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    Altered Concentrations of Copper, Zinc, and Iron are Associated With Increased Levels of Glycated Hemoglobin in Patients With Type 2 Diabetes Mellitus and Their First-Degree Relatives. Atari-Hajipirloo Somayeh,Valizadeh Neda,Khadem-Ansari Mohammad-Hassan,Rasmi Yousef,Kheradmand Fatemeh International journal of endocrinology and metabolism BACKGROUND:The altered levels of some essential trace elements and antioxidant minerals have been observed in diabetic patients. OBJECTIVES:The aim of the present study was to compare the concentrations of essential trace elements, copper (Cu), zinc (Zn), and iron (Fe) in the serum of patients who have type 2 diabetes mellitus (T2DM) with those of their non-diabetic first-degree relatives (FDR) and control subjects. The association between glycated hemoglobin (HbA1c) and levels of metals was also evaluated. PATIENTS AND METHODS:We studied 46 subjects with T2DM, 46 FDR, and 50 control subjects matched for age and sex. Serum concentrations of Cu, Zn, and Fe were measured by colorimetric kit. Fasting blood glucose (FBG) and HbA1c were assayed using the standard kit. RESULTS:An imbalance in the levels of the studied metals was observed in both patients with T2DM and FDR. We found significantly decreased levels of Zn and higher levels of Cu and Fe in the patients with T2DM and FDR when compared with the control subjects (P < 0.05). HbA1c levels were positively correlated with Cu and Fe and inversely correlated with Zn in the patients with T2DM and FDR (P < 0.05). CONCLUSIONS:The patients with T2DM and FDR had altered contents of Cu, Zn, and Fe that might be a predisposing factor to the development of diabetes in future or vice versa the result of diabetes development. Impaired metabolism of these elements may contribute to the augmented risk of developing type 2 diabetes mellitus later in the life of their first-degree relatives. 10.5812/ijem.33273
    Cross-sectional study of the determinants and associations of sex hormone-binding globulin concentrations in first degree relatives (FDR) of patients with Type 2 Diabetes Mellitus. Abdella N A,Mojiminiyi O A Diabetes research and clinical practice AIMS:This study explores the determinants of sex hormone binding globulin (SHBG) and associations with categories of glucose intolerance and undiagnosed diabetes in first-degree relatives (FDR) of patients with Type 2 Diabetes Mellitus (T2D). METHODS:Anthropometric indices, fasting lipids, glucose, insulin, adiponectin, leptin, SHBG, estradiol (E2), testosterone (TT), androstenedione (AND), dehydroepiandrosterone sulphate (DHEA-S), high-sensitivity C-reactive protein (hs-CRP) and alanine aminotransferase (ALT) were measured in 584 FDR. Homeostasis model assessment-estimate of insulin resistance (HOMA-IR), beta cell function (%B), insulin sensitivity (%S) and free androgen index (FAI) were calculated. RESULTS:266 subjects were normoglycemic; 237 had prediabetes and 81 had undiagnosed diabetes. SHBG decreased stepwise with worsening categories of glucose intolerance in females whereas FAI decreased stepwise with worsening categories in males only. SHBG showed significant positive correlations with adiponectin, and HDL-C and significant negative correlations with body mass index (BMI), waist circumference (WC), Waist:hip ratio (WHR), ALT, triglycerides (TG), %B, leptin and FAI. After adjustment for WHR, only HDL-C and FAI in men and FAI and HbA1c in females remained significantly associated with SHBG. Receiver Operating Characteristic (ROC) curve analysis for detection of diabetes showed that areas under the curve for FAI and SHBG were 0.711 and 0.386 for males and 0.430 and 0.660 for females respectively. CONCLUSION:Associations of SHBG with some anthropometric and metabolic variables in FDR suggests that lower levels is a marker for risk of developing T2D through obesity dependent metabolic pathways but low FAI is a better marker of state of diabetes in males. 10.1016/j.diabres.2017.08.024
    Beta-cell dysfunction in first-degree relatives of patients with non-insulin-dependent diabetes mellitus. Fernández-Castañer M,Biarnés J,Camps I,Ripollés J,Gómez N,Soler J Diabetic medicine : a journal of the British Diabetic Association To analyse the relationship between age, glucose tolerance, beta-cell function, and insulin sensitivity in preclinical states of non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), we have done a cross-sectional, age-stratified analysis of 86 non-diabetic first-degree relatives of NIDDM patients and 49 controls with similar age, sex, and BMI. A 5 mg kg ideal body weight-1 min-1 for 60 min of continuous infusion of glucose with model assessment (CIGMA) of serum glucose and C-peptide values at the end of the infusion was used to determine glucose tolerance and beta-cell function. Insulin sensitivity was estimated by modelling basal serum glucose and insulin values. Relatives and controls were divided into tertiles on the basis of age. Relatives