Early emergence of sexual dimorphism in offspring leukocyte telomere length was associated with maternal and children's glucose metabolism-a longitudinal study.

BACKGROUND: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children's LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life. METHODS: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children's glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction. RESULTS: Sex- and age-adjusted children's LTL was found to be associated with children's HOMA-IR (ß=-0.046 ± 0.016, p=0.005). Interestingly, both children's and maternal post-load glucose levels were positively associated with children's LTL. However, negative associations were observed between children's LTL and children's OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels. CONCLUSIONS: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.

Long-term maternal cardiometabolic outcomes 22 years after gestational diabetes mellitus.

AIMS/INTRODUCTION: Women with gestational diabetes mellitus are at increased risk for type 2 diabetes. We characterized the association between maternal glycemia during pregnancy with long-term outcomes. METHODS AND METHODS: In this prospective nested case-cohort study, participants were recalled for follow up with detailed evaluation including oral glucose tolerance test at 8, 15 and 22 years. Logistic regression was used to estimate the risk of developing impaired glucose tolerance/type 2 diabetes and metabolic syndrome at follow up. The association between maternal glycemia at pregnancy and follow up was evaluated by linear regression. We also charted trajectory of ß-cell function during follow up. RESULTS: The analysis included 121 women with a mean follow-up period of 22.5 years, and a mean age of 50.3 years. Gestational diabetes was associated with an adjusted odds ratio of 2.48 (95% confidence interval 1.03-5.99) for combined diabetes/impaired glucose tolerance at follow up (P = 0.04). Women with a pre-pregnancy body mass index ≥23 had an odds ratio of 5.43 (95% confidence interval 1.87-15.72) for metabolic syndrome at follow up, compared with those with body mass index <23 (P = 0.002). Both fasting and 2-h glucose during pregnancy were strongly associated with glycemic indices at follow up (P-value <0.001-0.016). Gestational diabetes was associated with impaired ß-cell function that remained relatively stable after the index pregnancy. CONCLUSIONS: Chinese women with a history of gestational diabetes have a high prevalence of impaired glucose tolerance/type 2 diabetes at 22-year follow up. Glucose levels during mid-pregnancy are strongly associated with those of middle age.

Gender, diabetes education, and psychosocial factors are associated with persistent poor glycemic control in patients with type 2 diabetes in the Joint Asia Diabetes Evaluation (JADE) program.

BACKGROUND: Factors associated with persistent poor glycemic control were explored in patients with type 2 diabetes under the Joint Asia Diabetes Evaluation (JADE) program. METHODS: Chinese adults enrolled in JADE with HbA1c ≥8% at initial comprehensive assessment (CA1) and repeat assessment were analyzed. The improved group was defined as those with a ≥1% absolute reduction in HbA1c, and the unimproved group was those with <1% reduction at the repeat CA (CA2). RESULTS: Of 4458 enrolled patients with HbA1c ≥8% at baseline, 1450 underwent repeat CA. After a median interval of 1.7 years (interquartile range[IQR] 1.1-2.2) between CA1 and CA2, the unimproved group (n = 677) had a mean 0.4% (95% confidence interval [CI] 0.3%, 0.5%) increase in HbA1c compared with a mean 2.8% reduction (95% CI -2.9, -2.6%) in the improved group (n = 773). The unimproved group had a female preponderance with lower education level, and was more likely to be insulin treated. Patients in the improved group received more diabetes education between CAs with improved self-care behaviors, whereas the unimproved group had worsening of health-related quality of life at CA2. Apart from female gender, long disease duration, low educational level, obesity, retinopathy, history of hypoglycemia, and insulin use, lack of education from diabetes nurses between CAs had the strongest association for persistent poor glycemic control. CONCLUSIONS: These results highlight the multidimensional nature of glycemic control, and the importance of diabetes education and optimizing diabetes care by considering psychosocial factors.

Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring.

