Prevalence of Metabolic Syndrome and Its Determinants in Newly-Diagnosed Adult-Onset Diabetes in China: A Multi-Center, Cross-Sectional Survey.
Li Xia,Cao Chuqing,Tang Xiaohan,Yan Xiang,Zhou Houde,Liu Jing,Ji Linong,Yang Xilin,Zhou Zhiguang
Frontiers in endocrinology
The study aimed to investigate the prevalence of metabolic syndrome (MetS) and its determinants in newly-diagnosed adult-onset diabetes in China. From April 2015 to October 2017, 15,492 consecutive patients with diabetes diagnosed within 1 year and aged ≥30 years were recruited from 46 tertiary care hospitals in 24 cities across China. Glutamic acid decarboxylase autoantibody was assayed centrally and clinical data were collected locally. Classic type 1 diabetes mellitus (T1DM), latent autoimmune diabetes in adults (LADA) and type 2 diabetes mellitus (T2DM) were defined using the criteria of American Diabetes Association, Immunology of Diabetes Society and World Health Organization. MetS was defined using Chinese Diabetes Society's criteria. Logistic regression analysis was used to obtain odds ratios (OR) of determinants of MetS. The overall prevalence of MetS was 66.5%, with the highest prevalence in T2DM (68.1%), followed by those in LADA (44.3%) and T1DM (34.2%) ( < 0.05 for all comparisons). After adjustment for traditional risk factors, T2DM had a 2.8-fold [95% confidence interval (CI): 2.36-3.37] MetS risk compared with LADA, whereas T1DM had significantly lower OR than LADA (OR: 0.68, 95% CI: 0.50-0.92). After further adjustment for insulin resistance, the OR of T2DM vs. LADA was slightly reduced but the OR of T1DM vs. LADA was greatly attenuated to non-significance (OR: 0.96, 95% CI: 0.70-1.33). In addition to types of diabetes, age, gender, geographical residence, education attainment, alcohol consumption and HOMA2-IR were independent determinants of MetS. MetS was highly prevalent, not only in T2DM but also in T1DM and LADA in Chinese newly diagnosed patients; higher risk of MetS in LADA than in T1DM was partially attributable to higher insulin resistance in LADA.
10.3389/fendo.2019.00661
Changes of Regulatory T Cells in the Early Stage of Obesity Mice and Their Modulation on Macrophage Subtypes in Visceral Adipose Tissue.
Li Xia,Tang Xiao-Han,Tang Li-Li,Yu Hai-Bo,Xie Zhi-Guo,Zhou Zhi-Guang
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
Objective To investigate the changes of regulatory T cells (Tregs) and whether Tregs can modulate the distribution of macrophage subtypes in visceral adipose tissue in the early stage of obesity.Methods After C57BL/6 mice obesity models were successfully established,metabolic parameters and numbers of Tregs and M1/M2 macrophage were measured at 4,10,and 20 weeks.The changes of metabolic parameters and adipose tissue inflammation in obesity mice after rapamycin intervention were evaluated. Results The early-stage obesity models were successfully established.Compared with normal diet mice,high fat diet mice had significantly higher epididymal adipose tissue mass and serum leptin levels(P<0.05).However,there was no statistical difference in blood glucose and insulin levels between these two groups(All P>0.05). Macrophages infiltration in adipose tissue in high fat diet mice gradually increased with time,coincident with decrease in Treg numbers. Increased numbers of Treg,improved metabolic parameters,and decreased ratio of M1/M2 can be seen after rapamycin intervention in mice.Conclusion The decrease of Tregs in the early stage of obesity may contribute to abnormal distribution of macrophage subtypes in visceral adipose.
10.3881/j.issn.1000-503X.2016.04.006
Decline Pattern of Beta-cell Function in Adult-onset Latent Autoimmune Diabetes: an 8-year Prospective Study.
Li Xia,Chen Yan,Xie Yuting,Xiang Yufei,Yan Xiang,Huang Gan,Zhou Zhiguang
The Journal of clinical endocrinology and metabolism
OBJECTIVE:To explore the decline pattern and possible determinants of beta-cell function progression in patients with latent-onset autoimmune diabetes in adults (LADA). RESEARCH DESIGN AND METHODS:In this 8-year prospective study, 106 LADA individuals underwent annual follow-up and their pattern of beta-cell function progression was assessed. Beta-cell function failure was defined by fasting C-peptide (FCP) < 75 pmol/L. Other clinical characteristics, including age of onset, body mass index (BMI), and glutamic acid decarboxylase autoantibody (GADA) titer, were analyzed to find out possible determinants of beta-cell function progression. RESULTS:The dropout rate was 4.7%. During the 8-year follow-up period, 29 (28.7%) of the 101 subjects developed beta-cell function failure. The decline pattern of C-peptide in LADA was biphasic, showing an initial rapid linear progression and then followed by a stable mode. The declination speed of FCP was 55.19 pmol/L/year (95% CI, -62.54 to -47.84, P < 0.001) during the first 5 years and 4.62 pmol/L/year (95% CI, -69.83 to 60.60, P = 0.790) thereafter. Further analysis showed that GADA titer was the most valuable discriminatory parameter related to a higher risk of development of beta-cell function failure (GADA titer of 173.5 WHO units/mL; area under the curve [AUC], 0.824). Beta-cell function failure occurred in 71.3% of high-GADA titer patients while only 6.2% of low-titer patients. CONCLUSIONS:The decline pattern of C-peptide was a fast-followed-by-slow biphasic mode, with about a quarter of LADA patients developing beta-cell function failure during the first 8 years. GADA titer less than 173.5 WHO units /mL was propitious for the preservation of beta-cell function.