had higher basal (5.3 vs 5 mmol l-1, p = 0.02) and achieved serum glucose (9.1 vs 8.4 mmol l-1, p = 0.01), lower beta-cell function (128 vs 145%, p = 0.007), and lower insulin sensitivity (37 vs 43%, p = 0.002). Beta-cell function declined with age in relatives (from 139% in young subjects to 134% in intermediate subjects and to 111% in older subjects, p = 0.002) and this decline was associated with an increase in basal serum glucose (from 5.1 to 5.3 and to 5.7 mmol l-1, p = 0.000) and achieved glucose (from 8.3 to 9.1 and to 9.3 mmol l-1, p = 0.038), without significant changes in insulin sensitivity. These trends were observed even after the exclusion of subjects with mild glucose intolerance. We conclude that both beta-cell dysfunction and insulin resistance are present in first-degree relatives of NIDDM. The progression of beta-cell dysfunction and glucose intolerance with age suggests that beta-cell dysfunction is the key factor in the apparition and progression of the disease. 10.1002/(SICI)1096-9136(199611)13:11<953::AID-DIA257>3.0.CO;2-V
    Insulin action and secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes mellitus. Influence of body weight. Volk A,Renn W,Overkamp D,Mehnert B,Maerker E,Jacob S,Balletshofer B,Häring H U,Rett K Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association It is a matter of controversy, whether insulin action or secretion - or both - are disturbed in first degree relatives of patients with type 2 diabetes. We intended to assess both the compensatory and the obesity-related part of insulin secretion. In order to dissect out the latter, matching for insulin sensitivity was mandatory to normalize for the compensatory part of hyperinsulinemia. In 154 healthy, glucose tolerant first degree relatives of patients with type 2 diabetes we directly quantified both insulin sensitivity (by euglycemic-glucose-clamp technique) and insulin secretion (oral glucose load; stimulated serum c-peptide). Insulin sensitivity was scattered over a wide range with a considerable overlap of both first degree relatives of patients with type 2 diabetes and 97 controls without a family history of diabetes. Average insulin sensitivity was higher in controls (8.0+/-0.3 vs. 7.1 + 0.2 ml x kg-l x min-1, p < 0.05). Prevalence of insulin resistance (defined as controls, lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion after oral glucose was significantly increased in insulin resistant first degree relatives of patients with type 2 diabetes compared to insulin sensitive first degree relatives of patients with type 2 diabetes. Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first degree relatives of patients with type 2 diabetes than in insulin sensitive counterparts (5.3+/-0.4 vs. 7.3+/-0.5; p < 0.01). Body mass index was distributed over the whole range in insulin resistant first degree relatives of patients with type 2 diabetes. In the insulin sensitive subgroup absolute and relative secretion did not differ in obese (Body mass index >25 kg/m2) and insulin sensitivity-matched lean. In obese insulin resistant first degree relatives of patients with type 2 diabetes absolute hyperinsulinemia was combined with reduced and delayed relative early insulin release. In summary, degree and prevalence of insulin resistance is higher in first degree relatives of patients with type 2 diabetes than in controls. However, both groups are of heterogenous metabolic composition and family history as major discriminator should not be overestimated. Our data suggest, that hyperinsulinemia cannot simply be explained as a compensatory event to balance insulin resistance. Hypersecretion is associated with insulin resistance predominantly in combination with obesity. It might be speculated that adipose tissue derived signals to the beta-cell might lead to hypersecretion only in the genetic background that also leads to insulin resistance. 10.1055/s-0029-1212089
    Prevalence of insulin resistance in first degree relatives of type-2 diabetes mellitus patients: A prospective study in north Indian population. Kumar Arvind,Tewari Poornima,Sahoo Sibasis S,Srivastava Arvind Kumar Indian journal of clinical biochemistry : IJCB A total of 172 first degree relatives (FDRs) and 178 controls were included in this study. All the cases and controls were subjected to various anthropometric measurements, fasting and postprandial glucose estimation, fasting insulin measurement and fasting lipid profile. Results revealed the prevalence of Impaired Fasting Glucose (IFG) (cases 37% Vs controls 11.6%), Impaired Glucose Tolerance (IGT) (cases 34.3% Vs controls 11.2%) and diabetes (cases 11.05% controls 3.37%) was significantly higher in first degree relatives. Insulin resistance was measured using various methods, which included fasting plasma insulin (FPI), Homeostasis Model Assessment for Insulin Resistance (HOMA(IR)), insulin sensitivity index (ISI) (Mffm/l). Prevalence of insulin resistance (Insulin Resistance) as observed comparing FPI and HOMA(IR) in cases