Pongamorn Bunnag

A Risk Score for Predicting Incident Diabetes in the Thai Population

OBJECTIVE—The objective of this study was to develop and evaluate a risk score to predict people at high risk of diabetes in Thailand. RESEARCH DESIGN AND METHODS—A Thai cohort of 2,677 individuals, aged 35–55 years, without diabetes at baseline, was resurveyed after 12 years. Logistic regression models were used to identify baseline risk factors that predicted the incidence of diabetes; a simple model that included only those risk factors as significant (P < 0.05) when adjusted for each other was developed. The coefficients from this model were transformed into components of a diabetes score. This score was tested in a Thai validation cohort of a different 2,420 individuals. RESULTS—A total of 361 individuals developed type 2 diabetes in the exploratory cohort during the follow-up period. The significant predictive variables in the simple model were age, BMI, waist circumference, hypertension, and history of diabetes in parents or siblings A cutoff score of 6 of 17 produced the optimal sum of sensitivity (77%) and specificity (60%). The area under the receiver-operating characteristic curve (AUC) was 0.74. Adding impaired fasting glucose or impaired glucose tolerance status to the model slightly increased the AUC to 0.78; adding low HDL cholesterol and/or high triglycerides barely improved the model. The validation cohort demonstrated similar results. CONCLUSIONS—A simple diabetes risk score, based on a set of variables not requiring laboratory tests, can be used for early intervention to delay or prevent the disease in Thailand. Adding impaired fasting glucose or impaired glucose tolerance or triglyceride and HDL cholesterol status to this model only modestly improves the predictive ability.

Association Between Plasma Triglycerides and High-Density Lipoprotein Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2 Diabetes Mellitus A Global Case–Control Study in 13 Countries

Background— Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. Methods and Results— The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11–1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88–0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16–1.31) with triglycerides and decreased by 0.86 (0.82–0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. Conclusions— Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Association Between Plasma Triglycerides and HDL-Cholesterol and Microvascular Kidney Disease and Retinopathy in Type 2 Diabetes: A Global Case-Control Study in 13 Countries

Background— Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. Methods and Results— The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11–1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88–0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16–1.31) with triglycerides and decreased by 0.86 (0.82–0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. Conclusions— Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

The effects of oestrogen exposure on bone mass in male to female transsexuals

The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men.

Relation of β3-adrenergic receptor gene mutation to total body fat but not percent body fat and insulin levels in Thais

A Trp64Arg mutation in the beta3-adrenergic receptor gene has been implicated in the pathophysiology of non-insulin-dependent diabetes mellitus and obesity. However, the findings have been controversial due to the use of different populations and different methods for the estimation of body fat. In the present study, the prevalence of Trp64Arg mutation of the beta3-adrenergic receptor gene was determined and its relation to body fat as assessed by dual-energy x-ray absorptiometry (DEXA) was evaluated in Thai men and women. The effect on insulin sensitivity as assessed by the serum insulin to glucose ratio was also examined. The subjects were 76 men and 135 women aged 20 to 80 years. Body fat and its regional distribution were assessed by DEXA. Mutation in the beta3-adrenergic receptor gene was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Data are expressed as the mean +/- SEM. Fifty-nine subjects (28.0%) had the Trp64Arg mutation in the beta3-adrenergic receptor gene; 54 (25.6%) were heterozygotes and five (2.4%) were homozygotes. The gene frequency of Trp64Arg mutation was 15.2% in these subjects. In women, Trp64Arg mutation was not associated with the difference in total body fat (Trp/Arg or Arg/Arg, 19.4 +/- 1.0 kg; Trp/Trp, 19.2 +/- 0.6 kg) or percent body fat (Trp/Arg or Arg/Arg, 34.6% +/- 1.2%; Trp/Trp, 34.3% +/- 0.6%). In contrast to the findings in women, men with Trp64Arg mutation had lower total body fat after controlling for age (Trp/Arg or Arg/Arg, 13.2 +/- 1.1 kg; Trp/Trp, 15.8 +/- 0.7 kg; P < .05). However, no difference was found in percent body fat (Trp/Arg or Arg/Arg, 20.9% +/- 1.3%; Trp/Trp, 23.3% +/- 0.7%). No difference in the fasting insulin resistance index (FIRI) was found between subjects with and without Trp64Arg mutation. The data suggest that Trp64Arg mutation of the beta3-adrenergic receptor is common in Thais and appears to exert effects on total body fat but not percent body fat in men. Trp64Arg mutation is not associated with insulin resistance as assessed by the FIRI in Thais.

Hepatic fat content is a determinant of postprandial triglyceride levels in type 2 diabetes mellitus patients with normal fasting triglyceride.

