archives of medical research BACKGROUND AND AIMS:Nonalcoholic fatty liver disease (NAFLD) is reported to contribute to the development of type 2 diabetes (T2DM). We aimed to compare the risk for development of T2DM among the four groups of NAFLD status divided by the combined assessment of liver enzyme and ultrasonographic steatosis in a retrospective cohort of Korean subjects. METHODS:This study included 7,849 individuals without diabetes who underwent annual health check-ups for 5 consecutive years. Based on the presence or absence of fatty liver on ultrasound and serum alanine aminotransferase (ALT) values at baseline, subjects were classified into controls, an increased ALT group without steatosis, a steatosis group with normal ALT, and a group with both steatosis and elevated ALT (combined abnormality). RESULTS:During a 4-year period, the incidence of diabetes was 3.5% in the control group, 4.6% in the increased ALT group, 7.3% in the steatosis group, and 11.8% in the combined abnormality group. The hazard ratio (HR) (95% confidence interval [CI]) of incident diabetes was increased in the elevated ALT group, the steatosis group, and the combined abnormality group in a stepwise fashion. Subjects with combined abnormality group had a significantly increased HR of 1.64 (1.27-2.13) even after multivariate adjustment. CONCLUSIONS:NAFLD subjects with both elevated ALT and ultrasonographic steatosis have significantly increased risk for future diabetes development. 10.1016/j.arcmed.2013.01.007
    Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes. Lv Wen-Shan,Sun Rui-Xia,Gao Yan-Yan,Wen Jun-Ping,Pan Rong-Fang,Li Li,Wang Jing,Xian Yu-Xin,Cao Cai-Xia,Zheng Ming World journal of gastroenterology AIM:To evaluate the correlation between nonalcoholic fatty liver disease (NAFLD) and microvascular complications in type 2 diabetes mellitus (T2DM). METHODS:Data were obtained from 1217 inpatients with T2DM (757 females, 460 males; aged 63.39 ± 12.28 years). NAFLD was diagnosed by hepatic ultrasonography. Diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR) were diagnosed according to their respective criteria. The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression, respectively. RESULTS:Approximately 61% of inpatients with T2DM in Qingdao, China had NAFLD, which decreased significantly with increase in age and prolonged course of diabetes. The prevalence of NAFLD in patients presenting with DN, DPN and DR was 49.4%, 57.2% and 54.9%, respectively. These rates were significantly lower than those of patients without DN, DPN and DR (65.9%, 65.6% and 66.1%, respectively, P < 0.05). Participants with NAFLD had greater body weight, waist circumference (WC), body mass index (BMI), fasting blood glucose (FBG), hemoglobin A1c, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, blood pressure, as well as triglyceride (TG) levels and lower high-density lipoprotein (HDL) concentration than those without NAFLD (P < 0.05). NAFLD was positively correlated with BMI, WC, TG, FBG, diastolic blood pressure, and systolic blood pressure but negatively correlated with the duration of diabetes, DR, DPN, DN, and HDL. CONCLUSION:Despite the benign nature of NAFLD, efforts should be directed toward early diagnosis, intensive blood glucose and blood pressure control, and effective dyslipidemia correction. 10.3748/wjg.v19.i20.3134
    [Adipokines and liver function in patients with nonalcoholic fatty liver disease, type 2 diabetes mellitus and its combination]. Zhuravleva L V,Ogneva E V Eksperimental'naia i klinicheskaia gastroenterologiia = Experimental & clinical gastroenterology UNLABELLED:The aim of the study was to assess the links between leptin, resistin and tumor necrosis factor-alpha (TNF-α) and indexes of the functional liver condition in patients with non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (DM 2) and with its combination. MATERIALS AND METHODS:It were examined 110 patients: 20 of them were with NAFLD, 20 patients with DM 2 and 70 patients with combined disorders (NAFLD+ DM 2), which were divided into 2 subgroups -20 patients with normal body weight and 50 patients with obesity (body mass index ≥ 30 kg/m2). The control group included 20 healthy individuals. It was a complex clinical, laboratory (with definition of indexes of protein, pigment, enzyme and carbohydrate metabolism, levels of adipokines) and instrumental (ultrasound of the liver and liver biopsy (for 8 patients)) investigation. RESULTS:It was shown a significant increase of plasma levels of leptin, resistin, TNF-α in patients with this combined pathology. It was established the significant correlations between leptin, resistin, TNF-α and indexes of functional liver condition in these patients. CONCLUSION:In patients with NAFLD, DM 2 and with its combination, particularly with concomitant obesity, there is an imbalance of the products of adipose tissue, which sign is increasing of leptin, resistin and TNF-α. Relationships between leptin, resistin, TNF-α and indexes of the functional liver condition mainly in subgroup 3-b would give a reason to believe that obesity is activated and compounded te hormone-metabolic disorders that affect liver function.
    [Determinants of nonalcoholic fatty liver disease in men and women with type 2 diabetes]. Trojak Aleksandra,Idzior-Waluś Barbara,Waluś-Miarka Małgorzata,Małecki Maciej Przeglad lekarski Nonalcoholic fatty liver disease (NAFLD) is recognized in 20-30% of general population but among the people with impaired glucose metabolism this percentage is about 70-90%. The aim of this study is to assess the determinants of NAFLD with respect to patients' gender. We examined 180 patients, 73 women and 107 men. Increased body mass index (BMI), waist circumference above the norm are the determinants of NAFLD irrespectively to gender. Besides it has been observed that in the women group the increase of HDL-cholesterol by 1 mmol/l decreases the chances of NAFLD occurrence by 90%.
    Nonalcoholic fatty liver disease is associated with aortic valve sclerosis in patients with type 2 diabetes mellitus. Bonapace Stefano,Valbusa Filippo,Bertolini Lorenzo,Pichiri Isabella,Mantovani Alessandro,Rossi Andrea,Zenari Luciano,Barbieri Enrico,Targher Giovanni PloS one BACKGROUND:Recent epidemiological data suggest that non-alcoholic fatty liver disease (NAFLD) is closely associated with aortic valve sclerosis (AVS), an emerging risk factor for adverse cardiovascular outcomes, in nondiabetic and type 2 diabetic individuals. To date, nobody has investigated the association between NAFLD and AVS in people with type 2 diabetes, a group of individuals in which the prevalence of these two diseases is high. METHODS AND RESULTS:We recruited 180 consecutive type 2 diabetic patients without ischemic heart disease, valvular heart disease, hepatic diseases or excessive alcohol consumption. NAFLD was diagnosed by liver ultrasonography whereas AVS was determined by conventional echocardiography in all participants. In the whole sample, 120 (66.7%) patients had NAFLD and 53 (29.4%) had AVS. No patients had aortic stenosis. NAFLD was strongly associated with an increased risk of prevalent AVS (odds ratio [OR] 2.79, 95% CI 1.3-6.1, p<0.01). Adjustments for age, sex, duration of diabetes, diabetes treatment, body mass index, smoking, alcohol consumption, hypertension, dyslipidemia, hemoglobin A1c and estimated glomerular filtration rate did not attenuate the strong association between NAFLD and risk of prevalent AVS (adjusted-OR 3.04, 95% CI 1.3-7.3, p = 0.01). CONCLUSIONS:Our results provide the first demonstration of a positive and independent association between NAFLD and AVS in patients with type 2 diabetes mellitus. 10.1371/journal.pone.0088371
    The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Miyasato Mai,Murase-Mishiba Yuko,Bessho Megumi,Miyawaki Masahiro,Imbe Hisashi,Tsutsumi Chiharu,Tanimoto Keiji,Imagawa Akihisa,Terasaki Jungo,Hanafusa Toshiaki Clinica chimica acta; international journal of clinical chemistry BACKGROUND:The serum cytokeratin-18 fragment (CK-18) concentration has been suggested to be a biomarker of nonalcoholic fatty liver disease (NAFLD), although its usefulness in patients with type 2 diabetes mellitus (T2DM) is unknown. METHODS:The study was divided into two parts. In the first cross-sectional study, a total of 200 patients with T2DM and 58 healthy control subjects were recruited. NAFLD was diagnosed using ultrasonography. In the subsequent longitudinal study, we evaluated the three-month change (Δ) in the CK-18 concentration and other parameters in 40 T2DM patients with NAFLD. RESULTS:The serum CK-18 values were significantly higher in the NAFLD group than in the nonNAFLD group among both diabetic and nondiabetic subjects. The CK-18 concentration was found to be an independent determinant of NAFLD and was positively correlated with the ultrasonography score and AST and ALT concentrations in the T2DM patients. Positive correlations were also identified between the CK-18 and transaminase concentrations in the T2DM and NAFLD cohorts. ΔCK-18 was found to be significantly associated with ΔBMI in the T2DM patients with NAFLD. CONCLUSIONS:A dose effect between the CK-18 concentration and the severity of NAFLD was found in the T2DM patients; thus, the CK-18 concentration is a potentially useful biomarker for assessing the efficacy of treatment and the improvement in NAFLD in patients with T2DM. 10.1016/j.cca.2014.03.018
    Association of nonalcoholic fatty liver disease with QTc interval in patients with type 2 diabetes. Targher Giovanni,Valbusa Filippo,Bonapace Stafano,Bertolini Lorenzo,Zenari Luciano,Pichiri Isabella,Mantovani Alessandro,Zoppini Giacomo,Bonora Enzo,Barbieri Enrico,Byrne Christopher D Nutrition, metabolism, and cardiovascular diseases : NMCD BACKGROUND AND AIMS:The relationship between nonalcoholic fatty liver disease (NAFLD) and prolonged heart rate-corrected QT (QTc) interval, a risk factor for ventricular arrhythmias and sudden cardiac death, is currently unknown. We therefore examined the relationship between NAFLD and QTc interval in patients with type 2 diabetes. METHODS AND RESULTS:We studied a random sample of 400 outpatients with type 2 diabetes. Computerized electrocardiograms were performed for analysis and quantification of QTc interval. NAFLD was diagnosed by ultrasonographic detection of hepatic steatosis in the absence of other liver diseases. Mean QTc interval and the proportion of those with increased QTc interval (defined as either QTc interval above the median, i.e. ≥416 ms, or QTc interval >440 ms) increased steadily with the presence and ultrasonographic severity of NAFLD. NAFLD was associated with increased QTc interval (odds ratio [OR] 2.16, 95% CI 1.4-3.4, p < 0.001). Adjustments for age, sex, smoking, alcohol consumption, BMI, hypertension, electrocardiographic left ventricular hypertrophy, diabetes-related variables and comorbid conditions did not attenuate the association between NAFLD and increased QTc interval (adjusted-OR 2.26, 95% CI 1.4-3.7, p < 0.001). Of note, the exclusion of those with established coronary heart disease or peripheral artery disease from analysis did not appreciably weaken this association. CONCLUSION:This is the first study to demonstrate that the presence and severity of NAFLD on ultrasound is strongly associated with increased QTc interval in patients with type 2 diabetes even after adjusting for multiple established risk factors and potential confounders. 10.1016/j.numecd.2014.01.005