and controls was 43.6% and 11.24% (P=0.005) and 37.8% and 12.47% (P=0.000) respectively. Prevalence of IR (Insulin Resistance) observed in cases having Normal Glucose Tolerance (NGT), Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) and diabetes mellitus measuring FPI Vs HOMA(IR) was 37.5% vs 30.2%, 45% vs 40%, 38.98% vs 37.28% and 36.84% vs 31.57% as accordingly. However, ISI (Mffm/l) was not found to be a promising index for IR due to its poor specificity. Though HOMA is taken as gold standard for measurement of IR globally, our study observed fasting plasma insulin representing high sensitivity (89.7%) and specificity (93.3%) as compared to HOMA. Thus FPI had emerged in this work as a simple and reliable test for diagnosing insulin resistance across the population susceptible to develop diabetes including FDRs. 10.1007/BF02867394
    First-degree relatives of patients with type 2 diabetes mellitus and risk of non-alcoholic Fatty liver disease. Adibi Atoosa,Janghorbani Mohsen,Shayganfar Sanaz,Amini Masoud The review of diabetic studies : RDS AIMS:The aim of this study was to determine whether first-degree relatives (FDR) of patients with type 2 diabetes mellitus (T2DM) are at higher risk of non-alcoholic fatty liver disease (NAFLD) than healthy controls. METHODS:A total of 222 FDR of consecutive patients with T2DM aged between 35 and 55 years and 202 healthy individuals with no family history of diabetes were investigated for NAFLD. Fatty liver was diagnosed by ultrasonography using standard criteria. Height, weight, fasting glucose, alanine aminotransferase (ALT), total cholesterol and triglyceride were determined by routine laboratory methods. RESULTS:Compared to subjects with no family history of diabetes, the age and sex adjusted odds ratio (OR) of NAFLD was 1.83 (95% CI: 1.11-3.03) for FDR of patients with T2DM. After further adjusting for BMI, fasting glucose, ALT, asparate aminotransferase (AST), triglyceride and cholesterol, the multivariate OR of prevalent NAFLD in FDR of patients with T2DM compared with individuals with no family history of diabetes was 1.56 (95% CI: 0.85-2.86). CONCLUSIONS:The present study suggests that the relation between FDR of patients with T2DM and NAFLD is affected by the other covariates, in particular obesity, which points to a more complex relationship between the diseases. It appears that obesity and diabetes may independently predispose to NAFLD. 10.1900/RDS.2007.4.236
    Impaired endothelial function and insulin action in first-degree relatives of patients with type 2 diabetes mellitus. Sonne Mette P,Højbjerre Lise,Alibegovic Amra A,Vaag Allan,Stallknecht Bente,Dela Flemming Metabolism: clinical and experimental First-degree relatives (FDR) of patients with type 2 diabetes mellitus are at increased risk of developing type 2 diabetes mellitus. We studied if endothelial dysfunction of the resistance vessels is present and may coexist with metabolic insulin resistance in FDR. Male FDR (n = 13; 26 +/- 1 years; body mass index, 25 +/- 1 kg m(2) [mean +/- SEM]) and matched control subjects (CON) (n = 22; 25 +/- 1 years; body mass index, 24 +/- 1 kg m(2)) were studied by hyperinsulinemic (40 mU min(-1)m(-2)) isoglycemic clamp combined with brachial arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography upon stimulation with systemic hyperinsulinemia (291 +/- 11 pmol/L, pooled data from both groups) and upon intraarterial infusion of adenosine (ADN) and acetylcholine (ACH) +/- hyperinsulinemia. Forearm blood flow response to ADN and ACH was less in FDR vs CON (P < .05); systemic hyperinsulinemia added to the FBF effect of ADN in CON (P < .05) but not in FDR. In addition, FDR demonstrated impaired FBF to hyperinsulinemia (2.1 +/- 0.2 vs 4.0 +/- 0.6 mL 100 mL(-1) min(-1)) in FDR and CON, respectively (P < .05). Both M-value (5.0 +/- 0.7 vs 7.0 +/- 0.5 mg min(-1) kg(-1)) and forearm glucose clearance (0.6 +/- 0.1 vs 1.4 +/- 0.4 mL 100 mL(-1)min(-1)) were diminished in FDR compared with CON (all P < .05). FDR demonstrated endothelial dysfunction of the resistance vessels in addition to impaired insulin-stimulated increase in bulk flow. Moreover, FDR demonstrated whole-body insulin resistance as well as decreased basal and insulin-stimulated forearm glucose uptake. It remains to be established whether FDR also demonstrate impaired insulin-stimulated microvascular function. 10.1016/j.metabol.2008.08.011
