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Biomedical subjects

M B Davidson

Publications and source records attributed to M B Davidson.

At least 73 records · Page 4Linked to original sources
PubMed1991

Insulin plus a sulfonylurea agent for treating type 2 diabetes.

PURPOSE: To review the recent literature on the efficacy of combined insulin and sulfonylurea therapy in patients with type 2 diabetes. DATA SOURCES: Pertinent articles were obtained through an English-language MEDLINE search from 1979 to 1990 and from the references of these articles. STUDY SELECTION: We reviewed the studies in which patients with poorly controlled diabetes received insulin and a sulfonylurea agent and in which insulin treatment alone (usually given in conjunction with a placebo) was compared with insulin plus sulfonylurea therapy. DATA EXTRACTION: Pre- and post-treatment insulin doses, blood glucose levels, glycated hemoglobin values, C-peptide levels, and insulin levels were analyzed. Other data were analyzed separately. RESULTS OF DATA SYNTHESIS: Data from similar trials were compared. Data from concurrent trials were analyzed separately from data derived from cross-over trials. Weighted mean fasting blood glucose levels, glycated hemoglobin levels, insulin dosage, and fasting C-peptide concentrations were determined for insulin plus placebo and insulin plus sulfonylurea agent groups for both types of studies. In concurrent trials, the weighted mean post-treatment glycated hemoglobin level was 11.1% after insulin plus placebo compared with 10.0% after insulin plus a sulfonylurea agent. In cross-over trials, the corresponding values were 10.6% and 9.8%. CONCLUSIONS: Combination therapy with insulin and a sulfonylurea agent only slightly improved glycemic control in patients with type 2 diabetes. When a sulfonylurea agent was used, less exogenous insulin was needed, but fasting serum insulin levels were not different between the treatment groups. Such therapy did not produce nearly normal blood glucose concentrations and therefore should not be used in patients with poorly controlled type 2 diabetes receiving insulin.

Clinical Trials as Topic↗
PubMed1991

Glyburide-stimulated glucose transport in cultured muscle cells via protein kinase C-mediated pathway requiring new protein synthesis.

To study the mechanism of action of sulfonylurea agents on peripheral tissues without the potentially confounding influences of insulin, the direct effect of glyburide (i.e., in the absence of insulin) was evaluated in the L6 cultured myogenic cell line. Glyburide approximately doubled the incorporation of [14C]-glucose into glycogen. The rate-determining enzymes of glycogen metabolism, glycogen synthase and glycogen phosphorylase, were unaffected by the drug. Glucose transport (2-deoxyglucose uptake) was also approximately doubled. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) also doubled glucose transport and showed the same lag period (4-6 h) as glyburide before an effect occurred. Blockade of protein kinase C activity by either 1-(5-isoquinolinesulfonyl)-2 methyl piperazine (H7) or chronic exposure to TPA completely abolished the stimulation by glyburide. Cycloheximide, a protein synthesis inhibitor, also completely eliminated the effect of glyburide. The presence of ATP-sensitive K+ channels was assessed by measuring 86Rb efflux in ATP-depleted L6 muscle cells and RINm5F cells (which served as a positive control). Such channels were present and responded appropriately to glyburide and diazoxide in pancreatic beta-cells but were not present in muscle cells. Glyburide stimulation of glucose transport was completely eliminated by both Quin 2, an intracellular chelator of Ca2+, and verapamil, a Ca2+ channel blocker. However, glyburide did not raise intracellular Ca2+ levels. We conclude that glyburide stimulates glucose transport in cultured L6 muscle cells by a protein kinase C-mediated pathway that requires new protein synthesis. Although intracellular Ca2+ metabolism may also be involved, the initial step in the mechanism of action is probably different between pancreatic beta-cells and muscle cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Antidiabetic action of vanadyl in rats independent of in vivo insulin-receptor kinase activity.