    Nonalcoholic fatty liver disease is independently associated with an increased incidence of chronic kidney disease in patients with type 1 diabetes. Targher Giovanni,Mantovani Alessandro,Pichiri Isabella,Mingolla Lucia,Cavalieri Valentina,Mantovani William,Pancheri Serena,Trombetta Maddalena,Zoppini Giacomo,Chonchol Michel,Byrne Christopher D,Bonora Enzo Diabetes care OBJECTIVE:There is no information about the role of nonalcoholic fatty liver disease (NAFLD) in predicting the development of chronic kidney disease (CKD) in type 1 diabetes. RESEARCH DESIGN AND METHODS:We studied 261 type 1 diabetic adults with preserved kidney function and with no macroalbuminuria at baseline, who were followed for a mean period of 5.2 years for the occurrence of incident CKD (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 and/or macroalbuminuria). NAFLD was diagnosed by ultrasonography. RESULTS:At baseline, patients had a mean eGFR of 92 ± 23 mL/min/1.73 m2; 234 (89.7%) of them had normoalbuminuria and 27 (10.3%) microalbuminuria. NAFLD was present in 131 (50.2%) patients. During follow-up, 61 subjects developed incident CKD. NAFLD was associated with an increased risk of incident CKD (hazard ratio [HR] 2.85 [95% CI 1.59-5.10]; P < 0.001). Adjustments for age, sex, duration of diabetes, hypertension, A1C, and baseline eGFR did not appreciably attenuate this association (adjusted HR 2.03 [1.10-3.77], P < 0.01). Results remained unchanged after excluding those who had microalbuminuria at baseline (adjusted HR 1.85 [1.03-3.27]; P < 0.05). Addition of NAFLD to traditional risk factors for CKD significantly improved the discriminatory capability of the regression models for predicting CKD (e.g., with NAFLD c statistic 0.79 [95% CI 0.73-0.86] vs. 0.76 [0.71-0.84] without NAFLD, P = 0.002). CONCLUSIONS:This is the first study to demonstrate that NAFLD is strongly associated with an increased incidence of CKD. Measurement of NAFLD improves risk prediction for CKD, independently of traditional cardio-renal risk factors, in patients with type 1 diabetes. 10.2337/dc13-2704
    High Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. Portillo Sanchez Paola,Bril Fernando,Maximos Maryann,Lomonaco Romina,Biernacki Diane,Orsak Beverly,Subbarayan Sreevidya,Webb Amy,Hecht Joan,Cusi Kenneth The Journal of clinical endocrinology and metabolism CONTEXT AND OBJECTIVE:NAFLD, and its more severe form with steatohepatitis (NASH), are common in patients with T2DM. However, they are usually believed to affect largely those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD (by the gold-standard liver magnetic resonance and spectroscopy or (1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. PARTICIPANTS AND METHODS:We recruited 103 patients with T2DM and normal plasma aminotransferases (age: 60±8 years, BMI: 33±5 kg/m(2), A1c: 7.6±1.3%). We measured: i) liver triglyceride content by (1)H-MRS; ii) systemic insulin sensitivity (HOMA-IR), and iii) adipose tissue insulin resistance (IR), both fasting (as the adipose tissue IR index: fasting plasma FFA x insulin) and during an OGTT (as the suppression of FFA). RESULTS:The prevalence of NAFLD and NASH were much higher than expected (76% and 56%, respectively). The prevalence of NAFLD was higher in obese compared to non-obese patients, as well as with increasing BMI (p=0.03 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (p<0.01). Compared to non-obese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle), and particularly, adipose tissue (fasting/postprandial) insulin resistance (all p<0.01). CONCLUSIONS:The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of severe liver disease (NASH). Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH. 10.1210/jc.2014-2739
    Nonalcoholic Fatty liver disease and risk of diabetes and cardiovascular disease: what is important for primary care physicians? Ahmed Mohamed H,Husain Nazik Elmalaika Os,Almobarak Ahmed O Journal of family medicine and primary care Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver condition in Western World and across the globe. NAFLD prevalence is estimated to be around one-third of the total population. There are no published data that project the future prevalence of NAFLD, but with an increase in epidemic of diabetes and obesity, it is possible to suggest an increase in a number of individuals with NAFLD. NAFLD is associated with insulin resistance and occurs with an increase in cluster of features of metabolic syndrome and type 2 diabetes. Therefore, it is important to exclude the possibility of diabetes in those individuals with evidence of fatty liver. The global diabetes epidemic continues to grow, and it is estimated that the number of people with diabetes will double by year 2030. NAFLD is also a risk factor for an increase in cardiovascular incidence independent of age, sex, low-density lipoprotein-cholesterol, smoking, and cluster of metabolic syndromes. It is expected that NAFLD will be an important challenge for health providers in the near future. Taking all these factors into consideration, we believe that increasing awareness of metabolic and cardiovascular impact of NAFLD among general practitioners and health authorities may decrease the serious consequences of late diagnosis of NAFLD. Importantly, the collaboration between medical specialties is vital in decreasing the impact of the epidemic of NAFLD. The focus of this review is in the role of primary care physician in diagnosis, treatment and prevention of NAFLD and patients education. 10.4103/2249-4863.152252
    Nonalcoholic fatty liver disease is associated with coronary artery calcium score in diabetes patients with higher HbA1c. Kwak Min-Sun,Yim Jeong Yoon,Kim Donghee,Park Min Jung,Lim Seon Hee,Yang Jong In,Chung Goh Eun,Kim Young Sun,Yang Sun Young,Kim Mi Na,Lee Chang-Hoon,Yoon Jung-Hwan,Lee Hyo-Suk Diabetology & metabolic syndrome BACKGROUND:In patients with diabetes, studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and coronary artery calcium score (CACS) have shown conflicting results. The aim of this study was to evaluate the association between NAFLD and CACS in diabetic patients. METHODS:This is the cohort study performed in Seoul National University Hospital Gangnam Healthcare Center. NAFLD was defined as cases with the typical ultrasonographic findings without excessive alcohol consumption, medications causing hepatic steatosis or other chronic liver diseases. CACS was evaluated using the Agatston method. Diabetes was defined as cases with fasting serum glucose ≥ 126 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or those taking anti-diabetic medications. Multivariate linear regression analyses were performed with use of the interaction term of NAFLD × glycemic level and other confounders of CACS such as age, sex, hypertension, body mass index, waist circumference, HDL cholesterol and triglyceride. RESULTS:A total of 213 participants with diabetes were included in the study. As 77 subjects (36.2%) had CACS 0, causing left sided skewness, CACS was analyzed after log transformation to Ln (CACS + 1). A statistically significant interaction was observed between NAFLD and HbA1c ≥ 7% (P for interaction = 0.014). While NAFLD was not associated with CACS in the group with HbA1c < 7% (P = 0.229), it was significantly associated in the group with HbA1c ≥ 7% (P = 0.010) after adjusting for covariates in multivariate analyses. CONCLUSIONS:This study demonstrated an effect modification of glycemic level on the association between NAFLD and CACS. NAFLD was independently associated with CACS only in diabetes patients with higher HbA1c, after adjustment for confounders. 10.1186/s13098-015-0025-4
    Serum retinol binding protein 4 is associated with visceral fat in human with nonalcoholic fatty liver disease without known diabetes: a cross-sectional study. Chang Xinxia,Yan Hongmei,Bian Hua,Xia Mingfeng,Zhang Linshan,Gao Jian,Gao Xin Lipids in health and disease BACKGROUND:High serum Retinol Binding Protein 4 (RBP4) levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured serum RBP4 and hepatic fat content (HFC), visceral (VFA) and subcutaneous abdominal fat area (SFA) in 106 subjects with non-alcoholic fatty liver disease (NAFLD) without known diabetes. METHODS:106 patients with NAFLD (M/F: 61/45, aged 47.44±14.16 years) were enrolled. Subjects with known diabetes, chronic virus hepatitis, and those with alcohol consumption≥30 g/d in man and ≥20 g/d in woman were excluded. Anthropometrics and laboratory tests, including lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (γ-GT) were conducted. HFC, VFA and SFA were determined by CT scan. Serum RBP4 was detected by an enzyme immunoassay kit and validated by quantitative Western blotting. RESULTS:Circulating RBP4 was negatively associated with high-density lipoprotein cholesterol (HDL-c) (r=-0.392, p<0.001), but positively with waist-to-hip ratio (WHR) (r=0.343, p=0.001), triglyceride (r=0.330, p=0.002), VFA (r=0.298, p=0.027), systolic blood pressure (r=0.247, p=0.020), diastolic blood pressure (r=0.241, p=0.023), γ-GT (r=0.239, p=0.034), waist circumference (r=0.218, p=0.040). Differently, serum RBP4 levels were not associated with HFC (r=0.199, p=0.071), SFA, age, BMI, total cholesterol, low-density lipoprotein cholesterol (LDL-c), ALT or AST (all p>0.05). Multiple linear regression analysis revealed that RBP4 correlated independently with VFA (Standard β=0.357, p=0.019) and HDL-c (Standard β=-0.345, p=0.023) in all subjects, HDL-c (Standard β=-0.315, p=0.040) in men, VFA/SFA in women (Standard β=0.471, p=0.049), not with HFC. However, serum RBP4 was positively correlated with HFC when HFC below 6.34% (r=0.574, p=0.001). CONCLUSIONS:RBP4 could be a marker of abdominal obesity, however, the role of RBP4 in the pathogenesis of NAFLD is not sufficiently elucidated. 10.1186/s12944-015-0033-2