    Different pathophysiology of impaired glucose tolerance in first-degree relatives of individuals with type 2 diabetes mellitus. Emerson Peter,Van Haeften Timon W,Pimenta Walkyria,Plummer Elena,Woerle Hans J,Mitrakou Asimina,Szoke Ervin,Gerich John,Meyer Christian Metabolism: clinical and experimental To assess whether an increased genetic predisposition for type 2 diabetes mellitus (T2DM) influences the contributions of insulin resistance and impaired insulin secretion to impaired glucose tolerance (IGT), 437 subjects not known to have T2DM underwent an oral glucose tolerance test and a 3-hour hyperglycemic clamp. Plasma insulin responses and insulin sensitivity were compared between all subjects (unselected for demographic or anthropometric characteristics) who had normal glucose homeostasis and no first-degree T2DM relative (n = 133), IGT with a first-degree T2DM relative (IGT/FH+, n = 74), or IGT without a first-degree T2DM relative (IGT/FH-, n = 50). Compared with those with normal glucose homeostasis, first- and second-phase plasma insulin responses were reduced approximately 45% and 30%, respectively (both P < .001), in IGT/FH+, whereas insulin sensitivity was only approximately 20% reduced (P = .011). In contrast, in IGT/FH-, first-phase plasma insulin responses were only approximately 20% reduced (P = .016), second-phase plasma insulin responses were not reduced, but insulin sensitivity was approximately 40% reduced (P < .001). The IGT/FH+ group differed significantly from the IGT/FH- group by having 25% to 30% lower first-phase plasma insulin responses (P = .026) and 25% to 30% greater insulin sensitivity (P = .027). Adjustment for obesity abolished the differences in insulin resistance but not plasma insulin responses. However, when the IGT groups were stratified into subgroups based on body mass index (BMI), first-phase plasma insulin responses were approximately 30% lower in IGT/FH+ with a BMI of at least 27 kg/m(2) (P = .018) but similar in IGT/FH+ with a BMI less than 27 kg/m(2) compared with the corresponding IGT/FH- subgroups. We conclude that, in IGT, an increased genetic predisposition for T2DM increases the contribution of impaired insulin secretion to its pathophysiology. This effect is enhanced by obesity. 10.1016/j.metabol.2008.12.004
    Does frank diabetes in first-degree relatives of a pregnant woman affect the likelihood of her developing gestational diabetes mellitus or nongestational diabetes? Kim Catherine,Liu Tiebin,Valdez Rodolfo,Beckles Gloria L American journal of obstetrics and gynecology OBJECTIVE:We sought to examine the associations between patterns of family histories of diabetes and a history of gestational diabetes mellitus (hGDM). STUDY DESIGN:Parous women participating in the National Health and Nutrition Examination Survey III (n=4566) were classified as having hGDM only, diagnosed diabetes, or neither. Family history of diabetes was categorized as: maternal only, paternal only, biparental, and sibling only. The covariate-adjusted prevalence and odds of having hGDM were estimated. RESULTS:Compared to women without a family history of diabetes, women with a maternal (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.2-7.3), paternal (OR, 3.3; 95% CI, 1.1-10.2), or sibling (OR, 7.1; 95% CI, 1.6-30.9) history of diabetes had greater odds of hGDM, after adjustment for age and race/ethnicity. CONCLUSION:Women with a sibling history of diabetes were more likely to have hGDM than women with other family history patterns. 10.1016/j.ajog.2009.06.069
    [Association between both resistin, visfatin and insulin resistance as well as β cell function in the first-degree relatives of type 2 diabetes mellitus]. Zhang Xiu-juan,Wang Zhi,Li Hai-hui,Yu Ling,Gao Shan Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi OBJECTIVE:To study the association between the levels of serum resistin, visfatin and insulin resistance as well as β-cell dysfunction in the first-degree relatives (FDR) of type 2 diabetes mellitus (T2DM), and to investigate the role of these adipocytokines in pathogenesis of T2DM. METHODS:Serum levels of resistin, visfatin as well as fasting true insulin (FTI), proinsulin (FPI) levels were measured in 71 patients with newly diagnosed T2DM. 55 subjects with IGT/IFG and 174 NGT from first-degree relatives of T2DM, and 114 subjects of NGT without T2DM family history served as control group (NC). Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR) and β-cell function was evaluated by HOMA-β and fasting PI-to-TI ratio (FPI/TI). Lipid profile, liver function and kidney function were also tested. Anthropometrical parameters such as body mass index (BMI), waist circumference and blood pressure were also recorded and life style and food intake spectrum investigated. RESULTS:(1) There were no significant differences of serum resistin levels among the four groups (P>0.05). The serum resistin level was not correlated with HomA-IR, HomA-β and obesity markers (P>0.05).(2) The serum visfatin levels of DM group, IGT/IFG and NGT group were lower than the NC group (P<0.05). There were no significant difference among DM group, IGT/IFG group and NGT. The serum visfatin level was not correlated with HOMA-IR and obesity markers (P>0.05), but negatively correlated with fasting blood glucose, 2 h postprandial blood glucose and blood pressure (P<0.05). CONCLUSION:The adipokine profile in FDRs of T2DM had distinctively altered before the development of impaired glucose tolerance. Serum levels of visfatin, showed a favorable effect on glucose metabolism also had a significant decrease on serum levels in the early stage of T2DM.
