Sg Wannamethee

Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men.

Abstract Objective: To determine the risk factors for non-insulin dependent diabetes in a cohort representative of middle aged British men. Design: Prospective study. Subjects and setting: 7735 men aged 40-59, drawn from one group practice in each of 24 towns in Britain. Known and probable cases of diabetes at screening (n=158) were excluded. Main outcome measures: Non-insulin dependent diabetes (doctor diagnosed) over a mean follow up period of 12.8 years. Results: There were 194 new cases of non-insulin dependent diabetes. Body mass index was the dominant risk factor for diabetes, with an age adjusted relative risk (upper fifth to lower fifth) of 11.6; 95% confidence interval 5.4 to 16.8. Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes, relative to the physically inactive men, after adjustment for age and body mass index (0.4; 0.2 to 0.7), an association which persisted in full multivariate analysis. A non-linear relation between alcohol intake and diabetes was observed, with the lowest risk among moderate drinkers (16-42 units/week) relative to the baseline group of occasional drinkers (0.6; 0.4 to 1.0). Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration, high density lipoprotein cholesterol concentration (inverse association), heart rate, uric acid concentration, and prevalent coronary heart disease. Conclusion: These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes and coronary heart disease and the potential value of an integrated approach to the prevention of these conditions based on the prevention of obesity and the promotion of physical activity. Key messages Key messages This study shows a strong, graded association between body mass index and risk of diabetes in middle aged men, with no evidence of a threshold effect The risk of diabetes is reduced by more than 50% among men who take moderately vigorous exercise Cardiovascular disease risk factors that are linked with insulin resistance, such as hypertriglyceridaemia and hyperuricaemia, predict non-insulin dependent diabetes These findings support an integrated approach to the prevention of non-insulin dependent diabetes and cardiovascular disease based on the prevention of obesity and the promotion of physical activity

Prospective Study of Serum γ-Glutamyltransferase and Risk of NIDDM

OBJECTIVE Serum γ-glutamyltransferase (GGT) levels are raised inobese individuals, and a particularly strong association with central obesity has been described. We hypothesized that elevated GGT levels are a marker for visceral fat, and specifically for hepatic steatosis (fatty liver), and that hepatic steatosis leads to hepatic insulin resistance. To test this hypothesis, we examined the association between GGT levels and risk of NIDDM. RESEARCH DESIGN AND METHODS We carried out a prospective cohort study of incident cases of doctor-diagnosed NIDDM in a group of 7,458 nondiabetic men (aged 40–59 years) followed for a mean of 12.8 years (range 11.5–13.0). The men were randomly selected from general practice lists in 24 British towns. Cases of NIDDM were ascertained by repeated postal questionnaires to the men and by regular systematic review of primary care records. RESULTS A total of 194 men developed NIDDM during follow-up. Mean serum GGT at baseline (geometric mean [95% Cl]) was significantly higher in the NIDDM patients than in the rest of the cohort (20.9 [19.3–22.6] vs. 15.3 U/l [15.0–15.6], P < 0.0001). There was a smooth, graded increase in the age-adjusted risk of NIDDM with increasing GGT levels, with a relative risk in the top fifth of the distribution of 6.8 (3.5–12.9) relative to the bottom fifth (trend P < 0.0001). This association was independent of serum glucose and BMI and of other predictors of NIDDM with which GGT is associated, including alcohol intake and physical activity level (adjusted upper to lower fifth relative risk: 4.8 [2.0–11.8], trend P < 0.0001]). CONCLUSIONS These findings suggest that a raised serum GGT levelis an independent risk factor for NIDDM. Serum GGT level may be a simple andreliable marker of visceral and hepatic fat and, by inference, of hepatic insulin resistance.

Body weight: implications for the prevention of coronary heart disease, stroke, and diabetes mellitus in a cohort study of middle aged men

Abstract Objective:To determine the body mass index associated with the lowest morbidity and mortality. Design:Prospective study of a male cohort. Setting:One general practice in each of 24 British towns. Subjects:7735 men aged 40-59 years at screening. Main outcome measures:All cause death rate, heart attacks, and stroke (fatal and non-fatal) and development of diabetes, or any of these outcomes (combined end point) over an average follow up of 14.8 years. Results:There were 1271 deaths from all causes, 974 heart attacks, 290 strokes, and 245 new cases of diabetes mellitus. All cause mortality was increased only in men with a body mass index (kg/m2) <20 and in men with an index ≥30. However, risk of cardiovascular death, heart attack, and diabetes increased progressively from an index of <20 even after age, smoking, social class, alcohol consumption, and physical activity were adjusted for. For the combined end point the lowest risks were seen for an index of 20.0-23.9. In never smokers and former smokers, deaths from any cause rose progressively from an index of 20.0-21.9 and for the combined end point, from 20.0-23.9. Age adjusted levels of a wide range of cardiovascular risk factors rose or fell progressively from an index <20. Conclusion:A healthy body mass index in these middle aged British men seems to be about 22. Key messages The body mass index associated with the lowest mortality and the lowest incidence of coronary heart disease, stroke, and diabetes mellitus is not known In this study of middle aged men the risk of cardiovascular mortality, heart attack, and diabetes increased progressively from a body mass index <20 For a combined end point (heart attack, stroke, diabetes, or death from any cause) the lowest risk was in the range 20-24 Levels of a wide range of cardiovascular risk factors increased progressively from an index of <20 A healthy body mass index in middle aged men seems to be around 22