Postprandial hypertriglyceridemia is common in type 2 diabetes mellitus (T2D). Significant numbers of T2D patients who have normal fasting triglyceride (TG) have postprandial hypertriglyceridemia. The role of regional adipose tissue and adiponectin on postprandial TG responses in this group of T2D patients is unclear. This study aimed to examine the contribution of regional adipose tissue and adiponectin to the variation of postprandial TG responses in T2D patients who have normal fasting TG levels. Thirty-one Thai T2D patients who had fasting TG<1.7 mmol/L were studied. All were treated with diet control or sulphonylurea and/or metformin. None was treated with lipid-lowering agents. Mixed-meal test was performed after overnight fast. Plasma glucose, insulin, and TG were measured before and 1, 2, 3, and 4 hours after the test. Adiponectin was measured in fasting state. Visceral as well as superficial and deep subcutaneous abdominal adipose tissues were determined by magnetic resonance imaging, and hepatic fat content (HFC) was determined by magnetic resonance spectroscopy. Univariate and multivariate regression analyses of postprandial TG and regional adipose tissue and metabolic parameters were performed. The TG levels before and 1, 2, 3, and 4 hours after the mixed meal were 1.32+/-0.40 (SD), 1.40+/-0.41, 1.59+/-0.40, 1.77+/-0.57, and 1.80+/-0.66 mmol/L, respectively (P<.0001). The area under the curve (AUC) of postprandial TG was positively and significantly correlated with fasting TG (r=0.84, P<.0001) and log.HFC (r=0.456, P=.033) and was inclined to be correlated with log.deep subcutaneous adipose tissue (r=0.38, P=.05) and sex (r=0.326, P=.073). The AUC of postprandial TG was not correlated with age, body mass index, waist circumference, log.superficial subcutaneous adipose tissue, log.visceral adipose tissue, hemoglobin A1c, fasting glucose, AUC.glucose, log.fasting insulin, log.AUC.insulin, log.homeostasis model assessment%B, log.homeostasis model assessment of insulin resistance, and adiponectin. Only fasting TG (beta=.815, P<.0001) and log.HFC (beta=.249, P=.035) predicted AUC of postprandial TG in regression model (adjusted R2=0.84, P<.0001). In conclusion, in T2D patients with normal fasting TG, the increase of postprandial TG levels is directly determined by fasting TG level and the amount of hepatic fat.

Glycaemic responses in Asian and non-Asian people with type 2 diabetes initiating insulin glargine 100 units/mL: A patient-level pooled analysis of 16 randomised controlled trials

AIMS To compare outcomes between Asian and non-Asian patients with type 2 diabetes (T2D) inadequately controlled on oral antidiabetic drugs (OADs) initiating insulin glargine 100 units (U)/mL (Gla-100) in randomised controlled clinical trials. METHODS Post hoc analysis of patient-level data (Asian n = 235; non-Asian n = 3351) from 16 trials. RESULTS At baseline, Asian patients were younger with lower body mass index (BMI), fasting C-peptide, and fasting plasma glucose (FPG) than non-Asian patients (all P < .001). Asian patients had a higher mean glycosylated haemoglobin (HbA1c) at Week 24 and less reduction in HbA1c from baseline (7.4% vs. 7.2%; -1.3% vs. -1.6%, respectively; P = .0001), and were less likely to achieve HbA1c <7.0% (40% vs. 47%; P = .002) than non-Asian patients. Reductions in FPG and rates of hypoglycaemia were similar between Asian and non-Asian patients. Asian patients had less weight gain than non-Asian patients (+1.3 vs. +1.9 kg, respectively, P = .013). CONCLUSIONS In our post hoc meta-analysis, Gla-100 effectively lowers HbA1c and FPG in Asian patients with T2D uncontrolled on OADs with similar incidence of hypoglycaemia and less absolute weight gain compared with non-Asian patients. At a similar FPG reduction, fewer Asian patients achieved HbA1c target <7.0%, suggesting that prandial glucose needs to be addressed.

Hypogonadism in thalassemia major patients

Highlights • Hypogonadism is a common problem in patients with thalassemia major.• The cause of hypogonadism is usually iron deposition in pituitary gonadotropic cells.• Pituitary MRI is useful for early detection of pituitary iron deposition.• Ovarian failure can often occur after bone marrow transplantation.• Fertility, using reproductive techniques, is possible and depends on gonadal reserve.

Serum dehydroepiandrosterone sulfate in assessing the integrity of the hypothalamic-pituitary-adrenal axis

Objective To evaluate the relationship between age- and gender-adjusted dehydroepiandrosterone sulfate (DHEA-S) levels and low-dose adrenocorticotropic hormone (ACTH) stimulation in assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis, in patients who were at risk of HPA insufficiency, including those currently being treated with glucocorticoids. Methods Forty-six participants with a suspicion of secondary adrenal insufficiency were recruited from the Diabetes and Endocrinology Clinic at Ramathibodi Hospital, Mahidol University, Bangkok. Low-dose (1 μg) ACTH stimulation was performed in every participants, and serum DHEA-S was measured at baseline before ACTH injection. Results Individuals with normal age- and gender-specific DHEA-S levels had baseline serum cortisol and peak cortisol levels higher than those with reduced DHEA-S. Normal age- and gender-specific DHEA-S levels predicted intact HPA function with a sensitivity of 87.1%, a specificity of 86.7%, a positive predictive value of 93.1%, and a negative predictive value of 76.5%. To account for the age and gender dependency of DHEA-S, the DHEA-S ratio was calculated by measured DHEA-S divided by the lower limit of the respective reference range for all participants. A DHEA-S ratio of more than 1.78 had 100% sensitivity regarding intact HPA function. Area under the receiver operating characteristic [ROC] curve was 0.920. (95% CI, 0.844–0.997). Conclusion Normal age- and gender-specific DHEA-S level or a DHEA-S ratio of more than 1.78 are valuable markers of HPA integrity. Serum DHEA-S may be a candidate for a less costly approach where ACTH stimulation is unavailable.