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A L Drash

Publications and source records attributed to A L Drash.

At least 19 recordsLinked to original sources
PubMed1992

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.

Adolescent↗
PubMed1992

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.

Adult↗
PubMed1992

Hypoplasia of the pancreas in a patient with type I diabetes mellitus.

Pancreatic hypoplasia is an uncommon developmental defect that has not been well documented in association with type I diabetes mellitus. We report the case of a patient with an atypical clinical onset of type I diabetes mellitus who died following pancreas transplantation. Autopsy showed the surprising finding of hypoplasia of the native pancreas with other features indicating the concurrence of type I diabetes mellitus. These findings lead to speculation about the occurrence and interaction of these two diseases in our patient.

Adult↗
PubMed1992

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 B-cells. Relatives ascertained through the Children's 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The dawn phenomenon: comparison between normal and insulin-dependent diabetic adolescents.

To determine the role of insulin clearance in the dawn phenomenon, we studied 10 adolescents with IDDM in comparison to 10 healthy, matched control subjects reported previously. In diabetics, metabolic clearance rate of insulin was calculated during i.v. infusion of insulin from 0100 to 0430 h and from 0430 to 0800 h (0.17 and 0.33 mU/kg/min, respectively), with a Harvard pump, while maintaining nocturnal euglycemia. In controls, metabolic clearance rate of insulin was calculated from the prehepatic insulin secretion rate based on C-peptide levels. In diabetic and control subjects, plasma glucose, free insulin, and glucagon concentrations were similar and did not change during the dawn period. However, metabolic clearance rate of insulin increased during the dawn period in diabetic (9.42 +/- 0.91 to 19.89 +/- 1.52 mL/kg/min, p less than 0.0001) and control subjects (4.87 +/- 1.11 to 9.30 +/- 1.50 mL/kg/min, p = 0.008). Plasma cortisol and adrenocorticotropic hormone levels increased and growth hormone (GH) decreased significantly during the dawn period. Diabetic adolescents had significantly higher plasma GH levels than control subjects throughout the night. We conclude the 1) increased insulin clearance is responsible for the dawn phenomenon in healthy and diabetic adolescents and 2) insulin resistance due to GH is an unlikely cause for the dawn phenomenon because diabetic subjects, despite higher GH levels, maintain plasma glucose levels similar to control subjects without requiring higher plasma free insulin concentrations.

Adolescent↗
PubMed1992

Pittsburgh Epidemiology of Diabetes Complications Study. Measuring diabetic neuropathy follow-up study results.

OBJECTIVE: This project evaluated the utility of quantitative sensory techniques in predicting the development of neuropathy for subjects participating in a prospective study. RESEARCH DESIGN AND METHODS: Distal symmetric polyneuropathy was evaluated in 77 insulin-dependent diabetes mellitus individuals via quantitative sensory testing, nerve conduction studies, and clinical examination. RESULTS: Although the specificity and positive predictive value were low for the quantitative sensory techniques as predictors of neuropathy diagnosed on clinical exam approximately 2 yr later, the sensitivity for vibratory thresholds was high (100%). Variability over the 2-yr interval was shown on follow-up testing for each of the objective assessment modalities and it was not explained by differences for potential risk factors measured at baseline. CONCLUSION: Despite a cross-sectional relationship between the assessment modalities and clinically overt neuropathy at baseline, these follow-up data suggest that the potential for the objective modalities as predictors of clinically diagnosed neuropathy may be limited.

Adult↗
PubMed1992

Sex differences in secondary attack rate of IDDM to siblings of probands through older ages. Pittsburgh Etiology of IDDM Study.

