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Biomedical subjects

D J Becker

Publications and source records attributed to D J Becker.

At least 145 records · Page 8Linked to original sources

Prolactin responses to thyrotropin-releasing hromone in protein-calorie malnutrition.

Basal plasma prolactin (hPRL) concentration is low, but the response to thyrotropin-releasing hormone (TRH) is within the normal range, in children with protein-carlorie malnutrition (PCM) before treatment. Treatment results in increased basal hPRL concentration and an increased response to TRH. The above findings contrast with normal or high basal TSH and the normal or exaggerated response to TRH provocation in untreated PCM. The reason for this divergence is obscure.

Child, Preschool↗

Can management strategies alter the course of diabetic nephropathy?

End Stage Renal Disease (ESRD) is a common consequence of diabetic nephropathy (DN). DN is the major cause of death in patients with IDDM, accounting for greater than 40% of deaths with this form of diabetes. There is no clearly documented therapeutic technique that will prevent or reverse progressive renal damage in IDDM. While pancreatic transplantation and "cure" of diabetes in experimental animals may be associated with some histological reversal of renal pathology, this has not been documented in humans. Most studies agree that once diabetic renal disease is present (as documented by proteinuria), progression is inevitable, albeit the rate of progression may be altered by different therapeutic methods. There is considerable hope that "tight metabolic control" will prevent the initial damage that leads to DN and ESRD, but evidence remains inconclusive. There is some evidence that careful monitoring for microalbuminuria will allow for very early detection of damage and alterations in therapy. Our studies have documented a decrease in both morbidity and mortality in IDDM in patients who have been competitive athletes, suggesting that promotion of physical fitness may be a valuable means of delaying progression of renal disease while control of BP delays progression. Early detection and aggressive therapy is recommended. Some studies utilizing diets low in sodium and/or protein appear beneficial but more studies are needed before pediatric application.

Adult↗

Psychosocial correlates of glycemic control: the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study.

The psychosocial correlates of glycemic control were examined in an incident cohort of childhood onset insulin-dependent diabetic subjects aged 18 years or older (n = 592). Glycosylated hemoglobin was measured at subjects' clinical examination, and questionnaires on diabetes self-care activity, barriers to regimen adherence and social support were completed. Demographic information was also collected. Glycosylated hemoglobin (GHb) was correlated with age, income and educational attainment (correlations coefficients between -0.1 and -0.2; P < 0.01), suggesting that older, more educated and wealthier patients have better glycemic control. GHb was also inversely associated with the degree of self-care activity (r = -0.11; P < 0.01), in particular administering injections at the recommended times and the frequency of performing blood/urine tests. Factors related to self-care behavior were identified, and included degree of social support (r = 0.14; P < 0.001) and patients' reports of difficulties adhering to their self-care regimen (r = -0.3; P < 0.0001). Gender was also related to self-care activities, with women reporting more self-care behavior than men (mean self-care scores 17.9 +/- 3.7 vs. 16.9 +/- 4.0; P < 0.01). Thus psychosocial factors (e.g. low income and education) may have an important effect on glycemic control in adults, and also (e.g. social support and adherence difficulties) seem particularly important in influencing the performance of self-care. As good metabolic control may help avoid the progression of diabetic complications, efforts need to be directed towards patients with these characteristics who are more likely to experience difficulties with self-care.

Adolescent↗

Measuring subclinical neuropathy: does it relate to clinical neuropathy? Pittsburgh epidemiology of diabetes complications study-V.

We report results from 120 (25- to 34-year-old) participants in a neuropathy substudy of subjects with insulin-dependent diabetes mellitus (IDDM) taking part in a cohort follow-up study. Diabetic neuropathy was evaluated by quantitative sensory testing, nerve conduction studies, and clinical examination. Mean quantitative sensory thresholds differed significantly by clinical category of abnormal sensation and ankle reflex activity. Mean sural and peroneal amplitudes and conduction velocities were also significantly lower for subjects classified as having abnormal ankle reflex activity. Modeling potential correlates in logistic analyses showed glycemic control, triglyceride levels, and hypertension status to be independently associated with clinically overt neuropathy. Similar lipid and hemodynamic parameters were associated with abnormality by any single assessment method used to define neuropathy. Although follow-up is needed to resolve the best assessment methods for determining neuropathy, these results suggest that good glycemic control as well as control of blood pressure and lipids is advisible.

