The association of diabetes specialist care with health care practices and glycemic control in patients with type 1 diabetes: a cross-sectional analysis from the Pittsburgh epidemiology of diabetes complications study.

OBJECTIVE: To determine whether diabetes care characteristics and glycemic control differ by use of specialist care in a representative cohort of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Health care, sociodemographic characteristics, and glycemic control were compared between participants in the Pittsburgh Epidemiology of Diabetes Complications Study who reported receiving specialist care (n = 212) and those who did not (n = 217). Specialist care was defined as having received care from an endocrinologist or diabetologist or diabetes clinic attendance during the last year. RESULTS: Patients who reported receiving specialist care were more likely to be female, to have an education level beyond high school, to have an annual household income >$20,000, and to have health insurance. Additionally, patients receiving specialist care were more likely to have received diabetes education during the previous 3 years, to have knowledge of HbAlc testing and to have received that test during the previous 6 months, to have knowledge of the Diabetes Control and Complications Trial results, to self-monitor blood glucose, and to inject insulin more than twice daily. A lower HbA1 level was associated with specialist care versus generalist care (9.7 vs. 10.3%; P = 0.0006) as were higher education and income levels. Multivariate analyses suggest that the lower HbA1 levels observed in patients receiving specialist care were restricted to patients with an annual income >$20,000. CONCLUSIONS: Specialist care was associated with higher levels of participation in diabetes self-care practices and a lower HbA1 level. Future efforts should research and address the failure of patients with low incomes to benefit from specialist care.

Was there an epidemic of diabetes in nonwhite adolescents in Allegheny County, Pennsylvania?

OBJECTIVE: To determine the incidence of IDDM in children aged < 20 years at diagnosis in Allegheny County, Pennsylvania, for the period from 1 January 1990 to 31 December 1994 and to compare the incidence between whites and nonwhites in the same area and for the same time period. RESEARCH DESIGN AND METHODS: All new patients diagnosed between January 1990 and December 1994 who were aged < 20 years, on insulin, and residents of Allegheny County at diagnosis were identified from medical records of 23 hospitals in the Allegheny County area. To verify the completeness of the hospitals using the capture-recapture method, pediatricians and diabetologists were used as a secondary source. RESULTS: A total number of 257 patients were identified. The overall age-standardized incidence rate was 16.7/100,000. Nonwhites had a slightly higher incidence (17.6/100,000) than whites (16.5/100,000). In the 15-19 years age-group, the incidence in nonwhites (30.4/100,000) was almost three times higher than that in white (11.2/100,000) and more than two times higher than that in the previous period (from 1985 to 1989) (13.8/100,000). CONCLUSIONS: For the first time in the Allegheny County registry, and in any other registry, nonwhites showed a higher incidence of IDDM than whites. The high incidence in the 15-19 years age-group was responsible for this phenomenon. This epidemic of diabetes in adolescent nonwhites may be the result of a rising incidence of classical IDDM or another type of diabetes. Further studies using population-based registries are needed to determine whether this increase is being seen in other areas and other ethnic groups and to clarify the reasons for the increase in IDDM among blacks.

Plasma leptin in children: relationship to puberty, gender, body composition, insulin sensitivity, and energy expenditure.