Comparison of the associations of body mass index and measures of central adiposity and fat mass with coronary heart disease, diabetes, and all-cause mortality: a study using data from 4 UK cohorts

BACKGROUND Measures of regional adiposity have been proposed as alternatives to the measurement of body mass index (BMI) for identifying persons at risk of future disease. OBJECTIVE The objective was to compare the magnitudes of association of BMI and alternative measurements of adiposity with coronary heart disease, diabetes, and cardiovascular disease risk factors and all-cause mortality. DESIGN Data from 4 cohorts of adults [3937 women from the British Womens Heart and Health Study (BWHHS); 2367 and 1950 men from phases 1 and 3, respectively, of the Caerphilly Prospective Study (CaPS); 403 men and women from the Boyd Orr Study; and 789 men and women from the Maidstone-Dewsbury Study] were analyzed. RESULTS The magnitudes of associations of BMI with incident coronary heart disease and cardiovascular disease risk factors were similar to those with measurements of central adiposity [waist circumference (WC), waist-hip ratio (WHR), or waist-height ratio (WHtR)] and more direct measurements of fat mass (bioimpedance/skinfold thickness). In CaPS (men only), there was no strong evidence of differences in the strengths of association with incident diabetes between BMI, WC, WHR, and WHtR (P for heterogeneity > 0.49 for all). In the BWHHS (women only), there was statistical evidence that WC [hazard ratio (HR): 2.35; 95% CI: 2.03, 2.73] and WHtR (HR: 2.29; 95% CI: 1.98, 2.66) were more strongly associated with diabetes than with BMI (HR: 1.80; 95% CI: 1.59, 2.04) (P for heterogeneity < 0.02 for both). Central adiposity measurements were positively associated with all-cause mortality, as was BMI, but only when those with a BMI (in kg/m(2)) <22.5 were removed from the analyses. CONCLUSION No strong evidence supports replacing BMI in clinical or public health practice with other adiposity measures.

Serum urate and the risk of major coronary heart disease events.

OBJECTIVE: To examine the relation between serum urate and the risk of major coronary heart disease events. DESIGN: A prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7688 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: Fatal and non-fatal coronary heart disease events. RESULTS: There were 1085 major coronary heart disease events during the average follow up period of 16.8 years. Serum urate was significantly associated with a wide range of cardiovascular risk factors including body mass index, alcohol intake, antihypertensive treatment, pre-existing coronary heart disease, serum triglycerides, cholesterol, and diastolic blood pressure. There was a significant positive association between serum urate and risk of coronary heart disease after adjustment for lifestyle factors and disease indicators. This relation was attenuated to non-significance upon additional adjustment for diastolic blood pressure and serum total cholesterol: cholesterol appeared to be the critical factor in attenuating this relation. When the association between serum urate and risk of coronary heart disease was examined by presence and grade of pre-existing coronary heart disease, a positive association was seen only in men with previous definite myocardial infarction, even after full adjustment (P = 0.07). CONCLUSIONS: The relation between serum urate and the risk of coronary heart disease depends heavily upon the presence of pre-existing myocardial infarction and widespread underlying atherosclerosis as well as the clustering of risk factors. Thus serum urate is not a truly independent risk factor for coronary heart disease. Raised serum urate appears to be an integral part of the cluster of risk factors associated with the insulin resistance syndrome that include obesity, raised serum triglycerides, and serum cholesterol.

Physical activity and risk of cancer in middle-aged men

A prospective study was carried out to examine the relationship between physical activity and incidence of cancers in 7588 men aged 40–59 years with full data on physical activity and without cancer at screening. Physical activity at screening was classified as none/occasional, light, moderate, moderately-vigorous or vigorous. Cancer incidence data were obtained from death certificates, the national Cancer Registration Scheme and self-reporting on follow-up questionnaires of doctor-diagnosed cancer. Cancer (excluding skin cancers) developed in 969 men during mean follow-up of 18.8 years. After adjustment for age, smoking, body mass index, alcohol intake and social class, the risk of total cancers was significantly reduced only in men reporting moderately-vigorous or vigorous activity; no benefit seen at lesser levels. Sporting activity was essential to achieve significant benefit and was associated with a significant dose-response reduction in risk of prostate cancer and upper digestive and stomach cancer. Sporting (vigorous) activity was associated with a significant increase in bladder cancer. No association was seen with colo-rectal cancer. Non-sporting recreational activity showed no association with cancer. Physical activity in middle-aged men is associated with reduced risk of total cancers, prostate cancer, upper digestive and stomach cancer. Moderately-vigorous or vigorous levels involving sporting activities are required to achieve such benefit.

Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality.