OBJECTIVE: To determine the descriptive epidemiological patterns of the secondary attack rate of insulin-dependent diabetes mellitus (IDDM) among siblings of probands through older ages. RESEARCH DESIGN AND METHODS: A family history analysis was performed on 1774 IDDM probands who were diagnosed or seen within 1 yr of diagnosis at Children's Hospital of Pittsburgh from 1 January 1950 through 31 December 1981. The probands were discharged on insulin and were diagnosed at less than 17 yr of age. The time frame permitted the risk of IDDM for siblings of probands to be calculated over a broad spectrum of age. RESULTS: Risk estimates for the 3966 full natural siblings through 10, 20, and 30 yr of age were 1.6, 4.1, and 6.3%, respectively. Secondary attack rates were equivalent for male and female siblings through 15 yr of age (3%); however, the risk to males increased an additional 4% between 16 and 30 yr of age compared with 2.5% for females (P = 0.01). There was no evidence of an excess sex concordance among affected sibling pairs. CONCLUSIONS: Males have a greater secondary attack rate of IDDM at older ages than females. This may be due to an increased exposure to environmental agents among males or protective influences operating among females.

Adolescent↗
PubMed1992

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.

Birth Order↗
PubMed1992

Odyssey.

Explore the source record for details and available documents.

Diabetes Mellitus↗
PubMed1991

The epidemiology of diabetes complications study. IV. Correlates of diabetic background and proliferative retinopathy.

The roles of potential risk factors for background and proliferative retinopathy were evaluated in cross-sectional analyses from the Epidemiology of Diabetes Complications Study, Pittsburgh, Pennsylvania. This report presents results from the 657 insulin-dependent diabetic participants seen at the baseline examination (1986-1988). The presence of and severity of retinopathy were judged from stereoscopic photographs of three views of the ocular fundus using the modified Airlie House classification system. Fifty-three percent of the participants had background retinopathy, and 31% had proliferative retinopathy. Logistic regression analyses showed that among participants aged less than 18 years, those with background retinopathy were older and had higher levels of glycosylated hemoglobin compared with those without retinopathy. In the 18-29-year age group, participants with background retinopathy had a longer duration of diabetes, higher low density lipoprotein (LDL) cholesterol levels, and lower high density lipoprotein cholesterol levels and were more likely to have microalbuminuria compared with those without retinopathy. Participants aged 18-29 years with proliferative retinopathy had a longer duration of diabetes, higher diastolic blood pressure, and higher fibrinogen and LDL cholesterol levels than those with background retinopathy. In the age group greater than or equal to 30 years, diabetes duration, diastolic blood pressure, and fibrinogen, LDL cholesterol, and triglyceride levels were increased in participants with proliferative retinopathy versus those with background retinopathy. In a multivariate model of proliferative retinopathy, controlling for concurrent renal disease weakened the influence of blood pressure, fibrinogen, triglycerides, and LDL cholesterol and improved the overall fit of the model. These results suggest that diabetic nephropathy may contribute to the development of proliferative (but not background) retinopathy by increasing blood pressure and fibrinogen, by altering the lipoprotein profile, and possibly through other mechanisms.

Adolescent↗
PubMed1991

Familial and sporadic insulin-dependent diabetes: evidence for heterogeneous etiologies?

Heterogeneity within insulin-dependent diabetes mellitus (IDDM) has been hypothesized, but few studies have focused on differences which may exist between familial and sporadic IDDM cases. Presenting characteristics for 330 white, newly diagnosed IDDM cases were evaluated. Familial cases were older (10.2 +/- 5.1 years vs 7.9 +/- 4.2 years, P = 0.010) and had, on average, less severe metabolic disturbances at presentation, as demonstrated by lower mean hemoglobin A1 (12.6 +/- 2.4% vs 14.4 +/- 2.6%, P = 0.001) and mean insulin dose at discharge (0.62 +/- 0.35 U/kg/day vs 0.85 +/- 0.29 U/kg/day, P less than 0.001), and higher mean plasma bicarbonate concentrations (19.3 +/- 3.9 mmol/l vs 15.8 +/- 5.9 mmol/l, P = 0.023) and mean plasma C-peptide levels (0.35 +/- 0.36 pmol/ml vs 0.14 +/- 0.15 pmol/ml, P less than 0.001). Further analyses on a subset of IDDM cases (n = 100) indicated that initial differences in metabolic indices observed at diagnosis were no longer apparent at one-year post-diagnosis. These results suggest that the etiology of familial and sporadic IDDM is similar and that the less severe presentation observed at diagnosis in the familial cases may be due to earlier identification of the disease, reflecting increased parental knowledge of diabetic symptoms and/or frequent testing for diabetes.

