Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial.

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Gene expression profiling in ethnic Malays with type 2 diabetes mellitus, with and without diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) among type 2 diabetes mellitus patients (DM) in Malaysia. This study used microarray analysis to determine the gene expression profiling in ethnic Malay patients with type 2 DM. METHODS: A total of 312 patients were recruited; 25 were on dialysis due to ESRD, 128 were classified as normoalbuminuric, 93 as microalbuminuric and 66 as macroalbuminuric, based on urine albumin to creatinine ratio of <3.5, between 3.5 and 35 and =35 mg/mmol, respectively. RESULTS: Microalbuminuria was associated with up- and down-regulation of 2,694 and 2,538 genes, respectively, while macroalbuminuria was associated with up-regulation of 2,520 genes and down-regulation of 2,920 genes. There was significant up-regulation of 1,135 genes and down-regulation of 908 genes in the ESRD samples. Thirty-seven significantly up-regulated genes and 40 down-regulated genes were commonly expressed in all 3 groups of patients with worsening of renal functions. Up-regulated genes included major histocompatibility complex (HLA-C), complement component 3a receptor 1 (C3AR1), solute carrier family 16, member 3 (SLC16A3) and solute carrier family 9 (sodium/hydrogen exchanger) (SLC9A8). Consistently down-regulated genes included were bone morphogenetic phosphatase kinase (BMP2K), solute carrier family 12, member 1 (SLC12A1), solute carrier family 7 (SLC7A2), paternally expressed 10 (PEG10) and protein phosphatase 1 regulatory (inhibitor unit) (PPP1R1C). CONCLUSION: This study has identified several genes of interest, such as HLA-C, SLC16A3, SLC9A8, SLC12A1 and SLC7A2, that require verification of their roles as susceptibility genes for diabetic nephropathy in ethnic Malays with type 2 DM.

Prevalence, risk factors, and clinical features of thyroid-associated ophthalmopathy in multiethnic Malaysian patients with Graves' disease.

BACKGROUND: The prevalence of thyroid-associated ophthalmopathy (TAO) has been reported to be lower in several Asian populations than in Caucasians. The risk factors for TAO that have been demonstrated in Caucasians have not been studied in Asian populations. The aim of this study, therefore, was to determine the prevalence, risk factors, and clinical features of TAO in a cohort of multiethnic Malaysian patients with Graves' disease (GD). METHODS: This was a cross-sectional study of 167 consecutive patients with GD who attended two endocrine clinics from October 2003 to September 2004. The patients were classified as Malay, Chinese, and Indian based on their ethnic characteristics as detailed in the national identity card. The patients were examined by a single individual for the presence and characteristics of TAO. Thyroid function tests were performed, and smoking history and the extent of smoking history were recorded. RESULTS: The prevalence rate of TAO using the American Academy of Ophthalmology diagnostic criteria was 34.7%. This increased to 46.7% if lower lid retraction was added as an alternate criterion. The observed prevalence rate was higher than expected in the Chinese patient population based on a comparison with the Malay and Indian patients, but this was not statistically significant. Smokers with GD were at 2.75 times greater risk of TAO than nonsmokers (p = 0.019). Male gender was shown to confer higher risk of TAO on univariate analysis (p = 0.003), but not on multivariate analysis. The percentage of males who smoked in the study group was relatively high (79%). The most common presentation of TAO was exophthalmos, followed by lid retraction. CONCLUSIONS: TAO has relatively high prevalence rate (34.7%) in three populations of Asian patients with GD. This is similar to that reported for Caucasian patients with GD. As in Caucasian patients, smoking increases the risk of TAO. In the Asian populations we studied, exophthalmos was the most common eye sign. However, lower lid retraction was also common and present in 60% of cases with other signs of TAO. In Chinese, Malay, and Indian Asians with GD, lower lid retraction should be a diagnostic criterion for TAO.