The effects of oral vanadyl sulfate administration for 9-12 days on carbohydrate and lipid metabolism in the basal state and on glucose dynamics during submaximal hyperinsulinemic clamps were investigated in nondiabetic and streptozocin-induced diabetic rats. Decreases in growth rate and water and food consumption were the only significant alterations noted in control animals receiving vanadyl. Administration of vanadyl to diabetic rats resulted in weight loss; a significant decrease in plasma glucose, triglyceride, and cholesterol levels; and decreases in food and water intake, without a concomitant change in plasma insulin concentrations. Vanadyl treatment did not modify either peripheral glucose utilization or hepatic glucose production in control rats during submaximal insulin clamps. In contrast, vanadyl therapy increased insulin-induced glucose utilization significantly and had a small but nonsignificant effect on insulin-mediated suppression of glucose production in diabetic rats. The tyrosine kinase activity of liver- and muscle-derived insulin receptors from diabetic rats that underwent clamp study, which reflected the in vivo phosphorylation state of insulin receptor, was not altered by vanadyl treatment. In conclusion, these results show that augmentation of peripheral glucose utilization is the major determinant of the antidiabetic action of vanadyl and support the notion that the action of vanadyl is independent of insulin-receptor kinase activity.

Animals↗
PubMed1990

Rearrangement of chromosome 15 in the region q11.2----q12 in an individual with obesity syndrome and her normal mother.

Rearrangement of the proximal long arm of chromosome 15 have been found in most patients with the Prader-Willi syndrome (PWS) and in some with Angelman syndrome. We present an individual with syndromic obesity and her normal mother, who both have an abnormal chromosome 15. The proposita is a 26-year-old women with marked obesity, acanthosis, nigricans, short fingers, and severe cone degeneration of the retina. She has high plasma insulin levels, hypothyroidism, and an empty sella on CT scan. High-resolution chromosome banding demonstrated an increase in band 15q12. Further analysis showed the same abnormal 15 in her normal mother but not in her normal sister. This case and recent reports in the literature indicate that duplication of chromosome 15q in the PWS region may be associated with a syndrome of obesity, acanthosis nigricans, empty sella, and rodcore dystrophy as well as with a normal phenotype. Whether normal individuals with such a duplication carry increased risk of having offspring with an obesity syndrome is yet to be determined.

Acanthosis Nigricans↗
PubMed1990

Insulin-like growth factor I receptors in adult rat liver: characterization and in vivo regulation.

Although the presence of significant amounts of insulin-like growth factor (IGF)-I receptors in fetal tissues is well documented, adult liver has been reported to contain little or no IGF-I binding activity. In the present investigation, substantial amounts of specific IGF-I receptors were detected in crude membrane fractions and in partially purified receptor preparations of female adult rat liver. Insulin was 100 times less potent than IGF-I in competing for 125I-IGF-I binding. IGF-I binding activity was much less than that of insulin binding in both the microsomal fraction and partially purified receptor preparations. Affinity cross-linking of 125I-IGF-I to purified receptors and microsomal fractions followed by electrophoretic analysis under nonreducing conditions revealed labeling of proteins with relative molecular weight (Mr) of 350,000 and 210,000-220,000, corresponding to the molecular mass of the intact tetramer and alpha-beta dimers, respectively. Under reducing conditions, the labeling of proteins with Mr of 130,000 and 260,000, corresponding to the alpha-subunit of IGF-I receptor and its dimer, respectively, was observed. Treatment of microsomes as well as partially purified receptors with 0.5-1 mM dithiothreitol resulted in decreased IGF-I binding, and this correlated with structural changes in the receptor as detected by affinity labeling and electrophoretic analysis. Hepatic IGF-I binding activity was significantly diminished in female rats exposed to chronic growth hormone excess, suggesting down-regulation of IGF-I receptors by the enhanced circulating levels of IGF-I in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients.

Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia.

Adult↗
PubMed1990

Use of sulfonylurea agents in older diabetic patients.

