Aims/hypothesis New genetic variants associated with susceptibility to type 2 diabetes mellitus have been discovered in recent genome-wide association (GWA) studies. The aim of the present study was to examine the association between these diabetogenic variants and gestational diabetes mellitus (GDM). Methods The study included 869 Korean women with GDM and 345 female and 287 male Korean non-diabetic controls. We genotyped the single nucleotide polymorphisms (SNPs) rs7756992 and rs7754840 in CDKAL1; rs564398, rs1333040, rs10757278 and rs10811661 in the CDKN2A−CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8. In addition, rs7903146 and rs12255372 in TCF7L2; rs5215 and rs5219 in KCNJ11; and rs3856806 and rs1801282 in PPARG were genotyped. The genotype frequencies in the GDM patients were compared with those in the non-diabetic controls. Results Compared with controls (men and women combined), GDM was associated with rs7756992 and rs7754840 (OR 1.55, 95% CI 1.34-1.79, p=4.17×10 −9 ) in CDKAL1; rs10811661 (OR 1.49, 95% CI 1.29-1.72, p=1.05×10 −7 ) in the CDKN2A−CDKN2B region; rs1111875 (OR 1.27, 95% CI 1.09-1.49, p=0.003), rs5015480, and rs7923837 in HHEX; rs4402960 (OR 1.18, 95% CI 1.01-1.38, p=0.03) in IGF2BP2; rs13266634 (OR 1.24, 95% CI 1.07-1.43, p=0.005) in SLC30A8; and rs7903146 (OR 1.58, 95% CI 1.03-2.43, p=0.038) in TCF7L2. The risk alleles of the SNPs rs7756992 and rs7754840 in CDKAL1; rs10811661 in the CDKN2A-CDKN2B region; and rs1111875, rs5015480 and rs7923837 in HHEX were associated with significant decreases in the insulin AUC during a 100 g OGTT performed at the time of diagnosis of GDM. Conclusions/interpretation Some of the type 2 diabetesassociated genetic variants that were discovered in the recent GWA studies are also associated with GDM in Koreans.

Aims/hypothesis. Resistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations. Methods. We examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotypebased promoter activity assays and the gel electrophoretic mobility shift assay. Results. The −420G and the −537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (−537A and −420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the −420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects. Conclusions/interpretation. Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. [Diabetologia (2004) . Moreover, obese mice given an antiresistin antibody had increased insulin-stimulated glucose uptake, whereas the treatment of normal mice with recombinant resistin impaired insulin action [4]. Resistin therefore could link obesity with insulin resistance and diabetes in mouse models. However, subsequent studies in rodent models have produced disparate findings on the role of resistin in obesity and insulin resistance [5,6,7].In humans, the expression of resistin in adipocytes is much lower than that seen in rodents and does not differ between normal, insulin-resistant or Type 2 diabetic patients [8,9,10]. Little is known about the relationship between circulating resistin concentrations Resistin belongs to a novel family of cystein-rich C-terminal domain proteins called resistin-like molecules, which are identical to those found in inflammatory

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Gestational diabetes mellitus (GDM), which is defined as carbohydrate intolerance of variable severity with onset or first recognition during the present pregnancy [1], is associated with adverse outcomes of pregnancy including macrosomia, birth trauma and metabolic complications of the newborn [2±4]. Although most women with GDM have a normal glucose tolerance when tested several weeks postpartum, impairment of insulin secretory capacity or increased insulin resistance or both have been reported in these women [5,6], and a substantial proportion of the women with previous GDM will eventually develop Type II diabetes mellitus [7±9]. The reported prevalence of GDM has ranged widely from less than 1 % to more than 10 % [10]. To some extent, this wide variation is thought to reflect a lack of a standardization of screening test procedures and diagnostic criteria of GDM. However, it may also be attributed to the heterogeneous nature of GDM with respect to ethnic or racial influence or both, genetic factors, admixture Diabetologia (1998) Summary We examined the associations between demographic characteristics including short stature and the prevalence of gestational diabetes mellitus (GDM) in Korean women. In this study, a total of 9005 pregnant women underwent universal screening for GDM. Oral glucose tolerance tests (100 g OGTT) were performed in positive screenees (1 h plasma glucose ³ 7.2 mmol/l) and GDM was diagnosed using National Diabetes Data Group criteria. Women with GDM were older and heavier than those with a positive screen and normal OGTT, as well as those with a negative screen. However, height of women with GDM was significantly shorter than those with a positive screen and normal OGTT, and a negative screen. When the study subjects were stratified according to height quartiles, the plasma glucose at the screening test decreased as height increased. Furthermore, the prevalence of GDM was highest in the shortest quartile ( £ 157 cm) group; the odds ratio for GDM was two times greater compared with the highest quartile ( ³ 163 cm) group, even after controlling for age and body mass index (BMI). In addition, multiple logistic regression analysis revealed that greater prepregnancy BMI, age, weight gain, a parental history of diabetes mellitus, and shorter maternal height were directly and independently associated with the prevalence of GDM. We have found that short stature is an independent risk factor for GDM in the racially homogenous population of Seoul, Korea. It is suggested that this propensity may be conveyed primarily by environmental influences. However, genetic factors may also modify the response to the environmental insult. Our findings also emphasize the heterogeneity of factors which predispose to GDM. [Diabetologia (1998) 41: 778±783]

Aims/hypothesis. Type 2 diabetes mellitus is a complex genetic disease, which results from interactions between multiple genes and environmental factors without any single factor having strong independent effects. This study was done to identify gene to gene interactions which could be associated with the risk of Type 2 diabetes. Methods. We genotyped 23 different loci in the 15 candidate genes of Type 2 diabetes in 504 unrelated Type 2 diabetic patients and 133 non-diabetic control subjects. We analysed gene to gene interactions among 23 polymorphic loci using the multifactor-dimensionality reduction (MDR) method, which has been shown to be effective for detecting and characterising gene to gene interactions in case-control studies with relatively small samples.Results. The MDR analysis showed a significant gene to gene interaction between the Ala55Val polymorphism in the uncoupling protein 2 gene (UCP2) and the 161C>T polymorphism in the exon 6 of peroxisome proliferator-activated receptor γ (PPARγ) gene. This interaction showed the maximum consistency and minimum prediction error among all gene to gene interaction models evaluated. Moreover, the combination of the UCP2 55 Ala/Val heterozygote and the PPARγ 161 C/C homozygote was associated with a reduced risk of Type 2 diabetes (odds ratio: 0.51, 95% CI: 0.34 to 0.77, p=0.0016). Conclusions/interpretation. Using the MDR method, we showed a two-locus interaction between the UCP2 and PPARγ genes among 23 loci in the candidate genes of Type 2 diabetes. The determination of such genotype combinations contributing to Type 2 diabetes mellitus could provide a new tool for identifying high-risk individuals. [Diabetologia (2004)