Background The insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased coronary heart disease (CHD), although the mechanism of this association is not apparent. We tested the hypothesis that the deletion allele of the ACE gene is associated with insulin resistance. Methods and Results We related ACE genotype to components of the insulin-resistance syndrome in 103 non–insulin-dependent diabetic (NIDDM) and 533 nondiabetic white subjects. NIDDM subjects with the DD genotype had significantly lower levels of specific insulin (DD 38.6, ID 57.1, and II 87.4 pmol · L −1 by ANOVA, P =.011). Non–insulin-treated subjects with the DD genotype had increased insulin sensitivity by HOMA % (DD 56.4%, II 29.4%, P =.027) and lower levels of des 31,32 proinsulin (DD 3.3, II 7.6 pmol · L −1 , P =.012) compared with II subjects. There were no differences in prevalence of CHD or levels of blood pressure, serum lipids, or plasminogen activator inhibitor–1 (PAI-1) activity between the three ACE genotypes. In nondiabetic subjects there were no differences in insulin sensitivity, levels of insulin-like molecules, blood pressure, PAI-1, serum lipids, or CHD prevalence between the three ACE genotypes. Conclusions We conclude that increased cardiovascular risk of the DD genotype is not mediated through insulin resistance or abnormalities in fibrinolysis. Conversely, we report an increased sensitivity in NIDDM subjects with the ACE DD genotype.

Objectives-To study the association(s) between microalbuminuria and cardiovascular risk factors in non-diabetic subjects.Design-Patients aged 40-75 years were randomly selected from a general practice list and invited to participate.Setting-Health centre in inner city London. Subjects-Of those invited, 1046 out of 1671 (62/6%) attended. Subjects were excluded for the following reasons: not being white (44); urinary albumin excretion rate >200 pLg/min (3); having a urinary infection (5); taking penicillamine or angiotensin converting enzyme inhibitors (7); older than 75 (2); having diabetes (25); missing data on glucose concentration (1).Main outcome measures-Glucose tolerance test results, albumin excretion rate from overnight and timed morning collections of urine; blood pressure; height.Results-Mean albumin excretion rate was significantly lower in women than men (mean ratio 0-8, 950/0 confidence interval (0-69 to 0.91)). Mean albumin excretion rate was significantly associated with age, blood pressure, and blood glucose concentration (fasting, 1 hour, and 2 hour) in men and inversely with height. Men who had microalbuminuria in both samples were significantly shorter (by 5 cm (1.3 to 9 3 cm)) than those who had no microalbuminuria in either sample when age was taken into account. In the case of women only systolic pressure was significantly associated with albumin excretion rate.Conclusions-Microalbuminuria and short stature in men are associated. Cardiovascular risk has been associated with both of these factors and with lower birth weight. The inverse association of microalbuminuria with height is compatible with the suggestion that factors operating in utero or early childhood are implicated in cardiovascular disease. The higher prevalence of microalbuminuria in men compared with women may indicate that sex differences in cardiovascular risk are reflected in differences in albumin excretion rate.

Objectives To assess the quality and completeness of a database of clinical outcomes after cardiac surgery and to determine whether a process of validation, monitoring, and feedback could improve the quality of the database.

Aims/hypothesis. We examined the association between plasma insulin and cardiovascular mortality in non-diabetic European men and women based on data from eleven prospective studies. Methods. The study population comprised 6156 men and 5351 women aged 30-89 years. Baseline measurements included oral glucose tolerance test, fasting and 2-h plasma insulin, and conventional risk factors. Cox models were used to calculate hazard ratios (HRs) and their 95% confidence intervals, and overall HRs were assessed by meta-analyses. Results. During the 8.8-year follow-up, 362 men and 70 women died from cardiovascular disease. The ageand smoking-adjusted overall HR of cardiovascular mortality for the highest vs the lower quartiles of fasting insulin was 1.58 (95% CI: 1.26-1.97) in men and 2.64 (1.54-4.51) in women. Adjusting for other risk factors in addition, the HR was 1.54 (1.16-2.03) in men and 2.66 (1.45-4.90) in women. For 2-h insulin these HRs were 1.28 (0.99-1.66), 1.87 (0.87-4.02), and 0.85 (0.60-1.21), 1.36 (0.53-3.45). The overall HRs for interquartile ranges for fasting and 2-h insulin, with full adjustment, were 1.13 (1.05-1.22) and 1.11 (1.01-1.23) in men, and 1.25 (1.08-1.45) and 1.11 (0.91-1.36) in women. Conclusions/interpretation. Hyperinsulinaemia, defined by the highest quartile cut-off for fasting insulin, was significantly associated with cardiovascular mortality in both men and women independently of other risk factors. Associations between high 2-h insulin and cardiovascular mortality were weaker and non-significant. Weak positive associations of fasting and 2-h insulin with cardiovascular mortality over interquartile ranges were, however, more similar. Diabetologia (2004) 47:1245-1256 DOI 10.1007/s00125-004-1433 Plasma insulin and cardiovascular mortality in non-diabetic European men and women: a meta-analysis of data from eleven prospective studies The DECODE Insulin Study Group IntroductionThe role of hyperinsulinaemia as an independent risk factor for cardiovascular disease (CVD) has previously been debated. An association between elevated plasma insulin, fasting or oral glucose load, and the risk of CHD or atherosclerotic CVD has been found in many [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16] but not in all [17,18,19,20,21] prospective studies. Among the studies showing the positive association between plasma insulin and CVD, the effect of adjustment for other risk factors has varied. In several studies the association remained statistically significant, although attenuated [1,2,3,5,6,7,9,10,12,13,15,16] , whereas in other studies it became non-significant [4,8,11,14]. The majority of the published Corresponding author of the DECODE Insulin Study Group: G. Hu, Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland, Phone: +358-9-19127366, Fax: +358-9-19127313, e-mail: hu.gang@ktl.fi Members of the DECODE Insulin Study Group are listed at the end of the paper studies were carried...