Dairy products and the metabolic syndrome in a prospective study, DESIR.

OBJECTIVE: In previous cross-sectional analyses of the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, we have found inverse associations between dairy product consumption and metabolic syndrome (MetS) traits. We have now analyzed in a prospective way the influence of dairy product and calcium consumption at inclusion on the 9-year cumulative incidence of the MetS and associated traits in the French prospective study with a 9-year follow-up, DESIR. METHODS: After exclusion of diabetic subjects and those being on a diet at inclusion, 3417 men and women who completed a food frequency at baseline could be studied. Logistic regression models were used to study associations between dairy products and dietary calcium density at baseline and incident MetS and impaired fasting glycemia/type 2 diabetes (IFG/T2D) after adjusting for gender, age, and lifestyle parameters (alcohol, smoking, physical activity, fat intake). An additional model adjusting for the same covariates and for body mass index (BMI) was also used. Associations between dairy products and continuous variables were studied by repeated measures analysis of covariance, using the same covariates. RESULTS: Total dairy product consumption, dairy (except cheese) consumption, and dietary calcium density were inversely associated with incident MetS and IFG/T2D. Cheese consumption was negatively associated with incident MetS but not with glycemic disorders. All parameters were associated with lower diastolic blood pressure and triglycerides (average over the 9-year period) and with a lower BMI gain in the same period. Higher total dairy and cheese intake and calcium density were associated with a lower increase in waist circumference and triglycerides during the 9-year follow-up. CONCLUSION: In the French general population, these results show beneficial effects of dairy product consumption on the metabolic syndrome and glycemic disorders. Therefore, dairy product consumption could be protective against cardiovascular risk.

Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes.

BACKGROUND: Adiponectin levels are high in cases of diabetic nephropathy, but it remains unclear whether these high levels are a cause or a consequence of the disease. We investigated the possible association of polymorphisms in the adiponectin gene and baseline adiponectin levels with the incidence of renal events in subjects with type 2 diabetes. METHODS: We studied three adiponectin polymorphisms (-11391G > A, +45T > G and +276G > T) in 3086 subjects with type 2 diabetes and high levels of albumin excretion from the diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events and ramipril (DIABHYCAR) trial. Baseline concentrations of total adiponectin and of adiponectin isoforms were determined in cases with incident renal events and in controls matched for sex, age, body mass index (BMI) and adiponectin genotype. We used another cohort of type 2 diabetes patients-the survie, diabète de type 2 et génétique(SURDIAGENE) study (n = 1004)-for the replication of genetic data. RESULTS: In DIABHYCAR, the -11391A and +45G alleles were associated with a higher incidence of renal events [hazard ratio (HR) = 1.73; 95% confidence interval (CI), 1.10-2.71; and HR = 1.68; 95% CI, 1.14-2.47, respectively]. The haplotype containing susceptibility alleles, -11391A/+45G/+276G, was more frequent in cases with renal events (5.1% vs. 1.9% in those without, P = 0.005). In SURDIAGENE, the -11391A/+45G/+276G haplotype was also associated with renal events (5.6% vs. 1.9% in those without, P = 0.03). In DIABHYCAR, all isoforms were more abundant in subjects carrying the -11391A or +45G alleles. Medium- (MMW) and low-molecular weight (LMW) isoforms were more abundant in cases with renal events. CONCLUSIONS: In subjects with type 2 diabetes and early renal dysfunction, adiponectin gene variants are determinants of the renal risk. The -11391A and +45G alleles may affect renal risk by leading to high circulating adiponectin concentrations, at least those of MMW and LMW isoforms.

The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study.

Although cross-sectional studies have associated the Pro12Ala polymorphism of PPARG with type 2 diabetes, prospective studies offer more opportunities to investigate genetic variants. Associations between PPARG polymorphisms with insulin resistance parameters and with the 6-year incidence of impaired fasting glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort. In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66 [95% CI 0.44-0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR = 0.65 [0.44-0.96], P = 0.036). Both alleles are in strong linkage disequilibrium (D' = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No association with insulin levels or HOMA-IR was found with C1431T. In this cohort, the APM1 G-11391A SNP is associated with the development of hyperglycemia. The combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively high protective effect in developing hyperglycemia and hyperinsulinemia during a 6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and APM1 SNPs on diabetes risk are suggested.

Dairy consumption and the incidence of hyperglycemia and the metabolic syndrome: results from a french prospective study, Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR).

OBJECTIVE: In the French Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, cross-sectional analyses have shown that a higher consumption of dairy products and calcium are associated with a lower prevalence of the metabolic syndrome (MetS). We assess the influence of dairy products on 9-year incident MetS and on impaired fasting glycemia and/or type 2 diabetes (IFG/T2D). RESEARCH DESIGN AND METHODS: Men and women who completed a food frequency questionnaire at baseline and after 3 years were studied (n = 3,435). Logistic regression models were used to study associations between the average year 0 and year 3 consumption of milk and dairy products, cheese, dietary calcium density, and incident MetS and IFG/T2D after adjusting for 1) sex, age, alcohol, smoking, physical activity, fat intake and 2) additionally for BMI. Associations between dairy products and continuous variables were studied by repeated-measures ANCOVA, using the same covariates. RESULTS: Dairy products other than cheese, and dietary calcium density, were inversely associated with incident MetS and IFG/T2D; cheese was negatively associated with incident MetS. All three parameters were associated with lower diastolic blood pressure, and with a lower BMI gain. Higher cheese intake and calcium density were associated with a lower increase in waist circumference and lower triglyceride levels. Calcium density was also associated with a lower systolic blood pressure and a lower 9-year increase in plasma triglyceride levels. CONCLUSIONS: A higher consumption of dairy products and calcium was associated with a lower 9-year incidence of MetS and IFG/T2D in a large cohort drawn from the general population.

The CETP TaqIB polymorphism is associated with the risk of sudden death in type 2 diabetic patients.

OBJECTIVE: Type 2 diabetic patients have a high risk of coronary heart disease (CHD) and sudden death. This cardiovascular risk can be partly attributed to low levels of HDL cholesterol. The B2 allele of the CETP TaqIB polymorphism has been repeatedly reported to be associated with high HDL cholesterol levels in both healthy and type 2 diabetic subjects, but its association with CHD is unclear. We investigated the association of the CETP TaqIB polymorphism with CHD, and sudden death in particular, in a prospective cohort of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: The CETP TaqIB polymorphism was genotyped in 3,124 type 2 diabetic subjects with high cardiovascular risk: the Noninsulin-Dependent Diabetes, Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) study. We used Cox regression analysis to estimate the impact of the TaqIB single nucleotide polymorphism on the CHD events (myocardial infarction or sudden death) during follow-up. RESULTS: The incidence of CHD was higher in B1B1 homozygotes than in B2 carriers (P = 0.02). This effect was mainly due to sudden death (hazard ratio [B1B1 vs. B2+] = 1.51 [95% CI = 1.05-2.18]). Although the B1 allele was associated in a dose-dependent fashion with lower HDL cholesterol (P < 0.001), the association with sudden death persisted after adjustment for multiple risk factors, including HDL cholesterol levels. CONCLUSIONS: In type 2 diabetic patients, the CETP TaqIB polymorphism is a good genetic predictor of cardiac mortality. This association is partly independent of the effect on HDL cholesterol levels.