Comparative effects of glucagon-like peptide-1 receptors agonists, 4-dipeptidyl peptidase inhibitors, and metformin on metabolic syndrome.

AIMS: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients. METHODS: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires. RESULTS: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: -1.7 mg/dL(± 13.5); ∆ metformin: - 2.5(± 23.9) mg/dL; ∆ DPP-4I: - 4.5(± 42.6); mg/dL ∆ GLP-1RA: - 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: - 0.1(± 0.7) %; ∆ DPP-4I: - 0.1(± 1.0) %; ∆ GLP-1RA: - 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: -0.8(± 1.6) kg/m2; ∆ metformin: - 0.8(± 1.5) kg/m2; ∆ DPP-4I: - 0.6(± 1.3) kg/m2; ∆ GLP-1RA: - 0.5(± 1.2) kg/m2. and their waist circumference (∆ untreated: -2.8(± 5.2) cm; ∆ metformin: - 2.6(± 15.2) cm; ∆ DPP-4I: - 2.1(± 4.8) cm; ∆ GLP-1RA: - 2.4(± 4.1) cm. CONCLUSION: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest.

The apolipoprotein A5 gene -1131T-->C polymorphism affects vitamin E plasma concentrations in type 2 diabetic patients.

BACKGROUND: Variations of the apolipoprotein A5 (APOA5) gene are strongly associated with hypertriglyceridemia. Vitamin E is transported in triglyceride (TG)-rich lipoproteins and therefore could also be modulated by apoAV. Patients with type 2 diabetes have a tendency towards high TG values and increased oxidative stress. METHODS: We examined the impact of genetic APOA5 variation (-1131T-->C) on vitamin E and oxidative status in 169 non-smoker type 2 diabetic patients. Plasma samples were analyzed for lipids, lipoproteins, vitamin E, oxidized low-density lipoprotein (oxLDL), lipoperoxides, autoantibodies against oxLDL and diene formation of LDL. RESULTS: Vitamin E concentrations were higher in TC carriers compared with TT carriers (45.48+/-8.20 micromol/L vs. 40.32+/-10.47 micromol/L; p=0.02). The prevalence of the TC genotype was 2.6-fold higher among individuals with high vitamin E concentrations (p=0.02). The APOA5 polymorphism did not determine any differences in oxidative status. Fasting TG concentration was a significant 21% higher in carriers of the TC genotype (p=0.04) due to higher TG concentrations in very-low-density lipoprotein (VLDL) and high-density lipoprotein. CONCLUSIONS: The APOA5-1131T-->C polymorphism is associated with both higher vitamin E concentrations and higher VLDL-TGs in diabetic patients.

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients.

BACKGROUND AND AIM: Type 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients. METHODS AND RESULTS: We studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (-108C>T, 55T>A, and 192A>G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P=0.016), OxLDL/HDL (18%; P=0.024) and OxLDL-Ab (12%; P=0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P<0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (-108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P=0.040) in patients with atherosclerosis. CONCLUSION: OxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.

Plasma fatty acid-binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evaluated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. METHODS: In 263 individuals (161 type 2 diabetic patients and 102 healthy nondiabetic controls), we analyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR <30 mL/min/1.73 m(2)) or albuminuria were not included. RESULTS: FABP4 concentrations were higher in diabetic patients with MDRD-GFR <60 mL/min/1.73 m(2) (P <0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P <0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = -0.511, P <0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those patients without microalbuminuria were analyzed (r = 0.414, P <0.001 and r = -0.510, P <0.001, respectively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8-30.7), P = 0.005 and 15.3 (3.1-76.4), P = 0.001; respectively], independent of microalbuminuria. CONCLUSIONS: High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consideration as an early marker of kidney damage in patients with type 2 diabetes.