The elderly patient with type II diabetes should be treated in much the same fashion as a younger person with the same disease, although emphasis needs to be placed on minimizing side effects, drug interactions, and hypoglycemia. Chlorpropamide should not be used in these patients, unless there is no other choice. The remaining agents--tolbutamide, acetohexamide, tolazamide, glyburide, and glipizide--should be started at low doses and gradually increased until optimal diabetic control is reached. The initial treatment goal is a FPG level of less than 180 mg/dl and a final goal is a 1- to 2-hour PPG concentration between 140 and 180 mg/dl. The glycosylated hemoglobin value should be no greater than 1.5% above the upper limit of normal, and should be lower, if possible. It must be kept in mind, however, that the closer diabetic patients are to achieving euglycemia, the more likely is hypoglycemia. Treatment goals therefore may have to be relaxed in someone at increased risk of hypoglycemia (e.g., patients with irregular eating habits or renal insufficiency) or when hypoglycemia may pose a greater hazard (e.g., patients with coronary artery or cerebral vascular disease). Patients on sulfonylurea agents should have blood glucose values measured once a month and glycosylated hemoglobin levels determined once every 3 months to alert the clinician to the possible need to adjust therapy. In this way, potential hypoglycemia can be avoided if blood glucose levels are drifting too low and chronic hyperglycemia can be identified and treated within a short period of time. When a patient's status changes--e.g., he is placed on new medication, becomes depressed and anorexic, or develops another medical problem--care must be taken to re-evaluate his diabetes management. Drugs such as sulfonamide antibiotics can potentiate the action of the sulfonylureas and cause hypoglycemia, renal insufficiency may necessitate changing the type of sulfonylurea agent or decreasing the dose, and malnutrition may obviate any need for therapy with an oral hypoglycemic agent. If these guidelines are kept in mind, the older diabetic patient can be managed on a sulfonylurea agent in conjunction with the appropriate diet. Should these measures prove to be ineffective, then insulin therapy should be instituted. Controlling chronic hyperglycemia will help improve the quality of life for patients with diabetes and decrease the probability of developing some of the devastating complications associated with this disease.

Aged↗
PubMed1989

Lack of glucose elevation after simulated tube feeding with a low-carbohydrate, high-fat enteral formula in patients with type I diabetes.

PURPOSE: Commercially available enteral formulas frequently cause hyperglycemia. This often leads to difficult and complex diabetes management with glucosuria and urinary losses of calories, fluid, and electrolytes. In this study, we compared a new product, EN-8715 (8% soluble fiber, 18% Polycose, 7% fructose, 50% fat, 17% protein), with a standard feeding product, Ensure HN (53% simple carbohydrates, 30% fat, 17% protein), to determine whether the new product would lower the glucose response. PATIENTS AND METHODS: Ten subjects (four women and six men) with type I diabetes were evaluated in paired, simulated tube feeding studies. After an overnight fast, a Biostator (artificial endocrine pancreas) was attached to each subject, and a steady-state blood glucose level of 150 mg/dL (8.4 mM) was established. The Biostator was then programmed to deliver a small basal amount of insulin (0.1 mU/kg/minute [718 pmol/kg/minute]), and the patients were given 20 mL of the randomly assigned formula every 15 minutes for 240 minutes (320 mL). Counterregulatory hormone responses to bringing the initial glucose response to the two enteral feeding formulas were measured and compared. RESULTS: The glucose response (mg/dL/four hours +/- SEM) essentially did not rise after EN-8715 (-2 +/- 33 mg/dL/four hours [-0.11 +/- 1.83 mM/four hours]) compared with that for Ensure HN (190 +/- 32 mg/dL/four hours [10.64 +/- 1.79 mM/four hours]). Urinary glucose losses (g +/- SEM) were significantly (p = 0.01) less after the new product (1.4 +/- 0.6 g [7.8 +/- 3.3 mmol] versus 5.7 +/- 1.5 g [30.2 +/- 8.3 mmol]). There were no significant differences in counterregulatory hormone responses. Side effects were minimal and product acceptance was similar. CONCLUSION: A low-carbohydrate, fiber-containing enteral feeding formula can limit hyperglycemia in patients with type I diabetes.

