PubMed Health⌕ Search

Biomedical subjects

D J Becker

Publications and source records attributed to D J Becker.

At least 127 records · Page 7Linked to original sources

Plasma insulin and lipoprotein concentrations: an atherogenic association?

Plasma insulin concentrations have been shown to be predictive of future cardiovascular disease in men. Though many clinical studies have documented correlations between plasma insulin and triglyceride concentrations, few epidemiologic studies have reported insulin-lipid correlations. In this report, the authors present correlations obtained from 323 non-diabetic first degree relatives of insulin dependent diabetic patients who underwent 4 hour oral glucose tolerance tests at Children's Hospital, Pittsburgh, Pennsylvania, in February 1980-December 1981 as part of an epidemiologic study of insulin dependent diabetes mellitus. Significant positive correlations were seen between insulin (measured as fasting insulin and the 3 hour area under the insulin curve during the oral glucose tolerance test) and the atherogenic lipids, total and low density lipoprotein cholesterol and triglycerides ranging from r = +0.14 (p less than 0.01) to r = + 0.35 (p less than 0.001). An inverse correlation with high density lipoprotein cholesterol was also noted r = -0.27 (p less than 0.001). A computed score of insulin activity, which the authors call the insulin-glucose sensitivity index, shows equally strong correlations but of reverse sign. In multivariate analyses, these insulin measures and age largely account for the associations of sex and obesity (measured as body mass index) with the atherogenic lipids, though this was only partly true for high density lipoprotein cholesterol. The biologic plausibility of these findings and their relevance to the development of atherosclerosis are discussed.

Adolescent↗

Diabetic nephropathy in adolescence: appearance during improved glycemic control.

Two girls, aged 15 and 14 years, with poorly controlled insulin-dependent diabetes (IDD) of 9 and 7 years duration, respectively, developed overt and persistent proteinuria shortly after rapid increases in insulin therapy and improved glycemic control. Renal biopsies showed diffuse diabetic glomerulosclerosis. Both patients maintained normal or increased creatinine clearances. Direct ophthalmoscopy and fluorescein retinal angiography demonstrated nonproliferative diabetic retinopathy in the first patient, which deteriorated after 6 weeks of strict metabolic control; the second patient had normal retinas. The appearance of clinical proteinuria during this brief period of good glycemic control suggests that the latter may have unmasked a preexisting condition. Possible pathophysiologic mechanisms initiating the proteinuria in these patients are reviewed.

Adolescent↗

Age and sex variations in glucose tolerance and insulin responses: parallels with cardiovascular risk.

The venous plasma glucose and insulin concentrations recorded during oral glucose tolerance testing of over 300 1st degree relatives (parents and siblings) of insulin dependent diabetics are presented. Men had higher glucose concentrations than women, the difference increasing with age, while insulin responses appeared greater in adolescent girls and young women than their male counterparts. The possible relationship between the different insulin responses in the two sexes and the sex difference in cardiovascular risk factors is discussed. It is suggested that the absence of a marked sex differential in heart disease mortality amongst diabetics may partly result from the loss by diabetic women of their greater insulin production relative to men in young adult life.

Adolescent↗

Diurnal glucose--dependent fluctuations in glycosylated hemoglobin levels in insulin-dependent diabetes.

In order to evaluate the relationship between short-term glycemic control and the stable and labile fractions of GHb, we performed hourly blood glucose samplings for 24 hr on 31 occasions in 13 children with IDDM of varying duration. GHb was measured both in hemolysates of whole blood and after 48 hr incubation at 4 degrees C in normal saline to remove the labile fraction of GHb. SI-GHb was always lower than WB-GHb (p less than 0.0001). MGB correlates closely with WB-GHb (r = 0.58, p less than 0.001) and less closely with SI-GHb (r = 0.45, p less than 0.05). The daily fluctuations in SI-GHb were always significantly less than in WB-GHb (p less than 0.005). The labile fraction correlated closely with MAGE (r = 0.62, p less than 0.0001). In one subject WB-GHb decreased by 4.4% and SI-GHb by 3.1% over a 7 wk period of good glycemic control. These results (1) confirm the presence of the stable and liable forms of GHb; (2) a closer correlation of short-term control with WB-then SI-GHb; and (3) highlight the possible relationship of the labile fraction of GHb to diabetic instability as assessed by MAGE.

Adolescent↗

Factors affecting glycosylated hemoglobin values in children with insulin-dependent diabetes.

