J S Dorman

Insulin-dependent diabetes mellitus mortality. The risk of cigarette smoking.

The relation between cigarette smoking and mortality was examined prospectively in a population of adult insulin-dependent diabetes mellitus (IDDM) patients. In 1981, information on smoking history and other health and lifestyle factors was obtained by questionnaire from 93% of the 723 patients included in the Childrens Hospital of Pittsburgh IDDM registry who were diagnosed between 1950 and 1964. Vital status as of January 1, 1988 was ascertained for 98% of the 548 patients who participated in the baseline survey and were alive as of January 1, 1982. Fifty-four cases died during the 6-year follow-up (32 male, 22 female). Proportional hazards analysis revealed that heavy smoking was a significant independent predictor of all-cause mortality among females but not males. The excess mortality in female diabetics was explained primarily by a marked excess risk of coronary heart disease mortality in smokers. These data strongly suggest that cigarette smoking, especially among diabetic females, should be avoided in order to improve longevity.

Height at diagnosis of insulin dependent diabetes in patients and their non-diabetic family members.

Height at the onset of insulin dependent diabetes mellitus was evaluated in 200 newly diagnosed children, 187 non-diabetic siblings, and 169 parents. Diabetic children 5-9 years of age at diagnosis were consistently taller than the national average. Non-diabetic siblings of the same age were also tall. Diabetic children aged 14 or over at diagnosis were short, while their siblings and parents were of normal height. Diabetic children positive for islet cell antibodies were taller than those without islet cell antibodies. No association between height and HLA antigens was found. Non-diabetic siblings at high risk for the disease were closer in height to the diabetic children than were the lower risk, non-diabetic siblings. Siblings, particularly those under 10, were also significantly more obese than the general population. Deviations in growth in patients with insulin dependent diabetes mellitus appear to be related to age at diagnosis and a factor(s) not related to parental height.

Human Insulin Use and Hypoglycaemia: Insights from the Pittsburgh Epidemiology of Diabetes Complications Study

Recently, concern has arisen that human (as opposed to beef or pork) insulin may cause more frequent and/or severe hypoglycaemia in association with reduced warning symptoms. This question was examined from questionnaire data of 628 Type 1 diabetic patients (mean age 28 years and duration of diabetes 19 years) participating in the baseline examination of a follow‐up study of diabetes complications. Those using human insulin (n = 73) reported an insignificantly higher frequency of hypoglycaemic reactions in the last year than those using animal insulin (66 vs 55 % with reactions at least monthly) and only a weak trend was seen overall for the prevalence of human insulin use to increase with increasing frequency of hypoglycaemia (p = 0.06). Hypoglycaemic reactions resulting in unconsciousness were too rare to permit analysis by type of insulin used. The prevalence of reduced awareness of hypoglycaemia was similar among human insulin users to that seen in animal insulin users (25 vs 19 %, NS). However, prevalence of reduced awareness showed a strong relationship to current blood glucose in the animal (r = −0.18, p<0.001) but not human (r = −0.06, NS) insulin users. Excluding patients with autonomic symptoms or neuropathy did not alter the results, nor did excluding the 34 individuals taking more than three insulin injections per day. It is concluded that human insulin use is not associated with either any substantial increased frequency of hypoglycaemia or reduction in awareness of hypoglycaemia. However, human insulin use does appear to be associated with reduced awareness of hypoglycaemia in those whose blood glucose control is relatively poor.

