The prevalence of childhood-onset Type 1 diabetes mellitus is important for determining health care provisions. In Leicestershire 13.5% of the childhood population (0-14 years) is of South Asian origin (census 1991). This study determined the prevalence of Type 1 diabetes in Whites and South Asians in Leicestershire, using a capture/recapture method to coincide with the 1991 Census day. Children (0-14 years) with Type 1 diabetes were captured from the central diabetic register. The health visitor and consultant records were used to recapture the cases. Total ascertainment of cases was 95-100%. The prevalence of Type 1 diabetes in White children (107 cases) was 0.75/1000 children (95% CI 0.61-0.89) compared with the South Asian prevalence (18 cases) of 0.77/1000 (95% CI 0.41-1.13). The overall prevalence in White males was 0.82/1000 (0.61-1.03) compared with 0.68/1000 (0.48-0.87) in females. In South Asian males it was 0.59/1000 (0.15-1.03) compared with 0.96/1000 (0.39-1.53) in females. The prevalence of Type 1 diabetes in children of South Asian migrants to the United Kingdom cannot be said to be different from White children.

AIMS/HYPOTHESIS: Estimates of incidence of Type I (insulin-dependent) diabetes mellitus in childhood populations vary around the world. This study aimed to estimate and compare the incidence of Type I diabetes in Leicestershire of children of South Asian and White or Other ethnic backgrounds. METHODS: All new cases of childhood-onset Type I diabetes diagnosed before 15 years of age in Leicestershire during the period 1989-98 were studied. Population data for Leicestershire from the 1991 census was used. Ethnicity was assigned to all children in the study according to their surnames. Incidence rates (95%-Confidence limits) for the South Asian and white or other ethnic group were estimated and compared. RESULTS: Over the 10-year period, 46 South Asian children and 263 children who were white or from another ethnic group fulfilled the criteria for inclusion in the study. Crude incidence rates per 100,000 person-years were 19.2 (12.0, 29.1) girls and 20.3 (13.0, 30.3) boys for South Asians and 17.7 (14.8, 21.1) girls and 17.7 (14.8, 20.9) boys for whites/others. Age and sex-specific rates were higher for South Asians over 5 years of age but differences were not statistically significant. CONCLUSION/INTERPRETATION: Type I diabetes incidence rates for South Asian children in Leicestershire were very similar to those for children who were in the white/other ethnic group, in contrast to very low rates reported from Asia. The convergence of rates for South Asians with other ethnic groups in Leicestershire suggests that environmental factors are more important than genetic predisposition in causing Type I diabetes in people of South Asian ethnic background.

Sudden death at night is known to occur in young patients with insulin-dependent (Type 1) diabetes mellitus (IDDM) but the aetiology is uncertain. A cardiac arrhythmia has been postulated, but there has been little evidence to support this. We present the case of a 31-year-old man with IDDM of 17 years duration, who died suddenly while asleep. Over preceding months, he had had strict glycaemic control (HbA1 8.9%), normal 24 h blood pressure (mean 131 +/- 2.1/76 +/- 2.2 mmHg), no evidence of microangiopathy or endothelial dysfunction and normal standard clinical tests of autonomic function. An electrocardiogram was similarly unremarkable, with a QTc interval of 0.414 s, and an echocardiogram had demonstrated normal left ventricular mass index (96.4 g m-2). However, there was no nocturnal dip in heart rate (daytime 74 +/- 2.7, and nocturnal 68 +/- 1.6 beats min-1), and he had grossly impaired baroreflex sensitivity during Phase 4 of the valsalva manoeuvre (0.5 ms mmHg-1), with power spectral analysis studies suggesting an abnormality of parasympathetic function. The coroner's autopsy demonstrated no structural abnormalities. We hypothesize that abnormal baroreflex sensitivity could either predict a risk of or account for some of the unexplained deaths in IDDM, in that relative overactivity of the sympathetic nervous system could cause ventricular arrhythmias.

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4%(95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84%(95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.

This study investigated the relationship between the development of diabetic retinopathy and pubertal status at onset of diabetes in 521 Type 1 diabetic patients diagnosed between 1950 and 1985. Pubertal status was based on age at onset (girls > or = 11 years and boys > or = 12 years). Retinopathy (all forms) developed in 112 patients (21.5%; 65 background and 47 proliferative retinopathy). For subjects diagnosed in either the prepubertal or postpubertal period, a similar proportion survived without developing retinopathy for any given duration of diabetes (chi 2 = 0.3822, p = 0.54). However, if only the postpubertal duration of diabetes is considered, then the proportion of patients surviving without retinopathy was significantly less for those diagnosed in the prepubertal period (chi 2 = 14.2, p = 0.002). This study suggests that the prepubertal duration of diabetes is an important phase and that the years prior to puberty do contribute to the risk of developing microvascular injury.

