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Biomedical subjects

D J Becker

Publications and source records attributed to D J Becker.

At least 73 records · Page 4Linked to original sources
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

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↗
PubMed1991

Health, life, and automobile insurance characteristics in adults with IDDM.

OBJECTIVE: To determine whether people with insulin-dependent diabetes mellitus (IDDM) were compromised in their access to insurance. RESEARCH DESIGN AND METHODS: A case-control study of 158 people with IDDM and 158 nondiabetic siblings matched for age and sex was conducted to evaluate the health, life, and automobile insurance characteristics and history of people with IDDM. RESULTS: Health insurance coverage (yes/no) among the IDDM and sibling control subjects was similar. More than 90% of the IDDM and control respondents had insurance through a private third-party source, and this insurance did not differ by type of plan, coverage, or premium. However, Medicare coverage was more common among the IDDM subjects and was associated with the presence of severe diabetic complications. IDDM subjects were also more likely to have been denied a health insurance policy by an insurer than were the control subjects (23 vs. 1%, P less than 0.001). Similarly, there was no difference between the IDDM and sibling control subjects in the number who had a life or automobile insurance policy. However, life and automobile insurance refusal was much more frequent among the IDDM respondents, more so for life (55 vs. 0%, P less than 0.001) than for automobile (12 vs. 4%, P less than 0.05) insurance. CONCLUSIONS: These results suggest that access to insurance is severely compromised for people with IDDM. Although most of those with IDDM are able to find some form of insurance, it is evident that on average they must go to extra lengths to find it. These data and a changing insurance environment emphasize the need to reexamine, as a society, the importance of insurance for people with chronic disease, particularly IDDM.

Adult↗
PubMed1991

The interface between epidemiology and molecular biology in the search for the causes of insulin-dependent diabetes mellitus.

Epidemiological techniques have been utilized to accumulate new knowledge about insulin-dependent diabetes mellitus (IDDM), leading to important insights into the disease process and the alteration of these mechanisms when viewed from a geographic or population base. More recently, highly powerful and sophisticated techniques of molecular biology have been added to the research arsenal, extending the knowledge on the genetic basis for IDDM and the probable environmental factors involved. The development and growth of the new discipline of epidemiological genetics promises exciting new developments for the future of our field as well as that of other major medical problems having a genetic base, but significantly influenced by environmental factors. This review stresses the importance of carefully validated diabetes registries in the study of the epidemiology of IDDM. The Children's Hospital of Pittsburgh and the University of Pittsburgh Medical Center have spear-headed the development of such registries, worldwide. The first international meeting on IDDM epidemiology in 1983 gave as a result, i.e., the finding that there were truly remarkable differences in the risk of developing IDDM depending upon the geographic location of the individual. Later collaborative work via the Diabetes Epidemiology Research International (DERI) group has confirmed the previous finding and added the description of secular trends and epidemics of IDDM. It is remarkable that the incidence rate of IDDM in children below 15 years vary from 1/100,000/yr in the Orient to 35/100,000/yr in Finland. The epidemiological approach in the study of IDDM has also stimulated research into the various facets of the etiology of the disease, genetic factors, autoimmune mechanisms and environmental factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1991

Cross-sectional and longitudinal relationship of sodium-lithium countertransport to insulin, obesity and blood pressure in healthy perimenopausal women.

The objectives of this study were to assess the possible role of insulin as a regulator of red blood cell sodium-lithium countertransport and to examine the relationship of countertransport activity to change over time in insulin, blood pressure, and other variables. At baseline, countertransport was measured, and at baseline and after 2-3 years of follow-up, blood pressure, body mass index (BMI), lipids, fasting and two-hour plasma insulin and glucose were measured in 144 white healthy, premenopausal women, age 42-50 years. At baseline, using high and low categories of fasting insulin, triglycerides and BMI, countertransport was independently related to fasting insulin (P = 0.017), and triglycerides (P = 0.001), but not to BMI by analysis of variance. In similar analyses with fasting insulin, BMI, and countertransport, diastolic blood pressure was independently related only to countertransport (P = 0.003). Among the 73 who remained premenopausal after 2-3 year follow-up, baseline countertransport was significantly correlated with increases in fasting and two-hour insulin (r = 0.37, 0.38, P = 0.003, respectively), and these relationships remained significant after adjustment for change in BMI. Among subjects with high baseline countertransport, systolic blood pressure increased 5.6 mmHg compared with -2.2 mmHg with low countertransport, P = 0.001 after adjusting for baseline and change in BMI, triglycerides, and fasting and two-hour insulin. The data are consistent with a role for insulin and lipids in the regulation of sodium transport which may, in turn, play a role in blood pressure regulation. A relatively short follow-up in this healthy population suggests a relationship of baseline countertransport to changes in insulin metabolism, and blood pressure.

Adult↗
PubMed1990

Evolution of the Pittsburgh studies of the epidemiology of insulin-dependent diabetes mellitus. Pittsburgh Diabetes Epidemiology and Etiology Research Group.

The Pittsburgh project evaluating the epidemiology and etiology of insulin-dependent diabetes mellitus (IDDM) is currently one of the large ongoing studies of childhood diabetes. This paper traces the evolution of the project, from the initial basic epidemiologic approach in the early 1980s, to the current thrust where complex molecular genetic approaches are being incorporated into population-based research. The epidemiology models employed in the Pittsburgh project are similar to those that could be used in many areas of chronic disease research. The integration of immunogenetics into epidemiology produces a powerful approach for understanding the complex interaction of host susceptibility and environmental agents that contribute to the development of IDDM.

Adolescent↗
PubMed1990

Demonstration of a dawn phenomenon in normal adolescents.