    [Prevalence of diabetes and prediabetes mellitus in the first-degree relatives of patients with type 2 diabetes in Chengdu]. Ma Hong,Gong Yuan,Liu Yuan-yuan,Song Jie,Tian Hao-ming,Chen Tao,Ran Xing-wu,Yu Hong-ling,Zhang Xiang-xun,Ren Yan Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition OBJECTIVE:To investigate the prevalence of diabetes and prediabetes mellitus in the first-degree relatives (FDR) of patients with type 2 diabetes (T2DM) in Chengdu. METHODS:A cross-sectional study was undertaken in Chengdu. A total of 2306 adults were recruited, including 535 FDR of T2DM patients and 1771 people without a family history of diabetes. All participants received glucose tolerance tests and measurements of waist, blood pressure and blood lipids. RESULTS:(1) The FDR of T2DM patients had greater standardized prevalence of diabetes than those without a family history of diabetes (26.6% vs. 9.2%). The standardized prevalence of prediabetes in these two groups was 15.0% and 14.1%, respretively. (2) Greater standardized prevalence of diabetes were found in both female (25.5%) and male (28.5%) FDR of T2DM patients compared with their counterparts without a family history of diabetes (women 8.7%, men 11.2%). The standardized prevalence of prediabetes between those with and without a family history of diabetes was 15.9% and 13.4% in women, 13.7% and 15.3% in men, respretively. (3) The younger than 40 years old FDR of T2DM patients had greater prevalence of diabetes and prediabetes than their counterpart without a family history of diabetes, while the FDR of T2DM with an age of > or =40 years old had greater prevalence of diabetes than their counterparts only (P > 0.05). The FDR of T2DM patients with <25 kg/m2 body mass index (BMI) had greater prevalence of diabetes and prediabetes than their counterparts without a family history of diabetes (25.1% vs. 7.4%, 13.2% vs. 9.3%, P < 0.05). The FDR of T2DM patients with > or = 25 kg/m2 BMI had greater prevalence of diabetes (33.0% vs. 13.7%, P < 0.05) but less prevalence of prediabetes (19.2% vs. 26.8%, P < 0.05) than their counterparts without a family history of diabetes. (4) The logistic regression showed that triglyceride (TG) was a risk factor for diabetes in those FDR of T2DM patients (OR = 1.363) and those without a family history of diabetes (OR = 1.27), and high density lipoprotein cholesterol (HDL-C) was a protective factor for diabetes in those without a family history of diabetes (OR = 0.546). CONCLUSION:The FDR of T2DM patients have high risk of diabetes and those younger than 40 years or with <25 kg/m2 BMI also have high risk of prediabetes.
    Insulin resistance and alanine amino transaminase (ALT) levels in first degree relatives of type 2 diabetes mellitus. Kuzhandai velu V,Jyothirmayi B,Kumar J S Diabetes & metabolic syndrome INTRODUCTION:Insulin resistance is established as an independent predictor of a range of disorders such as obesity, hypertension, dyslipidemia, type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. There is an association of hyperinsulinemia with hypertriglycerdemia, low level of HDL and high level of LDL. In nonalcoholic fatty liver disease, there is an elevation of ALT, raising the possibility that the prospective relationship between ALT and type 2 diabetes may reflect cross-sectional associations with insulin resistance or obesity. AIM AND OBJECTIVE:To find the significance of insulin resistance and alanine aminotransferase level in first degree relatives of type 2 diabetes mellitus. MATERIALS AND METHODS:The study included 50 first degree relatives of type 2 diabetes (25 men and 25 women) aged 20-60 years and 30 control of similar age. All cases were taken from SRM Medical College Hospital and Research Centre, Chennai. All the cases were analyzed for HOMA(IR), QUICKI, IR ratio, fasting glucose, insulin (ELISA), lipid profile and alanine aminotransferase. Student's 't' test was applied for statistical analysis. RESULT:The data show the significance of insulin resistance (HOMA(IR)) (2.76±1.46, 1.35±0.8, p<0.001) in the first degree relatives of type 2 diabetes mellitus when compared with controls respectively and increased level fasting plasma insulin (12.28±6.16, 6.12±3.04, p<0.001). In the lipid profile the total cholesterol and TAG are significant. No statistical significance was found in ALT (24.8±9.84, 20.08±11.02). CONCLUSION:Results of the study conclude that there is a high prevalence of insulin resistance in the first degree relatives of type 2 diabetes mellitus. ALT levels in the first degree relatives of type 2 diabetes mellitus had increased levels of insulin resistance, the pathogenesis suggesting increase in ALT levels as seen in insulin resistance condition. In our study, ALT was not statistically significant. 10.1016/j.dsx.2012.02.011
    Serum visfatin and vaspin levels in normoglycemic first-degree relatives of Iranian patients with type 2 diabetes mellitus. Akbarzadeh Samad,Nabipour Iraj,Jafari Seyed Mojtaba,Movahed Ali,Motamed Niloofar,Assadi Majid,Hajian Najmeh Diabetes research and clinical practice AIM:To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction. METHODS:Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. RESULT:Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71±0.93 ng/ml versus 2.69±2.02 ng/ml, p=0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452±0.254 ng/ml versus 0.409±0.275 ng/ml, p>0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR)=1.71, 95% confidence interval (1.30-2.25); p<0.0001]. CONCLUSION:The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group. 10.1016/j.diabres.2011.10.004
