Andrew C. Burden

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes

Aims/hypothesisAlthough ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age.MethodsA cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated.ResultsThere were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5–85.0) at ages 20–29 and 41.6 (26.7–61.9) at ages 30–39.Conclusions/interpretationThe risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.

Cancer incidence and mortality in patients with insulin-treated diabetes : a UK cohort study

Raised risks of several cancers have been found in patients with type II diabetes, but there are few data on cancer risk in type I diabetes. We conducted a cohort study of 28u2009900 UK patients with insulin-treated diabetes followed for 520u2009517 person-years, and compared their cancer incidence and mortality with national expectations. To analyse by diabetes type, we examined risks separately in 23u2009834 patients diagnosed with diabetes under the age of 30 years, who will almost all have had type I diabetes, and 5066 patients diagnosed at ages 30–49 years, who probably mainly had type II. Relative risks of cancer overall were close to unity, but ovarian cancer risk was highly significantly raised in patients with diabetes diagnosed under age 30 years (standardised incidence ratio (SIR)=2.14; 95% confidence interval (CI) 1.22–3.48; standardised mortality ratio (SMR)=2.90; 95% CI 1.45–5.19), with greatest risks for those with diabetes diagnosed at ages 10–19 years. Risks of cancer at other major sites were not substantially raised for type I patients. The excesses of obesity- and alcohol-related cancers in type II diabetes may be due to confounding rather than diabetes per se.

Mortality From Cerebrovascular Disease in a Cohort of 23 000 Patients With Insulin-Treated Diabetes

Background and Purpose— Disease of the cardiovascular system is the main cause of long-term complications and mortality in patients with type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. Cerebrovascular mortality rates have been shown to be raised in patients with type II diabetes but have not previously been reported by age and sex in patients with type I diabetes. Methods— A cohort of 23 751 patients with insulin-treated diabetes, diagnosed under the age of 30 years from throughout the United Kingdom, was identified during 1972 to 1993 and followed up for mortality until the end of December 2000. Age- and sex-specific mortality rates and standardized mortality ratios (SMRs) were calculated. Results— There were 1437 deaths during the follow-up, 80 due to cerebrovascular disease. Overall, the cerebrovascular mortality rates in the cohort were higher than the corresponding rates in the general population, and the SMRs were 3.1 (95% CI, 2.2 to 4.3) for men and 4.4 (95% CI, 3.1 to 6.0) for women. When stratified by age, the SMRs were highest in the 20- to 39-year age group. After subdivision of cause of death into hemorrhagic and nonhemorrhagic origins, there remained a significant increase in mortality from stroke of nonhemorrhagic origin. Conclusions— Analyses of mortality from this cohort, essentially one of patients with type I diabetes, has shown for the first time that cerebrovascular mortality is raised at all ages in these patients. Type I diabetes is at least as great a risk factor for cerebrovascular mortality as type II diabetes.

Growth of Children Before Onset of Diabetes

OBJECTIVE To examine the growth of children before the onset of diabetes. RESEARCH DESIGN AND METHODS Heights before diagnosis, expressed as SDS, of each diabetic child identified from the diabetes register and of two age- and sex-matched control subjects were obtained from records of routine examinations performed at 3.5, 6, 11, and 13 yr. The heights of their siblings, with control subjects, also were obtained. RESULTS Diabetic children were considerably taller than control subjects before diagnosis (0–1 yr before diagnosis SDS 0.82 ± 0.26 vs. 0.16 ± 0.14, P < 0.05, n = 24; 1–2 yr before diagnosis SDS 1.02 ± 0.17 vs. 0.16 ± 0.14, P < 0.001, n = 30; 2–3 yr before diagnosis SDS 0.97 ± 0.23 vs. 0.04 ± 0.20, P < 0.005, n = 16). At more than 3 yr before diagnosis, the diabetic children were not significantly taller than control subjects (SDS 0.8 ± 0.2 vs. 0.27 ± 0.13, respectively; n = 33). The siblings of the diabetic children were no taller than control subjects. CONCLUSIONS Diabetic children, but not their siblings, were taller than control subjects before diagnosis, suggesting growth-inducing metabolic changes may precede the onset of clinical diabetes by at least 3 yr.

Mortality of South Asian patients with insulin-treated diabetes mellitus in the United Kingdom: A cohort study

Aimsu2003 To investigate mortality in South Asian patients with insulin‐treated diabetes and compare it with mortality in non South Asian patients and in the general population.

The American Diabetes Association Screening Questionnaire for Diabetes: Is it worthwhile in the U.K.?