    High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. Portillo-Sanchez Paola,Bril Fernando,Maximos Maryann,Lomonaco Romina,Biernacki Diane,Orsak Beverly,Subbarayan Sreevidya,Webb Amy,Hecht Joan,Cusi Kenneth The Journal of clinical endocrinology and metabolism CONTEXT AND OBJECTIVE:Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. PARTICIPANTS AND METHODS:We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). RESULTS:The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). CONCLUSIONS:The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH. 10.1210/jc.2015-1966
    Use of a Diabetes Self-Assessment Score to Predict Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis. Kim Gyuri,Lee Yong-Ho,Park Young Min,Kim Jungghi,Kim Heesuk,Lee Byung-Wan,Kang Eun Seok,Cha Bong-Soo,Lee Hyun Chul,Kim Dae Jung Medicine Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are strongly associated with obesity, insulin resistance, and type 2 diabetes. We recently developed and validated a self-assessment score in the Korean population to identify people at high risk for diabetes. The objective of this study was to evaluate whether the self-assessment risk score for diabetes can also be used to screen for the presence of NAFLD or NASH.The study population included 15,676 subjects (8313 men and 7363 women) over 20 years old who visited the National Health Insurance Service Ilsan Hospital in Korea between 2008 and 2010. Anthropometric, clinical, and laboratory data were analyzed during regular health checkups. Fatty liver disease was diagnosed using ultrasound, discrimination capability was assessed based on the area under the receiver operating characteristic curve (AUC), and evaluation measures, including sensitivity and specificity, were calculated. Multiple logistic analyses were also performed.We calculated a self-assessed risk score for diabetes (range: 0-11), and a cutoff of ≥5 identified 60% (50%) of men (women) at high risk for NAFLD, reflecting a sensitivity of 79% (85%), a specificity of 60% (66%), a positive predictive value (PPV) of 68% (51%), and a negative predictive value (NPV) of 73% (91%), with an AUC of 0.75 (0.82) for men (women). A cutoff point of ≥6 identified 43% (31%) of men (women) at high risk for NASH, reflecting a sensitivity of 80% (86%), a specificity of 64% (75%), a PPV of 30% (28%), and a NPV of 94% (98%), with an AUC of 0.77 (0.86) for men (women). The odds ratios that a 1-point increase in the diabetes risk scores would be associated with an increased risk for NAFLD and NASH were 1.20 [95% confidence interval (CI): 1.16-1.25] and 1.57 (95% CI: 1.49-1.65), respectively, in men, and 1.28 (95% CI: 1.21-1.34) and 1.89 (95% CI: 1.73-2.07), respectively, in women.The present study indicates that our self-assessment risk score for diabetes could be an effective primary screening tool for the presence of NAFLD or NASH. 10.1097/MD.0000000000001103
    Nonalcoholic Fatty Liver Disease Is Independently Associated with Early Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes. Mantovani Alessandro,Pernigo Matteo,Bergamini Corinna,Bonapace Stefano,Lipari Paola,Pichiri Isabella,Bertolini Lorenzo,Valbusa Filippo,Barbieri Enrico,Zoppini Giacomo,Bonora Enzo,Targher Giovanni PloS one Accumulating evidence suggests that nonalcoholic fatty liver disease (NAFLD) is associated with left ventricular diastolic dysfunction (LVDD) in nondiabetic individuals. To date, there are very limited data on this topic in patients with type 2 diabetes and it remains uncertain whether NAFLD is independently associated with the presence of LVDD in this patient population. We performed a liver ultrasonography and trans-thoracic echocardiography (with speckle-tracking strain analysis) in 222 (156 men and 66 women) consecutive type 2 diabetic outpatients with no previous history of ischemic heart disease, chronic heart failure, valvular diseases and known hepatic diseases. Binary logistic regression analysis was used to examine the association between NAFLD and the presence/severity of LVDD graded according to the current criteria of the American Society of Echocardiography, and to identify the variables that were independently associated with LVDD, which was included as the dependent variable. Patients with ultrasound-diagnosed NAFLD (n = 158; 71.2% of total) were more likely to be female, overweight/obese, and had longer diabetes duration, higher hemoglobin A1c and lower estimated glomerular filtration rate (eGFR) than those without NAFLD. Notably, they also had a remarkably greater prevalence of mild and/or moderate LVDD compared with those without NAFLD (71% vs. 33%; P<0.001). Age, hypertension, smoking, medication use, E/A ratio, LV volumes and mass were comparable between the two groups of patients. NAFLD was associated with a three-fold increased odds of mild and/or moderate LVDD after adjusting for age, sex, body mass index, hypertension, diabetes duration, hemoglobin A1c, eGFR, LV mass index and ejection fraction (adjusted-odds ratio 3.08, 95%CI 1.5-6.4, P = 0.003). In conclusion, NAFLD is independently associated with early LVDD in type 2 diabetic patients with preserved systolic function. 10.1371/journal.pone.0135329
    Plasma osteoprotegerin levels are inversely associated with nonalcoholic fatty liver disease in patients with type 2 diabetes: A case-control study in China. Niu Yixin,Zhang Weiwei,Yang Zhen,Li Xiaoyong,Fang Wenjun,Zhang Hongmei,Wang Suijun,Zhou Houguang,Fan Jiangao,Qin Li,Su Qing Metabolism: clinical and experimental OBJECTIVE:Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF) receptor superfamily, is a decoy receptor for the receptor activator of nucleus factor-κB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). OPG has an effect on systemic insulin sensitivity and glucose homeostasis. The objective of this study was to evaluate the relationship between plasma osteoprotegerin (OPG) levels and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes. MATERIALS/METHODS:A case-control study was performed with 746 patients with type 2 diabetes. Of the study population, 367 patients had B-mode ultrasound-proven NAFLD and 379 were controls. The plasma OPG levels were measured using ELISA methods. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. RESULTS:The OPG levels were significantly decreased in patients with NAFLD (2.3±1.1μg/L vs. 2.8±1.3μg/L, p=3.75×10(5)) compared to controls. Pearson correlation analysis showed that the OPG levels were associated with age and systolic blood pressure (both p<0.05). The participants in the lowest OPG quartile had a significantly increased risk for NAFLD (OR=3.49, 95% CI 1.86-6.94) after adjusting for potential cofounders. CONCLUSIONS:The plasma OPG level is negatively associated with NAFLD independent of potential cofounders. 10.1016/j.metabol.2015.12.005
    Urine uric acid excretion is associated with nonalcoholic fatty liver disease in patients with type 2 diabetes. Zhao Cui-Chun,Wang Ai-Ping,Li Lian-Xi,Li Ting-Ting,Chen Ming-Yun,Zhu Yue,Yu Tian-Pei,Bao Yu-Qian,Jia Wei-Ping Journal of diabetes and its complications AIMS:Elevated serum uric acid is closely associated with nonalcoholic fatty liver disease (NAFLD). However, the association of urine uric acid excretion (UUAE) with NAFLD has not been investigated. Our aims were to explore the associations between UUAE and NAFLD and serum alanine aminotransferase (ALT) in type 2 diabetes mellitus (T2DM). METHODS:This cross-sectional study included 2042 Chinese inpatients with T2DM. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartile based on UUAE levels. NAFLD was determined by ultrasonography. Elevated ALT level was defined with an ALT value >65U/L. RESULTS:There was an obvious increase in both NAFLD prevalence (26.3%, 34.6%, 43.8%, and 56.2%, respectively, p<0.001 for trend) and ALT value [16 (12-24), 17 (13-27), 20 (14-30), and 24 (15-38) U/L, respectively, p<0.001 for trend] across the UUAE quartiles after controlling for confounders. Multiple logistic regression analyses revealed independent associations between UUAE and NAFLD (p=0.002) and elevated ALT level (p<0.001). Compared with the patients in the first quartile of UUAE, those in the second, third and fourth quartiles had 1.528-, 1.869-, and 1.906-fold risk of NAFLD, and 3.620-, 6.223-, and 10.506-fold risk of elevated ALT level in T2DM, respectively. CONCLUSIONS:Increased UUAE levels were significantly associated with the presence of NAFLD and increase of ALT in T2DM. UUAE may be a clinically significant measure in assessing the risk of NAFLD in T2DM. 10.1016/j.jdiacomp.2016.04.017
    Metabolically healthy obesity is associated with an increased risk of diabetes independently of nonalcoholic fatty liver disease. Chang Yoosoo,Jung Hyun-Suk,Yun Kyung Eun,Cho Juhee,Ahn Jiin,Chung Eun Chul,Shin Hocheol,Ryu Seungho Obesity (Silver Spring, Md.) OBJECTIVE:This study examined whether the metabolically healthy obesity (MHO) phenotype was associated with an increased risk of diabetes in a large cohort of metabolically healthy individuals and whether that association differed by presence of nonalcoholic fatty liver disease (NAFLD). METHODS:The cohort consisted of 74,509 Korean adults who were metabolically healthy at baseline, defined as not having any metabolic syndrome component except large waist circumference and having homeostasis model assessment of insulin resistance <2.5. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or any other identifiable cause. RESULTS:Over 304,852.6 person-years of follow-up, 472 participants developed diabetes (incidence density, 1.5 per 1,000 person-years). The multivariable-adjusted hazard ratios (95% confidence intervals) for incident diabetes in subjects with overweight and obesity compared with subjects with normal weight were 1.29 (1.00-2.16) and 1.57 (1.14-2.16), respectively, for subjects without NAFLD and 1.90 (0.95-3.80) and 2.57 (1.32-5.02), respectively, for those with NAFLD (P for interaction =0.57). CONCLUSIONS:In this metabolically healthy population, individuals with overweight and obesity exhibited an increased incidence of diabetes, regardless of the presence of NAFLD. This finding suggests that the obese phenotype per se, independent of the presence of NAFLD, can increase the development of diabetes. 10.1002/oby.21580
