Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.

BACKGROUND: Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN. AIM AND METHODS: The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients. RESULTS: Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population. CONCLUSIONS: In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.

Twelve-month treatment with Liraglutide ameliorates Visceral Adiposity Index and common cardiovascular risk factors in type 2 diabetes outpatients.

AIM: In addition to the effects on glycemic control and body weight, GLP-1 receptor agonists may favorably affect other major cardiovascular disease (CVD) risk factors, although currently available data are still sparse. In this retrospective study, we evaluated the effects of 12-month treatment with liraglutide on major CVD risk factors in 115 type 2 diabetes outpatients (60 men and 55 women), on stable hypoglycemic, anti-hypertensive and/or lipid-lowering therapy. METHODS: Clinical and anthropometric data, metabolic and lipid profile, as well as the Visceral Adiposity Index (VAI), an obesity-related CVD risk factor, were measured in all participants at baseline and after 12-month treatment. RESULTS: Treatment with liraglutide was associated with a significant reduction from baseline values of fasting blood glucose (-42.1 mg/dl, P < 0.05), HbA1c (-1.5 %, -17 mmol/mol, P < 0.05), body weight (-7.1 kg, P < 0.05), waist circumference (-6.8 cm, P < 0.001), total-cholesterol (-27.4 mg/dl, P < 0.05), LDL-cholesterol (-25.4 mg/dl, P < 0.05), triglycerides (-56.1 mg/dl, P < 0.05), and non-HDL-C (-36.6 mg/dl, P < 0.05) and an increase of HDL-cholesterol concentrations (+9.3 mg/dl, P < 0.001), a significant reduction in both systolic and diastolic blood pressure (-14.7 mmHg, P < 0.001 and -9.0 mmHg, P < 0.05, respectively) and a decrease of VAI values (-1.6, P < 0.001). All these differences were independent of changes in BMI and comparable in men and women. CONCLUSIONS: In conclusion, 12-month treatment with liraglutide in add-on to on-going hypoglycemic therapy significantly ameliorates all major CVD risk factors and reduces cardiometabolic risk, as estimated by VAI values.

Lipid and non-lipid cardiovascular risk factors in postmenopausal type 2 diabetic women with and without coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death in diabetic women. In addition to hyperglycemia, other factors may contribute to the excessive cardiovascular risk. AIM: In this study we evaluated common and emerging risk factors in a selected group of postmenopausal type 2 diabetic women with (n = 36) and without CHD (n = 59), not taking lipid-lowering medications. METHODS: Clinical and lifestyle data were collected, and metabolic and lipid profile, as well as fasting plasma levels of total homocysteine (tHcy), folate, vitamin B12, C-reactive protein (hsCRP), interleukin 6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) were measured in all participants. RESULTS: Age, menopause and diabetes duration, family history for cardiovascular disease, prevalence of hypertension and current insulin use were greater in diabetic women with than without CHD (P < 0.05 for all comparisons). CHD women also showed higher levels of triglycerides, small dense LDL (sdLDL), remnant-like particle cholesterol, tHcy, and VCAM-1, and a lower creatinine clearance (P < 0.05 all). Conversely, the two groups were comparable for BMI, waist circumference, smoking habit, fasting plasma glucose, HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol, folate, vitamin B12, hsCRP and IL-6 levels. At multivariate analysis, lower creatinine clearance (OR = 0.932, P = 0.017) and higher sdLDL serum concentration (OR = 1.224, P = 0.037) were the strongest risk factors associated with CHD in this population, whereas no significant association was noted with LDL-C. CONCLUSIONS: Our data suggest that beyond LDL-C, a lower creatinine clearance and more subtle alterations of LDL particles, together with a constellation of several well known and emerging cardiovascular risk factors, are stronger contributors to the high CHD risk of diabetic women.

Influence of high-normal serum TSH levels on major cardiovascular risk factors and Visceral Adiposity Index in euthyroid type 2 diabetic subjects.

Although several observations indicate that serum TSH levels in the high normal range are related to cardiovascular (CVD) risk factors in the general population, similar data are limited in diabetic subjects. The aim of this study was to investigate the potential associations between TSH serum levels within the normal range and major metabolic and non-metabolic CVD risk factors in a cohort of euthyroid type 2 diabetic subjects. Thyroid hormones, TSH levels, anthropometric parameters, lipid profile, glucose control, and blood pressure were measured in 490 euthyroid type 2 diabetic subjects, consecutively attending two outpatient diabetic units in Southern Italy. In all subjects, we also calculated the Visceral Adiposity Index (VAI), an obesity-related index associated with CVD risk. Diabetic women showed higher mean serum TSH levels and lower FT4 concentration than diabetic men, while FT3 levels were comparable in the two genders. Stratifying the study population according to quartiles of TSH levels, subjects in the highest TSH quartile were more likely to be female and younger, with higher values of BMI and waist circumference (P = 0.05 both), higher triglycerides (P = 0.002) and non-HDL cholesterol concentrations (P = 0.01), higher VAI values (P = 0.02), and lower FT4 levels (P = 0.05), when compared to those in the lowest quartile. At multivariate analysis, a younger age, female gender, triglycerides levels, and waist circumference were independently associated with higher TSH levels. In conclusion, in type 2 diabetic subjects with no evidence of thyroid disease, higher TSH concentrations within the normal range were more frequent in women and in younger subjects, and they were associated with visceral obesity and higher triglycerides concentrations, two well-known CVD risk factors.