Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of two second generation sulphonylureas, gliquidone and glibenclamide, on insulin secretion has been studied in the basal state and in combination with glucose infusions in normal controls, patients with mild maturity-onset diabetes, and subjects with normal glucose tolerance but low insulin response. When injected intravenously, gliquidone caused rapid elevation of plasma insulin, peaking at 5 min in all groups, while glibenclamide induced a slow rise in insulin. Insulin response was somewhat smaller than normal in diabetics and low insulin responders. In all groups, 25 micrograms/kg glibenclamide and 200 micrograms/kg gliquidone were equipotent in generating an insulin response at the basal state. Equipotent amounts of sulphonylureas were combined with glucose in fusions at three different dose levels. The glucose-insulin dose relationships, established by giving glucose alone, demonstrated curves that were flatter, and shifted to the right of the control in diabetics and low insulin responders, the changes being more marked in the former group. Addition of sulphonylurea induced a left shift in the dose-response relationships in controls and low insulin responders; under these conditions the effect of glibenclamide was more pronounced than that of gliquidone. The dose-response relation for glucose-induced insulin release was completely normalized in low responders when sulphonylureas were added. In the group of mild diabetics, insulin response to glucose was enhanced by sulphonylureas only to a modest extent, the dose-response curves remaining grossly abnormal.
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PMID:Effect of two sulphonylureas on the dose kinetics of glucose-induced insulin release in normal and diabetic subjects. 11 49

The effects of various experimental conditions during the isolation of monkey islets by the collagenase method on the insulinogenic response of the isolated islets to glucose have been studied and compared with rat islets isolated under similar conditions. The monkey islets gave a normal response for at least 120 min. The results are compared with available studies on primate islets.
Diabetes 1979 Sep
PMID:Studies on insulin secreted by isolated islets of the monkey, Macaca radiata radiata. 11 84

Diabetic glomerulopathy continues as a major problem in the management of the patient with diabetes mellitus; however, evidence in man and in animals underlines the fact that good control of diabetes favorably alters the course of this complication. Islet transplantation in the diabetic rat returns plasma glucose and insulin levels to normal. In parallel mesangial matrix thickening, mesangial deposition of immunoglobulin and urinary excretion of albumin markedly improve following islet transplantation. Although amelioration of diabetes affects the course of glomerulopathy, other factors (most notably measures that increase glomerular capillary pressure) enhance the development of the diabetic renal lesions. Following uninephrectomy or clipping of a renal artery, the remaining (in the case of uninephrectomy) or unclipped diabetic kidney develops the morphologic and functional changes of diabetic nephropathy at a rate greater than in kidneys in an intact diabetic rat. The clipped kidney demonstrates diminished diabetic changes, suggesting a protective effect with decreased glomerular capillary pressures. In addition to measures improving the control of diabetes, procedures reducing factors accelerating diabetic complications may improve the prognosis in diabetic glomerulopathy.
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PMID:The development, enhancement, and reversal of the secondary complications of diabetes mellitus. 11 28

Eight years ago, in caring for persons with diabetes at Grady Memorial Hospital, Atlanta, priority was given to the use of oral hypoglycemic agents and insulin, with only minimal attention to nutrition. In 1971, an "expanded nutritional care program" was instituted, with emphasis on nutritional education and follow-up. Use of oral agents was discontinued, and, since 1972, less insulin has been used. The new dietary program, with dietitians playing a key role, includes a one-week total fast, stringent low-calorie diets, individualized dietary planning and instruction, and careful follow-up monitoring. Comparative pre-1971 and current data show: a 50 per cent reduction in lower extremity amputations, less diabetic ketoacidosis, fewer hospitalizations, weight reduction of 40 per cent with no increase in plasma glucose (in a 127-patient cohort with complete follow-up), and a savings to the hospital of more than $96,000 in the cost of medications and $3,700,000 in hospitalizations in eight years.
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PMID:Spin-off cost/benefits of expanded nutritional care. 11 38

In 56 patients with maturity onset diabetes receiving combined therapy with different oral hypoglycemic drugs, biguanide treatment was stopped while sulphonylurea compounds were continued without major changes. In four patients insulin therapy had to be initiated rapidly. In 14 other patients follow-up observations could not be performed for various reasons. The reamining 38 patients were divided into four groups according to their treatment. On the average, chemical control could not be maintained in any group after discontinuation of biguanide therapy. Blood glucose concentrations and glycosuria increased. Later, in 6 of 38 patients secondary failure of sulphonylurea treatment became apparent.
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PMID:[Treatment of diabetes without biguanides. Observation on the course after changing treatment (author's transl)]. 11 74

