R.J. Jarrett

Microalbuminuria Predicts Mortality in Noninsulin‐dependent Diabetes

Forty‐four non‐insulin‐dependent diabetics (NIDD), all with urine negative to Albustix, were studied in 1966/67. By the end of 1980, 17 had died, all but two from cardiovascular causes. All causes of mortality and time to death were significantly related in univariate analyses to age and to the overnight urinary albumin excretion rate (AER), but not to systolic and diastolic blood pressure levels or to duration of diabetes when the latter was corrected for age. Age and duration were highly correlated with each other. In multivariate analyses age and AER were independent predictors of both mortality and time to death, with AER having the greater degree of significance.

The Bedford Survey: Ten year mortality rates in newly diagnosed diabetics, borderline diabetics and normoglycaemic controls and risk indices for coronary heart disease in borderline diabetics

SummaryMortality rates from coronary heart disease and from all causes have been ascertained over ten years in three groups of people participating in the Bedford Survey — newly-diagnosed diabetics, borderline diabetics and control subjects with normal glucose tolerance. Age corrected mortality rates, from all causes and coronary heart disease, were highest in the diabetics and intermediate in the borderline diabetics and in both groups were similar in men and women. When statistical allowance was made for baseline differences in age, blood pressure and obesity, female borderline diabetics still had a significantly increased risk over their controls of death from ‘all causes’. Much of the difference appeared to be due to a relative excess of deaths due to coronary heart disease. It is concluded that borderline diabetes (or impaired glucose tolerance) is associated with a relatively greater increase in mortality risk in women than men. During the 10-year follow-up of the Bedford borderline diabetics, coronary heart disease morbidity and mortality rates were similar in men and women. Age at entry to the study was the major independent and significant predictor of mortality from all causes. The level of systolic blood pressure and current cigarette smoking at baseline were statistically significant predictors only of mortality due to coronary heart disease.

Glycaemia, arterial pressure and micro-albuminuria in Type 1 (insulin-dependent) diabetes mellitus

SummaryPlasma glucose control and arterial pressure were assessed in 28 Type 1 (insulin-dependent) diabetic patients with different degrees of micro-albuminuria. They were divided into two groups according to their urinary albumin excretion rate: a low micro-albuminuria group (n= 16) with albumin excretion ranging between 12.1 and 28.9 μg/min and a high micro-albuminuria group (n= 12) with albumin excretion between 32.4 and 91.3 μg/min. The groups were matched for age, sex and duration of diabetes with the same number of normo-albuminuric (2.0–10.4 μg/min) diabetic control subjects. Both the low and high micro-albuminuria groups had significantly higher glycosylated haemoglobin levels and mean plasma glucose concentrations during a 24-h profile than their respective normo-albuminuric control subjects. A correlation between glycosylated haemoglobin level and urinary albumin excretion rate was found in the whole study group (r= 0.48; p< 0.001). Arterial pressure (both systolic and diastolic) was significantly higher in the high micro-albuminuria group than in either the control group or the low microalbuminuria group. A significant correlation was found between arterial pressure and albumin excretion rate in the whole study population (r= 0.49; p< 0.001) as well as in the pooled micro-albuminuria groups (r= 0.43; p< 0.05). Multiple regression analysis showed that glycosylated haemoglobin and arterial pressure levels were independently correlated with albumin excretion rates. Diabetic patients with micro-albuminuria of any degree have worse glycaemic control than normo-albuminuric patients. Higher levels of arterial pressure, though often sub-hypertensive, are associated with levels of micro-albuminuria predictive of later development of clinical proteinuria. Thus high plasma glucose and high arterial pressure, or both, characterise those diabetic patients at increased risk of nephropathy. These indices of risk are potentially reversible.

The ten-year follow-up of the Bedford Survey (1962–1972): Glucose tolerance and diabetes

SummaryIn a 10-year prospective study of 241 people with ‘borderline diabetes” (impaired glucose tolerance) identified by screening of the Bedford adult population, 36 (15%) worsened to diabetes and 128 (53%) substantially improved their glucose tolerance. The major predictor of worsening to diabetes was the level of blood glucose at baseline. This was statistically significant (p < 0.05), independent of other factors, both for deterioration in the first and in the second five years of observation. Body mass index, a measure of adiposity, did not predict worsening to diabetes during the first five years, but was an independent and significant predictor of worsening during the second five years (p < 0.05). The apparent effect of adiposity was complex, for it was also significantly related to improvement in glucose tolerance during the 10-year follow-up. Persons with impaired glucose tolerance are a heterogeneous group and with present knowledge the ability to predict metabolic deterioration is limited.

SMOKING AND OTHER RISK FACTORS FOR CORONARY HEART-DISEASE IN BRITISH CIVIL SERVANTS

A five-year follow-up of 18 403 male British civil servants between the age of 40 and 64, who had been the subject of an earlier clinical survey found 277 deaths from coronary heart-disease (C.H.D.). After adjusting for age, current cigarette smoking, systolic and diastolic blood-pressure, and blood-cholesterol were shown to be related to both the prevalence of one or more indices of cardiac ischaemia and to the risk of cardiac death. Neither blood-glucose two hours after a 50 g load nor weight/height showed any such simple linear association with mortality. Multivariate analysis confirmed that the main risk factors were independently related to cardiac morbidity and mortality. Irrespective of blood-pressure or plasma-cholesterol, current cigarette smokers thus had a higher risk of C.H.D. death than those not smoking cigarettes.