IDDM Incidence in a Multiracial Population: The Hawaii IDDM Registry, 1980–1990

OBJECTIVE The Hawaii IDDM Registry was created to determine the incidence rate of IDDM among children aged < 15 years of Oahu between 1980 and 1990. Because of the multiracial population living in Hawaii, it is an ideal state in which to study the effect of migration on IDDM incidence. RESEARCH DESIGN AND METHODS Data were collected by a retrospective hospital chart review and physician survey. Registry criteria included 0–14 years of age at IDDM diagnosis and primary residence on Oahu. Children who were military dependents were excluded. Denominator data were compared from two sources. RESULTS A total of 113 new-onset IDDM cases were identified. Case ascertainment was 97%. The unadjusted annual incidence rate was 7.04–7.61 per 100,000 (95% CI 5.83–9.19), depending on which denominator source was used. Race- and ethnicity-specific rates varied greatly (all rates per 100,000): part Hawaiian, 15.34–16.58; Caucasian, 6.21–6.71; Filipino, 3.66–3.96; and Japanese, 2.85–3.08. Temporally, the incidence fluctuated between a low of 2.96 per 100,000 in 1981 to highs of 11.11 and 11.85 per 100,000 in 1985 and 1989, respectively. Ascertainment-corrected rates for these years (3.70, 11.76, and 13.48 per 100,000, respectively) show that the fourfold incidence increase between 1980 and 1989 was not due to ascertainment differences. CONCLUSIONS IDDM incidence among children < 15 years of age in Hawaii was the lowest documented in the U.S. The incidence among part-Hawaiian children was 2.5 times > that of Caucasian children in Hawaii. IDDM incidence rates among Japanese children in Hawaii were comparable with rates in Japan. The temporal variation in IDDM incidence corresponded with a mid-1980s pandemic of IDDM documented elsewhere.

The incidence of insulin-dependent diabetes mellitus in urban districts of Shanghai (1989-1993).

A retrospective study on the incidence of insulin-dependent diabetes mellitus (IDDM) among children aged 0-14 years was carried out from 1989-1993 in urban Shanghai, China. The average annual population at risk (0-14 yr) consisted of 1,401,664 children. All the cases were collected from the hospitals (primary source) and from primary and middle schools and kindergartens (second source) with independent validation of case ascertainment. There were 53 IDDM cases from the primary source, 23 from the secondary source, with a total of 58. The ascertainment corrected total number of IDDM cases was 67 by the capture-recapture method. The average crude annual incidence rate was 0.83 [95% confidence interval (CI) 0.61-1.04] and ascertainment corrected incidence rate 0.96 (95% CI 0.80-1.12) per 100,000. Peak incidence fell in 1992 and in the 9 year-old group. The incidence of childhood IDDM in the urban districts of Shanghai was reconfirmed to be the lowest in the world but by comparing the results of former investigations a trend was found of increasing incidence of IDDM.

Genetic, immunological, and metabolic determinants of risk for type 1 diabetes mellitus in families.

Prospective studies of the relatives of people with Type 1 diabetes can provide insights into risk factors for processes leading to the ultimate destruction of the pancreatic islet 8‐cells. Relatives ascertained through the Childrens Hospital of Pittsburgh diabetes registry were followed and rates of conversion to diabetes were determined. We studied the role of genetic and immunological markers, and used the oral glucose tolerance test (OGTT) to study metabolic disturbances among first‐degree relatives. A group of siblings was serotyped for the HLA‐A and ‐B antigens, and the degree of HLA haplotype sharing with the diabetic sibling was established. Later, islet cell antibody (ICA) assays were performed, and subjects were followed to determine the predictive value of ICA testing for the subsequent development of diabetes. The rate of conversion to diabetes among the siblings was 14 times greater than the rate observed in the general population from which they come. This is comparable to rates observed by other centres following relatives of people with Type 1 diabetes. Impaired glucose tolerance (by National Diabetes Data Group (USA) criteria) carried a three‐fold greater risk for subsequent Type 1 diabetes than did a normal OGTT. Those relatives with detectable ICA were about 50 times more likely to convert to diabetes than were those without ICA. In a group of siblings in whom HLA haplotype sharing was determined, the prevalence of detectable ICA was greater among those who were HLA‐identical to the diabetic sibling (9.9 %) than among those who were haplo‐identical (5.3 %) or completely dissimilar (2.4 %) at the HLA‐A and ‐B regions. Similarly, the incidence of Type 1 diabetes was greater among those who were HLA‐identical (8.4 per 103 sibling‐years), than among those who were not HLA‐identical to the proband (4.2 per 103). The greatest risk for subsequent diabetes was found among HLA‐identical siblings who were ICA‐positive. Approximately 7 % of those who were HLA non‐identical or haplo‐identical and ICA‐positive became diabetic within 5 years, while more than 30 % of HLA‐identical siblings who were ICA‐positive became diabetic during the 5 years after ICA were detected.