Age Factors↗
PubMed1991

Cholesterol screening in childhood: sixteen-year Beaver County Lipid Study experience.

To determine the extent to which cholesterol measured in childhood is predictive of values in adulthood, the investigators conducting the second follow-up of the Beaver County Lipid Study tracked the cholesterol values of 295 adults who had initially participated as children (ages 11 to 14 years) in a countywide school screening program. The follow-up study was conducted 16 years after the initial study, when the participants had reached a mean age of 28 years. The overall correlation (r) between baseline (1972-1973) total cholesterol values and the values found at the present follow-up was 0.44 (p less than 0.0001). Women had a higher correlation (r = 0.51) than men (r = 0.38). In addition, the efficacy of childhood screening for cholesterol levels was assessed by considering currently recommended borderline values (greater than 175 mg/dl (4.6 mmol/L) for children and greater than 200 mg/dl (5.2 mmol/L) for adults) as a "positive" test result. The sensitivity of screening at age 12 years for predicting elevated adult total cholesterol concentrations was 63%, specificity was 67%, and the predictive value of a positive test result was 47%. Comparison of false-positive results (above the borderline cutoff point as a child but not as an adult) and false-negative results (below the borderline cutoff point as a child but above it as an adult) showed that male subjects with false-positive results smoked significantly less than those with false-negative results (p less than 0.05) and had a greater improvement during the preceding 7 years in cholesterol-lowering dietary practices (p less than 0.01). Female subjects with false-positive results smoked significantly less than those with false-negative results (p less than 0.05), were less overweight (p less than 0.05), and had a lower prevalence of oral contraceptive use (p less than 0.01). These results support the potential value of screening for hypercholesterolemia in childhood on a population basis. Although some subjects were misclassified as a result of childhood screening, some of this misclassification was associated with adopting changes that a screening and intervention program would be designed to promote--nonsmoking, weight control, and a prudent diet.

Adolescent↗
PubMed1991

The investigation of age at onset as a risk factor for mortality in persons with insulin-dependent diabetes mellitus using Cox proportional hazards models.

Proportional hazards models measuring the effect of age at onset of insulin-dependent diabetes mellitus on mortality risk are presented. The study population consisted of 924 insulin-dependent diabetic patients who were seen within 1 year of diagnosis at Children's Hospital of Pittsburgh between 1950 and 1981 and were more than 20 years old at follow-up. Age at diabetes onset was categorized as prepubertal or pubertal, defined by age. Individuals with pubertal onset of diabetes had a significantly higher risk of mortality compared with those with prepubertal onset by diabetes duration but not by attained age. It is proposed that age at onset is an independent determinant of mortality in diabetic individuals and may represent either heterogeneity within insulin-dependent diabetes mellitus with respect to long-term prognosis or an interactive effect of diabetes duration and puberty on prognosis.

Adolescent↗
PubMed1991

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 less than 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.

Adult↗
PubMed1991

Sexual dimorphism in insulin sensitivity in adolescents with insulin-dependent diabetes mellitus.

