The combination of UCP3-55CT and PPARγ2Pro12Ala polymorphisms affects BMI and substrate oxidation in two diabetic populations.

BACKGROUND AND AIM: To evaluate the combined contribution of UCP3-55CT and PPARγ2 Pro12Ala polymorphisms as correlates of BMI, energy expenditure (REE) and substrate oxidation in people with type 2 diabetes. METHODS AND RESULTS: Two independent population with type 2 diabetes were studied: population A, n = 272; population B, n = 269. Based on both UCP3 and PPARγ2 genotypes three groups were created. Carriers of the PPARγ2 Pro12Ala in combination with the CC genotype of UCP3 (ProAla/CC, group 1); carriers of only one of these genotypes (either CC/ProPro or CT-TT/ProAla, group 2); people with neither variants (CT-TT/ProPro, group 3). In both populations BMI (kg/m(2)) was highest in group 1, intermediate in group 2 and lowest in group 3, independent of energy intake (i.e 35.3 ± 6.7 vs 33.4 ± 5.4 vs 31.8 ± 3, p < 0.02, population A; 32.4 ± 4.2 vs 31.7 ± 3.8 vs 30.1 ± 2.7; p < 0.03, population B). People with the ProAla/CC genotype (group 1) showed similar REE, but lower lipid oxidation (10.9 vs 13.9 g/kg fat free mass/day; p = 0.04) and higher carbohydrate oxidation (23.6 vs 15.6 g/kg fat free mass/day; p = 0.02) than carriers of other genotypes. CONCLUSIONS: The combination of UCP3-55 CC and PPARγ2 Pro12Ala genotypes is associated with significantly higher BMI than other PPARγ2-UCP3 genotype combinations, partly due to a reduced ability in lipids oxidation. The relative importance of these mechanism(s) may be different in non diabetic people.

The energy intake modulates the association of the -55CT polymorphism of UCP3 with body weight in type 2 diabetic patients.

BACKGROUND: Previous association studies of the -55CT polymorphism of the uncoupling protein 3 (UCP3) gene with body mass index (BMI) have provided inconsistent results. The study aim is twofold: (1) to evaluate the association of the -55CT polymorphism of UCP3 with BMI in two independent populations to verify the reproducibility of the finding; (2) to evaluate whether this association is modulated by energy intake. METHODS: Study participants are 736 males and females with type 2 diabetes belonging to independent populations (N=394 population 1; N=342 population 2). Anthropometry and laboratory parameters were measured; in population 2, energy intake and physical exercise were also assessed. RESULTS: The -55CT polymorphism was associated with a significantly lower BMI in population 1 (27.8±3.9 vs 28.9±4.6 kg m(-2); P<0.02), the finding was confirmed in population 2 (that is, 30.3±6.0 vs 32.1±5.9 kg m(-2); P<0.01) independent of gender, age, HbA1c, use of drugs and energy intake. To evaluate the role of diet in population 2, the study participants were stratified by genotype and tertiles of energy intake. In both genotype groups, BMI increased with increasing caloric intake with a significant trend (P<0.001), the BMI difference between the two genotype groups was large and statistically significant in the lower tertile (27.6 vs 31.2 kg m(-2); P<0.001), intermediate in the second tertile and negligible in the upper tertile (32.8 vs 32.9; kg m(-2); nonsignificant). The multivariate regression analysis confirmed a significant interaction between genotype and energy intake as correlates of BMI independent of age, gender, glucose control, physical activity and medications for diabetes (P=0.004). CONCLUSIONS: The study replicates in two independent populations the association between the -55CT polymorphism of UCP3 and a lower BMI. This association was modulated by energy intake, thus suggesting that the unmeasured effect of diet may partly account for inconsistencies of prior association studies.

Fasting APO B48 levels are associated with microalbuminuria in patients with type 2 diabetes.

In view of the high incidence of macrovascular diseases in patients with type 2 diabetes mellitus and microalbuminuria, the study evaluates the association of microalbuminuria with fasting plasma Apo B48 levels, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic. We studied 50 patients with type 2 diabetes aged 35-75 years. Exclusion criteria were overt macrovascular disease, overt nephropathy (Glomerular filtration rate (GFR) <45 ml/min/1.73 m(2)), or use of hypolipidemic agents. Anthropometry, fasting plasma lipids, plasma creatinine, and HbA1c were measured. Urinary albumin excretion was measured on a morning urine sample with the ELISA and expressed as albumin/creatinine ratio. GFR was estimated using the MDRD formula. The plasma fasting Apo B48 was measured by ELISA. Age, gender distribution, fasting plasma lipids, HbA1c, smoking status, plasma creatinine, estimate GFR, and the proportion of patients treated with insulin or antihypertensive drugs were similar for patients with or without microalbuminuria. People with microalbuminuria had longer diabetes duration (borderline significance) and significantly higher Apo B48 (1.765 ± 1.379 µg/ml vs. 1.022 ± 0.692 µg/ml, p = 0.01) than those without microalbuminuria. Multivariate logistic regression analysis confirmed that fasting Apo B48 levels were significantly associated with microalbuminuria independent of major confounders measured in the study. In patients with type 2 diabetes, microalbuminuria is associated with elevated Apo B48 levels, independent of major confounders; this may partly explain the excess cardiovascular risk of these patients.