Leptin has been demonstrated to reflect body fat mass (FM) in humans, but the regulation of leptin levels during childhood growth and development is poorly understood. We studied the relation between plasma leptin, fasting insulin, insulin sensitivity, and resting energy expenditure in 22 healthy prepubertal children and 27 adolescents. Body composition was assessed by the H2(18)O-dilution principle, insulin sensitivity by a hyperinsulinemic (40 mU/m2/min)-euglycemic clamp, and energy expenditure by indirect calorimetry. Plasma leptin in prepubertal children (9.3 +/- 2.0 ng/mL) was not different from that in pubertal adolescents (10.9 +/- 2.2 ng/mL). Plasma leptin correlated with FM (r = .77, P < .001). There were no gender differences in leptin after controlling for FM differences. In prepubertal and pubertal subjects, plasma leptin correlated with fasting insulin independently of FM (r = .60, P < .001), but did not correlate with insulin sensitivity independently of body fat content. Leptin showed no relationship to resting energy expenditure after adjusting for body composition. The present cross-sectional evaluation of normal children shows that (1) plasma leptin reflects body fat content, (2) leptin concentrations are similar between prepubertal children and pubertal adolescents, (3) there are no gender differences in leptin independent of adiposity, and (4) leptin correlates with fasting insulin but not with insulin sensitivity. Contrary to animal data, our cross-sectional results in healthy children do not suggest a role for leptin in puberty or a female-related leptin resistance as reported in adults. It remains to be determined at which stage of human development the sexual dimorphism in leptin becomes evident.

Impaired counterregulatory hormone responses to hypoglycemia in children and adolescents with new onset IDDM.

Children with long-standing IDDM have impaired counterregulatory responses to hypoglycemia. To determine whether children with new onset IDDM also have altered counterregulation, we studied the counterregulatory responses to hypoglycemia in twenty children with new onset IDDM (5-6 days, age 12.6 +/- 2.9 yr, mean +/- SD), and compared these responses to 47 subjects with long-standing IDDM (duration 7.8 +/- 3.6 yr, age 15.3 +/- 2.5 yr) and 21 controls (age 14.2 +/- 2.8 yr). Six new onset subjects were restudied three months later during their remission. Glucose nadir in new onset (2.7 +/- 0.1 mmol.l-1) was similar to controls (2.4 +/- 0.1 mmol.l-1), but was higher than in long-standing IDDM (2.2 +/- 0.1 mmol.l-1). Both groups of diabetic subjects had lower glucagon responses to hypoglycemia than controls (p < 0.005). Glucagon responses in new and long-standing diabetes did not differ. Epinephrine was diminished in new IDDM compared to controls (p < 0.01). Glucose recovery was faster in new onset than in long-standing IDDM (p < 0.001) and the same as in controls. Responses remained diminished 3 months after diagnosis despite increased C-peptide and lower glycosylated hemoglobin. Thus, children with IDDM have diminished counterregulatory responses to hypoglycemia at diagnosis, that are similar to those in long-standing IDDM. The reasons for this impairment and its clinical application in childhood require further investigation.

Abnormal alpha cell hypoglycemic recognition in children with insulin dependent diabetes mellitus (IDDM).

Children with IDDM have diminished glucagon responses to hypoglycemia. We evaluated possible mechanisms in 60 children and adolescents with IDDM (age 15.4 +/- 2.6 years, duration 7.8 +/- 3.5 years [mean +/- SD]) and without diabetic complications. These were: 1) suppression by hyperinsulinism, 2) autonomic neuropathy, 3) a pan-islet cell defect, and 4) a glucotoxic effect. Glucagon and pancreatic polypeptide responses to hypoglycemia (insulin bolus 0.15-0.75 U/kg) were studied after insulin withdrawal and 3 days of intensive insulin therapy. Responses to arginine and mixed meal were also studied. The control group consisted of children with non-growth hormone deficient short stature. IDDM children had lower glucagon responses to hypoglycemia than controls (p < 0.001), the response to arginine did not differ from controls, and was greater than the response to hypoglycemia (p < 0.001). Responses to hypoglycemia after insulin withdrawal and intensive therapy did not differ. Basal pancreatic polypeptide levels were lower in IDDM than in controls (p < 0.05) but responses to hypoglycemia did not differ between groups. Thus the diminished glucagon response to hypoglycemia reflects a defect in hypoglycemic recognition or response by the alpha cells.

Clinical care of the patient with diabetes. What is the role of the diabetes professional?

