Bivariate genetic modelling of the response to an oral glucose tolerance challenge: A gene x environment interaction approach

AIMS/HYPOTHESIS: Twin and family studies have shown the importance of genetic factors influencing fasting and 2 h glucose and insulin levels. However, the genetics of the physiological response to a glucose load has not been thoroughly investigated. METHODS: We studied 580 monozygotic and 1,937 dizygotic British female twins from the Twins UK Registry. The effects of genetic and environmental factors on fasting and 2 h glucose and insulin levels were estimated using univariate genetic modelling. Bivariate model fitting was used to investigate the glucose and insulin responses to a glucose load, i.e. an OGTT. RESULTS: The genetic effect on fasting and 2 h glucose and insulin levels ranged between 40% and 56% after adjustment for age and BMI. Exposure to a glucose load resulted in the emergence of novel genetic effects on 2 h glucose independent of the fasting level, accounting for about 55% of its heritability. For 2 h insulin, the effect of the same genes that already influenced fasting insulin was amplified by about 30%. CONCLUSIONS/INTERPRETATION: Exposure to a glucose challenge uncovers new genetic variance for glucose and amplifies the effects of genes that already influence the fasting insulin level. Finding the genes acting on 2 h glucose independently of fasting glucose may offer new aetiological insight into the risk of cardiovascular events and death from all causes

Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study

Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study. Spijkerman AM, Henry RM, Dekker JM, Nijpels G, Kostense PJ, Kors JA, Ruwaard D, Stehouwer CD, Bouter LM, Heine RJ. Institutes for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. [email protected] OBJECTIVES: Screening for type 2 diabetes has been recommended and targeted screening might be an efficient way to screen. The aim was to investigate whether diabetic patients identified by a targeted screening procedure differ from newly diagnosed diabetic patients in general practice with regard to the prevalence of macrovascular complications. DESIGN: Cross-sectional population-based study. SETTING: Population study, primary care. SUBJECTS: Diabetic patients identified by a population-based targeted screening procedure (SDM patients), consisting of a screening questionnaire and a fasting capillary glucose measurement followed by diagnostic testing, were compared with newly diagnosed diabetic patients in general practice (GPDM patients). Ischaemic heart disease and prior myocardial infarction were assessed by ECG recording. Peripheral arterial disease was assessed by the ankle-arm index. Intima-media thickness of the right common carotid artery was measured with ultrasound. RESULTS: A total of 195 SDM patients and 60 GPDM patients participated in the medical examination. The prevalence of MI was 13.3% (95% CI 9.3-18.8%) and 3.4% (1.0-11.7%) in SDM patients and GPDM patients respectively. The prevalence of ischaemic heart disease was 39.5% (95% CI 32.9-46.5%) in SDM patients and 24.1% (15.0-36.5%) in GPDM patients. The prevalence of peripheral arterial disease was similar in both groups: 10.6% (95% CI 6.9-15.9%) and 10.2% (4.7-20.5%) respectively. Mean intima-media thickness was 0.85 mm (+/-0.17) in SDM patients and 0.90 mm (+/-0.20) in GPDM patients. The difference in intima-media thickness was not statistically significant. CONCLUSIONS: Targeted screening identified patients with a prevalence of macrovascular complications similar to that of patients detected in general practice, but with a lower degree of hyperglycaemi

Cardiovascular Disease Mortality in Europeans in Relation to Fasting and 2-h Plasma Glucose Levels Within a Normoglycemic Range

OBJECTIVE - To study mortality in relation to fasting plasma glucose (FPG) and 2-h plasma glucose levels within the normoglycemic range

Differences in Cardiovascular Risk Profile of Diabetic Subjects Discordantly Classified by Diagnostic Criteria Based on Glycated Hemoglobin and Oral Glucose Tolerance Test

OBJECTIVE - To characterize the cardiovascular risk profile of subjects categorized differently by A1C- and oral glucose tolerance test (OGTT)-based diagnostic criteria for diabetes according to the recommendations of the American Diabetes Association (ADA). RESEARCH DESIGN AND METHODS - An OGTT, A1C, and several cardiovascular risk factors were assessed in 964 individuals without known diabetes participating in a cross-sectional epidemiological survey in Gran Canaria, Spain. RESULTS - Taking the OGTT as the gold standard, the sensitivity and specificity of an A1C value ≥6.5% were 38.7 and 99.6%, respectively. Subjects who fulfilled A1C-based criterion presented greater measures of BMI and waist circumference, lower values for HDL cholesterol, and higher values for fasting plasma glucose, homeostasis model assessment of insulin resistance, and fibrinogen than subjects with diabetic OGTT but A1C <6.5%. CONCLUSIONS - Newly diagnosed diabetic individuals who fulfill A1C-based diagnostic criterion for the disease display a more unfavorable cardiovascular risk profile than individuals who only meet the glucose-based criteria.267326717,141Q1SCI

Comparison of body mass index at diagnosis of diabetes in a multi-ethnic population:a case-control study with matched non-diabetic controls

Aims: To investigate the probability of developing type 2 diabetes mellitus (T2DM) at different body mass index levels compared to matched non-diabetic controls in a multi-ethnic population. Materials and methods: This was a case-control study of 90 367 patients with incident diabetes and 362 548 age-sex-ethnicity matched controls from UK primary care. The probability of developing T2DM was estimated. Results: Case and control patients were 56 years old at index and 56% were male. Patients with T2DM had significantly higher mean BMI levels by about 5 kg/m2 at diagnosis (32.2 kg/m2) compared to the matched controls (27.4 kg/m2). White Europeans (n = 79 270), African-Caribbeans (n = 4115) and South Asians (n = 7252) were 58, 48 and 46 years old with a mean BMI of 32.5, 31.1 and 29.2 kg/m2, respectively, at diagnosis. More South Asians developed T2DM at BMI below 30 kg/m2 (38%) than White Europeans (26%) and African-Caribbeans (29%) (all P <.01). Within the 18 to 70-year age range, South Asian males and females had a significantly higher probability of developing diabetes in the continuously measured BMI range of 18 to 30 kg/m2, compared to White Europeans and African-Caribbeans. Across all age groups <70 years, South Asians and African-Caribbeans had a significantly higher probability of developing T2DM in the normal weight and overweight categories, compared to White Europeans. However, this risk pattern of developing diabetes was reversed amongst the obese in all age groups. Conclusion: Risk patterns of developing diabetes at different levels of obesity varies among ethnic groups across all ages, while South Asians and African-Caribbeans carry the highest risk at a younger age and at lower adiposity burden