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A 42-year-old patient died of fulminant necrotising vasculitis with acute renal failure. During life neither paraproteins nor immune complexes or cryo-globulins could be demonstrated in the blood. At necropsy an intraabdominal lympho-plasmocytoid immunocytoma was found as underlying disease.

The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 European countries: the EURODIAB IDDM Complications study. The anticipated significant relationships between both plasma fibrinogen and plasma von Willebrand factor concentrations and age and glycaemic control, and between fibrinogen and body mass index, were noted. Fibrinogen, adjusted for age and glycated haemoglobin concentration, was also related to smoking habits and was higher in the quartiles with highest systolic and diastolic blood pressures. There was a clustering of vascular risk factors, with a positive relationship between plasma fibrinogen and serum triglyceride concentrations in both genders and between fibrinogen and total cholesterol in males. An inverse relationship between fibrinogen and high density lipoprotein cholesterol was also apparent in males. A prominent feature was a positive relationship between both fibrinogen and von Willebrand factor and albumin excretion rate (p < 0.001 and p < 0.003 respectively) in those with retinopathy but not in these without this complication. In view of previous observations on blood pressure and albuminuria in these subjects the findings are consistent with the hypothesis that microalbuminuria and increased plasma von Willebrand factor are due to endothelial cell perturbation in response to mildly raised blood pressure in subjects with retinopathy. Fibrinogen may also contribute to microvascular disease and its relationships to lipid vascular risk factors suggest a possible pathogenic role in arterial disease in diabetes.

OBJECTIVE To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean ± SD duration of diabetes was 14.7 ± 9.3 years. RESULTS The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15–29 years old to 25% in patients 45–59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS The overall prevalence of CVD in these IDDM patients was ∼ 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

OBJECTIVE To examine the relationship between smoking and both glycemic control and microvascular complications in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS This was a prevalence survey of 3,250 men and women aged 15–60 years with IDDM from 31 diabetes centers in 16 European countries. Participants completed a questionnaire, had retinal photographs taken, and performed a 24-h urine collection. HbA1c, frequency of hypoglycemic and ketoacidotic episodes, urinary albumin excretion rates, and retinopathy were compared by smoking category. RESULTS The prevalence of smoking was 35% in men and 29% in women. Current smokers had poorer glycemic control and, among men, were more likely to have had a ketoacidotic episode than were those who never smoked. Ex-smokers had equivalent glycemic control and marginally more hypoglycemic episodes did than those who never smoked. Current smokers had a higher prevalence of microalbuminuria and total retinopathy than did those who never smoked. Ex-smokers had a higher prevalence of macroalbuminuria and proliferative retinopathy than did those who never smoked, but both had a similar prevalence of microalbuminuria. Adjustment for either current or long-term glycemic control could not fully account for these differences. CONCLUSIONS Smoking is associated with poorer glycemic control and an increased prevalence of microvascular complications compared with not smoking. Ex-smokers can achieve glycemic control equivalent to and have a prevalence of early complications similar to that of those who never smoked. We suggest that poorer glycemic control can account for some of the increased risk of complications in smokers, and that quitting smoking would be effective in reducing the incidence of complications. Urgent action is required to reduce the high smoking rates in people with IDDM.

The effects of indapamide on diabetic patients with micro-albuminuria were evaluated in a multicentre study to assess the advantages of this compound in long-term renal protection. Thirty-two hypertensive diabetic patients (10 males, 22 females, aged 46-84 years) were given indapamide at 2.5 mg/day for a 2-month period. There was a significant fall in systolic blood pressure (174 +/- 18 to 148 +/- 12 mmHg, P less than 0.001) and diastolic blood pressure (95 +/- 13 to 85 +/- 8 mmHg, P less than 0.001) and in the albumin excretion rate (median, 40.8 to 18.9 mg/l; P less than 0.05). Blood glucose, glycosylated haemoglobin, electrolytes, creatinine and serum lipids remained unchanged. There was a small but significant correlation between changes in systolic blood pressure and changes in albuminuria (r = 0.04, P less than 0.05). Thus, the effect of indapamide on albumin excretion cannot be explained by a decrease in the intraglomerular perfusion pressure alone. Indapamide, therefore, might be of potential interest in the long-term renal protection of the diabetic patient with elevated blood pressure values and/or micro-albuminuria.