The American Diabetes Association (ADA) screening recommendations include a questionnaire to limit the need for blood testing (1), thus reducing expense and the risks of exposure to blood. We therefore performed a retrospective study to investigate whether this method of screening was appropriate for use in the U.K. We have compared questionnaire responses to random blood glucose concentration (RBG) using Boehringer Mannheim 1-44, Reflolux with rigorous internal and external quality control. (The external quality control results for all screening staff were < 5% coefficient of variation.) The ADA suggested a score of >5 (maximum 22) carried a high risk of diabetes. The general population of Leicestershire was invited to attend a health promotion exhibition, and we compared the ADA questionnaire score to their RBG. Risk of diabetes was considered to be RBG >6.5 mM. Of the 540 people screened with RBG values, 10 were from people with known diabetes who were excluded from further analysis. Some did not complete the questionnaire mainly because of language difficulties; however, 383 questionnaires and RBG values could be matched. Of the matches, 50 had elevated RBG estimations, and of these, Table 1—RBG concentrations of screening participants

IDDM and celiac disease.

A n association between celiac disease and diabetes has been widely reported both in clinical surveys and in case histories (1-7). We studied this relationship, the extent of the association between celiac disease and diabetes, and whether this association was with insulin-dependent diabetes mellitus (IDDM). Leicestershire has a population of 867,521 (1991 census) and is unusual in that the Health Authority follows geographical boundaries. This makes establishing population-based registers possible. Leicestershire has a register of childhood diabetes dating from the 1940s (8). This was extended in 1983 to include all people taking insulin in Leicestershire who had non-insulindependent diabetes mellitus and IDDM. Ascertainment previously has been found to be >95%. The celiac disease register was started in 1989. The two registers are similar in their methods of ascertainment and were derived from multiple sources. The insulin-taking register was separately obtained from consultant records, patient associations, general practitioners, and diabetes specialist nurse records (8). The celiac register (9) was obtained from consultant records, patient associations, general practitioners, histopathological records, and dietitian records. Ascertainment was calculated using capture-mark-recapture methodology (10).

Relationship of Maternal and Fetal Outcome to Glucose Tolerance During Pregnancy in Whites and Indian Asians

Naylors (1) timely review on diagnosing gestational diabetes emphasizes the need to reevaluate established criteria and find better diagnostic tests and criteria for the future. Several variables may confound the interpretation of an oral glucose tolerance test (OGTT) during pregnancy, and ethnicity is one such factor (2), especially if the ethnic group in question has an overall high prevalence of diabetes. Great Britain has a large immigrant population from the Indian subcontinent. Indian Asians have a significantly higher prevalence of diabetes compared with the indigenous White population (3). We studied 554 consecutive pregnancies (356 Whites, 198 Indian Asians) who had a 75-g OGTT in the third trimester of pregnancy from the 28th to the 32nd wk. These were analyzed for maternal (toxemia of pregnancy, cesarean sections) and fetal (macrosomia, microsomia, congenital abnormalities, perinatal mortality, prematurity) complications according to a 2-h venous plasma glucose stratified as follows: 4.0, 4 . 1 5.0, 5.1-5.5, 5.6-6.6, 6.7-7.7, 7.8-11.0, and 11.1 mM. Our results were previously published in detail (4) and are summarized as follows. In Whites, fetal complications ranged from 19 to 40%, and maternal complications ranged from 7 to 40%, but there was no relationship to 2-h blood glucose in either case. In Indians, fetal complications in each stratified group were 33, 10, 23, 12, 4, 50, and 10% and maternal complications were 0, 17, 19, 21, 1, 45, and 20%. There was a significant linear trend in proportions of Indian Asian maternal complications as glucose concentrations increased (P < 0.05; 5). There was also a significant overall difference in Indian Asian fetal complications (P < 0.01), with a higher prevalence at the ends of the glycemic range. The World Health Organization suggested that the same criteria should be applied for interpreting an OGTT during pregnancy as in the nonpregnant state (6). There is some evidence that even within the so-called normal range, increasing degrees of glycemia may confer an added risk to pregnancy (7). Our study emphasized that, not only do new criteria for gestational diabetes need to be derived, but also these need to be validated especially in differing ethnic groups before they are universally recommended. In Whites, fetal and maternal complications were common if 2-h plasma glucose levels were >11.1 mM (40% for either complication), but for Indians, the major risk appeared to be at >7.8 mM (38% for either complication). One hundred seventy Whites with 2-h plasma glucose levels ranging from <4.0 to 5.5 mM had 38 (22%) pregnancies with fetal complications and 18(11 %) pregnancies with maternal complications. This was compared with the Indian Asian population, which produced 15 (17%) pregnancies with fetal complications and 13 (15%) pregnancies with maternal complications. In the range 5.6-7.7 mM, 154 Whites produced 35 (23%) pregnancies with fetal complications and 19 (12%) pregnancies with maternal complications. In 80 Indian Asians, 7 (9%) pregnancies had fetal complications, and 14 (17%) pregnancies had maternal complications. Higher percentages were found in the range 7.8-11 mM; of 27 Whites, there were 6 (27%) complications in both groups compared to the Indian Asian total of 22 pregnancies, in which there were 11 (50%) fetal cornplications and 10 (45%) maternal complications. In those with 2-h plasma glucose levels >11.1 mM, of 5 Whites examined, 2 (40%) pregnancies had fetal and maternal complications, whereas of 10 Asians, 1 (10%) pregnancy had fetal complications and 2 (20%) pregnancies had maternal complications.