Allan L. Drash

Development of Questionnaire to Examine Relationship of Physical Activity and Diabetes in Pima Indians

There was a need to design a questionnaire that could accurately assess the activity patterns of Native Americans to evaluate the relationship between physical activity and diabetes. Such a questionnaire was developed and implemented into the data collection scheme of the prospective Pima Indian Study of Arizona. The questionnaire, which assesses historical, past-year, and past-week leisure and occupational activity, was examined in 29 Pima individuals aged 21–36 yr and was shown to be reliable with test-retest correlations (rank-order correlations ranged from 0.62 to 0.96 for leisure and occupational activity). Reproducibility of the past-year leisure physical-activity estimate was determined in 69 participants aged 10-59 yr and was found to be reliable in all age-groups with the exception of the 10- to 14-yr-old age-group (rank-order correlations were 0.31 in the 10- to 14-yr-old age-group compared to 0.88 to 0.92 in those >20 yr of age). Validity of the current-activity section of the questionnaire was demonstrated indirectly through comparisons with activity monitors. The past-week leisure-activity estimate was related to the Caltrac activity monitor counts per hour (p = 0.62, P > 0.05, n = 17). In summary, a physical-activity questionnaire has been developed that is both reliable and feasible to use in the Pima Indian population to evaluate the relationship of physical activity to non-insulin-dependent diabetes mellitus.

Prevalence of Complications in IDDM by Sex and Duration: Pittsburgh Epidemiology of Diabetes Complications Study II

The prevalence of and interrelationships among all four major complications of insulin-dependent diabetes mellitus (IDDM) and their risk factors are being examined in a large epidemiologic study of IDDM subjects diagnosed in childhood. This article focuses on the baseline prevalence of complications in the 657 subjects diagnosed between 1950 and 1980 and currently aged 8–48 yr, with a mean duration of 20 yr. In addition to background retinopathy being virtually universal after 20 yr of diabetes, proliferative retinopathy affects 70% of IDDM subjects after 30 yr duration. As with overt nephropathy, prevalence of proliferative retinopathy is marginally higher in females than in males at short durations; the previously reported male excess is limited to the subjects with IDDM of longer duration (≥25 yr). Somewhat different patterns of microalbuminuria are also seen by sex. Males show a threefold increase in prevalence from 10 to 25 yr duration, whereas females show a more constant prevalence across these durations. A further rise in microalbuminuria is seen in males but not females at ≥30 yr duration, giving a combined prevalence of microalbuminuria and overt nephropathy at ≥30 yr duration of 84% (males) and 59% (females). Distal symmetrical polyneuropathy shows a constant rise with duration and is only marginally higher in men. Prevalence of cardiovascular (coronary and cerebral) disease shows no sex difference, whereas peripheral vascular disease is particularly common in women after 30 yr duration (>30%) compared with men (11%) when determined by ankle/arm blood pressure ratio <0.8 at rest or after exercise. These results suggest that the natural history of IDDM complications varies considerably by sex and that the prevalence of complications (especially renal complications in males) may be higher than previously recognized.

The Pittsburgh Insulin-dependent Diabetes Mellitus (IDDM) Morbidity and Mortality Study: Mortality Results

A follow-up study of 1966 patients with insulin-dependent diabetes mellitus (IDDM) who were diagnosed at Childrens Hospital of Pittsburgh (CHP) between 1950 and 1981 has been completed. The mean age of the population at follow-up was 21.2 yr with a mean duration of IDDM of 12.9 yr. Nine percent of the patients were deceased, a sevenfold excess in mortality compared with the U.S. population. The relative increase in mortality was greater for females than males and greater for blacks than whites. Before age 20, the primary excess in mortality was at onset of IDDM, or within 6 mo after onset, and was due to acute diabetic complications. After age 20, the annual mortality risk was approximately 2%, which was more than 20 times greater than for the U. S. population. Renal disease was responsible for the majority of these deaths. There was a reduced risk of dying for diabetic patients who were diagnosed between 1966 and 1971 compared with patients diagnosed during earlier years.