Adult↗

Spontaneous whole blood platelet aggregation, hematological variables and complications in insulin-dependent diabetes mellitus: the Pittsburgh Epidemiology of Diabetes Complications Study.

The role of platelet aggregation in the pathogenesis of diabetes complications remains unclear despite a number of reports suggesting associations in univariate analyses. The Pittsburgh Epidemiology of Diabetes Complications Study is a prospective study initiated in 1985 to determine risk factors for the development of complications in insulin-dependent diabetes mellitus (IDDM). This report focuses on the cross-sectional correlation between platelet count and aggregation and IDDM complications, in 563 participants aged 18 years and older seen at baseline. Spontaneous whole blood platelet aggregation (SWBPA) and other hematological variables [hematocrit, total platelet count (TPC), red blood cell count (RBC), fibrinogen and white blood cell count (WBC)] were evaluated as risk factors for IDDM complications (nephropathy, neuropathy, and retinopathy) in the baseline cross-sectional data of the Pittsburgh Epidemiology of Diabetes Complications Study. SWBPA was determined by a method based on the percentage fall in platelet count after shaking a fresh citrated blood sample kept at 37 degrees C. Subjects with chronic aspirin use or on dialysis were excluded from analysis. An increased TPC was observed in subjects with overt nephropathy (291.4 +/- 65.1 versus 261.2 +/- 64.9, p less than 0.001) compared with subjects without nephropathy. Similar results were found for proliferative retinopathy. The association with nephropathy (but not with retinopathy) persisted in multivariate analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The progression of retinopathy over 2 years: the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study.

This study examined potential risk factors for the incidence and progression of retinopathy in a large representative cohort of childhood onset insulin-dependent diabetic patients. Participants in the Epidemiology of Diabetes Complications (EDC) Study underwent a full clinical examination at baseline and again at a 2-year follow-up. Retinopathy status was ascertained using stereo fundus photographs graded according to the modified Airlie House System. The study population is based on a large cohort of childhood-onset insulin-dependent diabetic patients, seen within 1 year of diagnosis at the Children's Hospital of Pittsburgh between January 1950 and May 1980. A total of 657 subjects participated at baseline (1986-1988), with 80% of eligible survivors taking part in the follow-up examination. This report concerns risk factors associated with the progression of diabetic retinopathy over a 2-year period, and the interaction of these factors with the presence of nephropathy. Analyses showed that baseline diastolic blood pressure was significantly associated with the incidence of any retinopathy, while glycosylated hemoglobin, baseline severity of retinopathy, serum triglycerides, and, to a lesser extent, higher levels of low-density lipoprotein (LDL) cholesterol and fibrinogen were associated with the progression of retinopathy. Progression to proliferative retinopathy was related to higher LDL cholesterol, fibrinogen, serum triglycerides, albumin excretion rate, and glycosylated hemoglobin (GHb). Risk factors varied with the presence of nephropathy. In the absence of nephropathy, GHb was a significant predictor of progression, whilst this was not the case in the presence of nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cardiovascular disease and arterial calcification in insulin-dependent diabetes mellitus: interrelations and risk factor profiles. Pittsburgh Epidemiology of Diabetes Complications Study-V.