    Transient remission of nonalcoholic fatty liver disease decreases the risk of incident type 2 diabetes mellitus in Japanese men. Fukuda Takuya,Hamaguchi Masahide,Kojima Takao,Mitsuhashi Kazuteru,Hashimoto Yoshitaka,Ohbora Akihiro,Kato Takahiro,Nakamura Naoto,Fukui Michiaki European journal of gastroenterology & hepatology INTRODUCTION:It is unclear how the transient remission of nonalcoholic fatty liver disease (NAFLD) affects incident type 2 diabetes mellitus (T2DM). Here, we sought to determine the effect of the transient remission of NAFLD on incident T2DM in Japanese men. MATERIALS AND METHODS:We used a population-based health check-up program. The primary outcome was set as incident T2DM. We divided the participants who showed NAFLD at the time of enrollment into three groups according to their clinical course of NAFLD: the Regression group, in which the participants showed a regression of NAFLD and no relapse during the follow-up period; the Transient Remission group, in which participants achieved a transient remission of NAFLD, but had a relapse of NAFLD; and the Persistent group, in which participants showed NAFLD throughout the follow-up. The Never group of participants who did not show NAFLD throughout the follow-up served as a reference. RESULTS:The incidence rates of T2DM in the Never group, the Regression group, the Transient Remission group, and the Persistent group were 4.7% (62/1306), 9.2% (14/153), 18.0% (25/139), and 35.1% (120/342), respectively. In a multivariate Cox regression analysis with covariates, the adjusted hazard ratios for incident T2DM compared with the Never group were as follows: Regression group: 1.08 [95% confidence interval (CI) 0.53-2.04, P=0.81], Transient Remission group: 2.12 (95% CI 1.22-3.57, P<0.01), and Persistent group: 3.44 (95% CI 2.29-5.21, P<0.001). The adjusted hazard ratio of the Transient Remission group was significantly lower than that of the Persistent group (P<0.05). CONCLUSION:Transient remission of NAFLD significantly decreased the risk of developing T2DM. 10.1097/MEG.0000000000000736
    Nonalcoholic Fatty Liver Disease Is Prevalent in Women With Prior Gestational Diabetes Mellitus and Independently Associated With Insulin Resistance and Waist Circumference. Foghsgaard Signe,Andreasen Camilla,Vedtofte Louise,Andersen Emilie S,Bahne Emilie,Strandberg Charlotte,Buhl Thora,Holst Jens J,Svare Jens A,Clausen Tine D,Mathiesen Elisabeth R,Damm Peter,Gluud Lise L,Knop Filip K,Vilsbøll Tina Diabetes care OBJECTIVE:Type 2 diabetes increases the risk of nonalcoholic fatty liver disease (NAFLD), which is a potentially reversible condition but is also associated with progressive fibrosis and cirrhosis. Women with prior gestational diabetes mellitus (pGDM) have a higher risk for NAFLD. RESEARCH DESIGN AND METHODS:One hundred women without diabetes who had pGDM (median [interquartile range]: age 38.6 [6.4] years; BMI 31.0 [6.2] kg/m) and 11 healthy control subjects without NAFLD (age 37.9 [7.8] years; BMI 28.1 [0.8] kg/m) underwent a 75-g oral glucose tolerance test (OGTT), DXA whole-body scan, and ultrasonic evaluation of hepatic steatosis. RESULTS:Twenty-four (24%) women with pGDM had NAFLD on the basis of the ultrasound scan. None had cirrhosis. Women with NAFLD had a higher BMI (P = 0.0002) and waist circumference (P = 0.0003), increased insulin resistance (P = 0.0004), and delayed suppression of glucagon after the OGTT (P < 0.0001), but NAFLD was not associated with the degree of glucose intolerance (P = 0.2196). Visceral fat mass differed among the three groups, with the NAFLD group having the highest amount of fat and the control subjects the lowest (P = 0.0003). By logistic regression analysis, insulin resistance (P = 0.0057) and waist circumference (P = 0.0109) were independently associated with NAFLD. CONCLUSIONS:NAFLD was prevalent in this cohort of relatively young and nonseverely obese women with pGDM who are considered healthy apart from their increased risk for diabetes. Insulin resistance and a larger waist circumference were independently associated with the presence of NAFLD, whereas glucose intolerance was not. 10.2337/dc16-1017
    [Impact of physical activity on anthropometric indices in patients with nonalcoholic fatty liver disease and pre-diabetes or type 2 diabetes]. Івачевська Віталіна В Wiadomosci lekarskie (Warsaw, Poland : 1960) INTRODUCTION:Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in many developed countries. The first step, which is offered to all patients with NAFLD includes lifestyle modifications, low-calorie diet, increased physical activity and giving up smoking. OBJECTIVE:to evaluate the efficiency of the daily 30-minute walking at a fast pace on the dynamics of anthropometric indices in patients with NAFLD and pre-diabetes or type 2 diabetes. MATERIALS AND METHODS:The study included 59 patients with nonalcoholic fatty liver disease and impaired carbohydrate metabolism, which conducted a comprehensive clinical examination that included collection of anthropometric data, physical examination and taking venous blood for laboratory analysis, ultrasound of the abdomen. RESULTS:According to statistical analysis, patients on the background of NAFLD and pre-diabeetes / type 2 diabetes, performing daily 30-minute walks at a fast pace, found significant changes of anthropometric indices. CONCLUSIONS:Daily 30-minute walking at a fast pace is an effective method on reduction of body weight in patients with NAFLD and pre-diabetes or type 2 diabetes.
    Associations of Fatty Liver Disease with Hypertension, Diabetes, and Dyslipidemia: Comparison between Alcoholic and Nonalcoholic Steatohepatitis. Toshikuni Nobuyuki,Tsuchishima Mutsumi,Fukumura Atsushi,Arisawa Tomiyasu,Tsutsumi Mikihiro Gastroenterology research and practice Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are representative types of fatty liver disease (FLD) and have similar histologic features. In this study, we aimed to compare the associations of the two FLD types with hypertension (HT), diabetes mellitus (DM), and dyslipidemia (DL). A nationwide survey investigating FLD status included 753 Japanese subjects (median age 55 years; male 440, female 313) with biopsy-proven ASH ( = 172) or NASH ( = 581). We performed a multiple logistic regression analysis to identify the factors associated with HT, DM, or DL. Older age and a higher body mass index were significant factors associated with HT. Older age, female sex, a higher body mass index, advanced liver fibrosis, and the NASH type of FLD (odds ratio 2.77; 95% confidence interval 1.78-4.31; < 0.0001) were significant factors associated with DM. Finally, the NASH type of FLD (odds ratio 4.05; 95% confidence interval 2.63-6.24; < 0.0001) was the only significant factor associated with DL. Thus, the associations of NASH with DM and DL were stronger than those of ASH with DM and DL. In the management of FLD subjects, controlling DM and DL is particularly important for NASH subjects. 10.1155/2017/9127847
    Nonalcoholic fatty liver disease can be predicted by retinal vascular changes in patients with obesity without hypertension or diabetes. Romero-Ibarguengoitia Maria E,Herrera-Rosas Arturo,Domínguez-Mota Alfredo A,Camas-Benitez Jinny T,Serratos-Canales María F,León-Hernández Mireya,González-Chávez Antonio,López-Ortiz Eduardo,Mummidi Srinivas,Duggirala Ranvidranth,López-Alvarenga Juan C European journal of gastroenterology & hepatology OBJECTIVE:To evaluate the utility of predicting nonalcoholic fatty liver disease (NAFLD) and obesity by retinal vascular changes (RVC) found in fundoscopy and to determine whether this is related to a low-grade inflammatory process. METHODS:We carried out a cross-sectional analysis that included 152 (ages 18-45 years) patients divided into four groups: NAFLD and BMI less than 25, absence of NAFLD and BMI less than 25, NAFLD and BMI more than 30, and absence of NAFLD and BMI more than 30. Retinal fundoscopy, hepatic ultrasound, metabolic profile, and cytokine measurement were performed. We calculated odds ratio [95% confidence interval (CI)], performed diagnostic utility tests, and carried out a 2 factorial analysis. RESULTS:Obesity was associated with RVC (odds ratio: 21.25; 95% CI: 8.79-51.4) and NAFLD [25 (9.07-72.6)]. NAFLD was associated with RVC [11.24 (4.98-26.48)], and the prediction of NAFLD showed a sensitivity of 75% (95% CI: 68-82) and a specificity of 81% (75-86); when RVC-obesity were combined, sensitivity increased to 90% (88-91.7), with a specificity of 85% (84-85.8). C-reactive protein was associated with the three factors, suggesting an independent contribution. Thin patients with RVC and NAFLD had higher concentrations of interleukin-2, interleukin-6, tumor necrosis factor-α, and interferon-γ. CONCLUSION:NAFLD in patients with obesity without diabetes or hypertension can be predicted by RVC, a noninvasive technique carried out by eye fundoscopy. NAFLD alone can drive inflammatory conditions in the absence of obesity that manifests as RVC. 10.1097/MEG.0000000000000900
    Nonalcoholic fatty liver disease is associated with an increased risk of heart block in hospitalized patients with type 2 diabetes mellitus. Mantovani Alessandro,Rigolon Riccardo,Pichiri Isabella,Bonapace Stefano,Morani Giovanni,Zoppini Giacomo,Bonora Enzo,Targher Giovanni PloS one Recent studies suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of cardiac tachyarrhythmias (mainly atrial fibrillation) in patients with and without type 2 diabetes mellitus. The aim of this study was to examine whether an association also exists between NAFLD and heart block. We have retrospectively evaluated a hospital-based cohort of 751 patients with type 2 diabetes discharged from our Division of Diabetes and Endocrinology during years 2007-2014. Standard electrocardiograms were performed on all patients. Diagnosis of NAFLD was based on ultrasonography, whereas the severity of advanced hepatic fibrosis was based on the fibrosis (FIB)-4 score and other non-invasive fibrosis markers. Overall, 524 (69.8%) patients had NAFLD and 202 (26.9%) had heart block (defined as at least one block among first-degree atrio-ventricular block, second-degree block, third-degree block, left bundle branch block, right bundle branch block, left anterior hemi-block or left posterior hemi-block) on electrocardiograms. Patients with NAFLD had a remarkably higher prevalence of any persistent heart block than those without NAFLD (31.3% vs. 16.7%, p<0.001); this prevalence was particularly increased among those with higher FIB-4 score. NAFLD was associated with a threefold increased risk of prevalent heart block (adjusted-odds ratio 3.04, 95% CI 1.81-5.10), independently of age, sex, hypertension, prior ischemic heart disease, hemoglobin A1c, microvascular complication status, use of medications and other potentially confounding factors. In conclusion, this is the largest cross-sectional study to show that NAFLD and its severity are independently associated with an increased risk of prevalent heart block in hospitalized patients with type 2 diabetes. 10.1371/journal.pone.0185459
    Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus. Targher Giovanni,Lonardo Amedeo,Byrne Christopher D Nature reviews. Endocrinology Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases. 10.1038/nrendo.2017.173
    Nonalcoholic Fatty Liver Disease and Abdominal Fat Accumulation According to Vitamin D Status in Patients with Type 2 Diabetes. Choi Dug-Hyun,Jung Chan-Hee,Mok Ji-Oh,Kim Chul-Hee,Kang Sung Koo,Kim Bo-Yeon Journal of obesity & metabolic syndrome Background:Vitamin D deficiency is known to increase the incidence of metabolic syndrome. Nonalcoholic fatty liver disease is a common metabolic disease in patients with type 2 diabetes. This study evaluated nonalcoholic fatty liver disease and abdominal fat accumulation according to 25-hydroxyvitamin D status in patients with type 2 diabetes. Methods:The study comprised 302 patients with type 2 diabetes. Patients were divided into three groups based upon their 25-hydroxyvitamin D status: vitamin D deficient group (<10 ng/mL), vitamin D insufficient group (≥10 to <20 ng/mL) and vitamin D sufficient group (≥20 ng/mL). Patient clinical and laboratory markers were evaluated retrospectively. Results:Visceral fat thickness was significantly higher in the vitamin D deficient group. There were no differences in glycemic control, body mass index, and subcutaneous fat thickness correlated with 25-hydroxyvitamin D status. The prevalence of nonalcoholic fatty liver disease was significantly higher in the vitamin D deficient group compared to the vitamin D sufficient and vitamin D insufficient groups. In multivariate logistic analysis, after adjustment for age, sex, body mass index, glycated hemoglobin and homeostasis model assessment of insulin resistance, patients with type 2 diabetes in the vitamin D sufficient group showed significantly lower odds ratio for nonalcoholic fatty liver disease than those within the vitamin D deficient group. Conclusion:In type 2 diabetes, the vitamin D deficient group showed thicker visceral fat thickness and higher nonalcoholic fatty liver disease prevalence. 10.7570/jomes.2018.27.1.53
    Nonalcoholic fatty liver disease as a sentinel marker for the development of diabetes mellitus in non-obese subjects. Kim Soon Sun,Cho Hyo Jung,Kim Hyun Ji,Kang Dae Ryong,Berry Jacob R,Kim Jin Hong,Yang Min Jae,Lim Sun Gyo,Kim SooJin,Cheong Jae Youn,Cho Sung Won Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver BACKGROUND:Non alcoholic fatty liver disease (NAFLD) is associated with substantial cardiometabolic morbidity. AIMS:We evaluated the long-term extrahepatic complications of NAFLD and sought to evaluate NAFLD in non-obese subjects. METHODS:A total of 2920 participants were retrospectively selected from a health check-up center in 2000, and followed through to December 2010. NAFLD was diagnosed using ultrasonography. Subjects were stratified according to body mass index, NAFLD, and metabolic syndrome. RESULTS:The prevalence of non-obese NAFLD subjects and metabolically unhealthy non-obese subjects was 14.4% and 8.7%, respectively. In the multivariate analysis, non-obese NAFLD subjects had a significantly higher risk for diabetes mellitus (DM; HR 2.69, 95% CI 1.72-4.20, P < 0.001); no increase was observed for hypertension or cardiovascular disease. Metabolically unhealthy non-obese subjects had a significantly higher risk for hypertension (HR 2.75, 95% CI 2.02-3.74, P < 0.001), DM (HR 5.72, 95% CI 3.68-8.89, P < 0.001), and cardiovascular disease (HR 2.93, 95% CI 1.53-5.63, P = 0.001). Subgroup analysis of non-obese subjects showed that NAFLD, without metabolic syndrome, conferred a higher risk for DM (HR 3.60, 95% CI 2.03-6.39, P < 0.001). CONCLUSION:Non-obese subjects with NAFLD are at a higher risk for DM independent of metabolic syndrome. 10.1016/j.dld.2017.12.018
    The Relationship Between Liver Enzymes and Insulin Resistance in Type 2 Diabetes Patients with Nonalcoholic Fatty Liver Disease. Sheng Xia,Che Hui,Ji Qingming,Yang Fan,Lv Jie,Wang Yueqiu,Xian Huimin,Wang Lihong Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme Non-: alcoholic fatty liver disease (NAFLD) is prevalent worldwide, especially in patients with type 2 diabetes. Liver enzymes are the main warning signs of liver injury and insulin resistance (IR) is critical to NAFLD. This study was aimed to investigate the association between liver enzymes and insulin resistance in type 2 diabetes patients with NAFLD. Data from 212 diabetes patients with NAFLD were analyzed, including 118 males and 94 females who received care from 2014 to 2015. The patients were divided into three groups by severity (mild n=87, moderate n=89, severe n=36). All patients underwent standard clinical and laboratory examinations. Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT) were measured, serum fasting glucose and serum fasting insulin were obtained. IR was assessed using the homeostasis model assessment insulin resistance index (HOMA-IR). Age, sex, and BMI did not significantly differ in patients (p>0.05). Compared with normal levels, elevated ALT and AST were associated with a higher HOMA-IR (p=0.0035, p=0.0096, respectively). HOMA-IR did not significantly differ (p>0.05) between patients with normal and elevated GGT. HOMA-IR increased as the levels of liver enzymes increased, and each enzyme showed a significant association with HOMA-IR (p=0.0166, p<0.0001, and p <0.0001). HOMA-IR differs between normal and elevated ALT and AST. Liver enzymes are associated with HOMA-IR in type 2 diabetes patients with NAFLD. These findings can help evaluate the degree of IR and hepatocellular steatosis in patients and prevent the progression of type 2 diabetes and NAFLD in clinical practice. 10.1055/a-0603-7899
    Low serum CTRP3 levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Zhang Junxia,Zhang Bilin,Cheng Yangyang,Xu Jinxiu Cytokine Nonalcoholic fatty liver disease (NAFLD) commonly occurs in patients with type 2 diabetes mellitus (T2DM). C1q/TNF-related protein-3 (CTRP3) levels are decreased in type 2 diabetic patients. However, to date, it is unknown whether low CTRP3 level are correlated with the incidence of NAFLD. The aim of this study was to observe this association in Chinese patients with T2DM. Overall, 175 newly diagnosed T2DM were recruited in this study. The subjects were divided into NAFLD group (n=93) and control group (n=82). Anthropometric parameters, blood pressure, and several biochemical parameters were measured. The body composition was assessed with the bioelectrical impedance analysis (BIA) method. Insulin level was evaluated by radioimmunoassay. Levels of serum CTRP3 and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Our findings demonstrated that type 2 diabetic patients with NAFLD had lower levels of serum CTRP3 than did those without NAFLD (P=.002). Serum CTRP3 level was negatively correlated with body mass index (r=-0.271, P=.001), visceral fat area (r=-0.285, P<.001), glycosylated hemoglobin A1c (r=-0.270, P<.001), triglycerides (r=-0.267, P<.001), CRP (r=-0.222, P=.010), IL-6 (r=-0.212, P=.008), and HOMA-IR indices (r=-0.334, P<.001). When compared with the highest CTRP3 tertile, the odds ratio of the middle tertile for NAFLD incidence was 4.54 (95% CI, 1.53-13.47) and 5.80 (95% CI, 1.60-21.02) for the lowest tertile after adjustment for confounding factors. In summary, low serum CTRP3 is a strong predictor for the prevalence of NAFLD in Chinese patients with newly diagnosed T2DM. 10.1016/j.cyto.2017.10.023
    Management of nonalcoholic fatty liver disease: Lessons learned from type 2 diabetes. Alkhouri Naim,Poordad Fred,Lawitz Eric Hepatology communications Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of insulin resistance, which is the hallmark of type 2 diabetes (T2D). NAFLD is a known risk factor for developing T2D and has a very high prevalence in those with existing T2D. The diabetes spectrum includes several conditions from prediabetes to T2D to insulin-dependent diabetes leading to macrovascular and microvascular complications. Similarly, NAFLD has a histologic spectrum that ranges from the relatively benign nonalcoholic fatty liver to the aggressive form of nonalcoholic steatohepatitis with or without liver fibrosis to nonalcoholic steatohepatitis-cirrhosis leading to end-stage liver disease. The management of T2D has witnessed significant changes over the past few decades with multiple new drug classes entering the treatment algorithm. Unfortunately, there are no U.S. Food and Drug Administration-approved medications to treat NAFLD, and guidelines for the management of NAFLD are less established. However, the field of drug development in NAFLD has witnessed a revolution over the past 5 years with the establishment of a regulatory pathway for Food and Drug Administration approval; this has generated substantial interest from pharmaceutical companies. Several diabetes medications have been studied as potential treatments for NAFLD with promising results; moreover, drugs that target specific pathways that play a role in NAFLD development and progression are being developed at a rapid pace. Given the similarities between NAFLD and T2D in terms of pathogenesis, underlying risk factors, and disease spectrum, lessons learned from optimizing treatment for T2D can be extrapolated to the management of NAFLD. The aim of this review is to use the founding principles of the comprehensive type 2 diabetes management algorithm to optimize the management of NAFLD. ( 2018;2:778-785). 10.1002/hep4.1195
    Nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and its association with cardiovascular disease. Vanjiappan Sivabal,Hamide Abdoul,Ananthakrishnan Ramesh,Periyasamy Senthilkumar Gandhipuram,Mehalingam Vadivelan Diabetes & metabolic syndrome INTRODUCTION:Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver disease that ranges from hepatic steatosis to non-alcoholic steatohepatitis. Obesity and diabetes mellitus are the prime risk factors for NAFLD. The aim of this study was to find out the prevalence of NAFLD among patients with type 2 diabetes mellitus and to detect the association of NAFLD with cardiovascular disease in them. STUDY DESIGN:Prospective observational study. MATERIAL AND METHODS:The study was conducted on 300 patients with type 2 diabetes mellitus attending the outpatient department of a tertiary care teaching hospital. All patients underwent hepatic ultrasonography to look for hepatic steatosis. Among the 300 patients, 124 were divided into NAFLD and non-NAFLD groups based on the ultrasound findings. These patients were subjected to electrocardiogram, 2D echocardiogram, carotid intima media thickness (CIMT) measurement and ankle brachial pressure index measurement along with measurement of markers of oxidative stress. RESULTS:Hepatic steatosis was present in 61% of diabetic patients in this study. Cardiovascular disease was not found to be significantly associated in diabetic patients with NAFLD. However, cardiovascular risk factors like CIMT, high sensitivity c-reactive protein (hs-CRP) and malondialdehyde (MDA) were elevated in these patients. hs-CRP and MDA levels were found to be significantly associated with the severity of NAFLD. CONCLUSION:There is a high prevalence of NAFLD in type 2 diabetic patients. No correlation was detected between the presence of NAFLD and cardiovascular disease in them; although there was an association between cardiovascular risk factors and NAFLD. 10.1016/j.dsx.2018.01.001
    Nonalcoholic Fatty Liver Disease and Risk of Diabetes: A Prospective Study in China. Shen Xiuhua,Cai Jianfang,Gao Jingsheng,Vaidya Anand,Liu Xuemei,Li Wen,Chen Shuohua,Zhou Yong,Li Yinge,Zhang Yanmin,Zhao Jianqiu,Hu Frank B,Wu Shouling,Gao Xiang Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists OBJECTIVE:We aimed to investigate whether liver steatosis severity affects the risk of developing diabetes in a large cohort study. METHODS:We prospectively examined the association in 41,650 Chinese adults with negative hepatitis-B surface antigen who were free of alcohol consumption, diabetes, and liver cirrhosis at baseline. Cox proportional models were used to estimate the risk of diabetes after a mean of 3.6 years of follow-up. Nonalcoholic fatty liver disease (NAFLD) was assessed with hepatic ultrasonography. Elevated alanine transaminase (ALT) was defined as ALT concentrations >19 and >30 U/L in females and males, respectively. Diabetes was defined as a fasting glucose 7.0 mmol/L or treatment with hypoglycemic medication. RESULTS:Liver steatosis severity was significantly associated with higher risks of developing diabetes (adjusted hazard ratio [HR] for severe vs. without NAFLD = 2.66, 95% confidence interval [CI]: 2.17-3.25, P-trend<.001) and impaired fasting glucose (fasting glucose between 5.6 and 6.9 mmol/L, adjusted HR = 1.36, 95% CI: 1.16-1.59, P-trend<.001), as well as a faster increase rate of fasting glucose concentrations ( P-trend<.001), during 3.6 years of follow-up. Elevated ALT was also associated with incident diabetes (HR = 1.12, 95% CI: 1.02-1.22), adjusting for NAFLD and other covariates. CONCLUSION:We observed a dose-response relationship between liver steatosis severity and increased diabetes risk, and ALT may predict incident diabetes independently of NAFLD. ABBREVIATIONS:ALT = alanine transaminase; BP = blood pressure; CI = confidence interval; HCV = hepatitis C virus; HR = hazard ratio; IFG = impaired fasting glucose; NAFLD = nonalcoholic fatty liver disease; ULN = upper limit of normal. 10.4158/EP-2018-0098
    Twenty-five-year trajectories of insulin resistance and pancreatic β-cell response and diabetes risk in nonalcoholic fatty liver disease. VanWagner Lisa B,Ning Hongyan,Allen Norrina B,Siddique Juned,Carson April P,Bancks Michael P,Lewis Cora E,Carr John Jeffrey,Speliotes Elizabeth,Terrault Norah A,Rinella Mary E,Vos Miriam B,Lloyd-Jones Donald M Liver international : official journal of the International Association for the Study of the Liver BACKGROUND & AIMS:Insulin resistance is a risk marker for non-alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and β-cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non-alcoholic fatty liver disease. METHODS:Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi-racial cohort of adults age 18-30 years at baseline (1985-1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010-2011), non-alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25-year trajectories in homeostatic model assessment insulin resistance and β-cell response homeostatic model assessment-β. RESULTS:Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low-stable [47%]; moderate-increasing [42%]; and high-increasing [12%]) and homeostatic model assessment-β (low-decreasing [16%]; moderate-decreasing [63%]; and high-decreasing [21%]). Y25 non-alcoholic fatty liver disease prevalence was 24.5%. Among non-alcoholic fatty liver disease, high-increasing homeostatic model assessment insulin resistance (referent: low-stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0-31.9) and incident (OR = 10.5, 2.6-32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non-alcoholic fatty liver disease participants with low-decreasing homeostatic model assessment-β (referent: high-decreasing) had the highest odds of prevalent (OR = 14.1, 3.9-50.9) and incident (OR = 10.3, 2.7-39.3) diabetes. CONCLUSION:Trajectories of insulin resistance and β-cell response during young and middle adulthood are robustly associated with diabetes risk in non-alcoholic fatty liver disease. Thus, how persons with non-alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non-alcoholic fatty liver disease assessment. 10.1111/liv.13747
    Renal Dysfunction in Patients With Nonalcoholic Fatty Liver Disease is Related to the Presence of Diabetes Mellitus and Severity of Liver Disease. Nampoothiri Ram V,Duseja Ajay,Rathi Manish,Agrawal Swastik,Sachdeva Naresh,Mehta Manu,Dhaliwal Harpal S,Dhiman Radha K,Chawla Yogesh Journal of clinical and experimental hepatology Background and aims:There is sparse data on the prevalence of renal dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the presence of renal dysfunction in patients with NAFLD and correlate it with the severity of liver disease. Methods:One hundred nonalcoholic patients with ultrasound showing hepatic steatosis were enrolled into the study after exclusion of other causes. Presence of renal dysfunction was estimated by glomerular filtration rate and by evaluating 24 h urinary protein and microalbumin. Various risk factors including components of metabolic syndrome, severity of hepatic steatosis (as assessed on ultrasound), hepatic necro-inflammation (as assessed by hepatic transaminases) and hepatic fibrosis (as assessed by transient elastography) were correlated with the presence of renal dysfunction. Results:Twenty eight (28%) patients with NAFLD had evidence of impaired renal function with 5 (5%) having abnormal glomerular filtration rate, 18 (18%) having significant proteinuria and 5 (5%) having both. Presence of type 2 diabetes mellitus, raised hepatic transaminases and advanced fibrosis on transient elastography were found as independent predictors of impaired renal function with raised hepatic transaminases having the best sensitivity (89%) and presence of advanced fibrosis the best specificity (90%). A model comprising of these three parameters had good accuracy (AUROC = 0.763) in predicting impaired renal function in patients with NAFLD. Conclusions:Around one-third of patients with NAFLD have impaired renal functions. Prevalence of impaired renal function in patients with NAFLD is dependent on the severity of liver disease and presence of diabetes mellitus. 10.1016/j.jceh.2017.12.005
    Insulin Resistance Exacerbates Genetic Predisposition to Nonalcoholic Fatty Liver Disease in Individuals Without Diabetes. Barata Llilda,Feitosa Mary F,Bielak Lawrence F,Halligan Brian,Baldridge Abigail S,Guo Xiuqing,Yerges-Armstrong Laura M,Smith Albert V,Yao Jie,Palmer Nicholette D,VanWagner Lisa B,Carr J Jeffrey,Chen Yii-Der I,Allison Matthew,Budoff Matthew J,Handelman Samuel K,Kardia Sharon L R,Mosley Thomas H,Ryan Kathleen,Harris Tamara B,Launer Lenore J,Gudnason Vilmundur,Rotter Jerome I,Fornage Myriam,Rasmussen-Torvik Laura J,Borecki Ingrid B,O'Connell Jeffrey R,Peyser Patricia A,Speliotes Elizabeth K,Province Michael A Hepatology communications The accumulation of excess fat in the liver (hepatic steatosis) in the absence of heavy alcohol consumption causes nonalcoholic fatty liver disease (NAFLD), which has become a global epidemic. Identifying metabolic risk factors that interact with the genetic risk of NAFLD is important for reducing disease burden. We tested whether serum glucose, insulin, insulin resistance, triglyceride (TG), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, body mass index (BMI), and waist-to-hip ratio adjusted for BMI interact with genetic variants in or near the patatin-like phospholipase domain containing 3 () gene, the glucokinase regulatory protein () gene, the neurocan/transmembrane 6 superfamily member 2 () gene and the lysophospholipase-like 1 () gene to exacerbate hepatic steatosis, estimated by liver attenuation. We performed association analyses in 10 population-based cohorts separately and then meta-analyzed results in up to 14,751 individuals (11,870 of European ancestry and 2,881 of African ancestry). We found that rs738409 significantly interacted with insulin, insulin resistance, BMI, glucose, and TG to increase hepatic steatosis in nondiabetic individuals carrying the G allele. Additionally, rs780094 significantly interacted with insulin, insulin resistance, and TG. Conditional analyses using the two largest European ancestry cohorts in the study showed that insulin levels accounted for most of the interaction of rs738409 with BMI, glucose, and TG in nondiabetic individuals. Insulin, -rs738409, and their interaction accounted for at least 8% of the variance in hepatic steatosis in these two cohorts. Insulin resistance, either directly or through the resultant elevated insulin levels, more than other metabolic traits, appears to amplify the -rs738409-G genetic risk for hepatic steatosis. Improving insulin resistance in nondiabetic individuals carrying rs738409-G may preferentially decrease hepatic steatosis. 10.1002/hep4.1353