Adult↗
PubMed1988

Fructosamine.

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Biomarkers↗
PubMed1988

The variability in the action of unmodified insulin is more dependent on changes in tissue insulin sensitivity than on insulin absorption.

Eight normal subjects were studied twice for 360 min after the subcutaneous injection of unmodified insulin (0.15 U kg-1) during euglycaemic clamps. Insulin absorption was assessed by both the area under the insulin-time curve above baseline (AUC) and time course of absorption (time to 25% and 50% of total AUC). Insulin action was measured as the amount of glucose infused. The maximal serum insulin concentration was 0.27 +/- 0.02 (+/- SE) nmol l-1 at 112 +/- 10 min. Fifty percent of total glucose infused occurred at 218 +/- 7 min. The maximal glucose infusion rate was 5.11 +/- 0.70 mg kg-1 min-1 and occurred at 256 +/- 12 min. Intrasubject coefficients of variation (CV) for total insulin AUC (11.2%), time to 25% of maximum AUC (12.1%) and time to 50% of maximum AUC (10.2%) were considerably lower than that for total insulin action (22.6%). Total insulin AUC did not correlate with total glucose utilization (r = 0.06, NS). We conclude that when glucose concentrations are maintained by euglycaemic clamps the peak of unmodified insulin action is later and the duration longer than traditionally recognized, insulin AUC does not predict insulin action, and the higher variability of insulin action compared with the indices of absorption suggests that day-to-day changes in tissue insulin sensitivity contribute more to the variability in insulin action than changes in absorption.

Blood Glucose↗
PubMed1988

Peripheral and hepatic insulin antagonism in hyperthyroidism.

Eight hyperthyroid and eight normal subjects underwent 2-h oral glucose tolerance tests (OGTT) and euglycemic clamp studies to assess the presence of peripheral and hepatic insulin antagonism in hyperthyroidism. Although the mean total glucose area during the OGTT was similar in the hyperthyroid patients and normal subjects [16.4 +/- 0.8 (+/- SE) vs. 15.8 +/- 0.7 mmol/L.h], the mean insulin area was significantly elevated in the hyperthyroid group (1413 +/- 136 vs. 1004 +/- 122 pmol/L.h; P less than 0.05). Basal hepatic glucose production was measured during the second hour of a primed [3-3H]glucose infusion. A two-insulin dose euglycemic clamp study with [3-3H]glucose and somatostatin (500 micrograms/h) was carried out during the next 6 h. The insulin infusion rate was 0.05 mU/kg.min during the third, fourth, and fifth hours and 0.60 mU/kg.min during the sixth, seventh, and eighth hours. Hepatic glucose production and glucose utilization were measured during the final 0.5 h of each clamp period. Serum C-peptide concentrations were measured in the initial sample and in the last sample of each clamp period. The mean equilibrium serum insulin concentrations were similar in both groups during the final 0.5 h of the low (90 +/- 8 vs. 79 +/- 6 pmol/L) and high (367 +/- 11 vs. 367 +/- 15 pmol/L) insulin infusion rates. Basal serum C-peptide levels were significantly increased in the hyperthyroid patients (596 +/- 17 vs. 487 +/- 43 pmol/L; P less than 0.05) but were suppressed equally in both groups at the end of both clamp periods. The MCRs of insulin were similar in the hyperthyroid and normal subjects during the low (6.7 +/- 1.1 vs. 5.6 +/- 0.5 mL/kg.min) and high (11.9 +/- 0.4 vs. 12.1 +/- 0.5 mL/kg.mm) insulin infusion rates. Glucose production was significantly increased in the hyperthyroid patients during the basal state (17.6 +/- 0.9 vs. 11.5 +/- 0.5 mumol/kg.min; P less than 0.001) and remained elevated during the final 0.5 h of the low (12.1 +/- 1.1 vs. 5.9 +/- 1.7; P less than 0.01) and high (3.2 +/- 1.2 vs. 0.5 +/- 0.3; P less than 0.05) insulin infusion rates. Peripheral insulin action, assessed by Bergman's sensitivity index, was significantly decreased in the hyperthyroid patients (7.4 +/- 2.2 vs. 15.6 +/- 2.1 L/kg min-1/pmol/L; P less than 0.02). In conclusion, hyperthyroidism is characterized by 1) hyperinsulinemia after oral glucose loading, 2) increased basal hepatic glucose production, 3) impairment of insulin-mediated suppression of hepatic glucose production, and 4) antagonism to insulin-stimulated peripheral glucose utilization.