A review of diabetes management problems will be presented from the biased perspective of children and adolescents with insulin-dependent diabetes mellitus (IDDM), their families, and the team of professionals who attempt to provide broadly based quality care to ensure that these young people move into effective adult life with minimal physical and/or emotional disability from the disease or its management. Although there are many unique aspects of diabetes in the child and adolescent, it is expected that recommendations for future care of this group of patients will, in most cases, have direct relevance to management issues to most patients with IDDM.

The association of waist/hip ratio with diabetes complications in an adult IDDM population.

Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the relationships between waist to hip circumference ratio (WHR) and the presence of diabetes complications in IDDM adults ages 18-45 years (N = 586). Significantly higher WHRs were observed among both genders with proliferative retinopathy or peripheral vascular disease and only among males with either neuropathy or nephropathy compared to those free of these complications. Logistic regression to determine the strength of association between WHR and each complication demonstrated that although WHR was significantly related to each complication (except nephropathy among females), WHR was only independently related to neuropathy in males and PVD in females in the final model when hypertension, LDL- and HDL-cholesterol and fibrinogen were included. These findings suggest that WHR acts as a marker of risk for diabetes complications mainly through an influence on other complication risk factors.

Predictors of microalbuminuria in individuals with IDDM. Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: To examine the relationships between microalbuminuria and the development of overt diabetic nephrology, elevated blood pressure, and a more atherogenic lipid profile; and to identify risk factors for the development of microalbuminuria in individuals with IDDM. Microalbuminuria has been associated with the subsequent development of overt diabetic nephropathy in individuals with IDDM. It is associated with elevated blood pressure and a more atherogenic lipid profile, but the temporal relationship between the development of microalbuminuria and the changes in these factors is unclear. RESEARCH DESIGN AND METHODS: Baseline characteristics were examined in 256 individuals with IDDM who had normal albumin excretion (urinary AER < or = 20 micrograms/min in > or = 2 timed urine collections) and were re-examined 2 yr later. RESULTS: At follow-up, 24 had developed microalbuminuria (AER 20-200 micrograms/min in > or = 2 timed urine collections) and 1 had developed overt nephropathy (AER > 200 micrograms/min). Overall, the significant independent predictors of microalbuminuria were HbA1 (P < 0.001), low-density lipoprotein (P < 0.01), duration of IDDM (P < 0.05), and systolic blood pressure (P = 0.05). Sex-specific analyses showed HbA1, age, and baseline AER were particularly important for men; whereas, for women, the main predictors were duration of IDDM and triglycerides. Duration-specific analyses showed that HbA1 was an important predictor both for individuals with < and > 20-yr duration. Low-density lipoprotein cholesterol was more important for subjects with shorter durations; whereas triglycerides were important for those with longer durations. CONCLUSIONS: These results suggest that glycemic control, age or duration of IDDM, disturbed lipids, and possibly elevated blood pressure all may contribute to the development of microalbuminuria; and, further, that the adverse cardiovascular risk profile seen in individuals with overt nephropathy may begin to develop even before the detection of microalbuminuria.

Lipoprotein(a) concentration shows little relationship to IDDM complications in the Pittsburgh Epidemiology of Diabetes Complications Study cohort.

OBJECTIVE: To examine the potential associations of lipoprotein(a) and the complications of IDDM and their risk factors. RESEARCH DESIGN AND METHODS: This report focuses on 186 individuals with IDDM (mean age = 34 yr) participating in a 10-yr prospective study examining various complications. Lp(a) concentrations were evaluated for those with and without complications. RESULTS: A weak correlation was seen between Lp(a) and HbA1 (r = 0.16, P < 0.05). Lp(a) concentrations were not significantly different for those with or without proliferative retinopathy, overt nephropathy, peripheral vascular disease, or definite myocardial infarction or angina. However, an inverse association (P < 0.05) was seen with distal symmetric polyneuropathy. These results were also confirmed by categorical analyses (i.e., Lp(a) levels < or = 30 vs. > 30 mg/dl). CONCLUSIONS: These results suggest that any association of Lp(a) concentration with IDDM complications is likely to be weak or nonexistent. However, prospective studies are needed before its full role can be determined.