    Prevalence of diabetes mellitus and glucose metabolism disorders in the first degree relatives of type 2 diabetic patients. Karaman A,Bayram F,Gundogan K,Ozsan M,Karaman H,Kelestimur F Bratislavske lekarske listy BACKGROUND AND OBJECTIVES:We designed this study to observe the DM prevalence, insulin resistance, beta cell reserve and the interaction of these parameters in the first degree relatives of Type 2 diabetic patients in Turkish population. METHODS:125 subjects were included in the study. 25 subjects without the first degree diabetic relatives were selected as the control group; they were matched by age, BMI, socio-economical, cultural and environmental factors. (OGTT), (IVGTT), (GST), and (ITT), were performed on all subjects and controls. RESULTS:12 (9.6 %) DM and 23 (18. 4 %) impaired glucose tolerance (IGT) cases of 125 subjects were diagnosed according to OGTT results. The mean BMI of diabetic subjects was significantly higher than of controls and subjects with normal glucose tolerance (p<0.05). When compared to the control group, the mean AUCinsulin levels were significantly lower in diabetic subjects (p<0.05). To observe the correlation between HOMAIR and KITT values, a statistically significant correlation was found (p<0.05, r: 0.222). There was a deficiency in the C-peptide response to glucagon stimulation in diabetic relatives (p<0.05, F: 4.59 One Way ANOVA). CONCLUSION:We demonstrated that the first degree relatives of Type 2 diabetic patients constitute a high risk group for DM, IGT and insulin resistance by using four different tests in Turkish population.The significant finding(s) of the study: We demonstrated a high prevalence of glucose metabolism disorders in the relatives of type 2 diabetic patients.This study adds our knowledge; insulin resistance and decreased beta cell reserve occur before diabetes mellitus begin in relatives (Tab. 5, Ref. 42). 10.4149/bll_2012_082
    The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels. Akbarzadeh Samad,Nabipour Iraj,Assadi Majid,Movahed Ali,Jafari Seyed Mojtaba,Motamed Niloofar,Nazem Habibollah,Haraghy Mehrnoosh,Pourbehi Abdolreza,Bargahi Afshar,Hajian Najmeh Cytokine OBJECTIVE:It has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). METHOD:Serum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. RESULTS:There was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06-11.52]ng/ml versus 10.50 [4.30-20.60]ng/ml, p=0.004) and adiponectin (mean±SD, 10.07±4.0 μg/ml versus 20.66±8.12 μg/ml, p<0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30-0.79]; p=0.004 and OR=0.74, CI [0.67-0.82]; p<0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. CONCLUSIONS:The FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs' increased risk of diabetes needs to be further elucidated. 10.1016/j.cyto.2012.02.005
    Acylated ghrelin and leptin concentrations in patients with type 2 diabetes mellitus, people with prediabetes and first degree relatives of patients with diabetes, a comparative study. Sharifi Faranak,Yamini Mahdi,Esmaeilzadeh Abdolreza,Mousavinasab Nouraddin,Shajari Zahra Journal of diabetes and metabolic disorders BACKGROUND:Ghrelin is known as a new endocrine component supposed to have an influence in control of feeding behavior and energy balance. Recent studies have shown that ghrelin concentration in the subjects with diabetes mellitus type 2 (DM 2) is lower than normal. To clarify the relationship between ghrelin and insulin resistance and also DM 2, a cross-sectional study was designed. METHODS:In a cross-sectional study, 87 subjects were enrolled in three groups, 29 with DM2, 29 pre-diabetes state and 29 normoglycemic subjects of first-degree relatives of diabetic group. After clinical examination, blood samples were taken to measure fasting blood glucose, HbA1c, lipids, insulin, leptin and acylated ghrelin concentrations. RESULTS:Mean serum concentrations of acylated ghrelin in all groups (47.4 ± 27.9 pg/ml) were lower than normal values (150.3 ± 56.4 pg/ml) (P: 0.006) without significant difference within groups comparison(P: 0.1). A significant correlation was found between ghrelin concentration with body mass index (BMI) (r: -0.23, p <0.02) and abdominal circumference (AC) (r: -0.28, P < 0.008). Also inverse relationship between ghrelin level and insulin resistance (HOMA-IR) (r: -.032, p: 0.002) was seen in all subjects. Leptin level has a significant correlation with abdominal circumference (AC) and BMI (P < 0.0001) but not with ghrelin. CONCLUSION:This study showed that obesity has a strong association with the reduced level of ghrelin concentration. It seems that the process of ghrelin reduction is initiated in earlier stages of insulin resistance prior to the onset of overt DM. 10.1186/2251-6581-12-51