1. An increase in capillary blood flow and pressure has been implicated in the pathogenesis of diabetic microangiopathy. Abnormal vascular reactivity of the resistance vasculature may play a contributory role by permitting alterations in regional haemodynamics. 2. We have studied the contractile behavior of isolated resistance arteries from normotensive patients with insulin-dependent diabetes mellitus and non-diabetic matched control subjects. Contractile responses to potassium (123 mmol/l), noradrenaline (10(-8) to 3 x 10(-5) mol/l) and angiotensin II (10(-11) to 3 x 10(-8) mol/l) were recorded. Relaxation studies were performed in maximally contracted vessels using acetylcholine (10(-8) to 10(-5) mol/l) and bradykinin (10(-9) to 10(-6) mol/l)(endothelium-dependent) and sodium nitroprusside (10(-9) to 10(-5) mol/l)(endothelium-independent). 3. The maximal contractile responses to potassium (P < 0.05), noradrenaline (P < 0.01) and angiotensin II (P < 0.01) were depressed in diabetic patients. Relaxation to acetylcholine was impaired (P < 0.05), but was normal with bradykinin and sodium nitroprusside. 4. These results suggest that there may be a defect in the endothelial cell acetylcholine receptor excitation-coupling in diabetes mellitus rather than a decreased ability to synthesize and release endothelium-derived relaxing factor. Impaired contraction and endothelium-dependent relaxation of resistance arteries in diabetic patients may contribute to the development of diabetic microangiopathy by causing an increase in tissue blood flow, a rise in capillary pressure and, as a result, an increase in vascular permeability.

A retrospective case-control study was undertaken to investigate the relationship between the early introduction of cow's milk and the subsequent risk of developing Type 1 diabetes (< 15 years at diagnosis). A total of 268 children who developed diabetes during the period 1980-1990 (11 years inclusive) in Leicestershire were identified. Age-, sex-, and race-matched controls were identified using the Leicestershire population register. Parents of children with diabetes and their controls completed a structured questionnaire on infant feeding habits from birth. A total of 184 questionnaires (67%) were analysed. There was no difference between the diabetic and control children with respect to the introduction of cow's milk at an early age and the risk of developing diabetes (odds ratio: 0.98 (0.65-1.47)). In addition, short duration of breast-feeding (< 3 months) had no influence on the incidence of diabetes (1.05 (0.64-1.75)). This study does not support the hypothesis that the early introduction of cow's milk or a short duration of breast-feeding increases the risk of developing Type 1 diabetes.

Impaired reactivity of the resistance vasculature may contribute to the development of diabetic microangiopathy by altering microvascular haemodynamics. This study investigates the acute effects of insulin on the contractility and relaxation properties of isolated human resistance arteries (< 300 microns internal diameter) taken from gluteal subcutaneous fat of 33 (18 male: 15 female) normotensive healthy volunteers (supine blood pressure 115.6 +/- 1.6/70.0 +/- 1.5 mm Hg [mean +/- SEM], with no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after incubation in 1 mU/ml of insulin for 20 min (p < 0.01; Group 1). Increasing concentrations of insulin were found to reduce the contractile response to noradrenaline in a dose-dependent manner (Group 2; 0.1 mU/ml by 8%[p < 0.01], 1 mU/ml by 17%[p < 0.02] and 10 mU/ml by 22%[p < 0.01]). Sensitivity to insulin (ED50) only decreased at the highest concentration of insulin. However, acetylcholine-induced relaxation was not altered by insulin (Group 2). Time control studies (Group 3) showed that contractile and relaxation responses over the 4-h study period were unchanged. Furthermore, the length of time the vessels were exposed to insulin did not progressively impair responses (Group 4). These findings suggest that insulin may induce abnormalities in vascular smooth muscle contractility, a factor that may contribute to or exacerbate the abnormal haemodynamics observed in the capillary microcirculation of numerous vascular beds in diabetes.

Objective: There is a lack of continuous longitudinal population based lower extremity amputation (LEA) data in the UK. We present here accurate data on trends in diabetes related (DR)LEAs and non-DRLEAs in the South Tees area over a continuous 5 year period. Research Design and Methods: All cases of LEA from 1(st) July 1995 to 30(th) June 2000 within the area were identified. Estimated ascertainment using capture-recapture analysis approached 100% for LEAs in the area. Data was collected longitudinally using the standard method of the Global Lower Extremity Amputation Study protocol. Results: Over 5 years there were 454 LEAs (66.3% male) in the South Tees area, of which 223 were diabetes related (49.1%). Among persons with diabetes LEA rates went from 564.3 in the 1(st) year to 176.0 per 100,000 persons with diabetes in the 5(th) year. Over the same period non-DRLEAs increased from 12.3 to 22.8 per 100,000 persons without diabetes. The relative risk of a person with diabetes undergoing an LEA went from being 46 times that of a person without diabetes to 7.7 at the end of the 5 years. The biggest improvement in LEA incidence was seen in the reduction of repeat major DRLEAs. Conclusion: Our data shows that in the South Tees area at a time when major non-DRLEA rates increased major DRLEA rates have fallen. These diverging trends mark a significant improvement in care for patients with diabetic foot disease as a result of better organized diabetes care.