Insulin-dependent diabetes mellitus, physical activity, and death.

The beneficial effect of physical activity in the general population is well known, but, to the authors' knowledge, has not been reported for persons with insulin-dependent diabetes mellitus. In a cohort of 548 diabetes patients followed as part of the Pittsburgh Insulin-dependent Diabetes Mellitus Morbidity and Mortality Study, physical activity was ascertained by survey in 1981, and mortality was ascertained through January 1, 1988. Cases were also compared with non-diabetic sibling controls. Activity level among cases varied inversely with the occurrence of diabetic complications. Overall activity level was inversely related to mortality risk. Sedentary males (< 1,000 kcal/week) were three times more likely to die than active males (> 2,000 kcal/week). A similar, but statistically nonsignificant, relation was seen in females. Cox proportional hazards analysis controlling for potential confounders (age, body mass index, insulin dose, reported diabetes complications, cigarette smoking, and current alcohol drinking) similarly revealed that activity level was inversely associated with mortality risk. Comparison of cases with non-diabetic sibling controls identified similar activity levels for the two groups. The results suggest that activity is not detrimental with regard to mortality, and may in fact provide a beneficial effect in terms of longevity in diabetes patients.

Autoimmunity and genetics contribute to the risk of insulin-dependent diabetes mellitus in families: islet cell antibodies and HLA DQ heterodimers.

The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1,592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-aspartate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies may be relatively common, it progresses only in those with variant HLA-DQ molecules.

Early infant diet and risk of IDDM in blacks and whites. A matched case-control study.

OBJECTIVE: To investigate the role of early infant feeding in the development of insulin-dependent diabetes mellitus (IDDM) and to determine whether an association exists in both blacks and whites. RESEARCH DESIGN AND METHODS: Black and white diabetic subjects were recruited from the Allegheny County and Children's Hospital of Pittsburgh IDDM Registries. Extensive infant diet histories were obtained from the diabetic subjects and their nondiabetic siblings, who were used as nondiabetic control subjects. Each diabetic subject was matched outside his/her family to an unrelated nondiabetic control subject on birth order, birth year (+/- 2 yr), and race, which resulted in 211 case-control pairs with a mean birth year of 1967. RESULTS: In whites, diabetic subjects were less likely to have been breast-fed than control subjects (odds ratio [OR] 0.5, 95% confidence interval [CI] 0.3, 0.9). Breast-feeding prevalence did not differ between black diabetic subjects and control subjects. Duration of overall and exclusive breast-feeding did not differ between diabetic and control subjects in the black and white cohorts. The following analyses, which examined whether the timing of the first breast milk substitute to which the infant was exposed differed between diabetic and control subjects, were conducted for exposure to any breast milk substitute and to breast milk substitutes that were cow's milk based. In whites, age at exposure to any breast milk substitutes and cow's milk-based substitutes were similar between diabetic and control subjects. In blacks, the first exposure to breast milk substitutes occurred significantly earlier for any substitute (5.1 vs. 11.9 wk, P = 0.02) and marginally earlier for cow's milk-based substitutes (3.9 vs. 8.5 wk, P = 0.07) in diabetic subjects compared with control subjects. The first exposure to breast milk substitutes was more likely to occur by 3 mo of age in black diabetic subjects compared with black control subjects (OR 3.3, 95% CI 1.1-10.0) after adjusting for maternal age at birth. The addition of breast-feeding status to the model only slightly weakened this association in blacks. CONCLUSIONS: The analyses of this study cohort suggest that the observed protective effect of breast-feeding on the risk of IDDM may be related to differences in the age at exposure to breast milk substitutes in blacks but not in whites.

The impact of the apolipoprotein E polymorphism on the lipoprotein profile in insulin-dependent diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study IX.

The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.