A review of therapies for diabetes mellitus reveals little that is new for the diabetic today. Also, there is little evidence that progression of diabetic complications can be slowed or halted with currently available therapeutic modalities that are acceptable to patients and can be applied in an everyday clinical setting. Few new drugs are likely to be ready for marketing in the immediate future, and most of the pharmacologic approaches that are now under study do not address the basic problem of lost sensitivity of the beta cell to endogenous glucose. In the longer term, it is likely that an oral insulin, allowing more convenient management of diabetes, will be available, as well as several new drug classes that may offer therapy adjunctive to insulin. As more is learned of the cellular physiology of the islet cell and the pathology of diabetes mellitus, some additional therapeutic breakthrough may occur. It is highly likely that an implantable or portable infusion system, either of the closed- or open-loop type, will be available when technologic problems are overcome. Islet cell transplantation may provide a definitive treatment for diabetes. At the very least, the questions should be resolved relating to careful physiologic control of the metabolic aberrations of diabetes mellitus. Unfortunately, because of the relatively slow evolution of diabetic vascular pathology, it will be several decades before current studies can provide the answers. If present hypotheses are confirmed, future therapeutic approaches can be more clearly defined; if the hypotheses must be rejected, the therapeutic dilemmas will remain.
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PMID:Future management of diabetes mellitus. 11 91

The purpose of the study was to investigate whether the potency of effect on the beta cell differs with type of sulfonylurea (SU) and with degree of severity of diabetes. 12 maturity onset diabetics were classed according to fasting blood glucose (FBG) in three groups of 4 patients each. Each patient served as his own control. Glibenclamide, Gliquidone, Glusoxepide and placebo were administered in random order with degree dosage adjusted according to degree of severity of diabetes. All patients were given a standardized diet with 150 g carbohydrates per day. Fullday profiles of blood glucose, insulin, C-peptide and sulfonylurea level in serum were made on the third day under each preparation. Results showed that with proper nutrition and sufficient weight reduction, patients in group I (FBG 80--130 mg/dl) needed no oral medication and in fact showed a tendency towards hypoglycaemic episodes under oral therapy. In group II (FBG 130--200 mg/dl) the effect of nutrients on beta cell secretion appeared to be both enhanced and accelerated by SU administration. Satisfactory metabolic control was achieved with SU, but not with placebo. This group seems to represent the type of patient most likely to benefit from SU therapy. In spite of high dosage levels, satisfactory control was not achieved with SU in any patient in group III (FBG greater than 200 mg/dl). Depending on individual factors such as ketosis-proneness, vascular complications, age and psycho-social aspects, insulin administration should be considered for these patients. There were not differences between the individual SU preparations in the parameters studied. There was insufficient evidence for a pharmacokinetic differential diagnosis.
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PMID:[Comparison of glibenclamide, gliquidone, glisoxepide and placebo in maturity onset diabetics of differing degrees of severity (author's transl)]. 11 59

Subjects with borderline glucose tolerance are at a higher risk of suffering and dying from cardiovascular disease than subjects with normal glucose tolerance. Our data on the progression to overt diabetes and our data on cardiovascular morbidity and mortality suggests that tolbutamide treatment reduces these risks. In any case, we have no data supporting the theory that tolbutamide promotes cardiovascular damage.
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PMID:Long-term treatment of subjects with borderline glucose tolerance. 11 34

The effects of glibenclamide and glipizide on the concentrations of S-glucose, S-insulin and S-lipids and on the 24-hour urinary glucose excretion were studied in 37 patients with maturity onset diabetes. A double-blind, cross over double-dummy technique was used. The fasting S-insulin concentration was higher during glibenclamide therapy, while the increase in insulin concentration one hour postprandially was stronger during glipizide therapy, supporting the concept that glibenclamide has a more prolonged and glipizide a more fast-acting effect on insulin secretion. The S-glucose concentration was lower in the fasting state as well as one hour postprandially during glibenclamide therapy which, together with a lower 24-hour urinary glucose excretion, indicates that glibenclamide has a stronger blood glucose-lowering effect. Although statistically significant, the differences were marginal from a clinical point of view. The lipid levels remained unchanged.
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PMID:Glibenclamide and glipizide in maturity onset diabetes. A double-blind cross-over study. 11 80

Aortic atherosclerosis is minimal in normal Macaca nigra; development of atherosclerosis correlates with increasing severity of diabetes mellitus. The extent of aortic involvement (plaque plus sudanophilia) was quantified and compared with metabolic and clinical parameters. Increasing atherosclerosis correlated with decreasing ability to clear glucose in a tolerance test (P less than 0.01), decreasing insulin (P = 0.02), and increasing glucose (P less than 0.01) and triglycerides (P less than 0.01). A diabetic index, established as a summation of several metabolic measurements, correlated with atherosclerosis at P less than 0.001. On the average, involvement of the thoracic aorta was about 3-fold greater than in the abdominal portion; involvement reached over 40% in severely diabetic monkeys. Atherosclerosis development is unique in these monkeys since they consume a natural ration low in fat and cholesterol. Serum cholesterol did not correlate with diabetes or artherosclerosis. Increasing age alone was associated with slight sudanophila, some intima-media thickening, and occasional small lesions. However, only with increasing severity of diabetes was there significant atherosclerosis.
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PMID:Aortic atherosclerosis in normal and spontaneously diabetic Macaca nigra. 11 65


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