    Diet-Induced Alteration of Microbiota and Development of Obesity, Nonalcoholic Fatty Liver Disease, and Diabetes: Study Protocol of a Prospective Study. Uittenbogaart Martine,Leclercq Wouter Kg,Bonouvrie Danielle,Romeijn Marleen M,Luijten Arijan Apm,Olde Damink Steven Wm,van Dielen Francois Mh,Rensen Sander S JMIR research protocols BACKGROUND:Development of obesity and obesity-related diseases, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), is associated with altered gut microbiota composition. The aim of this study is to investigate associations among dietary compounds, intestinal cell function, and gut microbiota composition. We hypothesize that dietary lipid intake is associated with Paneth cell and goblet cell properties that affect gut microbiota composition. OBJECTIVE:The primary objective of this study is to determine whether a difference in dietary intake is associated with a difference in intestinal mucin-2 expression and gut microbiota composition. METHODS:This is a single-center prospective study, including 1 obese group undergoing laparoscopic Roux-en-y gastric bypass and 2 lean control groups undergoing either laparoscopic cholecystectomy or upper gastrointestinal endoscopy (n=228). During laparoscopy, biopsies will be taken of visceral fat (omentum majus), liver, muscle tissue of the abdominal wall, and subcutaneous fat. In the obese group, a small segment of the jejunum will be collected for analysis, which will be compared with an endoscopically derived jejunal biopsy from the upper gastrointestinal endoscopy control group. Stool samples for microbiota profiling will be collected at baseline and 1 year after surgery. Primary outcomes are fecal microbiota composition and mucus characteristics. Secondary outcomes include Paneth cell phenotype, body weight, diet composition, glucose tolerance, resolution of comorbidities, and weight loss 1 year after surgery. RESULTS:This trial is currently open for recruitment. The anticipated completion date is December 2019. CONCLUSIONS:The Diet-Induced Alteration of Microbiota and Development of Obesity, NAFLD, and Diabetes study will improve insight into the pathophysiology of obesity and its associated metabolic disorders. Better understanding of weight loss failure and weight regain following bariatric surgery might also behold new therapeutic opportunities for obesity and obesity-related comorbidities. TRIAL REGISTRATION:Netherlands Trial Register NTR5660; https://www.trialregister.nl/trial/5540 (Archived by WebCite at http://www.webcitation.org/78l7jOZre). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/11553. 10.2196/11553
    Serum fetuin-B level is an independent marker for nonalcoholic fatty liver disease in patients with type 2 diabetes. El-Ashmawy Hazem M,Ahmed Azza M European journal of gastroenterology & hepatology OBJECTIVE:Previous studies have assessed serum fetuin-B and its relation to nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) and as a link between them through inducing insulin resistance (IR). Therefore, we examined the potential of serum fetuin-B to be an independent marker for NAFLD in patients with T2DM. PATIENTS AND METHODS:The study group consisted of 270 patients with T2DM. Clinical and laboratory features were evaluated. The NAFLD severity was graded by ultrasound into three subgroups: grade 0 (no fatty liver), grade 1 (mild fatty liver), and grade 2-3 (medium to severe fatty liver). Fetuin-B, retinol-binding protein-4, and adiponectin were measured. RESULTS:Patients with grade 2-3 NAFLD had high fetuin-B levels in comparison with non-NAFLD group. Age and sex adjusted fetuin-B demonstrated positive correlations with triglycerides, γ-glutamyl transferase, fasting plasma glucose, 2-h postprandial plasma glucose, homeostasis model assessment of IR, fasting insulin, glycated hemoglobin, high-sensitivity C-reactive protein, and estimated glomerular filtration rate, but it had a negative correlation with serum creatinine. Adiponectin level was decreased with increasing NAFLD severity, but no difference was found in retinol-binding protein-4. The estimated odds ratio (OR) for the occurrence of grade 2-3 NAFLD was increased significantly with increasing levels of fetuin-B (OR: 3.92; 95% confidence interval: 2.14-8.32 vs. OR: 8.91; 95% confidence interval: 4.22-18.41). The OR of fetuin-B in the uppermost tertile group was still significant after controlling for homeostasis model assessment of IR, glycated hemoglobin, waist circumference, BMI, hepatic enzymes, high-density lipoprotein cholesterol, triglycerides, and high-sensitivity C-reactive protein. CONCLUSIONS:Our study demonstrated that serum fetuin-B had an independent association with NAFLD in patients with T2DM. 10.1097/MEG.0000000000001354
    Evaluation of left atrial function in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease by two-dimensional speckle tracking echocardiography. Chang Wenxing,Wang Ying,Sun Lihua,Yu Dong,Li Ying,Li Guangsen Echocardiography (Mount Kisco, N.Y.) OBJECTIVE:To assess left atrial function in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD) by two-dimensional speckle tracking echocardiography (2D-STE). METHODS:We classified 97 patients with T2DM into three groups according to the results of liver ultrasonography: group A (without NAFLD), group B (mild fatty liver), and group C (moderate to severe fatty liver). Conventional echocardiography parameters included left atrial end-systolic diameter (LAD), left ventricular end-systolic and end-diastolic diameter (LVDs, LVDd), end-diastolic thickness of ventricular septumi and LV posterior wall (IVSTd, LVPWTd), peak E and A of mitralis (E, A), septal and lateral early (e') mitral annular diastolic tissue velocities, then calculated E/A and E/mean e'. We measured LV ejection fraction (LVEF) and left atrial (LA) volumes (max, min, and preatrial contraction volume) by Simpson's rule, then calculated LA passive and active ejection fraction (LAPEF, LAAEF), left atrial maximum volume index (LAVImax). The global peak longitudinal systolic strain (LASRs), early diastolic strain (LASRe), and late diastolic strain (LASRa) rates of the LA were obtained by 2D-STE. RESULTS:No differences were found between groups A and B (all P > 0.05). In group C, LAAEF and LASRa were obviously higher, while LAPEF, LASRe, and LASRs were obviously decreased compared with those values in groups A and B (all P < 0.05). The association between the severity of NAFLD and the differences in LA strain values remained significant after adjustment for confounders. CONCLUSION:Two-dimensional speckle tracking echocardiography can evaluate the left atrial function in T2DM patients with NAFLD. 10.1111/echo.14400
    [Predictive value of body mass index combined with waist circumference for new-onset nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus]. Wang Shan,Zhang Jian,Zhang Weihuan,Wang Haitao,Hou Jingyue,Zhang Ruixiu,Liu Hongfen,Wu Shouling Nan fang yi ke da xue xue bao = Journal of Southern Medical University OBJECTIVE:To investigate the predictive value of body mass index (BMI) combined with waist circumference (WC) for new-onset nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS:This community-based prospective cohort study was conducted among 3501 T2DM patients without NAFLD recruited from the staff of Kailuan Company, who underwent routine physical examination in the year 2006 and 2007, and a total of 2920 subjects were included in the final analysis. According to the baseline BMI and WC, the subjects were divided into group A (with normal BMI and WC), group B (with normal BMI but elevated WC), group C (with elevated BMI but a normal WC) and group D (with elevated BMI and WC). The subjects in the 4 groups were followed for the occurrence of NAFLD by reviewing their reports of physical examinations during the periods of 2008-2009, 2010-2011, 2012-2013, 2014-2015 and 2016-2017. The cumulative incidence of NAFLD was compared across the 4 groups and Cox regression analysis was used to test the correlation of BMI and WC with new onset of NAFLD. RESULTS:The cumulative incidence of NAFLD increased progressively in the 4 groups (50%, 66%, 68% and 77%, respectively). Cox regression analysis showed that compared with group A, groups B, C and D had increased risks of NAFLD after adjusting for age, gender and other risk factors, with HR values of 1.62, 1.98 and 2.47, respectively. CONCLUSIONS:Elevated BMI and WC are both independent risk factors for NAFLD in type 2 diabetic patients, and the combination of BMI and WC has a greater predictive value for NAFLD than either of them alone. 10.12122/j.issn.1673-4254.2019.11.05
    Increased plasma osteopontin levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. Wang Cong,He Miao,Peng Jiajia,Li Shengbing,Long Min,Chen Wenwen,Liu Dongfang,Yang Gangyi,Zhang Lili Cytokine Nonalcoholic fatty liver disease (NAFLD) commonly occurs in patients with type 2 diabetes mellitus (T2DM). Osteopontin (OPN) is a multifunctional protein with pleiotropic physiological functions. This study aimed to investigate the interrelation between circulating OPN and NAFLD in T2DM patients. Overall, 249 subjects were classified into 4 groups: 53 patients with NAFLD and T2DM; 57 with newly diagnosed T2DM; 59 with NAFLD; and 80 healthy age- and sex-matched controls. Serum OPN was measured by ELISA. The OPN distribution in the pooled data was divided into quartiles; significant trends across increasing quartiles were estimated by the Cochran-Armitage trend test. Compared with the controls, circulating OPN concentrations were significantly elevated in NAFLD patients and T2DM patients with or without NAFLD. Serum OPN levels were higher in the overweight/obese group than that in the lean group. Circulating OPN levels were positively correlated with CRP, age, BMI, SBP, DBP, HbA1c, UA, TGs, WBCs, neutrophils, FBG, and HOMA-IR and negatively correlated with ADP, albumin and HDL. Age, albumin, HbA1c, HDL and hsCRP were independently related to circulating OPN. The relative risks for NAFLD, T2DM and T2DM with NAFLD increased significantly along with increasing OPN quartiles based on the Cochran-Armitage trend test. OPN is an optimal predictor in the diagnosis of T2DM with NAFLD and T2DM and may contribute to the aggravation of the metabolic state. 10.1016/j.cyto.2019.154837