Epidemiological Correlates of Diabetic Neuropathy: Report From Pittsburgh Epidemiology of Diabetes Complications Study

The natural history of diabetic neuropathy and its risk factors are not well understood, apart from the recognition that prevalence increases with duration and, in many studies, degree of glycemia. The role of potential risk factors was therefore evaluated in a cross-sectional analysis from the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study. We present results from the first 400 subjects seen at baseline examination. Neuropathy was determined by a trained internist with a standardized examination and was defined as the presence of at least two of three criteria: abnormal sensory or motor signs, symptoms consistent with neuropathy, and decreased tendon reflexes. The prevalence of neuropathy in this cohort was 34% (18%, 18-29 yr old, 58% ≥30 yr old) with no difference by sex. By focusing on subjects s 18 yr old, all significant univariate variables (e.g., duration, glycosylated hemoglobin [HbAJ) were analyzed in 3 multiple logistic regression models: all subjects ≥18 yr old and separating the same subjects into two groups based on age (18-29 and 2:30 yr). Duration, HbA1, smoking status, and high-density lipoprotein cholesterol were found to be associated with neuropathy in the models for the ≥18-yr-old group and the ≥30-yr-old group. In the 18- to 29-yr-old group, duration, HbA1, and hypertension status were found to be significantly associated with neuropathy. There was a univariate association of neuropathy with macrovascular disease, nephropathy, and retinopathy. Macrovascular disease, although borderline significant, remained in the original logistic model for the ≥18-yr-old subjects. The addition of either retinopathy or nephropathy to the original logistic model for the 18- to 29-yr-old subjects resulted in a statistically significantly improved fit (of model to data), suggesting that these complications may be a marker for something beyond the risk factors described. The results suggest that traditional cardiovascular risk factors (e.g., lipids and smoking) are important determinants of distal symmetric polyneuropathy and if confirmed in prospective follow-up, open new avenues to the prevention of diabetic neuropathy.

Contribution of Diabetes Duration Before Puberty to Development of Microvascular Complications in IDDM Subjects

The contribution of diabetes duration, both pre- and postpuberty, to the development of microvascular complications and mortality in diabetic subjects was investigated in three study populations from the Childrens Hospital of Pittsburgh Insulin-Dependent Diabetes Mellitus (IDDM) Registry. Life-table analyses by total and postpubertal IDDM duration were used to evaluate differences in the prevalence of microvascular complications and diabetes-related mortality in subjects diagnosed before and during puberty, as defined by an age at IDDM onset marker of 11 yr for girls and 12 yr for boys. The prevalence of retinopathy and overt nephropathy in 552 White adult diabetic subjects (population 1, mean IDDM duration 20.8 yr) was significantly greater in subjects diagnosed during puberty compared with those diagnosed before puberty. However, similar analyses by postpubertal duration showed no difference in microvascular complication prevalence between the two groups. These findings did not appear to be due to a confounding effect of age. Additional analyses of 239 adolescent diabetic subjects (population 2, mean duration 8.3 yr) revealed the same trend for the prevalence of retinopathy. Finally, results concerning the risk of diabetes-related mortality in a cohort of 1582 subjects (population 3, mean duration 12.9 yr) indicated that postpubertal duration of IDDM may be a more accurate determinant of the development of microvascular complications and diabetes-related mortality than total duration, and it is suggested that the contribution of the prepubertal years of diabetes to long-term prognosis may be minimal.

Geographic differences in the risk of insulin-dependent diabetes mellitus: the importance of registries.

There are marked geographic differences in the incidence of insulin-dependent diabetes mellitus (IDDM); for example, children in countries such as Finland are over 35 times more likely to develop IDDM than children in Japan. An understanding of the reasons for the geographic differences is likely to be important for understanding and, hopefully, preventing IDDM. There are problems, however, because of the lack of registries with adequate standardization. The major needs for the future studies include (1) to clarify the definition of IDDM for epidemiologic study, (2) to establish a standardized approach for IDDM registries, (3) to use registries to evaluate viral, immunologic, and genetic differences in order to explain differential risks across populations, and (4) to encourage the development of new population-based registries worldwide.

