Effect of adding vildagliptin to insulin in haemodialysed patients with type 2 diabetes: The VILDDIAL study, a randomized, multicentre, prospective study.

AIM: To evaluate the effect of adding the dipeptidyl-peptidase-4 inhibitor vildagliptin to insulin on the glycaemic control of patients with type 2 diabetes undergoing haemodialysis. METHODS: Overall, 65 insulin-treated patients with type 2 diabetes undergoing haemodialysis (HbA1c: 7.3% ± 1.1%; age: 70.5 ± 8.5 years) were randomized (1:1) either to receive vildagliptin 50 mg/day in addition to insulin (vildagliptin-insulin group) or to pursue their usual insulin regimen (insulin-only group). Continuous glucose monitoring (CGM) was performed for 48 ± 6 hours at baseline and at week 12. The primary study endpoint was change from baseline in mean interstitial glucose using CGM. The secondary endpoints included other CGM variables and glucose control markers. RESULTS: After 12 weeks, a greater reduction in mean CGM glucose from baseline was observed in the vildagliptin-insulin group compared with the insulin-only group, although the between-treatment difference was not statistically significant (mean difference [CI 95%]: -0.96 mmol/L [-2.09; 0.18] vs. -0.29 mmol/L [-1.29; 0.76], P = 0.32). However, a significant decrease from baseline in HbA1c, glycated albumin and insulin daily doses was observed in the vildagliptin-insulin group versus the insulin-only group (-0.6% [-1.19; -0.1], P < 0.01), in the vildagliptin-insulin group versus no change in the insulin-only group (-130.6 µmol/L [-271; 10.7] vs. +36.2 µmol/L [-164.4; 236.9], P = 0.04 and - 5.9 IU/day [-1.8; 7.1] vs. +1.1 IU/day [-14.5; 16.6], P = 0.01, respectively). There was no significant difference in the percentage of time spent in hypoglycaemia using CGM, occurrence of severe hypoglycaemia or number of adverse events. CONCLUSION: In this study, vildagliptin added to insulin improved glycaemic control with an associated insulin-sparing effect in patients with type 2 diabetes undergoing haemodialysis and was well tolerated.

Association of menopause and hormone replacement therapy with large artery remodeling.

OBJECTIVE: To evaluate the remodeling of large arteries according to age at menopause, duration of menopause, and use of hormone therapy (HT). DESIGN: A cross-sectional study consisting of baseline measurements of a multicentric randomized trial were used to evaluate arterial parameters. SETTING: The study was conducted in France, Belgium, and the Netherlands in academic hospitals and private clinics. PATIENT(S): Postmenopausal women (n = 538) with mild hypercholesterolemia. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Common carotid artery intima-media thickness (CCA-IMT), central pulse pressure, and aortic stiffness (carotid-femoral pulse wave velocity) were measured and centrally controlled for quality. Multivariate regression analysis was used to assess the possible covariates associated with arterial parameters. RESULT(S): Women were 58 ± 6 (mean ± SD) years of age with an age of 50 ± 5 at menopause and a mean duration of menopause of 8 ± 7 years. Lower age at menopause, time since menopause, and absence of HT use were independently associated with worsening of the arterial parameters. After multivariate analysis, HT was associated with a lower CCA-IMT (-40 µm [range -64 to -1]), whereas lower age at menopause and menopause duration were respectively associated with a CCA-IMT increase (25 µm/5 y and 27 µm/5 y). Similarly, values of central pulse pressure and pulse wave velocity were lower in HT users (-3.1 mm Hg [-5.1 to -0.9] and -0.31 m/s [-0.63 to -0.02], respectively) but worsened with age at menopause and menopause duration. CONCLUSION(S): The age at menopause, the time since menopause, and the use of HT are independently associated with the thickening and stiffening of the large arteries. CLINICAL TRIAL REGISTRATION NUMBER: NCT00163163.

[Obesity in haemodialysis: the paradox]. / Obésité et hémodialyse: le paradoxe.

Overweight, as well as obesity have become mass phenomena with an ever increasing prevalence in most countries all over the world, and are associated with a greater cardiovascular risk and mortality. Weight excess is usually directly related to an additional risk of morbidity and mortality in the general population. In contrast, in patients with end-stage renal disease (ESDR) under haemodialysis a paradox has been reported, showing that an increased body mass index (BMI) was associated with better survival, and vice versa. This paradox relationship, sometimes referred to as "reverse epidemiology" proved to be relatively constant in chronic haemodialysis and to a lesser extent in peritoneal dialysis. Reverse epidemiology is also found in haemodialysis patients for other risk factors, such hypertension, or hypercholesterolaemia. And, likewise, this phenomenon is also observed in other populations of heavy chronic disease suggesting a potential selection bias, such as a real survival benefit for obesity in case of the presence of another heavy chronic disease. The possible causes and mechanisms of reverse epidemiology are reviewed in this article.