The concomitants of raised blood sugar: studies in newly-detected hyperglycaemics: II. Urinary albumin excretion, blood pressure and their relation to blood sugar levels.

The albumin excretion rate following an oral glucose load was measured, using a sensitive radio-immunoassay method, in three groups drawn from the population of Bedford. The three groups ­ normal,borderline diabetic and diabetic ­ were classified by the level of the blood sugar 2 hours after the 50 -g glucose load. The degree of albumin excretion was positively correlated with the 2-hour blood sugar level, suggesting that hyperglycaemia may cause renal functional abnormality, which may be present at or before the time of diagnosis. In the diabetic group, only, the degree of albumin excretion was also positively correlated with the height of the blood pressure.

Obesity and overweight in relation to disease-specific mortality in men with and without existing coronary heart disease in London: the original Whitehall study.

OBJECTIVE: To examine the relations between obesity or overweight and coronary heart disease (CHD) mortality in men with and without prevalent CHD in a prospective cohort study. METHODS: In the Whitehall study of London-based male government employees, 18 403 middle age men were followed up for a maximum of 35 years having participated in a medical examination in the late 1960s in which weight, height, CHD status, and a range of other social, physiological, and behavioural characteristics were measured. RESULTS: In age-adjusted analyses of men with baseline CHD there was a modest raised risk in the overweight relative to normal weight groups for all cause mortality (hazard ratio 1.10, 95% confidence interval (CI) 1.00 to 1.20) and CHD mortality (1.28, 95% CI 1.11 to 1.47) but not for stroke mortality (1.01, 95% CI 0.73 to 1.40). Mortality was similarly raised in the obese group. While these slopes were much steeper in men who were apparently CHD-free at study induction, the difference in the gradients according to baseline CHD status did not attain significance at conventional levels (p value for interaction >or= 0.24). The weight-mortality relations were somewhat attenuated when potential mediating and confounding factors were added to the multivariable models in both men with and men without a history of CHD. CONCLUSIONS: Avoidance of obesity and overweight in adult life in men with and without CHD may reduce their later risk of total and CHD mortality.

Obesity and overweight in relation to organ-specific cancer mortality in London (UK): findings from the original Whitehall study.

OBJECTIVE: To examine the relation of obesity and overweight with organ-specific cancer mortality. METHODS: In the Whitehall prospective cohort study of London-based government employees, 18 403 middle-age men participated in a medical examination between 1967 and 1970. Subjects were followed up for cause-specific mortality for up to 35 y (median: interquartile range (25th-75th centile); 28.1 y: 18.6-33.8). RESULTS: There were over 3000 cancer deaths in this cohort. There was a raised risk of mortality from carcinoma of the rectum, bladder, colon, and liver, and for lymphoma in obese or overweight men following adjustment for range of covariates, which included socioeconomic position and physical activity. These relationships held after exclusion of deaths occurring in the first 20 y of follow-up. CONCLUSION: Avoidance of obesity and overweight in adult life may reduce the risk of developing some cancers.

High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study.

OBJECTIVE: To assess the association between high but nondiabetic blood glucose levels and the risk of death from all causes, coronary heart disease (CHD), cardiovascular disease, and neoplasms. RESEARCH DESIGN AND METHODS: We studied the 20-year mortality of non-diabetic, working men, age 44-55 years, in three European cohorts known as the Whitehall Study (n = 10,025), the Paris Prospective Study (n = 6,629), and the Helsinki Policeman Study (n = 631). These men were identified by their 2-h glucose levels following an oral glucose tolerance test and by the absence of a prior diagnosis of diabetes. As the protocol for the oral glucose tolerance test and methods for measuring glucose differed between studies, mortality was analyzed according to the percentiles of the 2-h and fasting glucose distributions, using the Cox's proportional hazards model. RESULTS: Men in the upper 20% of the 2-h glucose distributions and those in the upper 2.5% for fasting glucose had a significantly higher risk of all-cause mortality in comparison with men in the lower 80% of these distributions, with age-adjusted hazard ratios of 1.6 (95% CI 1.4-1.9) and 2.0 (1.6-2.6) for the upper 2.5%. For death from cardiovascular and CHD, men in the upper 2.5% of the 2-h and fasting glucose distributions were at higher risk, with age-adjusted hazard ratios for CHD of 1.8 (1.4-2.4) and 2.7 (1.7-4.4), respectively. CONCLUSIONS: If early intervention aimed at lowering blood glucose concentrations can be shown to reduce mortality, it may be justified to lower the levels of both 2-h and fasting glucose, which define diabetes.

The cardiovascular risk associated with impaired glucose tolerance.

Subjects with fasting and/or postprandial plasma glucose levels that are higher than those in normal subjects but less than those in patients with manifest NIDDM are at increased risk of cardiovascular disease (CVD). This association between glucose intolerance and cardiovascular disease was first hypothesized in the 1950s but was not substantiated until the results of several long-term prospective studies became available. The results suggest that there is not a continuously variable association between blood glucose levels and the risk of CVD but that the risk of CVD becomes evident at the upper end of the distribution of glucose tolerance, though different studies yield different threshold levels. With the introduction of the descriptive term Impaired Glucose Tolerance (IGT), studies were undertaken to establish the relations between IGT and CVD. To date most data refer to people of European origin. In several populations CVD has been observed to be more prevalent in subjects with IGT and/or the incidence of CVD is higher in subjects with IGT than in normoglycaemic controls. A causal link between hyperglycaemia and CVD seems unlikely from the published evidence. The most probable explanation of the association is "a common soil', that is, a number of associated metabolic abnormalities which may lead to CVD and IGT/NIDDM or both.

[Why is insulin tied to the prevalence of cardiovascular diseases without being a risk factor for their incidence?]. / Pourquoi l'insuline est-elle liée à la prévalence des maladies cardiovasculaires sans être un facteur de risque de leur incidence?

Insulin is frequently considered to be a risk factor for atherosclerosis (or for coronary and vascular disease). Furthermore, hyperinsulinaemia is claimed to be the primary cause underlying the other features which make up the insulin resistance syndrome. However, if proof of these assertions is based only on prospective studies, its value is limited. Only two studies, both carried out, surprisingly, in policemen, have shown convincingly that insulin was a coronary risk factor. In one of the studies, the Paris Prospective Study, the insulin-coronary disease correlation was shown to subside with increasing duration of follow-up. The other prospective studies have failed to evidence a correlation between insulinaemia and cardiovascular events, even with univariate analysis. One study even showed a negative correlation between insulinaemia and coronary complications. In view of the fact that insulinaemia has been shown repeatedly to be associated with classic cardiovascular risk factors--systolic hypertension, decrease in HDL cholesterol, increase in triglycerides, and abdominal obesity--it is highly surprising that univariate analysis has not been able to show the same correlation between insulin and cardiovascular complications. In fact, the combination of elevated insulinaemia and classic risk factors may result in protection against the deleterious effects of these factors. Another possibility would be that insulinaemia is associated with unknown protective factors. Both hypotheses would account for the existence of a correlation between insulin and current cardiovascular disease, as well as the absence of correlation between insulin and later onset of cardiovascular disease.