PubMed Health⌕ Search

Biomedical subjects

D J Becker

Publications and source records attributed to D J Becker.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparison of the effects of various vanadium salts on glucose homeostasis in streptozotocin-diabetic rats.

Oral administration of vanadium salts to severely diabetic rats lead to a spectacular decrease of plasma glucose levels in spite of the insulin deficiency of the animals. The insulin-like properties of vanadium have been attributed to the cationic form, vanadyl, into which the anionic form, vanadate, is reduced within cells. This has led to the suggestion that vanadyl is the form of choice for the treatment. In this study, rats made insulin-deficient and diabetic with streptozotocin were treated with three salts of vanadium: sodium orthovanadate, sodium metavanadate and vanadylsulfate. The salts were added to the drinking water, in concentrations that led to ingestion of the same amount of vanadium element by the three groups of rats (approximately 8 mg/kg per day). The initial, transient, loss of weight that affected the treated rats was slightly smaller in the vanadyl-treated group than in the vanadate-treated groups. However, during steady-state treatment, the three groups exhibited a similar food intake (lower than in controls) and growth rate (higher than in controls). The decreases in plasma glucose levels, in urinary volume and in glucosuria, and the improvement of the tolerance to an oral glucose load were similar regardless of the type of vanadium salt. Withdrawal of the treatment after 14 weeks was followed by a rapid increase in plasma glucose levels which, however, remained clearly lower than in controls for at least 4 weeks, whereas plasma insulin levels increased only transiently. A smaller glucosuria and a slightly better tolerance to oral glucose than in controls were still observed in the previously treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

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.

Adolescent↗
PubMed1994

Insulin as a predictor of coronary heart disease: interaction with apolipoprotein E phenotype. A report from the Multiple Risk Factor Intervention Trial.

The objective of this study was to examine whether fasting serum insulin is a predictor of coronary heart disease in high-risk US men, and whether any such predictive role explains the enhanced cardiovascular risk seen in subjects with the apolipoprotein (Apo) E 3/2 phenotype. This was a nested case-control study of participants in the Multiple Risk Factor Intervention Trial. Ninety-four subjects who died from coronary heart disease (post-trial follow-up) and 114 case patients with myocardial infarction (during trial) were compared to control subjects (n = 414) matched (1:2) by age, center, randomization date, and intervention group. Overall, fasting serum insulin at baseline was not associated with case-control status. (Means for cases versus controls: 16.8 and 16.6 microU/mL), although serum insulin showed significant correlations with low-density-lipoprotein cholesterol, triglycerides, and uric acid. When stratified by the three Apo E phenotypes, 3/2, 3/3, 3/4, a significant association of fasting insulin with case-control status was seen for Apo E 3/2 individuals (19.9 versus 14.5 microU/mL; P = 0.02) but not for those with the other two phenotypes. Though fasting insulin is not a risk factor overall in this high-risk male population, it appears to contribute to cardiovascular risk in those with the Apo E 3/2 phenotype but does not explain the increased risk seen in these subjects. This new finding, if confirmed, may throw further light on the role of insulin in atherosclerosis.

Adult↗
PubMed1994

Improvement of mild hypoinsulinaemic diabetes in the rat by low non-toxic doses of vanadate.

To exert their anti-diabetic effects in animals with overt alterations of glucose homeostasis, vanadium salts must be administered in high doses, which also cause decreases in food intake and body weight gain. In this study, we evaluated the effect of low doses of vanadate in rats made mildly diabetic (fed plasma glucose levels approximately 11 mmol/l) and moderately hypoinsulinaemic by the injection of streptozotocin 4 days after birth. Vanadate was added to food and drinking water, at concentrations that led to the consumption of about 1 mg vanadium element per day (approximately 2.65 mg vanadium/kg per day in adult rats), i.e. three to fivefold less than in previous studies. The treatment was started at weaning and lasted 22 weeks (V rats), or was administered for 9 weeks only from the age of 3 months (C-V rats). Food intake and body weight gain were not affected in V rats and decreased by no more than 10% in C-V rats. In V rats, fasted and fed plasma glucose levels were decreased by about 0.5 and 2-3 mmol/l, respectively. The rises in glycaemia after three oral glucose tolerance tests were also clearly attenuated. These effects were not accompanied by any changes in plasma insulin levels. Pancreatic insulin reserves (decreased by two-thirds as compared with normal rats) were not affected by the treatment. A decrease in plasma glucose levels was also noted in C-V rats, and this improvement disappeared upon cessation of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

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.

Adolescent↗
PubMed1993

Sodium-lithium countertransport activity is decreased after weight loss in healthy obese men.

Maximal red blood cell (RBC) sodium-lithium countertransport activity has been consistently related to essential hypertension and may be a marker for risk of developing hypertension. Although there is strong evidence for genetic control of sodium-lithium countertransport, increasing evidence suggests that obesity and insulin-glucose metabolism are related to countertransport activity. This study was performed to determine whether countertransport activity decreases with weight loss in healthy obese adults. Forty-five healthy, white, obese adults were studied at baseline and after 6 months of behavioral dietary intervention. Weight loss was 11.5 kg (25.4 lb) in 24 men and 8.1 kg (17.8 lb) in 21 women. Sodium-lithium countertransport activity decreased 55.0 mumol Li/L RBC/h in men (P < .001, paired t test) and 14.6 mumol Li/L RBC/h in women (NS). Change in countertransport activity was correlated with change in body mass index (BMI) in men (r = .52, P < .01) and women (r = .27, NS) and was also strongly correlated with change in fasting glucose levels in both men and women (r = .50 and r = .56, respectively; P < .01) and with change in fasting insulin levels in men (r = .42, P = .04). Change in countertransport activity was not significantly related to change in physical exercise or serum lipid levels. There was a large decrease in systolic blood pressure in men (10.0 mm Hg, P < .001) and a smaller decrease in women (4.1 mm Hg, P < .05). These changes were significantly correlated with change in weight, but not with change in countertransport or baseline countertransport activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

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.

Adult↗
PubMed1993

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.

Adult↗
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

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↗
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

Migrating a clinical laboratory information system between technologies.

The technical revolution that has strongly driven events in the clinical laboratory for the last thirty years is now threatening to make obsolete what has become the central pillar of operation in many laboratories, the minicomputer-based laboratory information system. Some of its functions could easily be absorbed by the personal computers which are proliferating in the laboratory, but any single step leap between systems risks replacing order with chaos. Appropriate use of networking tools, together with essential software development, can provide a systematic migrational path for both the administrative and technical computer support from one environment to another without the trauma of a massive replacement step.

Clinical Laboratory Information Systems↗