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 ≤20 μg/min in ≥2 timed urine collections) and were re-examined 2 yr later. RESULTS At follow-up, 24 had developed microalbuminuria (AER 20–200 (Ag/min in ≥2 timed urine collections) and 1 had developed overt nephropathy (AER ≥200 μg/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.

Factors Associated With Avoidance of Severe Complications After 25 Yr of IDDM: Pittsburgh Epidemiology of Diabetes Complications Study I

To identify characteristics associated with long-term avoidance of insulin-dependent diabetes mellitus (IDDM) complications, subjects taking part in an epidemiologic natural history study of childhood-onset IDDM, with a duration of disease ≥25 yr, were studied. Nineteen percent of 175 subjects had avoided overt nephropathy, definite cardiovascular and peripheral vascular disease, clinical neuropathy, and proliferative retinopathy. Approximately half of the nonrenal complications occurred in the absence of renal disease. Subjects free of these advanced complications were characterized by a longer duration of disease (P < 0.05), better lipid profile and blood pressure (P < 0.01), and considerably lower glycosylated hemoglobin levels (P < 0.001). Health-related behaviors, including recent medical contact, regular glucose monitoring, physical activity in youth, and avoidance of cigarette smoking, did not relate to complication status, although regular (at least weekly) alcohol consumption was more prevalent (P < 0.05) in those without complications. We conclude that a lower mean glycosylated hemoglobin level is strongly related to the avoidance of all IDDM complications.

Correlates of Insulin Antibodies in Newly Diagnosed Children with Insulin-dependent Diabetes Before Insulin Therapy

Insulin antibodies, as measured by plasma radiolabeled insulin-binding capacity, were determined in 124 newly diagnosed insulin-dependent diabetic (IDDM) children before and after 1, 3, and 5 days of insulin therapy. Controls were 35 nondiabetic children with plasma insulin binding capacity of 1.0 ± 0.7%. The patients were divided into three groups according to their plasma insulin-binding capacity. Group 1 (N = 79) had binding within two standard deviations (SD) of the control mean, group 2 (N = 20) had insulin binding 2–6 SD above controls, and group 3 (N = 25) showed insulin-binding capacity of more than 6 SD above the control mean. After exogenous insulin therapy, plasma 125I-insulin-binding capacity dropped significantly in both groups 2 and 3, concurrent with significant increases in plasma insulin levels. The three groups differed from each other in that patients in group 3 were significantly younger thanin the other groups and clinically seemed to be more severely dehydrated, as reflected in their higher levels of serum urea nitrogen, plasma glucose, potassium, and elevated pulse rate. The three groups did not differ in respect to sex, HLA-DR antigens, Coxsackie-B antibody titers, islet cell cytoplasmic antibodies, immunoglobulin level, and C-peptide levels. Only two of 446 siblings of IDDM children showed elevated insulin binding, one of whom developed IDDM 6 wk later. The presence of an insulin-binding substance probably representing insulin antibodies in some cases of newly diagnosed IDDM suggests that autoimmunity in this disorder is not limited to the B-cell membrane and cytoplasm and lends further support to the heterogeneity Of IDDM.

The Pittsburgh Insulin-dependent Diabetes Mellitus (IDDM) Registry: The Incidence of Insulin-dependent Diabetes Mellitus in Allegheny County, Pennsylvania (1965–1976)

An Insulin-dependent Diabetes Mellitus Registry has been developed in Allegheny County, Pennsylvania, through hospital record review and surveillance of pediatric practices. The yearly incidence ranged from 10/100,000 for nonwhite males to 16/100,000 for white males. There were no temporal trends in incidence for 1965–1976 nor major sex differences. Nonwhites had a slightly lower incidence, primarily in the younger age groups.