Worsening to diabetes in men with impaired glucose tolerance (“borderline diabetes”)

SummaryTwo hundred and four men with impaired glucose tolerance (borderline diabetes) discovered in a screening examination have been observed for five years and repeated tests of glucose tolerance performed. By pre-determined criteria 27 men ‘worsened to diabetes’ and this metabolic deterioration was not significantly influenced by treatment with carbohydrate restriction with or without a daily dose of 50 mg phenformin. Of the baseline variables measured prior to treatment allocation only the blood glucose values were significantly predictive of ultimate worsening to diabetes.

Type 2 (non-insulin-dependent) diabetes mellitus and coronary heart disease — chicken, egg or neither?

SummaryReview of the literature yields much evidence against a correlation between duration of non-insulin-dependent diabetes mellitus (Type 2 diabetes) and the degree of coronary atherosclerosis or the risk of clinically evident coronary heart disease (CHD). Furthermore, an increased risk of CHD, similar to that in previously diagnosed diabetic subjects, has been demonstrated in persons with impaired glucose tolerance. These observations suggest that an increased risk of CHD is not a consequence of the development of diabetes (i. e. persistent hyperglycaemia). It is more likely that diabetes develops in individuals who already possess characteristics which increase the risk of CHD in addition to the risk of developing diabetes.

Increased Glomerular Permeability to Albumin Induced by Exercise in Diabetic Subjects

SummaryThe urinary excretion of albumin was measured in insulin-dependent diabetics under ordinary conditions of life and in response to exercise. Possible mechanisms of exercise induced albuminuria in diabetics were also investigated. Under ordinary conditions of life the insulin-treated diabetics, as a group, had a higher mean urinary albumin excretion than normal controls; however, half of the diabetics had albumin excretion rates within the control range. A given exercise load (600 kpm/min for 20 min) produced an exaggerated albumin excretion in diabetics, particularly evident in the post-exercise period. The elevated urinary albumin excretion was due to an increased transglomerular passage of albumin, not to reduced tubular reabsorption. The increase was not associated with differences in blood pressure or urine flow between controls and diabetics. This exercise test has proved to be a suitable provocation test to unmask abnormalities in the glomerular handling of albumin that might not be recognisable at rest.

The Whitehall Study: Ten Year Follow‐up Report on Men With Impaired Glucose Tolerance With Reference to Worsening to Diabetes and Predictors of Death

Two‐hundred and four men with a defined degree of impaired glucose tolerance derived from the Whitehall Survey and its pilot study were enrolled in a therapeutic trial and followed for ten years. For the first five years of the trial approximately half the group received 50 mg phenformin daily and the other half an identical placebo. For the whole ten years of the trial approximately half the group were recommended a diet in which carbohydrate intake was limited to 120 g/day, while the other half was recommended a qualitative limitation of sugar intake. 60 men (29.4%) worsened to diabetes during the follow‐up period. The major independent predictor of worsening was the baseline blood glucose level (glucose tolerance). High baseline plasma triglyceride levels and low baseline systolic blood pressure levels were also independent predictors of worsening, though of lower significance (0.01

Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics

SummaryWe have examined the relationship between baseline variables and the incidence of new macrovascular complications amongst the 497 members of the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics over a mean 8.33-year follow-up. In univariate logistic regression analysis the incidence of new ischaemic electrocardiographic abnormality was significantly associated with systolic and diastolic blood pressure, diabetes duration and hypertension in patients with insulin-dependent diabetes, and with smoking in patients with non-insulin-dependent diabetes. New myocardial infarction was associated with systolic blood pressure, plasma cholesterol, proteinuria and smoking in patients with non-insulin-dependent diabetes; there were no significant associations among patients with insulin-dependent diabetes. All new ischaemic heart disease was associated with hypertension in patients with insulin-dependent diabetes, and plasma cholesterol and smoking in patients with non-insulin-dependent diabetes. New cerebrovascular disease was associated with systolic and diastolic blood pressure, ECG abnormality and hypertension. New peripheral vascular disease was associated with smoking. Multivariate analysis showed the following significant associations 1) in patients with insulin-dependent diabetes: ECG abnormality; hypertension, myocardial infarction; smoking, ischaemic heart disease; hypertension, diabetes duration and smoking, 2) in patients with non-insulin-dependent diabetes: ECG abnormality; smoking, myocardial infarction; serum cholesterol, proteinuria and smoking, ischaemic heart disease; smoking. For new cerebrovascular disease, proteinuria and ECG abnormality were significant predictors in multivariate analysis. Patients with diabetes share many of the established risk factors for non-diabetic subjects, in addition proteinuria may be of significance in the prediction of macrovascular disease in diabetes.