    Plasma miR-513a-5p as a Potential Biomarker for Diagnosis of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus Patients. Li Fuwu,Wu Xiyao,Zhang Yan,Wei Kaijun Clinical laboratory BACKGROUND:The current study aims to investigate the relationship between plasma levels of miR-513a-5p and lipid metabolism and insulin resistance in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). METHODS:Two hundred patients with T2DM were selected, including 104 patients with NAFLD diagnosed by ultrasound and 96 patients without NAFLD. They were divided into combined group (T2DM/NAFLD) and control group (T2DM). Height, weight, blood lipid, and blood sugar were measured. Additionally, body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA-IR) index were calculated. RT-PCR was carried out to analyze the level of plasma miR-513a-5p. The correlation between plasma miR-513a-5p level and clinical indicators was analyzed by Pearson's correlation assay. RESULTS:Compared with the T2DM group, BMI, AST, ALT, TG, GGT, LDL-C, 2hPBG, Fins, 2hIns, HbAIc (%), and HOMA-IR were significantly increased in the T2DM/NAFLD group, and plasma miR-513a-5p levels were significantly decreased. Pearson's correlation analysis showed that miR-513a-5p was negatively correlated with ALT, LDL-C, 2h Ins, and HomA-IR. Receiver operating characteristic (ROC) analysis showed plasma miR-513a-5p could differentiate T2DM/NAFLD patients from NAFLD patients. CONCLUSIONS:Decreased plasma miR-513a-5p level may act as a potential biomarker for diagnosis of NAFLD in T2DM patients. 10.7754/Clin.Lab.2019.190907
    The Role of Insulin Resistance and Diabetes in Nonalcoholic Fatty Liver Disease. Fujii Hideki,Kawada Norifumi,Japan Study Group Of Nafld Jsg-Nafld International journal of molecular sciences Nonalcoholic fatty liver disease (NAFLD) consists of the entire spectrum of fatty liver disease in patients without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to cirrhosis, with NASH recently shown as an important cause of hepatocellular carcinoma (HCC). There is a close relationship between insulin resistance (IR) and NAFLD, with a five-fold higher prevalence of NAFLD in patients with type 2 diabetes (T2DM) compared to that in patients without T2DM. IR is involved in the progression of disease conditions such as steatosis and NASH, as well as hepatic fibrosis progression. The mechanisms underlying these processes involve genetic factors, hepatic fat accumulation, alterations in energy metabolism, and inflammatory signals derived from various cell types including immune cells. In NASH-associated fibrosis, the principal cell type responsible for extracellular matrix production is the hepatic stellate cell (HSC). HSC activation by IR involves "direct" and "indirect" pathways. This review will describe the molecular mechanisms of inflammation and hepatic fibrosis in IR, the relationship between T2DM and hepatic fibrosis, and the relationship between T2DM and HCC in patients with NAFLD. 10.3390/ijms21113863
    The Intricate Relationship between Type 2 Diabetes Mellitus (T2DM), Insulin Resistance (IR), and Nonalcoholic Fatty Liver Disease (NAFLD). Tanase Daniela Maria,Gosav Evelina Maria,Costea Claudia Florida,Ciocoiu Manuela,Lacatusu Cristina Mihaela,Maranduca Minela Aida,Ouatu Anca,Floria Mariana Journal of diabetes research Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) remain as one of the most global problematic metabolic diseases with rapidly increasing prevalence and incidence. Epidemiological studies noted that T2DM patients have by two-fold increase to develop NAFLD, and vice versa. This complex and intricate association is supported and mediated by insulin resistance (IR). In this review, we discuss the NAFLD immunopathogenesis, connection with IR and T2DM, the role of screening and noninvasive tools, and mostly the impact of the current antidiabetic drugs on steatosis liver and new potential therapeutic targets. 10.1155/2020/3920196
    Eating Fast Is Associated with Nonalcoholic Fatty Liver Disease in Men But Not in Women with Type 2 Diabetes: A Cross-Sectional Study. Takahashi Fuyuko,Hashimoto Yoshitaka,Kawano Rena,Kaji Ayumi,Sakai Ryosuke,Kawate Yuka,Okamura Takuro,Ushigome Emi,Kitagawa Noriyuki,Majima Saori,Sennmaru Takafumi,Okada Hiroshi,Nakanishi Naoko,Hamaguchi Masahide,Asano Mai,Yamazaki Masahiro,Fukui Michiaki Nutrients Non-alcoholic fatty liver disease (NAFLD), often complicated by type 2 diabetes mellitus (T2DM), is reported to be associated with diet habits, including eating speed, in the general population. However, the association between eating speed and NAFLD in patients with T2DM, especially sex difference, has not been reported so far. This cross-sectional study included 149 men and 159 women with T2DM. Eating speed was evaluated by a self-reported questionnaire and divided into three groups: fast, moderate, and slow eating. Nutrition status was evaluated by a brief-type self-administered diet history questionnaire. NAFLD was defined as the hepatic steatosis index ≥36 points. Body mass index and carbohydrate/fiber intake in the fast-eating group were higher than those in the slow-eating group in men, whereas this difference was absent in women. In men, compared with eating slowly, eating fast had an elevated risk of the presence of NAFLD after adjusting for covariates (odds ratio (OR) 4.48, 95% confidence interval (CI) 1.09-18.5, = 0.038). In women, this risk was not found, but fiber intake was found to be negatively associated with the presence of NAFLD (OR 0.85, 95% Cl 0.76-0.96, = 0.010). This study indicates that eating speed is associated with the presence of NAFLD in men but not in women. 10.3390/nu12082174
    Screening strategies for nonalcoholic fatty liver disease in type 2 diabetes: Insights from NHANES 2005-2016. Ciardullo Stefano,Sala Isabella,Perseghin Gianluca Diabetes research and clinical practice AIM:Nonalcoholic fatty liver disease (NAFLD) is prevalent in patients with type 2 diabetes mellitus (T2DM), but controversy exists on whether to screen and how to manage these patients in clinical practice. Here, we estimate the number of patients with T2DM and NAFLD in the United States that should be evaluated for advanced liver fibrosis according to proposed screening strategies. METHODS:In this cross-sectional analysis of 2940 adult patients with T2DM (projected to 15.3 million) from the 2005-2016 National Health and Nutrition Examination Survey (NHANES) we applied validated noninvasive scores of liver steatosis and fibrosis to estimate the number of referrals to hepatologists. We followed two different approaches: (1) the flow-chart from the European Association for the Study of the Liver (EASL), Diabetes (EASD) and Obesity (EASO) guidelines; (2) a strategy recently proposed in patients with T2DM aimed at excluding advanced liver fibrosis with a negative predictive value of 100%. RESULTS:NAFLD (based on fatty liver index) was present in 78% of patients (projected to 11.9 million). According to the EASL-EASD-EASO guidelines 37.2-48.5% of patients (projected to 5.7-7.4 million) should be referred to experts, depending on the specific biomarker of fibrosis used. The second strategy, which is based sequentially on aspartate aminotransferase and Fibrosis-4 was able to exclude advanced fibrosis in 67.0% of patients. CONCLUSIONS:Screening strategies based on noninvasive scores are able to exclude advanced liver fibrosis in 50-67% of patients with T2DM. Novel biomarkers or combination of tests may be necessary to reduce the need for liver biopsy and related bleeding episodes in the remaining 33-50%. 10.1016/j.diabres.2020.108358
    Association between Thyroid Function and Nonalcoholic Fatty Liver Disease in Euthyroid Type 2 Diabetes Patients. Huang Bin,Yang Shengju,Ye Shandong Journal of diabetes research Thyroid function and type 2 diabetes mellitus (T2DM) are both associated with increased risks of adverse clinical outcomes in nonalcoholic fatty liver disease (NAFLD). Our study is aimed at evaluating the association between thyroid function and NAFLD in T2DM patients with normal thyroid function (euthyroid) and analyzing the potential effects of metformin on the pathological process. Overall, 369 T2DM patients were enrolled between July 2017 and September 2018 and stratified into NAFLD and non-NAFLD groups. Data on age, gender, body mass index (BMI, kg/m), metformin use, and basal metabolic rate (BMR) were obtained from participants' records. All patients were tested for biochemical markers, indexes of glucose metabolism, lipid metabolism, bone metabolism, and thyroid function at baseline. Multivariate analyses detected increased odds of NAFLD among individuals with T2DM per unit increase in their BMI and free triiodothyronine (FT3) and thyroid stimulating hormone (TSH); the odds ratios (OR) were 1.25, 3.02, and 1.58, respectively (all < 0.05). Positive correlations were detected between alanine aminotransferase (ALT) and FT3 ( = 0.221, = 0.010), and negative correlations were noted between TSH and BMR ( = -0.618, < 0.001) and between BMR and FT3 ( = -0.452, < 0.001) in T2DM subjects with NAFLD. A significant difference in serum FT3 ( = 2.468, = 0.0167) and TSH ( = 2.658, = 0.010) levels was found between obese individuals with NAFLD who used and did not use metformin. The pathological mechanism of T2DM complicated by NAFLD in euthyroid patients may be associated with insulin resistance and a thyroid hormone resistance-like manifestation, i.e., relevant hypothyroidism. Metformin can potentially decrease the double-resistance situation, especially in obese individuals. 10.1155/2020/6538208
    Clinical and Biochemical Predictors of Nonalcoholic Fatty Liver Disease among Type 2 Diabetes Mellitus Patients at Primary Health Care Level in South Western Saudi Arabia. Al Humayed Suliman M,Sabaani Abdullah A Al,Mahfouz Ahmed A,Awadalla Nabil J,Musa Mustafa Jafar,Patel Ayyub Diagnostics (Basel, Switzerland) OBJECTIVES:To predict the role of different clinical and biochemical parameters in identifying nonalcoholic fatty liver disease (NAFLD) among patients with type 2 diabetes mellitus (T2DM) in Abha city, southwestern Saudi Arabia. METHODS:A stratified random sample was selected. A detailed clinical and biochemical examinations were performed. Using portable abdominal ultrasound examination, NAFLD was identified. The study used receiver operating characteristic (ROC) analysis. RESULTS:The study covered 237 T2DM patients. NAFLD was detected among 174 patients. Area under the curve (AUC) calculations showed that the ability of age, duration of DM in years, and body mass index to predict NAFLD was poor (AUC < 0.6). Similarly, biochemical factors like HbA1c%, AST, cholesterol, triglycerides, HDL, LDL, and VLDL were poor in discriminating between those with and without NAFLD among T2DM. On the other hand, the ability of ALT to predict NAFLD among T2DM was good (AUC = 0.701, 95% CI: 0.637-0.761). The analysis identified the optimal cutoff point of ALT to be ≤22.1 nmol/L. The corresponding sensitivity was 60.7% (95% CI: 53.0-68.0) and specificity was 62.5% (95% CI: 49.5-74.3). CONCLUSIONS:Early identification of NAFLD among T2DM is important. A threshold cutoff value of 22.1 nmol/L of ALT has been identified to predict NAFLD. They should be referred for ultrasound examination for NAFLD. 10.3390/diagnostics10100809