In 477 children with IDD treated by conventional methods, GHb (microcolumn chromatography) and a simultaneous random blood glucose concentration were measured over an 18-month period as indicators of metabolic control (once in 61 children, twice in 99, three or more times in 317). The data were analyzed to assess the effects of patient's age, sex, disease duration, and, in a random subgroup of 273, the number of daily insulin injections and insulin dose (U/kg). The mean +/- SEM percent GHb over this period was 11.8 +/- 0.2% and blood glucose concentration 237 +/- 9 mg/dl. Only seven children (1.4%) had a normal GHb value. There was a highly significant correlation between GHb and both age and blood glucose concentration but not with disease duration greater than one year. The correlation with age was present only in the girls. In 416 children evaluated more than once, with a mean duration between initial and most recent evaluations of 11.3 months, GHb remained within +/- 1% of the initial value in 40.5%, decreased in 32.3%, and increased in 24.2%. These data indicate a closer relationship between metabolic control in children with IDD and age of the child, particularly in females, than with disease duration. In our clinic, using conventional therapeutic methods, the ability to improve control over the short term as measured by changes in percent GHb has been quite limited. This study helps to target those IDD children, especially adolescent girls, requiring a more aggressive therapeutic approach.

Adolescent↗

Electroencephalographic changes in diabetic ketosis in children with newly and previously diagnosed insulin-dependent diabetes mellitus.

Abnormal electroencephalograms in patients with long-standing diabetes mellitus have been attributed to hypoglycemia. EEG changes in newly diagnosed patients or in patients during episodes of diabetic ketoacidosis have not previously been reported. We performed serial EEGs at one, 12, 24 hours and five days after initiation of treatment for DKA on 39 patients aged 11 months to 16 years with newly or previously diagnosed insulin-dependent diabetes mellitus. Twenty-seven patients were in ketoacidosis and 12 patients ketotic only. Abnormal EEGs were found in 30 patients on admission. The EEG changes at one hour, classified in order of increasing severity, correlated with the serum glucose, osmolality, bicarbonate, beta-hydroxybutyrate, and acetoacetate values, but not with pH or glycosylated hemoglobin. The rate of improvement of the EEGs was unaffected by the addition of phosphate to the intravenous fluids during therapy. EEG changes persisted in five of the seven children who had follow-up studies at two to five months, and in two of the six children one year after admission. We conclude that EEG changes are common in children with DKA or ketosis, the severity of the abnormalities being most closely associated with the degree of hyperosmolality rather than acidosis. These changes may persist in some cases, possibly accounting for the increased frequency of EEG abnormalities in diabetic children.

Adolescent↗

The effects of water deprivation and water loading during treatment with 1-deamino-8-D-arginine vasopressin in central diabetes insipidus in childhood.

Nine children aged 7 2/12 to 17 9/12 years with central diabetes insipidus were subjected to water deprivation and water loading during treatment with 1-deamino-8-D-arginine vasopressin (DDVAP). Urine output remained unchanged despite the large differences in water intake. Serum osmolarity was not significantly affected by water deprivation. However, there was a marked decrease in serum osmolarity during water loading. This not accompanied by any symptoms of haemodilution. Thus patients apparently tolerate large variations in fluid intake during therapy with DDVAP.

Adolescent↗

Glucose polymer tolerance in premature infants.

Some formulas designed for premature infants contain glucose polymer (GP) as part of their carbohydrate content. GP tolerance tests and lactose tolerance tests were performed on 11 healthy premature infants at 2 to 3 weeks of age to compare their ability to digest and absorb GP and lactose. Total plasma reducing substances (TPRS), plasma insulin (PI), and plasma glucose were measured 10 minutes before and 30, 60, and 120 minutes after the oral carbohydrate test meal. Lactose and GP stimulated a significant increase in TPRS at 30 and 60 minutes and produced similar glycemic responses. However, GP stimulated PI response whether measured as the area under the PI response curve or as the PI/TPRS ratio. It was concluded that although GP and lactose evoke similar glycemic responses, they differ in their abilities to stimulate insulin secretion. The mechanism controlling this differential insulin response is unknown.

Administration, Oral↗

Diabetic retinopathy in Mauriac's syndrome. Paradoxical deterioration with improved metabolic control.

We report four children with marked short stature, hepatomegaly, and delayed adolescence. Initial funduscopy demonstrated only occasional microaneurysms in two children and a single intraretinal hemorrhage in another. Improved control required large increases in insulin dosage. Growth rate improved significantly and hepatomegaly regressed. Puberty progressed rapidly in two older patients with poor final height. Paradoxically, with improved control, retinopathy progressed rapidly. One child with proliferative retinopathy in both eyes developed vitreous hemorrhage and blindness in one eye. Two required pan retinal photocoagulation with no further progression of their retinopathy. These rapidly progressive retinal changes remain unexplained. We advise caution when correcting metabolic derangements of diabetic patients who have been poorly controlled for a prolonged period.

Adolescent↗

Glycosylated haemoglobin in children with insulin-dependent diabetes mellitus.