Cardiovascular disease is a frequent complication of insulin-dependent diabetes mellitus (IDDM), but the prevalence, interrelations, and risk factors of its principal components (coronary, cerebrovascular, and lower-extremity arterial disease) and of medial arterial wall calcification are not well understood. To address these issues, data from the Epidemiology of Diabetes Complications Study (n = 657) baseline examination were examined. The term coronary heart disease (CHD) was applied to those with myocardial infarction or angina, whereas lower-extremity arterial disease (LEAD) was applied to those who had undergone amputation of a lower limb or who had an ankle to arm blood pressure ratio less than 0.8 at rest or after exercise. Calcification of the lower-extremity arteries was considered to be present if ankle pressure was more than 100 mm Hg higher than brachial pressure. Although the prevalence of CHD was low, LEAD was significantly more common in women than in men (p less than 0.01), whereas calcification was more frequent in men than in women (p less than 0.01). Ten percent of those with LEAD also had CHD, and 8% with LEAD had calcification. Modeling of potential risk factors (e.g., diabetes duration and glycosylated hemoglobin) revealed that duration, female gender, fibrinogen, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and high density lipoprotein cholesterol to apolipoprotein A-I ratio were independent predictors of LEAD, whereas for CHD only, diabetes duration and hypertension contributed to CHD. Calcification revealed a mixed pattern, with duration, hypertension, and triglyceride to apolipoprotein A-I ratio being the statistically significant associated factors. The results suggest that although LEAD, CHD, and calcification often coexist, their risk factor profiles differ.

Adult↗

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

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

Adolescent↗

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

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

Adolescent↗

Residual beta-cell function in children with IDDM: reproducibility of testing and factors influencing insulin secretory reserve.

Reproducibility of C-peptide secretion was assessed in 20 children (group 1) by their responses to two Sustacal- (a mixed liquid meal) stimulation tests performed 7-14 days apart. For the 12 C-peptide-positive children (basal C-peptide greater than or equal to 0.03 pmol/ml) there were no differences in the basal or stimulated values between tests 1 and 2. The effect of exogenous insulin on C-peptide secretion was assessed in 20 other children (group 2) by their responses to two Sustacal tests, one test without and one with soluble insulin (0.25 U/kg) injected subcutaneously before testing. Eleven children were C-peptide positive and had no differences in C-peptide response between tests 1 and 2. The results from test 1 in groups 1 and 2 were combined with those from 44 others undergoing a single Sustacal test (group 3, N = 84). There was a close correlation between basal and peak C-peptide concentrations in the 44 C-peptide-positive children (r = .88, P less than .001). Peak C-peptide concentrations correlated inversely with HbA1 (r = -.29, P less than .01), insulin dose in units per kilogram (r = -.40, P less than .001), and duration of diabetes (r = .33, P less than .001) and positively with age at onset of diabetes (r = .34, P less than .001). The C-peptide-positive children had reduced glucose response to Sustacal, lower HbA1 concentration, lower insulin requirement, later age of onset, and shorter duration of diabetes than children who were C-peptide negative.

Adolescent↗

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 Children's 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.

Adolescent↗

Diabetes complications and glycemic control. The Pittsburgh Prospective Insulin-Dependent Diabetes Cohort Study Status Report after 5 yr of IDDM.

The relationship between glycemic control and complications of insulin-dependent diabetes mellitus (IDDM) remains controversial. With the use of glycosylated hemoglobin (HbA1) to assess glycemic control from diagnosis onward, the Pittsburgh Prospective Insulin-Dependent Diabetes Mellitus Cohort Study prospectively evaluated 80 new cases of IDDM diagnosed at Children's Hospital of Pittsburgh. This study presents findings in 62 patients at 5 yr postdiagnosis. Only 7 patients, all girls, had any retinopathy (microaneurysms). These subjects had an elevated 5-yr mean HbA1 compared to those with no retinopathy (13.0 vs. 11.7%; P less than .05). Six female subjects who had an elevated albumin excretion rate (AER; greater than or equal to 20 micrograms/min) had a higher 5-yr mean HbA1 (13.3%) than the 26 subjects with AER less than 20 micrograms/min (11.8%; P less than .05). Current HbA1 was correlated with AER (r = +.36, P less than .05) and systolic blood pressure (r = +.49, P less than .01) in females. However, these associations were not observed in males. Positive correlations were found between HbA1 (5-yr mean and current) and serum triglyceride and cholesterol, but only in females was HbA1 inversely related to high-density lipoprotein cholesterol. However, HbA1 was independent of sex, HLA-DR type, and urine C-peptide status. Age adjustment did not change the above results. These analyses suggest that glycemic control is related to AER, systolic blood pressure, presence of microaneurysms, and serum triglyceride and cholesterol concentrations during the first 5 yr of IDDM. However, these associations appear to be predominant in girls.

Adolescent↗