J. H. Fuller

Mortality and causes of death in the WHO multinational study of vascular disease in diabetes

Abstract.Aims/hypothesis: We aimed to examine the mortality rates, excess mortality and causes of death in diabetic patients from ten centres throughout the world. Methods: A mortality follow-up of 4713 WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) participants from ten centres was carried out, causes of death were ascertained and age-adjusted mortality rates were calculated by centre, sex and type of diabetes. Excess mortality, compared with the background population, was assessed in terms of standardised mortality ratios (SMRs) for each of the 10 cohorts. Results: Cardiovascular disease was the most common underlying cause of death, accounting for 44 % of deaths in Type I (insulin-dependent) diabetes mellitus and 52 % of deaths in Type II (non-insulin-dependent) diabetes mellitus. Renal disease accounted for 21 % of deaths in Type I diabetes and 11 % in Type II diabetes. For Type I diabetes, all-cause mortality rates were highest in Berlin men and Warsaw women, and lowest in London men and Zagreb women. For Type II diabetes, rates were highest in Warsaw men and Oklahoma women and lowest in Tokyo men and women. Age adjusted mortality rates and SMRs were generally higher in patients with Type I diabetes compared with those with Type II diabetes. Men and women in the Tokyo cohort had a very low excess mortality when compared with the background population. Conclusion/interpretation: This study confirms the importance of cardiovascular disease as the major cause of death in people with both types of diabetes. The low excess mortality in the Japanese cohort could have implications for the possible reduction of the burden of mortality associated with diabetes in other parts of the world. [Diabetologia (2001) 44 [Suppl 2]: S 14–S 21]

Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study

Summary The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study – namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA1c. Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy. [Diabetologia (1996) 39: 1377–1384]

MICROVASCULAR AND ACUTE COMPLICATIONS IN IDDM PATIENTS - THE EURODIAB IDDM COMPLICATIONS STUDY

SummaryThe prevalence of microvascular and acute diabetic complications, and their relation to duration of diabetes and glycaemic control were examined in a cross-sectional study of 3250 IDDM patients in Europe (EURODIAB IDDM Complications Study). Mean (SD) duration of diabetes was 14.7 (9.3) years. HbA1c and AER were measured centrally. Retinopathy was assessed by centrally graded retinal photography. Autonomic neuropathy was measured by heart rate and blood pressure responses to standing up. Sensory neuropathy was measured by biothesiometry. Normal HbA1c was found in 16% of patients. An AER of 20 μg/min or higher was found in 30.6% (95% CI 29.0%, 32.2%) of all patients, and 19.3% (15.6%, 23.0%) of those with diabetes for 1 to 5 years. The prevalence of retinopathy (46% in all patients; 82% after 20 or more years) was substantially lower than in comparable studies. Of all patients 5.9% (5.1%, 6.7%) had postural hypotension, 19.3% (17.9%, 20.7%) had abnormal heart rate variability, 32.2% (30.6%, 33.8%) reported one or more severe hypoglycaemic attacks during the last 12 months and 8.6% (7.6%, 9.6%) reported hospital admission for ketosis over the same period. Microvascular and acute complications were clearly related to duration of diabetes and to glycaemic control. However, the relation of glycaemic control to raised albuminuria differed qualitatively from its relation to retinopathy.

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO multinational study of vascular disease in diabetics). I, Causes and death rates

SummaryThe 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics have been followed for mortality from 1975 to 1987. During this period 92 patients died. The most common cause of death was myocardial infarction: 36 (39.1%) deaths, heart disease was responsible for 51.1% of deaths and all cardiovascular disease for 55.4%. Neoplastic disease accounted for 25% of the deaths and diabetic nephropathy for 5.4%. Age-standardised mortality rates were higher in men than in women in both Type 1 (insulin-dependent) diabetes and Type 2 (non-insulin-dependent) diabetes. Standardised mortality ratios for the first and second five year follow-up periods were higher for men than for women in Type 2 diabetes but were higher for women than men in Type 1. The results suggest that the female survival advantage seen in the general population may persist in Type 2 but not in Type 1 diabetes.

