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Aims/hypothesis: This study compared the incidence of vascular disease in subjects with younger-onset diabetes from different ethnic groups. Methods: The incidence of vascular disease end-points has been studied in a sub-group (n = 994) of participants of the World Health Organization Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) who had younger-onset diabetes (diagnosed before the age of 30 years). The study participants have been divided into European (n = 631), Asian (n = 84) and American Indian (n = 91) cohorts. Results: For Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus, American Indian men had a higher incidence of lower-extremity amputation and renal failure than the other cohorts, whereas European women had a higher incidence of angina than other cohorts. American Indians also had a higher incidence of any retinopathy, clinical proteinuria and albuminuria than the European and Asian cohorts. Conclusion/interpretation: This study confirms the high burden of large and small-vessel disease complications manifest in American Indian people with younger-onset diabetes. [Diabetologia (2001) 44 [Suppl 2]: S 78–S 81] [ABSTRACT FROM AUTHOR]

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] [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to examine the associations between classic cardiovascular risk factors and diabetes specific factors and the incidence of fatal and non-fatal end-points in a large cohort of diabetic patients. Methods: A cohort of 4743 diabetic patients participating in the WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD) has been followed up for about 12 years and the incidence of fatal and non-fatal cardiovascular disease outcomes assessed. Results: The importance of blood pressure, serum cholesterol and proteinuria as predictors for cardiovascular disease mortality, fatal and non-fatal myocardial infarction and stroke is confirmed for patients with Type I (insulin-dependent) and Type II (non-insulin-dependent diabetes mellitus. Serum triglyceride was associated with cardiovascular disease death in Type II diabetes and in women with Type I diabetes and with MI incidence in Type II diabetes and stroke in Type II diabetic women. Fasting plasma glucose was associated with cardiovascular disease death, incidence of myocardial infarction and stroke in Type II diabetes only. In Type II diabetes, multivariate analysis confirmed that fasting plasma glucose was related to cardiovascular disease mortality independent of other risk factors. The independent relation of triglyceride to cardiovascular disease death was statistically significant only for Type II diabetic men. The presence of retinopathy was related to cardiovascular disease death and incidence of myocardial infarction in both types of diabetes and to stroke in Type II diabetes. Conclusion/interpretation: This large cohort study shows that the assessment of cardiovascular disease risk in diabetes must include ’diabetes-related' variables such as glycaemic control, proteinuria and retinopathy, as well as the classic risk factors, blood pressure, smoking and dyslipidaemia. [Diabetologia (2001) 44 [Suppl 2]: S 54–S 64] [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to examine risk factors for, and differences in, renal failure in diabetic patients from 10 centres. Methods: Risk factors for renal failure were examined in 3558 diabetic patients who did not have renal disease at baseline in the WHO Multinational Study of Vascular Disease in Diabetes (WHO MSVDD). Results: In 959 subjects with Type I (insulin-dependent) diabetes mellitus and 2559 with Type II (non-insulin-dependent) diabetes mellitus, the average follow-up was 8.4 years ( ± 2.7). By the end of the follow-up period 53 patients in the Type I diabetic group and 134 patients in the Type II diabetic group had developed renal failure (incidence rate 6.3:1000 person years). Increasing age and duration of diabetes were associated with renal failure in Type II and Type I diabetes. In Type II diabetes duration of diabetes was a more important risk factor than age. In both Type I and Type II diabetic retinopathy and proteinuria were strongly associated with renal failure. Systolic blood pressure was associated with renal failure in Type I but not in Type II diabetic patients. ECG abnormalities at baseline, self-reported smoking and cholesterol were not associated with renal failure. Triglycerides were measured in a subset of centres. Among those with Type II, but not Type I diabetes, triglycerides were associated with renal failure independently of systolic blood pressure, proteinuria or retinopathy. In Type II diabetes fasting plasma glucose was associated with renal failure independently of other risk factors. Conclusion/interpretation: We have confirmed the role of proteinuria and retinopathy as markers of renal failure and the importance of hyperglycaemia in renal failure in Type I and Type II diabetes. Plasma triglycerides seem to be an important predictor of renal failure in Type II diabetes. In Type I diabetes systolic blood pressure is an important predictor of renal failure. [Diabetologia (2001) 44 [Suppl 2]: S 46–S 53] [ABSTRACT FROM AUTHOR]

