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Biomedical subjects

M B Davidson

Publications and source records attributed to M B Davidson.

At least 19 recordsLinked to original sources
PubMed1992

Rational use of sulfonylureas.

The clinical use of sulfonylureas described in this article is both rational and effective for diabetic patients. Sulfonylureas are not used (1) in patients with insulin-dependent (type I) diabetes, because they are completely ineffective or (2) in patients with non-insulin-dependent (type II) diabetes who respond satisfactorily to diet, because they are unnecessary. In a patient with type II diabetes who has few or no symptoms but does not respond satisfactorily to diet, a sulfonylurea is introduced at a low dose, with gradual increases until a satisfactory response occurs, thus avoiding hypoglycemia. When symptoms of type II diabetes are marked, initiation of therapy with maximum doses of a sulfonylurea quickly distinguishes patients who need insulin therapy from those who have a good chance of responding to an oral drug. Abuse of sulfonylureas occurs when patients who could benefit from diet alone are treated with the drugs unnecessarily or, more often, when patients with poorly controlled disease continue to take maximum doses of the drugs. The usual situation is one in which the patient refuses insulin therapy or the physician does not suggest starting it. In other cases, the poorly controlled patient may be allowed to continue with a combination of a sulfonylurea and an ineffective dose of insulin. In this circumstance, the oral drug should be discontinued and insulin doses increased until control is more satisfactory. Because evidence is so compelling that near euglycemia has a beneficial effect on diabetic retinopathy, nephropathy, and neuropathy, physicians really do patients a disservice by misusing sulfonylureas.

Aged↗
PubMed1992

Regulation of glucokinase and proinsulin gene expression and insulin secretion in RIN-m5F cells by dexamethasone, retinoic acid, and thyroid hormone.

In RIN-5mF cells, treatment with either dexamethasone or retinoic acid resulted in increased glucokinase activity. Treatment with dexamethasone (50 and 500 nM) increased glucokinase activity 140% and 260%, respectively, whereas treatment with retinoic acid (100 and 1000 nM) increased glucokinase activity by 50% and 80%, respectively. An additive effect was observed when 1000 nM retinoic acid was added to either 50 or 500 nM dexamethasone. Treatment with either of these factors resulted in increased glucokinase mRNA levels. In contrast, treatment with thyroid hormone (T3; 0.2 and 10 nM) had no effect on glucokinase activity, but decreased glucokinase mRNA levels. T3 did not affect the response of either activity or mRNA levels to retinoic acid. Binding experiments revealed the presence of a single class of T3 nuclear receptors, with a Kd of 0.46 x 10(-10) and a binding capacity of 3.84 pmol/mg protein in these cells. This suggests that the changes produced by T3 may be due to a physiological effect mediated via nuclear receptors. Proinsulin mRNA levels were increased by retinoic acid (10-100 nM) and dexamethasone (5-500 nM), but decreased by T3 (0.04-10 nM). Insulin secretion in the absence or presence of glucose and potassium was increased about 50% in cells previously treated with 1000 nM retinoic acid. T3 (0.2 nM) did not affect insulin secretion in the absence or presence of glucose or in the presence of secretagogues (potassium and glyceraldehyde). Dexamethasone (50 nM) did not significantly increase insulin secretion in the absence or presence of glucose or potassium. In contrast, dexamethasone decreased glyceraldehyde-induced insulin secretion by 60% (P less than 0.05). We conclude that the glucokinase and proinsulin genes respond in parallel to dexamethasone and retinoic acid (both increased) and to T3 (both decreased).

Animals↗
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.

Explore the source record for details and available documents.

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↗