10.1210/clinem/dgaa205
Serum Trypsinogen Levels in Type 1 Diabetes.
Li Xia,Campbell-Thompson Martha,Wasserfall Clive H,McGrail Kieran,Posgai Amanda,Schultz Andrew R,Brusko Todd M,Shuster Jonathan,Liang Faming,Muir Andrew,Schatz Desmond,Haller Michael J,Atkinson Mark A
Diabetes care
OBJECTIVE:The pancreas in type 1 diabetes exhibits decreased size (weight/volume) and abnormal exocrine morphology. Serum trypsinogen levels are an established marker of pancreatic exocrine function. As such, we hypothesized that trypsinogen levels may be reduced in patients with pre-type 1 diabetes and type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS:Serum trypsinogen levels were determined in 100 persons with type 1 diabetes (72 new-onset, 28 established), 99 autoantibody-positive (AAb) subjects at varying levels of risk for developing this disease, 87 AAb-negative (AAb) control subjects, 91 AAb relatives with type 1 diabetes, and 18 patients with type 2 diabetes. RESULTS:Trypsinogen levels increased significantly with age in control subjects ( = 0.71; < 0.0001) and were significantly lower in patients with new-onset (mean ± SD 14.5 ± 6.1 ng/mL; < 0.0001) and established type 1 diabetes (16.7 ± 6.9 ng/mL; < 0.05) versus AAb control subjects (25.3 ± 11.2 ng/mL), AAb relatives (29.3 ± 15.0 ng/mL), AAb subjects (26.5 ± 12.1 ng/mL), and patients with type 2 diabetes (31.5 ± 17.3 ng/mL). Multivariate analysis revealed reduced trypsinogen in multiple-AAb subjects ( < 0.05) and patients with type 1 diabetes ( < 0.0001) compared with AAb subjects (control subjects and relatives combined) and single-AAb ( < 0.01) subjects when considering age and BMI. CONCLUSIONS:These findings further support the interplay between pancreatic endocrine and exocrine dysfunction. Longitudinal studies are warranted to validate trypsinogen as a predictive biomarker of type 1 diabetes progression.
10.2337/dc16-1774
Revisiting multiple models of progression of β-cell loss of function in type 1 diabetes: Significance for prevention and cure.
Li Xia,Cheng Jin,Zhou Zhiguang
Journal of diabetes
Type 1 diabetes (T1D) results from a chronic autoimmune process that leads to β-cell destruction and exogenous insulin dependence. The natural history of T1D proposed by Eisenbarth suggested six relatively independent stages over the course of the entire disease process, which was considered to be linear and chronic. Based on this classical theory, immunotherapies aim to prevent or reverse all these periods of β-cell loss. Over the past 30 years, much novel information about the pathogenesis of T1D proved that there are complex metabolic changes occurring throughout the entire disease process. Therefore, new possible models for the natural history of the disease have been proposed; these models, in turn, may help facilitate fresh avenues for the prevention and cure of T1D. Herein, we briefly review recent findings in this field of research, with the aim of providing a better theoretical basis for clinical practice.
10.1111/1753-0407.12376
Latent autoimmune diabetes in adults with low-titer GAD antibodies: similar disease progression with type 2 diabetes: a nationwide, multicenter prospective study (LADA China Study 3).
Liu Lingjiao,Li Xia,Xiang Yufei,Huang Gan,Lin Jian,Yang Lin,Zhao Yunjuan,Yang Zhifang,Hou Can,Li Yijun,Liu Jie,Zhu Dalong,Leslie R David,Wang Xiangbing,Zhou Zhiguang,
Diabetes care
OBJECTIVE:This study investigated the relationship between GAD autoantibody (GADA) titers and changing of β-cell function in patients with latent autoimmune diabetes in adults (LADA). RESEARCH DESIGN AND METHODS:This 3-year prospective study enrolled 95 subjects from 15 Chinese cities including 25 high-titer (GADA ≥180 units/mL) LADA patients, 42 low-titer (GADA <180 units/mL) LADA patients, and 28 type 2 diabetic patients, the latter two groups as controls of similar age, sex, and BMI. Clinical characteristics were determined annually, including glycosylated hemoglobin (HbA1c), fasting C-peptide (FCP), and 2-h postprandial C-peptide (PCP). RESULTS:Despite similar initial FCP and PCP, FCP and PCP both decreased more in subjects with high GADA titer (FCP from mean 0.49 nmol/L at entry to 0.13 nmol/L at the third year; P < 0.05) than with low GADA titer (FCP from mean 0.48 to 0.38 nmol/L) and type 2 diabetes (FCP from mean 0.47 to 0.36 nmol/L); the latter two groups being similar. After 3 years, residual β-cell function (FCP >0.2 nmol/L) was detected in only 42% with an initial high GADA titer compared with 90% with a low GADA titer and 97% with type 2 diabetes (P < 0.01 for both). GADA positivity at the third year persisted more in subjects with initially high GADA (92%) than with low GADA (26%) titers (P < 0.01). CONCLUSIONS:In selected LADA patients, initial GADA titers identified subjects with different degrees of persistent autoimmunity and disease progression. LADA patients with a low GADA titer had metabolic phenotypes and loss of β-cell function similar to type 2 diabetic patients.
10.2337/dc14-1770