OBJECTIVES This study examined the effects of beer, spirits, and wine drinking on coronary heart disease (CHD) events (fatal and nonfatal) and all-cause mortality. METHODS Men aged 40 to 59 years (n = 7735) were drawn at random from one general practice in each of 24 British towns and followed up for an average of 16.8 years. RESULTS Regular drinkers showed a significantly lower relative risk of CHD, but no all-cause mortality, than occasional drinkers, even after adjustment for potential confounders. The benefit for CHD of regular drinking was seen within both beer drinkers and spirit drinkers but not among men who reported wine drinking. However, all men who reported wine drinking (both occasional and regular) showed significantly lower age-adjusted risks of CHD and all-cause mortality than men drinking beer or spirits; beer and spirit drinkers showed similar risks. CONCLUSIONS The findings suggest that regular intake of all alcoholic drinks is associated with a lower risk of CHD, but not all-cause mortality, than occasional drinking. A large part, but not all, of the greater benefit seen in wine drinkers relative to other drinkers can be attributed to advantageous lifestyle characteristics (e.g., low rates of smoking and obesity).

Alcohol consumption and the incidence of type II diabetes

Background: This study examines the relation between alcohol and type II diabetes and the possible mediating effects of HDL-cholesterol and serum insulin. Methods: Prospective study of 5221 men aged 40–59 years with no history of coronary heart disease, diabetes, or stroke drawn from general practices in 18 British towns. Results: During the mean follow up of 16.8 years there were 198 incident cases of type II diabetes. Occasional drinkers were the reference group. A non-linear relation was seen between alcohol intake and age adjusted risk of diabetes, with risk lowest in light and moderate drinkers and highest in heavy drinkers (quadratic trend p=0.03). Further adjustment for body mass index decreased risk in heavy drinkers. After additional adjustment for physical activity, smoking, and (undiagnosed) pre-existing coronary heart disease, only moderate drinkers showed significantly lower risk than occasional drinkers (RR=0.66 95% CI 0.44 to 0.99). Alcohol intake was inversely associated with serum insulin and positively associated with HDL-cholesterol. Adjustment for these factors reduced the “protective” effect in moderate drinkers (adjusted RR=0.73 95% CI 0.48 to 1.10) but the quadratic trend remained significant (p=0.02). Conclusion: There is a non-linear relation between alcohol intake and the risk of type II diabetes. Serum insulin and HDL-cholesterol explained a small amount (20%) of the reduction in risk of type II diabetes associated with moderate drinking. The adverse effect of heavy drinking seemed to be partially mediated through its effect on body weight.

Novel biochemical risk factors for type 2 diabetes: pathogenic insights or prediction possibilities?

This review critically appraises studies examining the association of novel factors with diabetes. We show that many of the most studied novel and apparently ‘independent’ risk factors are correlated with each other by virtue of their common origins or pathways, and that residual confounding is likely. Available studies also have other limitations, including differences in methodology or inadequate statistical analyses. Furthermore, although most relevant work in this area has focused on improving our understanding of the pathogenesis of diabetes, association studies in isolation cannot prove causality; intervention studies with specific agents (if available) are required, and genetic studies may help. With respect to the potential value of novel risk factors for diabetes risk prediction, we illustrate why this work is very much in its infancy and currently not guaranteed to reach clinical utility. Indeed, the existence of several more easily measured powerful predictors of diabetes, suggests that the additional value of novel markers may be limited. Nevertheless, several suggestions to improve relevant research are given. Finally, we show that several risk factors for diabetes are only weakly associated with the risk of incident vascular events, an observation that highlights the limitations of attempting to devise unified criteria (e.g. metabolic syndrome) to identify individuals at risk of both CHD and diabetes.

Cardiovascular disease incidence and mortality in older men with diabetes and in men with coronary heart disease

Objective: To examine the relation of diabetes and coronary heart disease (CHD; myocardial infarction (MI) or angina) to the incidence of major CHD and stroke events and total mortality. Methods: Prospective study of 5934 men aged 52–74 years followed up for 10 years. The men were divided into five groups according to their diabetes and CHD status. Results: During the follow up there were 662 major CHD events, 305 major stroke events, and 1357 deaths from all causes (637 cardiovascular disease (CVD) deaths, 417 CHD deaths). Men with diabetes had significantly increased cardiovascular and total mortality risk compared with non-diabetic men with no CHD but lower risk than men with prior MI only. The adjusted relative risk for CHD deaths was 2.82 (95% confidence interval (CI) 1.85 to 4.28) in men with diabetes only, 2.12 (95% CI 1.53 to 2.93) in men with angina only, 3.91 (95% CI 3.07 to 4.99) in men with MI, and 8.93 (95% CI 6.13 to 12.99) in men with both diabetes and CHD. Case fatality among men with diabetes only was similar to those with prior MI only. CHD and CVD mortality increased with increasing duration of diabetes with risk eventually approaching that of patients with MI without diabetes. Conclusion: Men with diabetes only have a CVD risk intermediate between men with angina and men with prior MI. Their absolute risk is high and the prognosis for diabetic patients who develop CHD is extremely poor.