Waist circumference and metabolic risk factors have separate and additive effects on the risk of future Type 2 diabetes in patients with vascular diseases. A cohort study.

AIMS: To assess the effect of various measures of adiposity and of metabolic risk factors, both separately and in combination, on the risk of future Type 2 diabetes in patients with manifest vascular diseases. METHODS: This was a prospective cohort study in 2924 patients (mean age 59 ± 12 years) with manifest atherosclerosis. Metabolic risk factors were defined according to National Cholesterol Education Program criteria for the metabolic syndrome. Incidence of Type 2 diabetes was assessed by questionnaire and subsequent verification. RESULTS: During a median follow-up of 4.9 years (range 3.0-7.6 years) there were 178 cases (6.1%) of incident Type 2 diabetes. An increase with 1 sd waist circumference showed a strong association with incident Type 2 diabetes in both men (hazard ratio 2.45, 95% CI 1.97-3.04) and women (hazard ratio 1.77, 95% CI 1.38-2.26). Compared with patients with normal (i.e. below the National Cholesterol Education Program criteria for abdominal adiposity) waist circumference and < 3 metabolic risk factors, both patients with normal waist circumference and ≥ 3 metabolic risk factors and patients with high (i.e. above the National Cholesterol Education Program criteria for abdominal adiposity) waist circumference and < 3 metabolic risk factors had an increased risk of Type 2 diabetes (hazard ratio 2.44, 95% CI 1.37-4.36 and hazard ratio 3.61, 95% CI 2.23-5.85, respectively). Patients with both high waist circumference and ≥ 3 metabolic risk factors had the highest risk of developing Type 2 diabetes (hazard ratio 10.76, 95% CI 6.95-16.64). CONCLUSIONS: In patients with manifest atherosclerosis, both presence of ≥ 3 metabolic risk factors and presence of a high waist circumference alone are associated with increased risk for developing Type 2 diabetes. The combined presence of ≥ 3 metabolic risk factors and high waist circumference, which is present in 15% of patients, is associated with a 10-fold increased risk of future Type 2 diabetes. To identify patients with manifest atherosclerosis at the highest risk of developing Type 2 diabetes, fat distribution in combination with metabolic risk factors should be considered.

Leisure-time physical activity and risk of type 2 diabetes in patients with established vascular disease or poorly controlled vascular risk factors.

AIM: To investigate the effect of leisure-time physical activity on the incidence of type 2 diabetes (T2DM) in patients with manifest arterial disease, or poorly controlled risk factors. METHODS: We examined 3940 patients with manifest arterial disease, hypertension or hyperlipidemia, aged 55.2+/-12.2 years. Leisure-time physical activity was measured by a questionnaire and metabolic equivalent (MET) hours per week (h/wk) were calculated. Incident T2DM was evaluated by a specific diabetes questionnaire. RESULTS: Most patients (65%) were physically inactive (0METh/wk), 12% were insufficiently physically active (0-10.5METh/wk) and 23% were sufficiently physically active (>or=10.5METh/wk). During a mean follow-up of 4.7 years, 194 (5%) incident cases of T2DM occurred. Sufficiently physically active patients had a lower incidence of diabetes (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.37-0.83). Patients who were physically active and not-obese (BMI<30kg/m(2)) were at the lowest risk for developing T2DM (HR 0.18, 95% CI 0.12-0.28) compared with patients who were physically inactive and obese. CONCLUSIONS: Leisure-time physical activity is associated with a decreased risk of T2DM in patients with manifest arterial disease, or poorly controlled risk factors. The combination of physical activity and non-obesity is associated with an even lower risk of the development of type 2 diabetes than the sum of their independent, protective effect.

The metabolic syndrome: metabolic changes with vascular consequences.

Despite criticism regarding its clinical relevance, the concept of the metabolic syndrome improves our understanding of both the pathophysiology of insulin resistance and its associated metabolic changes and vascular consequences. Free fatty acids (FFA) and tumour necrosis factor-alpha (TNF-alpha) play prominent roles in the development of insulin resistance by impairing the intracellular insulin signalling transduction pathway. Obesity is an independent risk factor for cardiovascular disease and strongly related to insulin resistance. In case of obesity, FFAs and TNF-alpha are produced in abundance by adipocytes, whereas the production of adiponectin, an anti-inflammatory adipokine, is reduced. This imbalanced production of pro- and anti-inflammatory adipokines, as observed in adipocyte dysfunction, is thought to be the driving force behind insulin resistance. The role of several recently discovered adipokines such as resistin, visfatin and retinol-binding protein (RBP)-4 in the pathogenesis of insulin resistance is increasingly understood. Insulin resistance induces several metabolic changes, including hyperglycaemia, dyslipidaemia and hypertension, all leading to increased cardiovascular risk. In addition, the dysfunctional adipocyte, reflected largely by low adiponectin levels and a high TNF-alpha concentration, directly influences the vascular endothelium, causing endothelial dysfunction and atherosclerosis. Adipocyte dysfunction could therefore be regarded as the common antecedent of both insulin resistance and atherosclerosis and functions as the link between obesity and cardiovascular disease. Targeting the dysfunctional adipocyte may reduce the risk for both cardiovascular disease and the development of type 2 diabetes. Although lifestyle intervention remains the cornerstone of therapy in improving insulin sensitivity and its associated metabolic changes, medical treatment might prove to be important as well.