HbA1c levels and all-cause mortality in type 2 diabetic patients: epidemiological evidence of the need for personalised therapeutic targets.

BACKGROUND AND AIM: The aim of the present case-control study is to explore the effect of case mix on the relationship between glycated haemoglobin (HbA1c) and mortality in type 2 diabetic patients. METHODS AND RESULTS: A nested case-control study data set was generated from the cohort-study data set (n = 4140 type 2 diabetic outpatients) by sampling controls from the risk sets. Cases (n = 427) were compared with an equal number of controls chosen from those members of the cohort who were at risk for the same follow-up time of the case, matched for age (±3 years), sex, body mass index (BMI) (±2 kg m(-2)), duration of diabetes (±5 years), and Charlson's Comorbidity Score (CCS) (±1). The main predefined analysis was the comparison of cases and controls for proportion of patients with each HbA1c class (<6.5%, 6.5-7.4%, 7.5-8.4% and ≥8.5%). During a mean follow-up of 5.7 ± 3.5 years, 427 deaths were recorded. The lowest risk of death was observed in the HbA1c 6.5-7.4% category; a lower HbA1c was associated with a non-significant trend towards a higher risk. The risk associated with a low (<6.5%) HbA1c was significantly greater in patients who were insulin-treated than in the rest of the sample. CONCLUSIONS: The present study suggests that glycaemic targets should be individualised on the basis of the characteristics of each patient, considering age, co-morbidity and duration of diabetes. Caution should be used in prescribing insulin to reach near-normoglycaemia, particularly in older, frail patients.

Adiponectin in outpatients with coronary artery disease: independent predictors and relationship with heart failure.

BACKGROUND AND AIMS: Chronic heart failure (HF) is characterised by a neurohormonal dysfunction associated with chronic inflammation. A role of metabolic derangement in the pathophysiology of HF has been recently reported. Adiponectin, an adipose-tissue-derived cytokine, seems to play an important role in cardiac dysfunction. We investigated the variation of circulating adiponectin in patients with coronary artery disease (CAD), with or without HF, in order to identify its independent predictors. METHODS AND RESULTS: A total of 107 outpatients with CAD were enrolled in the study and divided into three groups: CAD without left ventricular systolic dysfunction (group 1); CAD with left ventricular dysfunction without HF symptoms (group 2) and CAD with overt HF (group 3). Plasma adiponectin was determined by enzyme-linked immunosorbent assay. Adiponectin concentrations increased progressively from group 1 (7.6 ± 3.6 ng ml⁻¹) to group 2 (9.1 ± 6.7 ng ml⁻¹) and group 3 (13.7 ± 7.6 ng ml⁻¹), with the difference reaching statistical significance in group 3 versus 1 and 2 (p < 0.001). A multivariable model of analysis demonstrated that the best predictors of plasma adiponectin were body mass index, N-terminal pro-brain natriuretic peptide and high-density lipoprotein cholesterol. However, even after adjusting for all three independent predictors, the increase of adiponectin in group 3 still remained statistically significant (p = 0.015). CONCLUSION: Our data confirm the rise of adiponectin in overt HF. The levels of circulating adipokine seem to be mainly predicted by the metabolic profile of patients and by biohumoral indicators, rather than by clinical and echocardiographic indexes of HF severity.

Effects of antihypertensive treatments on incidence of diabetes: a case-control study.

AIMS: Aim of this case-control study is the assessment of the relationship between antihypertensive treatment and incidence of diabetes in an unselected cohort of subjects participating in a screening program for diabetes. METHODS: A case-control study nested within a cohort of nondiabetic subjects with a mean follow-up of 27.7 ± 11.3 months was performed, comparing 40 cases of incident diabetes and 160 controls matched for age, sex, body mass index, fasting plasma glucose, 2-h post-load glycemia, smoking and alcohol abuse. RESULTS: When considering antihypertensive treatment at enrolment, a lower proportion of cases was exposed to ACE-inhibitors/angiotensin receptor blockers (ACE-i/ARB) in comparison with controls. A non-significant trend toward a higher exposure to diuretics, which were mainly represented by thiazide diuretics, was observed in cases. In a multivariate analysis, including both ACE-i/ARB and diuretics, a protective effect of ACEi/ARB, and an increased risk with diuretics were observed. Similar results were obtained in alternative models, after adjusting for systolic and diastolic blood pressure at enrolment, diagnosis of hypertension, concurrent treatment with ß-blockers or calcium-channel blockers, and number of antihypertensive medications. CONCLUSIONS: Diuretics seem to be associated with a higher incidence of diabetes, whereas treatment with ACEi/ARB could have a protective effect.