Adult↗
PubMed1988

Suppression of sleep-induced growth hormone secretion by anticholinergic agent abolishes dawn phenomenon.

The dawn phenomenon was evaluated in eight C-peptide-negative type I (insulin-dependent) diabetic patients on two occasions by measuring glucose concentrations every 30 min from 2400 to 0800 h while the subjects were receiving an insulin infusion (0.12 mU.kg-1.min-1). In random order at 2230 h, they orally received either a sleeping medication alone or with 5.0 mg methscopolamine bromide, an anticholinergic agent. The peak growth hormone (GH) concentrations (ng/ml +/- SE) after sleep were markedly inhibited by methscopolamine (4.7 +/- 2.6 vs. 23.0 +/- 9.2). During the control night, the late (0400-0800 h) glucose response (area under curve but above 0400 h value) was significantly higher (P less than .02) than the early (2400-0400 h) glucose response (area under curve but above 2400 h value). After methscopolamine, the early and late glucose responses were virtually identical. The anticholinergic agent did not affect glucagon levels, overnight urinary catecholamine excretion, or the diurnal cortisol concentrations. The total area under the free fatty acid (FFA) curves was significantly (P less than .05) reduced by methscopolamine. We conclude that sleep-induced GH secretion may cause the dawn phenomenon by increasing FFA levels. Oral administration of methscopolamine at bedtime is a simple pharmacological approach that could test the clinical importance of the dawn phenomenon.

Blood Glucose↗
PubMed1988

Glucose transport is rate limiting for skeletal muscle glucose metabolism in normal and STZ-induced diabetic rats.

To test the hypothesis that glucose transport is rate limiting for skeletal muscle glucose metabolism, intracellular free glucose was measured in in situ abdominal wall muscle and liver that were rapidly freeze-clamped and removed from normal and streptozocin-induced diabetic (STZ-D) Sprague-Dawley rats exposed to different concentrations of serum insulin and glucose achieved by 90-min glucose clamps. Three groups of anesthetized normal (n = 17) and three groups of STZ-D (n = 19) animals were studied. In each group, infusions were adjusted to expose rats to basal, euglycemic-hyperinsulinemic, and hyperglycemic-hyperinsulinemic conditions. Final steady-state serum glucose and insulin concentrations (mean +/- SE) achieved in the six groups ranged from 112 +/- 2 to 467 +/- 26 mg/dl and from 5.8 +/- 1.9 to 3644 +/- 116 microU/ml, respectively. Intracellular free-glucose content of all tissue was calculated from total tissue glucose content minus the contribution of glucose in extracellular water estimated with [14C]inulin. Intracellular free glucose was not detected in muscle of any of the experimental groups. However, intracellular free glucose was detected in liver from all normal and STZ-D rats, and the calculated intracellular concentrations of free glucose correlated with serum glucose concentrations (r = .68, P less than .001). We conclude that intracellular free glucose does not accumulate, regardless of glucose or insulin concentration, in normal skeletal muscle and muscle made insulin resistant (by STZ-D), suggesting that glucose transport remains rate limiting.

Animals↗