Nach einer Entscheidung des Bundesgesundheitsamts in Berlin vom 1. Marz 1978 sollen die Biguanide Phenformin und Buformin im Hinblick auf die unter dieser Therapie beobachteten Falle von Laktazidose (Lit. bei 11) mit einer Ubergangsfrist bis zum 1. Juli 1978 vom Markt genommen werden. Dennoch beansprucht die Verabreichung von Dichlorazetat (DCA) beim Menschen weiterhin ein gewisses Interesse: einmal, weil es in Verbindung mit dem nach wie vor zugelassenen Biguanid Metformin von Bedeutung werden konnte, das in der Wirkung bzw. in den potentiellen Nebenwirkungen einschlieBlich des Laktazidoserisikos grundsatzlich ahnlich wie die iibrigen Biguanide einzuschatzen ist; zum anderen, wei! gezeigt worden ist, daB DCA als Monosubstanz unter bestimmten Bedingungen sowohl erhOhte Blutglukosespiegel als auch erhohte Blutlipide zu senken vermag [6]. DCA stimuliert nicht nur die Pyruvatdehydrogenase und damit die Pyruvatoxidation verschiedener Gewebe [2, 10], sondern hat dariiber hinaus eine noch nicht im einze1nen verstandene Hemmwirkung auf die Fettsauresynthese [2, 6].

Vascular responsiveness to infused angiotensin II and to norepinephrine was determined in 14 normal subjects and two groups of diabetic subjects, 16 with no clinically detectable diabetic complications and 14 with diabetic retinopathy but no clinical evidence of nephropathy. All were maintained on a 100-mEq. -Na- 100-mEq. -K diet. Serum electrolytes, 24-hour urinary sodium, creatinine clearance, and plasma renin activity did not differ significantly among the groups. Group mean baseline diastolic pressure in those with retinopathy was higher than in normal subjects but no significantly different from that of uncomplicated diabetics. The pressor dose of angiotensin II (ng./kg./min. to increase diastolic blood pressure 20 mm. Hg) for each group respectively was 11.5 +/-0.9, 12.9+/- 1.3, and 8.3 +/- 1.3, and the slope of the dose-response curve (mm. Hg rise in blood pressure resulting from the infusion of 1 ng./kg./min. following the initial increment in blood pressure) was 2.0 +/-0.2, 1.6+/-0.2, 3.3+/- 0.6. For norepinephrine, the pressor doses were 163 +/- 24, 212+/-21, and123 +/- 11 and slopes were 0.17 +/- 0.03, 0.13 +/- 0.02, and 0.20 +/-0.02. Neither diabetic group differed significantly from normal subjects. Diabetics with retinopathy were more sensitive to angiotensin II, pressor dose (P less than 0.059) and slope (P less than 0.02), and to norepinephrine, pressor dose (P less than 0.006) and slope (P =0.05) than those without complications. These data suggest that vascular reactivity is enhanced in diabetics with retinopathy.

Das haufigere Auftreten arteriosklerotischer Gefaskomplikationen bei Diabetikern wurde seit mehr als einem Jahrhundert erkannt [1]. Kontrare Ansichten finden sich jedoch in der Literatur uber den Einflus der Diabetesdauer und der Stoffwechselfuhrung auf die Entstehung der diabetischen Makroangiopathie. Bislang ist ungeklart, ob die arteriosklerotischen Gefasveranderungen der grosen Arterien eine von der Stoffwechselstorung unabhangige Begleiterscheinung des Diabetes darstellen oder ob sie Folge der Hyperglykamie sind. Eine klinisch leicht fasbare Form der Makroangiopathie stellt die arterielle Verschluskrankheit der Extremitaten (AVK) dar, die bei Diabetikern eine Pradilektion fur die Unterschenkelarterien zeigt [2–4].