Publications (3)7.95 Total impact
Article: Future perspective on pharmacogenomics of severe hypoglycemia associated with sulfonylureas: reply from the authors.[show abstract] [hide abstract]
ABSTRACT: A letter in response to: Holstein JD, Kovacs P, Patzer O, Stumvoll M, Holstein A. The Ser1369Ala variant of ABCC8 and the risk for severe sulfonylurea-induced hypoglycemia in German patients with Type 2 diabetes. Pharmacogenomics 13(1), 5-7 (2012).Pharmacogenomics 01/2012; 13(1):9-10. · 3.97 Impact Factor
Article: A cross-sectional study of glucose regulation in young adults with very low birth weight: impact of male gender on hyperglycaemia.[show abstract] [hide abstract]
ABSTRACT: To investigate glucose regulation in young adults with very low birth weight (VLBW; <1500 g) in an Asian population. Cross-sectional observational study. A general hospital in Hamamatsu, Japan. 111 young adults (42 men and 69 women; aged 19-30 years) born with VLBW between 1980 and 1990. Participants underwent standard 75 g oral glucose tolerance test (OGTT). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were glucose and insulin levels during OGTT and risk factors for a category of hyperglycaemia defined as follows: diabetes mellitus, impaired glucose tolerance (IGT), impaired fasting glycaemia (IFG) and non-diabetes/IGT/IFG with elevated 1 h glucose levels (>8.6 mmol/l). The secondary outcomes were the pancreatic β cell function (insulinogenic index and homeostasis model of assessment for beta cell (HOMA-β)) and insulin resistance (homeostasis model of assessment for insulin resistance (HOMA-IR)). Of 111 young adults with VLBW, 21 subjects (19%) had hyperglycaemia: one had type 2 diabetes, six had IGT, one had IFG and 13 had non-diabetes/IGT/IFG with elevated 1 h glucose levels. In logistic regression analysis, male gender was an independent risk factor associated with hyperglycaemia (OR 3.34, 95% CI 1.08 to 10.3, p=0.036). Male subjects had significantly higher levels of glucose and lower levels of insulin during OGTT than female subjects (p<0.001 for glucose and p=0.005 for insulin by repeated measures analysis of variance). Pancreatic β cell function was lower in men (insulinogenic index: p=0.002; HOMA-β: p=0.001), although no gender difference was found in insulin resistance (HOMA-IR: p=0.477). In male subjects, logistic regression analysis showed that small for gestational age was an independent risk factor associated with hyperglycaemia (OR 33.3, 95% CI 1.67 to 662.6, p=0.022). 19% of individuals with VLBW already had hyperglycaemia in young adulthood, and male gender was a significant independent risk factor of hyperglycaemia. In male young adults with VLBW, small for gestational age was associated with hyperglycaemia.BMJ open. 01/2012; 2(1):e000327.
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ABSTRACT: Sulfonylureas are categorized according to their binding sites of the ATP-sensitive K+ channel (K(ATP) channel) complex in pancreatic β-cells. The binding sites are classified as A, B and A + B site (both A and B sites), respectively. The Ser1369Ala variant in the sulfonylurea receptor gene ABCC8 which encodes a subunit of the K(ATP) channel complex has been demonstrated to be associated with the hypoglycemic effect of gliclazide, which binds to the A site. However, the hypoglycemic effect of the Ser1369Ala variant on treatment with A + B binding site sulfonylureas, such as glimepiride or glibenclamide, is still uncertain. In a case-control study, 32 patients with Type 2 diabetes admitted to hospital with severe hypoglycemia and 125 consecutive Type 2 diabetic outpatients without severe hypoglycemia were enrolled. We determined the genotypes of the ABCC8 polymorphism (Ser1369Ala) in the patients with or without severe hypoglycemia. All of the patients were taking glimepiride or glibenclamide. In the patients treated with glimepiride or glibenclamide, we found no significant differences in the distribution of the Ser1369Ala genotype between patients with or without severe hypoglycemia (p = 0.26). Moreover, the Ala1369 minor allele tended to be less frequent in the hypoglycemic group (31 vs 43%; OR: 1.65; 95% CI: 0.92-2.96; p = 0.09). Our findings suggest that the Ser1369Ala variant is not a major predictive factor of severe hypoglycemia due to glimepiride or glibenclamide, both of which bind to the A + B site. It is likely that severe hypoglycemia due to A + B binding site sulfonylureas will be mediated by other factors, and not the Ala1369 minor allele.Pharmacogenomics 12/2010; 11(12):1743-50. · 3.97 Impact Factor