To ascertain whether the dawn phenomenon occurs in normal adolescents and, if so, to determine its mechanism, we measured nocturnal plasma glucose, insulin, glucagon, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH) levels between 01.00 and 08.00 h in 10 healthy adolescents. The prehepatic insulin secretion rate was calculated based on C peptide levels. The metabolic clearance rate of insulin (MCRI) was calculated as the ratio of mean insulin secretion rate to mean insulin concentration. There was no change in plasma glucose, insulin, and glucagon between 01.00-04.00 and 05.00-08.00 h (paired t test). The MCRI was higher at 05.00-08.00 h compared to 01.00-04.00 h (9.30 +/- 1.50 vs. 4.87 +/- 1.11 ml.kg-1.min-1; p = 0.008). The prehepatic insulin secretion increased at 05.00-08.00 h relative to 01.00-04.00 h (1.1 +/- 0.2 vs. 0.6 +/- 0.1 pmol.kg-1.min-1; p = 0.013). Similarly, cortisol and ACTH levels were higher at 05.00-08.00 versus 01.00-04.00 h (323 +/- 33 vs. 102 +/- 22 nmol/l, p less than 0.001; 3.6 +/- 0.5 vs. 1.8 +/- 0.4 pmol/l, p = 0.006, respectively). Growth hormone was higher at 01.00-04.00 versus 05.00-08.00 h (7.6 +/- 1.2 and 3.0 +/- 0.9 microgram/l; p = 0.019). ACTH correlated with MCRI (r = 0.66; p = 0.002) and prehepatic insulin secretion (r = 0.75; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

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 Children's 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.

Cause of Death↗
PubMed1990

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 (greater than or equal to 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 greater than or equal to 30 yr duration, giving a combined prevalence of microalbuminuria and overt nephropathy at greater than or equal to 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 (greater than 30%) compared with men (11%) when determined by ankle/arm blood pressure ratio less than 0.8 at rest or after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

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 greater than or equal to 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 less than 0.05), better lipid profile and blood pressure (P less than 0.01), and considerably lower glycosylated hemoglobin levels (P less than 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 less than 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.

Adult↗
PubMed1990

Cyclosporin therapy for prevention and cure of IDDM. Epidemiological perspective of benefits and risks.

Cyclosporin and other immunosuppressive agents have been proposed as a preventive treatment against the development of insulin-dependent diabetes mellitus (IDDM) in relatives at increased risk for the disease, based on the understanding that its etiology is an ongoing process of autoimmune beta-cell destruction. We used an epidemiological approach to evaluate several recent trials of cyclosporin in newly diagnosed IDDM patients to determine the degree of benefit that is to be expected. We assessed these and other studies to estimate the potential adverse effects of such treatment, were it to be used in the future, either in newly diagnosed subjects or healthy high-risk relatives. Standard sample-size calculations were used to quantify the number of study subjects necessary to allow adequate statistical power to test the positive and negative effects of a future treatment (alpha = 0.05, beta = 0.20). The estimates were based on the data available from published studies of cyclosporin treatment. The importance of conducting an adequate trial of such a therapy, both from an ethical and a practical viewpoint, is discussed. Five small immunosuppression trials were evaluated. Remission rates in treated subjects exceeded those in control subjects by 15-59%. Variability in defining remission may account for the differences in rates across the studies. Estimates of the major beneficial and adverse effects of cyclosporin were derived from these trials and studies of patients who have undergone long-term immunosuppression. Indicators of kidney damage associated with cyclosporin treatment were reported in 5-47% of treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1990

Diabetic autonomic neuropathy and cardiovascular risk. Pittsburgh Epidemiology of Diabetes Complications Study III.

Diabetic autonomic neuropathy (DAN) has been shown to confer a high risk of mortality. The association between DAN and cardiovascular risk factors was examined in a well-defined cohort of 25- to 34-year-old insulin-dependent diabetes mellitus subjects (n = 168) with and without DAN as evaluated by heart rate response to deep breathing, standing, and the Valsalva maneuver. The autonomic tests were performed using both an office-based procedure and a method employed by the Diabetes Control and Complications Trial with analyses performed by the Diabetes Research and Analysis Association, Lexington, Ky. Good agreement was found between the procedures for the assessment modalities of heart rate response to deep breathing. Modeling potential correlates in logistic analyses, where heart rate response to deep breathing was the dependent variable, revealed hypertension status, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and gender (female) to be independent determinants of DAN. These results suggest that traditional cardiovascular risk factors are important correlates of DAN and may relate to both its cause and poor prognosis. Since these results are from a cross-sectional study, prospective follow-up of this cohort will be needed for confirmation.

Adult↗
PubMed1989

Computer aided manual leucocyte differential counting.

Over the last two decades numerous ways have been devised for automating the recording of the results of the leucocyte differential, ranging from computer-readable cards to very costly automated cell counters. The growing availability of inexpensive personal computers makes it possible to improve the counting and reporting of the manual differentials which still account for the bulk of these counts. This report describes the development of a system using a personal computer, either as a standalone device or integrated into a larger laboratory system, to assist the technologist in performing the differential count and in completely describing the results. It permits complete flexibility in function assignments and in information structuring to match the constraints of the laboratory host computer system.

Clinical Laboratory Information Systems↗
PubMed1989

Acute airway obstruction in achalasia. Possible role of defective belch reflex.

Achalasia presenting as an acute airway obstruction is a rarely reported phenomenon. The pathophysiology of this dramatic complication of achalasia remains an enigma. Our patient with achalasia presented with an acute airway compromise necessitating emergent endotracheal intubation. We review the available literature on this interesting yet rare complication of achalasia. We also add some information to help elucidate the possible pathophysiologic mechanism of this emergency, proposing that specific upper esophageal sphincter manometry may indicate abnormality of the "belch reflex."

Airway Obstruction↗