    Comparison of clinical and biochemical variables in type 2 diabetes mellitus patients and their first-degree relatives with metabolic syndrome in Benin City, Nigeria: A cross sectional case controlled study. Ogedengbe S,Ezeani I U,Aihanuwa E Endocrine regulations OBJECTIVE:Type 2 diabetes mellitus (T2DM) is characterized by a relative insulin deficiency or insulin resistance. It is also associated with a cluster of metabolic abnormalities, including hyper-tension and dyslipidemia. Although there are many studies that have studied the metabolic abnormalities in T2DM patients with metabolic syndrome (MetS), only few of them have assessed the metabolic abnormalities in their first-degree relatives (FDRs) who had MetS. The aim of this study is to compare the clinical and biochemical variables in T2DM subjects and their FDRs without diabetes in Benin City, Nigeria. METHODS:This is a cross sectional case control study including 124 T2DM patients, 96 FDR of T2DM subjects, and 96 controls recruited using convenience sampling. Data were collected using a questionnaire-administered technique. Variables of interest that were assessed included anthropometric indices like waist circumference (WC), hip circumference (HC), waist:hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum lipid profile, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), proteinuria, and microalbuminuria. The 1999 World Health Organization (WHO) criteria were used to make a diagnosis of metabolic syndrome. The Chi-square test was used for comparison of proportions. P-value of less than 0.05 was taken as statistically significant. The student t-test was used to compare means and test for significant differences in the anthropometric and the metabolic indices. RESULTS:The prevalence of the MetS in T2DM persons was 87.1%, 16.7% in the FDR group, and 13.5% in the control group according to the WHO criteria. The mean value of HbA1c was significantly higher in T2DM subjects with MetS (p<0.05). The mean values of WC, FPG, total cholesterol, HDL cholesterol, and LDL cholesterol were higher in subjects with MetS in the T2DM group than in persons with MetS in the FDR group though not significant (p>0.05). The mean values of WHR, BMI, SBP, DBP, and triglyceride were higher in persons with the MetS in the FDR group than in persons with the MetS in the T2DM group. The difference in the BMI and SBP was significant (p<0.05). CONCLUSION:The prevalence of MetS in subjects with T2DM in Nigeria is very high. Though, all the biochemical and clinical indices were higher in T2DM subjects with MetS, the mean HbA1c, BMI, and SBP was significantly higher when compared to their FDR who also have MetS. 10.1515/enr-2016-0007
    Fıbroblast growth factor 21 and ıts relatıonshıp wıth ınsulın sensıtıvıty ın fırst-degree relatıves of patıents wıth type 2 dıabetes mellıtus. Ors Damla,Eroglu Altinova Alev,Yalçın Mehmet Muhittin,Gulbahar Ozlem,Akturk Mujde,Arslan Metin,Balos Toruner Fusun Endokrynologia Polska INTRODUCTION:Fibroblast growth factor 21 (FGF 21) has been suggested as a predictor for the development of type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS:We aimed to determine FGF 21 levels in normoglycaemic (Group 1) and prediabetic (Group 2) first-degree relatives (FDR) of patients with T2DM in comparison with normoglycaemic subjects without a history of T2DM in their FDR (Group 3). RESULTS:There was a significant difference between Group 1, 2, and 3 with respect to plasma FGF 21 concentrations (143.3 ± 93.8, 221.9 ± ± 171.7 and 121.2 ± 119.8 pg/mL, respectively, p = 0.01). FGF 21 levels were significantly increased in prediabetic FDR of patients with T2DM compared to normoglycaemic subjects without a history of T2DM in their FDR (p = 0.02). FGF 21 levels did not differ between normoglycaemic FDR of patients with T2DM and normoglycaemic subjects without a history of T2DM in their FDR (p > 0.05). In the whole group, FGF 21 correlated positively with age (r = 0.31, p = 0.003), BMI (r = 0.38, p < 0.001), systolic blood pressure (r = 0.38, p = 0.001), diastolic blood pressure (r = 0.26, p = 0.02), fasting blood glucose (r = 0.24, p = 0.02), HOMA-IR (r = 0.23, p = 0.03), AUC glucose (r = 0.35, p = 0.001), and AUC insulin (r = 0.32, p = 0.003) and negatively with HDL cholesterol (r = -0.24, p = 0.02) and Matsuda ISI (r = -0.33, p = 0.002). In the regression analysis, BMI was the most predictive factor for FGF 21 levels (beta = 0.41, r2 = 0.17, p < 0.001). CONCLUSIONS:We showed that FGF 21 concentrations are increased in prediabetic FDR of patients with T2DM and that there is a significant association between FGF 21 and obesity and insulin sensitivity. (Endokrynol Pol 2016; 67 (3): 260-264). 10.5603/EP.a2016.0016
    Endothelial dysfunction in normoglycaemic first-degree relatives of type 2 diabetes mellitus complicated with hyperuricaemia. Zhang Junxia,Xiang Lin,Zhang Bilin,Cheng Yangyang Diabetes & vascular disease research OBJECTIVE:To reveal the effect of hyperuricaemia on endothelial function in normoglycaemic first-degree relatives of type 2 diabetes mellitus. METHODS:In all, 40 first-degree relatives of type 2 diabetes mellitus with hyperuricaemia, 40 first-degree relatives of type 2 diabetes mellitus with normouricaemia and 35 healthy subjects without diabetic family history were recruited in this study. Anthropometric parameters as well as blood pressure, blood lipids, fasting blood glucose, fasting insulin, C-reactive protein, tumour necrosis factor-α and interleukin-6 were measured. Insulin resistance was assessed with homoeostasis model assessment index-insulin resistance index. To assess endothelial function, high-resolution ultrasonography was used for measuring flow- and nitroglycerine-mediated brachial artery vasodilation. RESULTS:When compared with control, flow-mediated dilation was lower in first-degree relatives with or without hyperuricaemia (both p < 0.001). When compared with first-degree relative subjects with normouricaemia, there were lower flow-mediated dilation ( p < 0.001) and higher levels of uric acid ( p < 0.001), fasting blood glucose ( p < 0.001), C-reactive protein ( p = 0.001), tumour necrosis factor-α ( p < 0.001) and interleukin-6 ( p < 0.001) in first-degree relative subjects with hyperuricaemia. Flow-mediated dilation was found to be negatively related to uric acid ( r = -0.597, p < 0.001). Stepwise multiple regressions demonstrated that uric acid was a significant determinant of flow-mediated dilation independent of other variables in first-degree relatives of type 2 diabetes mellitus (β = -0.677, p < 0.001; confidence interval: -0.010 to -0.006). CONCLUSION:Further endothelial dysfunction is found in normoglycaemic first-degree relatives of type 2 diabetes mellitus complicated with hyperuricaemia. 10.1177/1479164116678158