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] [ABSTRACT FROM AUTHOR]

Aims/hypothesis. The role of infections in the aetiology of Type I diabetes is controversial. Certain enteroviral infections might be involved in triggering the beta-cell destruction but insufficient exposure to early infections might increase the risk. We studied how the number of infections experienced during several periods from birth to onset influence diabetes risk.¶Methods. The study group came from the five largest Lithuanian cities: 124 patients, selected from the 0–14 years-of-age childhood diabetes register and 372 population-based control subjects matched with them for age group and sex. Information about infections and duration of breastfeeding was collected from health care booklets, other data from a mailed questionnaire, returned by 94.4 % of patients and 72.6 % of control subjects.¶Results. One or more infections experienced during the first half year of life tended to reduce diabetes risk. Crude odds ratios (95 % confidence intervals) in the 0–14, 0–4 and 5–14 years-of-age groups were 0.66 (0.42–1.04), 1.06 (0.48–2.36) and 0.52 (0.30–0.90) respectively. Adjustment for the duration of breastfeeding, number of people in the household, duration of mother's education and birth order of the index child made little difference. Odds ratios (95 % confidence intervals) in the 0–14, 0–4 and 5–14 years-of-age groups were 0.60 (0.37–0.98), 0.94 (0.40–2.20) and 0.47 (0.26–0.87), respectively. The number of infections recorded during the last pre-onset year or from birth to onset did not influence diabetes risk.¶Conclusion/interpretation. Exposure to infections early in life could decrease diabetes risk, particularly for children diagnosed after the age of 4 years. [Diabetologia (2000) 43: 1229–1234] [ABSTRACT FROM AUTHOR]

Aims/hypothesis. To test whether cod liver oil or vitamin D supplements either taken by the mother during pregnancy or by the child in the first year of life is associated with lower risk of Type I (insulin-dependent) diabetes mellitus in children. Methods. We carried out a population-based case control study in Vest-Agder county of Norway, evaluating the use of supplements by a mailed questionnaire. We received responses from 85 diabetic subjects and 1071 control subjects. Odds ratios (OR) with 95 % confidence intervals (CI) were estimated using logistic regression analyses. Results. When mothers took cod liver oil during pregnancy their offspring had a lower risk of diabetes. The unadjusted OR was 0.30, 95 % CI: (0.12 to 0.75), p = 0.01. This association changed very little and was still significant after adjusting for age, sex, breastfeeding and maternal education. Mothers taking multivitamin supplements during pregnancy [adjusted OR = 1.11, 95 % CI: (0.69 to 1.77)], infants taking cod liver oil in the first year of life [adjusted OR = 0.82, 95 % CI: (0.47 to 1.42) and the use of other vitamin D supplements in the first year of life [adjusted OR = 1.27, 95 % CI: (0.70 to 2.31)] was significantly associated with the risk of diabetes. Conclusion/interpretation. We found that cod liver oil taken during pregnancy was associated with reduced risk of Type I diabetes in the offspring. This suggests that vitamin D or the n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid in the cod liver oil, or both, have a protective effect aginst Type I diabetes. [Diabetologia (2000) 43: 1093–1098] [ABSTRACT FROM AUTHOR]