Mortality and morbidity from diabetes in South Asians and Europeans : 11-year follow-up of the southall diabetes survey, London, UK

Over 20 % of middle aged and elderly South Asian people throughout the world have diabetes. The associated mortality and morbidity risks are unclear. We compared mortality and morbidity in a cohort of South Asian and European people with diabetes in London, UK, in an 11‐year follow‐up of a population‐based sample of 730 South Asians (mean age 55 in 1984) and 304 Europeans (mean age 67 in 1984) with diabetes aged 30 years and above in 1984. By 1995, 242 (33 %) of South Asians, and 172 (57 %) of Europeans had died. The all‐cause mortality rate ratio (South Asian versus European) was 1.50 (95 % CI 0.72–3.12) for those aged 30–54 years at baseline. Ethnic differences in mortality rates were abolished or reversed in people aged 65 years and above at baseline. The mortality rate ratio for circulatory deaths was 1.80 (95 % CI 1.03–3.16, p < 0.05) and for heart disease was 2.02 (95 % CI 1.04–3.92, p < 0.05) in those aged 30–64 years at baseline. Seventy‐seven per cent of South Asian deaths were caused by circulatory disease, compared with 46 % of European deaths. South Asian survivors were 3.8 times (95 % CI 1.8–8.0, p = 0.001) more likely to report a history of myocardial infarction than Europeans. South Asian adults with diabetes show a markedly increased predisposition to cardiovascular disease compared with Europeans, especially in younger people. This emphasizes the urgent need to reduce cardiovascular risk in this vulnerable group.

Proteinuria and Mortality in Diabetes: the WHO Multinational Study of Vascular Disease in Diabetes

The relation between proteinuria and mortality was investigated in 1188 patients with Type 1 diabetes and 3234 patients with Type 2 diabetes, aged 35–55 at baseline and followed up for a mean of 9.4 ± 3.1 years in the WHO Multinational Study of Vascular Disease in Diabetes. Baseline prevalence of light or heavy proteinuria was the same (25%) in both types of diabetes after adjustment for differences in diabetes duration. Compared with patients with no proteinuria, all cause mortality ratios were 1.5 (95% confidence interval 1.1–2.0) and 2.9 (2.2–3.8) for Type 1 patients with light and heavy proteinuria, respectively, and 1.5 (1.2–1.8) and 2.8 (2.3–3.4) for Type 2 patients, after adjustment for age, duration of diabetes, blood pressure, cholesterol, and smoking. Proteinuria was associated with significantly increased mortality from renal failure, cardiovascular disease, and all other causes of death. In both types of diabetes, the association was strongest for renal deaths, and of similar magnitude for cardiovascular and all other causes of death. In conclusion, proteinuria is a common, important, and rather non‐specific risk factor for increased morbidity and mortality in diabetes. The relation of proteinuria to mortality is similar for both types of diabetes. The benefits and risks of proteinuria reduction should be examined in large randomized trials with clinical endpoints.

The Relationship Between Smoking and Microvascular Complications in the EURODIAB IDDM Complications Study

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.

Excess mortality and its relation to hypertension and proteinuria in diabetic patients : The World Health Organization multinational study of vascular disease in diabetes

OBJECTIVE To determine the extent that mortality in IDDM and NIDDM patients is inexcess of that of the general population and examine its relation to hypertension and proteinuriain diabetic patients. RESEARCH DESIGN AND METHODS A stratified random sample of 4,714 diabetic patients aged 35–55 years participating in the World Health Organization MultinationalStudy of Vascular Disease in Diabetes has been followed up from 1975 to 1987. Excess mortality,compared with the background population, was assessed in terms of standardized mortalityratios (SMRs) for each of the 10 international cohorts. The relationship between excess mortalityand proteinuria/hypertension was examined by diabetes type and sex. RESULTS SMRs were in general higher in patients with IDDM (ranging from 188 to 686 formen and from 336 to 790 for women) than with NIDDM (from 138 to 370 for men and from 126to 435 for women). For both diabetes types and in both sexes, SMRs decreased with increasingage and increased with increasing diabetes duration. Patients with both hypertension and proteinuria experienced a strikingly high mortality risk: 11-fold for men with IDDM and 18-fold forwomen with IDDM and 5-fold for men with NIDDM and 8-fold for women with NIDDM. Evenin the absence of proteinuria and hypertension, SMRs were significantly increased in both IDDM(284 men and 360 women) and NIDDM (192 men and 236 women) patients. CONCLUSIONS Considerable international differences were found not only in mortalityrates for the two types of diabetes but also in the extent of excess mortality among centers. IDDM patients had a high excess mortality in comparison with the general population. The significantexcess mortality was demonstrated even in patients without proteinuria and without hypertension for both sexes and diabetes types.