    Effect of parental history of diabetes on markers of inflammation, insulin resistance and atherosclerosis in first degree relatives of patients with type 2 diabetes mellitus. Dash Deepak Kumar,Choudhury Arun Kumar,Singh Mamta,Mangaraj Swayamsidha,Mohanty Binoy Kumar,Baliarsinha Anoj Kumar Diabetes & metabolic syndrome AIM AND OBJECTIVE:To study the effect of parental history of diabetes on markers of inflammation, insulin resistance, adiposity indices and carotid intima media thickness (cIMT) in first degree relatives of patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS:Normal glucose tolerant (NGT) first degree relatives of T2DM patients of age group 20-40 years designated as FH were enrolled in the cross sectional study. Depending on the parental history of diabetes they were divided into three groups: family history positive in father (FH), family history positive in mother (FH) and family history positive in both (FH). Age, sex and BMI matched controls without any history of diabetes in their parents designated as FH were taken for comparison. All subjects underwent detailed clinical evaluation and biochemical investigations. cIMT and adiposity indices like visceral adipose tissue thickness (VAT) and subcutaneous adipose tissue thickness (SAT) were assessed using ultrasonography. RESULTS:No difference existed with regards to BMI, hsCRP, degree of insulin resistance, adiposity markers and cIMT between FH and FH group. Subjects in FH group had significantly higher degree of insulin resistance, subclinical inflammation, increased atherosclerosis and adiposity indices in contrast to those who have a single parent T2DM family history. CONCLUSIONS:hsCRP and cIMT are significantly higher in the first degree relatives of type2 diabetes mellitus patients than controls. Individuals with history of T2DM in both parents have significantly worse glycemic status, increased cIMT and adverse cardiovascular risk profile than those with T2DM history in only single parent. 10.1016/j.dsx.2017.12.004
    Subclinical Atherosclerosis in Young Adult Population with First Degree Relatives of Type 2 Diabetes Mellitus. Abdaly Muhammad Syah,Azizi Mohamad Syahrir,Wijaya Ika Prasetya,Nugroho Pringgodigdo,Purnamasari Dyah Acta medica Indonesiana Cardiovascular disease (CVD) remain a leading cause of death globally. The concept of acute myocardial infarction in young adults was uncommon. Atherosclerosis is the leading cause of CVD, including myocardial infarction, stroke, heart failure and peripheral artery disease. This condition is initiated early in childhood and progressive in nature. CVD risk factors includes hypertension, dyslipidemia and obesity play a role in the development of atherosclerosis and  components in insulin resistance syndrome.One of many risk factors for insulin resistance in healthy individuals is a first-degree relative (FDR) of Type 2 Diabetes Mellitus (T2DM) patients. This group shows a higher risk of insulin resistance and pancreatic beta cells disruption even in adolescence, although they often remains asymptomatic. Clinical manifestations of metabolic disorders and atherosclerosis will appear earlier in the FDR T2DM group who have sedentary lifestyles and obesity, when compared to the non-FDR group. Several studies have attempted to detect metabolic disorders and subclinical atherosclerosis that might occur; therefore an early prevention can be carried out in these high-risk groups.  Unfortunately, factors that affect the onset and the severity of the prospective clinical manifestations from the previous studies remained inconclusive.
    Carotid intima-media thickness among normoglycemia and normotension first-degree relatives of type 2 diabetes mellitus. Purnamasari Dyah,Abdaly Muhammad Syah,Azizi Mohamad Syahrir,Wijaya Ika Prasetya,Nugroho Pringgodigdo Vascular health and risk management Theoretically, first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) are predisposed to have earlier and more severe atherosclerosis than non-FDR due to hereditary insulin resistance. A previous study reported that atherosclerotic plaques were found in 45.2% of young adults FDR of T2DM, but the study did not include non-FDR as control group. The aim of this study was to compare subclinical atherosclerosis (carotid intima-media thickness, CIMT) between FDR of T2DM and non-FDR. This was a cross-sectional study involving 16 FDR subjects and 16 age-sex matched non-FDR subjects, aged 19-40 years, with normal glucose tolerance and no hypertension. Collected data included demographic characteristic, anthropometric measurement (BMI and waist circumference), laboratory analysis (fasting blood glucose, HbA1c, lipid profile), and CIMT examination (using B-mode ultrasound). The mean of CIMT in the FDR group was higher than that in the non-FDR group (0.44 mm vs 0.38 mm, =0.005). After adjusting for waist circumference, BMI, low-density lipoprotein cholesterol, and triglyceride, CIMT maintained significant difference between FDR and non-FDR subjects. BMI and waist circumference showed moderate correlation with CIMT. CIMT in young adult FDR of T2DM is thicker than that in age-and sex-matched non-FDR population. 10.2147/VHRM.S195776