Glycosylated haemoglobin (HbA1) was measured serially by microcolumn chromatography in 38 children with newly diagnosed insulin-dependent diabetes. Initial HbA1 levels of 13.6 +/- 0.5% fell signficiantly from day 0 (prior to therapy) both to day 1 (1.6 +/- 0.2% decrease) and to day 3-5 (2.6 +/- 0.4% decrease) (P < 0.001). This drop correlated closely with changes in blood glucose (P < 0.001), less closely and inversely with plasma bicarbonate levels (P < 0.01), but not with prior duration of symptoms or changes in serum cholesterol and triglyceride concentrations. HbA1 levels reached a nadir of 8.2 +/- 0.3% 3 weeks to 6 months after diagnosis, and correlated with decreasing insulin dosage (P < 0.001). HbA1 levels rose again to 11.4 +/- 0.5% in 21 patients followed for more than 3-6 months. Our results indicate that (1) HbA1 level change rapidly during initial stabilization of insulin-dependent diabetes suggesting that glycosylation may not be entirely irreversible, and (2) HbA1 levels are consistent with clinical assessment of control during remission and postremission phases.

Adolescent↗

1-deamino-8-D-arginine vasopressin in the treatment of central diabetes insipidus in childhood.

The effectiveness of therapy with carbamazepine and clofibrate (oral therapy), intramuscular pitressin-in-oil, and intranasal 1-deamino-8-D-arginine vasopressin has been compared in 15 children with partial or complete central diabetes insipidus. Mean daily urine volume without therapy was 5.4 l and dropped to 1.1 and 1.6 l/day while receiving pitressin and DDAVP, respectively. Oral agents decreased the daily urine volume to 2.2 l in patients with partial DI, with good symptomatic control except for some nocturia. These agents had no effect in patients with complete DI and did not alter pitressin requirements. Duration of pitressin action was 24 to 36 hours with a significant incidence of hyponatremia. The duration of DDAVP effect was 8 to 20 hours, varying in individual patients. Children with partial DI required smaller doses of DDAVP and the duration of action was longer than in those with complete DI. Control of serum electrolytes was excellent using two doses per day and nocturia was eliminated. All patients who had received pitressin had growth hormone antibodies, but continued to grow normally unless there was pre-existing growth hormone deficiency. These antibodies gradually disappeared after approximately one year of therapy with oral agents or DDAVP. DDAVP did not alter growth hormone, cortisol, or prolactin levels during sleep. DDAVP is the antidiuretic therapy of choice in children with either complete or partial DI; to date, no side effects have been demonstrated.

Adolescent↗

The effect of cyproheptadine and human growth hormone on adrenocortical function in children with hypopituitarism.

The cortisol response to insulin hypoglycemia was determined in ten hypopituitary children treated for four months with both growth hormone and cyproheptadine, and in six other children with hypopituitarism treated for four months with hGH alone. All patients had previously normal responses to orally administered metyrapone. There was no demonstrable difference in the F responses to insulin hypoglycemia before and four months following its discontinuation in the patients receiving hGH alone. In the ten patients on combined therapy the F response to insulin hypoglycemia was normal in five and subnormal in five patients. These ten patients were retested at least two months after cessation of CPH therapy. The F response reverted to normal in four of the five patients in whom it had been subnormal. There was no significant change in the five patients with initial normal response. No patients had signs or symptoms of glucocorticoid insufficiency. In some cases, long-term administration of CPH to children with hypopituitarism is associated with decreased F response to insulin hypoglycemia; this may represent decreased adrenocortical reserve in these patients. The previously reported enhancement of growth of hypopituitary children treated with hGH and CPH may in part be a result of decreased F production.

Adrenal Cortex↗

Early insulin release and its response to potassium supplementation in protein-calorie malnutrition.

Early insulin release after oral glucose is absent in protein-calorie malnutrition (PCM). There is an increase of the insulin-glucose ratio at 10 and 15 min induced by potassium supplementation compared to a similar group receiving an identical diet without supplementary potassium. This suggests that impaired insulin secretion in PMC is in part due to a potassium mediated disturbance of insulin release.

Blood Glucose↗

The effect of alanine infusions on growth hormone, insulin, and glucose in protein-calorie malnutrition.

In view of the previously reported inverse correlation between the elevated serum growth hormone (HGH) and low alanine in children with protein-calorie malnutrition (PCM), 30-min alanine infusions were performed in five children with PCM and 12-hr infusions in four children before and after therapy. These infusions did not lower basal HGH or improve its glucose suppressibility in untreated PCM, excluding a feedback relationship between HGH and alanine. There was no insulinotropic effect during 30-min infusions, but an improved insulin response to glucose after the 12-hr alanine infusion was found in three of four children before therapy. Plasma glucose rose slightly during alanine infusion in three of five children before treatment, but the magnitude of change was small and the relevance unclear.

Alanine↗

Potassium supplementation, serum immunoreactive insulin concentrations and glucose tolerance in protein-energy malnutrition.

The serum immunoreactive insulin (IRI) concentrations, and glucose dissappearance rate-constants after intravenous glucose administration were measured on admission and during recovery in children suffering from protein-energy malnutrition (PEM). 2. A high potassium intake resulted in a considerable increase in the serum IRI levels early in the treatment period. There was a definite relationship between potassium depletion and many measurements of insulin secretion. 3. The results are consistent with the hypothesis that impaired insulin release in children suffering from PEM is partly the result of potassium depletion.

Blood Glucose↗