Sex-related differences in insulin sensitivity were evaluated in male and female adolescents with insulin-dependent diabetes mellitus (IDDM). They were matched for age, pubertal staging, body mass index, and glycohemoglobin levels. During a 1.7 mU/kg.min hyperinsulinemic-euglycemic clamp, the insulin-mediated glucose disposal rate was lower (26.9 +/- 2.1 vs. 47.1 +/- 3.7 mumol/kg.min; P less than 0.001), and GH levels were higher (6.5 +/- 1.2 vs. 2.9 +/- 0.8 micrograms/L; P = 0.03) in females than in males. Plasma glucagon, cortisol, epinephrine, and norepinephrine levels during the clamp were similar in the two sexes, except for pancreatic polypeptide, which showed a tendency to be higher in females (19 +/- 4 vs. 11 +/- 1 pmol/L; P = 0.07). During insulin-induced hypoglycemia, the rate of drop in plasma glucose was faster (0.16 +/- 0.01 vs. 0.11 +/- 0.01 mmol/L.min; P = 0.001), and the rate of glucose recovery was slower in males than in females (0.04 +/- 0.01 vs. 0.06 +/- 0.01 mmol/L.min; P = 0.05). Plasma glucose concentrations were lower in males than in females (glucose nadir, 2.3 +/- 0.2 vs. 3.3 +/- 0.2 mmol/L; P = 0.002; glucose peak, 3.7 +/- 0.2 vs. 5.3 +/- 0.4 mmol/L; P = 0.002), with similar plasma free insulin concentrations. Despite a greater degree of hypoglycemia, GH responses were lower in males than in females. The remaining counterregulatory hormone responses were similar in both sexes. We conclude that there is a distinct sexual dimorphism in insulin sensitivity in adolescents with IDDM. This is likely to be due to sex-related differences in GH levels. Furthermore, male patients with IDDM are apt to develop greater degrees of hypoglycemia accompanied by lower GH responses.

Adolescent↗
PubMed1991

Plasma catecholamine responses to hypoglycemia in children and adolescents with IDDM.

OBJECTIVE: The goal of this study was to assess whether children and adolescents with insulin-dependent diabetes mellitus (IDDM) have decreased catecholamine responses to insulin-induced hypoglycemia as has been reported in adults and to explore the pathogenesis of the decreased response in terms of possible relationships to autonomic neuropathy or hyperinsulinism. RESEARCH DESIGN AND METHODS: A before-and-after trial on the effects of 3 days of intensive insulin therapy was conducted on 60 subjects with IDDM (age 15.4 +/- 2.6 yr, duration of diabetes 7.8 +/- 3.5 yr). The control group consisted of 5 children with non-growth hormone-deficient short stature (age 14.8 +/- 3.2 yr). Hypoglycemia was induced with an intravenous insulin bolus (0.15-0.75 U/kg) after insulin withdrawal and 3 days of intensive insulin therapy in diabetic subjects on an inpatient basis to assess the role of hyperinsulinism in suppressing the catecholamine response to hypoglycemia. Control subjects were studied once and received an insulin bolus of 0.1 microU/kg. Autonomic neuropathy was assessed by computerized assessment of the basal R-R variation during inspiration and expiration and the pancreatic polypeptide response to hypoglycemia. RESULTS: Basal plasma catecholamine levels were lower in diabetic subjects after intensive insulin therapy than in control subjects (P = 0.008). The peak and incremental catecholamine responses after insulin withdrawal and intensive insulin therapy in IDDM subjects were significantly decreased compared with control subjects (P less than 0.001). Peak catecholamine responses to hypoglycemia in IDDM were decreased after intensive insulin therapy (P = 0.002). This was particularly true in those with plasma glucose nadir levels of less than 2.2 mmol (P less than 0.001). The diminished catecholamine responses were primarily due to decreased peak epinephrine responses after intensive insulin therapy compared with insulin withdrawal (P = 0.011). There were no significant correlations between the catecholamine response to hypoglycemia and age, duration of diabetes, pancreatic polypeptide, or R-R interval. CONCLUSIONS: These results suggest that children and adolescents with IDDM after insulin withdrawal have diminished catecholamine response to hypoglycemia compared with control subjects and indicate that short-term intensive insulin therapy diminishes this response further. Thus, hyperinsulinism may play a role in suppressing the catecholamine response to hypoglycemia. There is no evidence for a clinical or subclinical role of autonomic neuropathy to explain the altered catecholamine responses.

Adolescent↗