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)

Aims We investigated the prevalence and risk factors for developing erectile dysfunction (ED) in 1312 Korean men with diabetes in a multicentre study. MethodsWe used the modified International Index for Erectile Function-5 criteria to identify mild, moderate and complete ED. A standardized face-toface questionnaire was used by trained interviewers, and validated against telephone interviews. We recorded the duration of diabetes, level of glycaemic control, vital signs, complications, exercise and alcohol and smoking habits, and diabetes treatments used. ResultsThe mean age and median duration of diabetes were 53.8 ± 6.65 and 6 years (range 1-43), respectively. The mean HbA 1c and fasting glucose levels were 7.9 ± 1.65% and 8.6 ± 2.82 mmol/l, respectively. The overall prevalences of mild, moderate, complete ED and all ED (mild-to-complete) were 20.1, 19.5, 25.8 and 65.4%, respectively. ED was more common with age, reaching 79.3% in men aged > 60 years. Subjects aged > 60 years and with a duration of diabetes > 10 years were at greatest risk for all ED (OR = 10.4, 95% CI 5.8-18.5, P < 0.001) and complete ED (OR = 13.2, 95% CI 7.3-23.9, P < 0.001) when compared with the reference group (age 40-50 years with duration < 6 years). Age, duration of diabetes, HbA 1c , insulin use, neuropathy and macrovascular complications were positively associated with ED, but alcohol consumption and exercise habits were negatively associated. ConclusionsThe prevalence of complete ED was approximately six times higher than in the general population.

Efficacy and safety of teneligliptin, a dipeptidyl peptidase-4 inhibitor, combined with metformin in Korean patients with type 2 diabetes mellitus: a 16-week, randomized, double-blind, placebo-controlled phase III trialThe aim of the present study was to assess the efficacy and safety of teneligliptin in combination with metformin in Korean patients with type 2 diabetes mellitus who were inadequately controlled with metformin monotherapy. Patients [glycated haemoglobin (HbA1c) 7.0-10.0%, on stable metformin ≥1000 mg/day] were randomized 2 : 1 to receive 20 mg teneligliptin plus metformin (n = 136) or placebo plus metformin (n = 68). The primary endpoint was the change in HbA1c levels from baseline to week 16. The mean baseline HbA1c was 7.9% in the teneligliptin group and 7.8% in the placebo group. The differences between the teneligliptin and placebo groups regarding changes in HbA1c and fasting plasma glucose levels were −0.78 % and −1.24 mmol/l (22.42 mg/dl), respectively, at week 16. The incidence of adverse events was similar between the groups. The addition of teneligliptin once daily to metformin was effective and generally well tolerated in Korean patients with type 2 diabetes.