De Angelis L, Marfella MA, Siniscalchi M, Marino L, Nappo F, Giugliano F, De Lucia D, Giugliano D: Erectile and endothelial dysfunction in type II diabetes: a possible link. Diabetologia 44:1155–1160, 2001
Findings. De Angelis et al. studied type 2 diabetic patients with symptomatic erectile dysfunction (ED) and control diabetic patients matched for age and disease without ED. Endothelial functions (using biochemical markers), hemostasis and fibrinolysis, and quantitative testing to assess peripheral or autonomic neuropathy were studied. There was a significant relation between HbA1c and erectile function score in patients with ED (r = −0.45). The decrease in blood pressure and platelet aggregation in response to l-arginine was lower in patients with ED, whereas soluble thrombomodulin, P-selectin, and intercellular cell ahhesion molecule-1 concentrations were higher. Indices of coagulation activation (F1 + 2 and d-dimers) and reduced fibrinolysis (plasmingen-activated inhibitor-1) were also found to be higher in ED patients. Heat-pain and warm perception thresholds, as well as cardiovascular reflex tests, were most commonly abnormal in patients with ED.
Significance. The aim of this study was to evaluate the relation between ED and endothelial functions, coagulation activation, and peripheral and autonomic neuropathy in men with type 2 diabetes. ED in diabetic men correlated with endothelial dysfunction. The authors suggest that reduced nitric oxide activity might provide a unifying explanation, although this was not actually measured in the study.
Clinical Impact. Unfortunately, the two groups of patients in this study were not matched for glycemic control, which may have been an important confounding factor in the results. Nevertheless, it may be helpful for clinicians to learn that ED is related to many of the cardiovascular risk factors associated with insulin resistance. We may then diagnose and treat the condition more appropriately (see next abstract).
Boulton AJ, Selam JL, Sweeney M, Ziegler D: Sildenafil citrate for the treatment of erectile dysfunction in men with type II diabetes mellitus. Diabetologia 44:1296–1301, 2001
Findings. This double-blind placebo-controlled trial evaluated the effects of sildenafil on men with ED and type 2 diabetes and also evaluated whether the response was related to glycated hemoglobin and chronic diabetic complications. Patients (mean age 59 years) were randomized to sildenafil (25–100 mg) or matching placebo for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF) (score range 0–5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions. After 12 weeks, the mean scores for IIEF questions 3 and 4 had improved significantly in patients receiving sildenafil compared with placebo. Similarly, the GEQ score was higher in the sildenafil than the placebo group. Even when correlating efficacy with glycated hemoglobin concentrations or number of diabetic complications, the improvement remained higher for all of the sildenafil groups compared with the placebo groups.
Significance. ED is common in men with type 2 diabetes and is frequently not treated. Although more common in those with poor glycemic control or neuropathic/vascular complications, ED may occur in men without complications who are well controlled. This study confirms previous findings that sildenafil was well tolerated and effective in improving ED in men with type 2 diabetes. It was effective even in patients with poor glycemic control and chronic complications.
Chambers JC, Eda S, Bassett P, Karim Y, Thompson SG, Gallimore JR, Pepys MB, Kooner JS: C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation 104:145–150, 2001
Findings. Chambers et al. measured serum C-reactive protein (CRP) concentrations and conventional coronary heart disease (CHD) risk factors in 1,025 healthy male subjects (518 Indian Asians and 507 European whites) aged 35–60 years. The mean CRP concentration was 17% higher in Indian Asians compared with European whites. CRP values were strongly associated with conventional CHD risk factors, measures of obesity, and metabolic disturbances associated with insulin resistance in both racial groups. The difference in CRP concentrations between Indian Asians and European whites remained after adjustment for conventional CHD risk factors but was eliminated by an adjustment for central obesity and insulin resistance score in Asians. On the basis of these results, they estimate that the processes underlying elevated CRP and/or increased CRP production itself are associated with an ∼14% increase in population CHD risk among Indian Asians compared with European whites.
Significance. Indian Asians in the U.K. and the U.S. have increased CHD mortality compared with whites, but the causes are not well understood. Insulin resistance and type 2 diabetes is common in Indians and may play a role. Increased circulating concentrations of CRP are an independent risk factor for CHD (possibly indicating low grade inflammation) and “clusters” with other risk factors in the insulin resistance syndrome. This study demonstrates that serum CRP concentrations are higher in healthy Indian Asians than in European whites and are accounted for by greater central obesity and insulin resistance in Indian Asians. Inflammation or other mechanisms underlying elevated CRP values may contribute to the increased CHD risk among Indian Asians.
Impact. The intriguing link among markers of inflammation, insulin resistance, and CHD appear to be even stronger in some ethnic groups in whom traditional risk factors do not explain a high prevalence of CHD. It is not yet clear, however, whether we should be measuring these risk factors routinely in such populations in clinical practice.
Stoney RM, O’Dea K, Herbert KE, Dragicevic G, Giles GG, Cumpston GN, Best JD: Insulin resistance as a major determinant of increased coronary heart disease risk in postmenopausal women with type 2 diabetes mellitus. Diabet Med 18:476–482, 2001
Findings. To investigate the risk factors associated with clinically defined coronary heart disease (CHD) in women with type 2 diabetes (based on history and electrocardiogram), Stoney et al. assessed several risk factors in postmenopausal diabetic and age- and BMI-matched nondiabetic women. Diabetic women with CHD had greater insulin resistance, calculated by homeostasis model assessment (10.2 vs. 6.5), and higher plasminogen activator inhibitor-1 (PAI-1) levels (45 vs. 24 ng/ml) than those without CHD. They also had higher triglycerides. In a logistic regression model, insulin resistance was a significant independent predictor of CHD status (OR 1.33, 95% CI 1.06–1.68, P = 0.015). In contrast, in nondiabetic women, the major risk factors for CHD were elevated cholesterol, apolipoprotein(a), apolipoprotein B, and systolic blood pressure.
Significance. Women with diabetes have an increased risk of CHD compared with nondiabetic women. The role of insulin resistance in this increased risk is not clear, as very few epidemiological studies have addressed this issue. Furthermore, most epidemiological studies on insulin resistance and cardiovascular disease have not included sufficient number of women. This study was carried out on a very small number of subjects and therefore needs to be interpreted cautiously. The increased insulin resistance in association with elevated PAI-1 and dyslipidemia appears to underpin the increased risk of CHD in women with type 2 diabetes. Therapeutic approaches that increase insulin sensitivity may serve to reduce CHD risk in this vulnerable group.
Clinical Impact. Because we now have well-defined criteria to recognize the insulin resistance syndrome in women, we should identify such women and address their increased risk of CHD.