There is a global epidemic of obesity and diabetes, and current efforts to curb the diabetes epidemic have had limited success. Epidemiological studies have highlighted increased risk of obesity, diabetes and cardiovascular complications in offspring exposed to maternal diabetes, and gestational diabetes increases the risk of diabetes in subsequent generations, thereby setting up a vicious cycle of "diabetes begetting diabetes". This relationship between maternal hyperglycaemia and long-term health in the offspring is likely to become even more important with an increasing proportion of young woman being affected by diabetes, and the number of pregnancies complicated by hyperglycaemia continuing to rise. Animal models of gestational diabetes or maternal hyperglycaemia have highlighted long-term changes in the offspring with some instances of sex bias, including increased adiposity, insulin resistance, ß-cell dysfunction, hypertension, as well as other structural and functional changes. Furthermore, several of these changes appear to be transmissible to later generations through the maternal line. Epigenetic changes play an important role in regulating gene expression, especially during early development. Recent studies have identified a number of epigenetic modifications in the offspring associated with maternal hyperglycaemia. In this review, we provide an overview of the epidemiological evidence linking maternal hyperglycaemia with adverse long-term outcome in the offspring, as well as of some of the studies that explore the underlying epigenetic mechanisms. A better understanding of the pathways involved may provide novel approaches for combating this global epidemic.

Metabolic profiles and treatment gaps in young-onset type 2 diabetes in Asia (the JADE programme): a cross-sectional study of a prospective cohort.

BACKGROUND: The prevalence of diabetes is increasing in young adults in Asia, but little is known about metabolic control or the burden of associated complications in this population. We assessed the prevalence of young-onset versus late-onset type 2 diabetes, and associated risk factors and complication burdens, in the Joint Asia Diabetes Evaluation (JADE) cohort. METHODS: JADE is an ongoing prospective cohort study. We enrolled adults with type 2 diabetes from 245 outpatient clinics in nine Asian countries or regions. We classified patients as having young-onset diabetes if they were diagnosed before the age of 40 years, and as having late-onset diabetes if they were diagnosed at 40 years or older. Data for participants' first JADE assessment was extracted for cross-sectional analysis. We compared clinical characteristics, metabolic risk factors, and the prevalence of complications between participants with young-onset diabetes and late-onset diabetes. FINDINGS: Between Nov 1, 2007, and Dec 21, 2012, we enrolled 41,029 patients (15,341 from Hong Kong, 9107 from India, 7712 from Philippines, 5646 from China, 1751 from South Korea, 705 from Vietnam, 385 from Singapore, 275 from Thailand, 107 from Taiwan). 7481 patients (18%) had young-onset diabetes, with age at diagnosis of mean 32·9 years [SD 5·7] versus 53·9 years [9·0] with late-onset diabetes (n=33,548). Those with young-onset diabetes had longer disease duration (median 10 years [IQR 3-18]) than those with late-onset diabetes (5 years [2-11]). Fewer patients with young-onset diabetes achieved HbA1c concentrations lower than 7% compared to those with late-onset diabetes (27% vs 42%; p<0·0001) Patients with young-onset diabetes had higher mean concentrations of HbA1c (mean 8·32% [SD 2·03] vs 7·69% [1·82]; p<0·0001), LDL cholesterol (2·78 mmol/L [0·96] vs 2·74 [0·93]; p=0·009), and a higher prevalence of retinopathy (1363 [20%] vs 5714 (18%); p=0·011) than those with late-onset diabetes, but were less likely to receive statins (2347 [31%] vs 12,441 [37%]; p<0·0001) and renin-angiotensin-system inhibitors (1868 [25%] vs 9665 [29%]; p=0·006). INTERPRETATION: In clinic-based settings across Asia, one in five adult patients had young-onset diabetes. Compared with patients with late-onset diabetes, metabolic control in those with young-onset diabetes was poor, and fewer received organ-protective drugs. Given the risk conferred by long-term suboptimum metabolic control, our findings suggest an impending epidemic of young-onset diabetic complications. FUNDING: The Asia Diabetes Foundation (ADF) and Merck.