Risk factors, ethnic differences and mortality associated with lower-extremity gangrene and amputation in diabetes. The WHO Multinational Study of Vascular Disease in Diabetes.

Abstract.Aims/hypothesis: We aimed to examine geographic differences, risk factors and mortality associated with amputation. Methods: Data from 10 of the original 14 centres of the WHO Multinational Study of Vascular Disease in Diabetes were used. This included 3443 men and women aged 35 to 55 years at baseline. Results: Incidences of amputation, adjusted for sex and duration in Type I (insulin-dependent) diabetes mellitus, were 31.0, 8.2, 3.5 and 1.0 per 1000 person years in the American Indian, Cuban, European and East Asian centres respectively. In Type II (non-insulin-dependent) diabetes mellitus, incidences of amputation were 9.7, 2.0, 2.5 and 0.7 per 1000 person years in the American Indian, Cuban, European and East Asian centres respectively. Key risk factors for amputation included glucose, triglyceride, and retinopathy, and were similar for American Indians and Europeans. The age, duration and sex adjusted relative risk for amputation in American Indians compared with Europeans was 11.48 (95 % CI 3.56, 36.98) in Type I diabetes and 3.86 (95 % CI 2.36, 6.32) in Type II diabetes. Adjusting for heart disease, retinopathy, proteinuria, glucose, blood pressure and triglyceride attenuated these relative risks to 10.83 (95 % CI 3.20, 36.65) and 3.15 (1.91, 5.20) in Type I and Type II diabetes respectively. Amputation doubled mortality rates in all groups. Conclusion/interpretation: Vascular complications and their risk factors are themselves risk factors for amputation in both Type I and Type II diabetes and are common to several geographical regions worldwide. However, reasons for differences between geographical regions and the degree to which different health care systems could be responsible is not clear. [Diabetologia (2001) 44 [Suppl 2]: S 65–S 71]

The Relationship Between Socioeconomic Status and Diabetes Control and Complications in the EURODIAB IDDM Complications Study

OBJECTIVE To determine whether there are socioeconomic differences in diabetes control and complications in people with IDDM. RESEARCH DESIGN AND METHODS We conducted a prevalence survey of 1,217 men and 1,170 women with IDDM age 25–60 years from European clinics. Age at completion of education defined socioeconomic status: ≤ 14 years defined those with primary education; 15–18 years, as secondary education; and > 19 years, as college education. Glycemic control, lipids, diet, retinopathy, neuropathy, and heart disease were assessed centrally. RESULTS People with a primary education were older and had diabetes for longer than those with a college education. The mean percentage of HbA1c was worst in the primary-educated men (6.6 vs. 6.1%, P = 0.0007 for trend) and women (6.5 vs. 6.0%, P = 0.0007). Total cholesterol level was higher in primary-educated than in college-educated men (5.6 vs 5.3 mmol/l, P = 0.002), as was triglyceride level (1.23 vs. 1.02 mmol/l, P = 0.0001). College-educated people were the least likely to be current smokers (P < 0.0001), and were most likely to partake in vigorous exercise (P < 0.001). Surprisingly, There was little difference in the prevalence of heart disease by educational status in men, while it was highest in the least educated women, but proliferative retinopathy was more common in primary- than in college-educated men (16 vs 10%, P = 0.04) as was macroalbuminuria (15 vs 9%, P = 0.03). Glycemic control could not fully account for these differences. CONCLUSIONS Healthy lifestyles are more prevalent in better educated men and women with IDDM, but these are not reflected in heart disease prevalence in men. The lower prevalence of severe microvascular complications in better educated men, unaccounted for by better glycemic control, requires further investigation.