Aims/hypothesis. To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood.¶Method. Seven centres in Europe with access to population-based registers of children with Type I diabetes diagnosed under 15 years of age participated in a case-control study of environmental risk factors. Control children were chosen at random in each centre either from population registers or from schools and policlinics. Data on maternal and neonatal infections, common childhood infections and vaccinations were obtained for 900 cases and 2302 control children from hospital and clinic records and from parental responses to a questionnaire or interview.¶Results. Infections early in the child's life noted in the hospital record were found to be associated with an increased risk of diabetes, although the odds ratio of 1.61 (95 % confidence limits 1.11, 2.33) was significant only after adjustment for confounding variables. None of the common childhood infectious diseases was found to be associated with diabetes and neither was there evidence that any common childhood vaccination modified the risk of diabetes. Pre-school day-care attendance, a proxy measure for total infectious disease exposure in early childhood, was found, however, to be inversely associated with diabetes, with a pooled odds ratio of 0.59 (95 % confidence limits 0.46, 0.76) after adjustment for confounding variables.¶Conclusion/interpretation. It seems likely that the explanation for these contrasting findings of an increased risk associated with perinatal infections coupled with a protective effect of pre-school day care lies in the age-dependent modifying influence of infections on the developing immune system. [Diabetologia (2000) 43: 47–53] [ABSTRACT FROM AUTHOR]

Aims/ hypothesis. In Finland, the incidence of Type I (insulin-dependent) diabetes mellitus in children aged 14 years or under is the highest in the world and the trend in incidence has been increasing. Our aim was to determine the most recent trends in incidence and the age distribution at diagnosis of Type I diabetes. Methods. Data on the incidence of Type I diabetes in Finland nationwide were obtained from two sources: for the period 1965 to 1986 from the Central Drug Registry of the Social Insurance Institution and for the period 1987 to1996 from the prospective childhood Type I diabetes registry. The annual incidence was calculated per 100 000 people. The increase and the trend in incidence were estimated by fitting the linear regression model with the annual incidence data. Results. During 1987 to 1993 the incidence of Type I diabetes seemed to be rather stable at 36 per 100 000 per year. The incidence has continued to increase thereafter and reached 45 per 100 000 per year in 1996. The analysis of the long-term trend in incidence between 1965 and 1996 showed an absolute incidence increase of 0.67 per year on average being 3.4 % compared with the incidence in 1965. The increase from 1987 to 1996 was highest in very young children 1–4 years old at diagnosis. Conclusion/ interpretation. The high incidence of Type I diabetes in Finnish children has thus far not levelled off but is increasing further. If the trend continues, the predicted incidence in Finland will be approximately 50 per 100 000 per year in the year 2010. [Diabetologia (1999) 42: 655–660] [ABSTRACT FROM AUTHOR]

Aims/hypothesis. There is substantial evidence for a role of genetic factors in the development of diabetic nephropathy. In Pima Indians, a link between susceptibility to diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus has been proposed. In this study, our aim was to examine the association between a family history of Type II diabetes and diabetic nephropathy in patients with Type I (insulin-dependent) diabetes mellitus. Methods. In a cross-sectional case-control study, we assessed the prevalence of Type II diabetes in the parents of 137 Type I diabetic patients with diabetic nephropathy (albuminuria > 300 μg/min in two of three overnight urine collections) compared with the parents of 54 Type I diabetic patients without nephropathy (albuminuria < 20 μg/min). Results. Thirty-four (25 %) of the patients with nephropathy compared with five (9 %) of the patients without nephropathy had a parental history of Type II diabetes ( p = 0.019). A parental history of Type II diabetes was associated with a three-fold risk [odds ratio 2.95 (95 % confidence interval: 1.03 to 8.40), p = 0.043] of diabetic nephropathy after adjustment for sex, glycaemic control and family history of hypertension. Furthermore, there was an excess of risk factors for development of Type II diabetes (higher fasting plasma glucose concentrations, higher prevalence of hypertension, higher waist-hip ratio and a tendency towards more glucose intolerance) among previously non-diabetic parents of patients with nephropathy. Conclusion/interpretation. Genetic or environmental factors or both related to familial Type II diabetes increase susceptibility to diabetic nephropathy in patients with Type I diabetes. [Diabetologia (1999) 42: 519–526] [ABSTRACT FROM AUTHOR]