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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In perfused livers of rats fasted for 24 h, glucagon (5 x 10(-10) M) significantly elevated tissue and perfusate levels of cyclic AMP and caused a twofold increase in glucose formation from lactate. Chlorpropamide (0.8 x 10(-3) M) consistently blocked these effects. Measurements of metabolic intermediates suggest that chlorpropamide may inhibit gluconeogenesis by antagonizing the action of glucagon on the phosphoenolpyruvate cycle. In the experiments described, chlorpropamide did not lower hepatic ATP concentration or energy charge, and exerted its effects at perfusate concentrations comparable to serum concentrations reported in patients on maintenance doses of the drug.
Diabetes 1979 Jul
PMID:Hepatic effects of chlorpropamide: inhibition of glucagon-stimulated gluconeogenesis in perfused livers of fasted rats. 22 Dec 98

Insulin dependent (IDD) and non-insulin dependent diabetes (NIDD) are separate disorders. Twin studies show that IDD cannot be entirely due to genetic causes as concordance is no more than about 50%, but there is some inherited predisposition to it as shown by HLA patterns. NIDD, on the other hand, is predominantly due to genetic causes since identical twins are nearly always concordant. Many cases of NIDD show chlorpropamide alcohol flushing (CPAF), a dominantly inherited feature which may precede the appearance of diabetes and thus act as a genetic marker for this type of diabetes. Diabetics who show chlorpropamide acohol flushing are less likely to develop retinopathy than those who do not. Genetic factors must therefore affect the incidence and severity of diabetic retinopathy. Chlorpropamide alcohol flushing is due to sensitivity to enkephalin. Enkephalin and other opioids affect carbohydrate metabolism and insulin release. It is possible therefore that they act as neurotransmitters and cause NIDD by a sympathetically mediated effect on the liver and pancreas--in other words, that as far as NIDD is concerned Claude Bernard's views on the cause of diabetes may have been right.
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PMID:Diabetes: the genetic connections. 39

Sixteen adult-onset diabetics, who were thought by current criteria to be well controlled on diet alone, had substantially elevated overnight, basal plasma glucose concentrations. Chlorpropamide had a sufficiently prolonged stimulatory effect on the beta cells such that normal basal plasma glucose levels were obtained in 13 patients. Both basal plasma C-peptide levels and the C-peptide response to meals became normal, with improved postprandial glycemia. Diurnal plasma triglyceride levels were reduced. Plasma growth hormone levels were normal both before and after therapy. When diet alone is insufficient to maintain basal normoglycemia in mild diabetes, chlorporpamide is as effective as basal insulin supplements in producing normal basal plasma glucose levels.
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PMID:Basal normoglycemia attained with chlorpropamide in mild diabetes. 56 57

The activity of the succinate dehydrogenase-coenzyme Q10 reductase from 120 diabetic patients was significantly lower (P less than 0.001) and the per cent deficiency was significantly higher (P less than 0.001) than that of the controls. The diabetes of 37 patients was controlled by diet; the enzyme activity was lower (P less than 0.001) and the deficiency was higher (P less than 0.02) than for controls. In decreasing effectiveness, Dymelor, Glyburide, Phenformin and Tolazamide inhibited the COQ10-enzyme, NADH-oxidase. Tolbutamide, Glypizide, and Chlorpropamide were noninhibitory to succinoxidase and NADH-oxidase. Patients receiving Tolazamide and Phenformin showed a higher incidence (P less than 0.001 to P less than 0.05) of COQ10-deficiency than patients controlled by diet or normal controls. Certain diabetic patients controlled by diet may have a deficiency of COQ10 which may be enhanced by the inhibition by certain commonly used antidiabetic drugs of COQ10-enzymes. A deficiency of COQ10 in the pancreas could impair bioenergetics, the generation of ATP, and the biosynthesis of insulin.
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PMID:Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus. 107 May 15

Three male siblings with diabetes mellitus are described, two of whom also had coexistent diabetes insipidus. The co-existence of diabetes mellitus and insipidus appears to represent a single genetic abnormality and may or may not be accompanied by primary optic atrophy. Chlorpropamide was effective in controlling the symptoms of diabetes mellitus and diabetes insipidus.
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PMID:Co-existent diabetes mellitus and diabetes insipidus, a familial disease. 120 90

Experiments were conducted on 162 female rats which had sustained alloxan diabetes during the period of sexual immaturity and had latent insular insufficiency (prediabetes and latent diabetes). Possibilities of chlorpropamide under conditions promoting decompensation development were studied. The animals were given propamide in daily doses of 100 mg per 1 kg of weight for one month, including the period of sexual maturation. Observation period--up to 5 months. A favourable effect of chlorpropamide was noted by the end of puberty and persisted in the course of further observation; the difference from control animals by the frequency of latent and manifest diabetes was intensified under the effect of glucose overfeeding during the perinatal period. Chlorpropamide improved the course of latent insular insufficiency in the rats and was capable of preventing its change into manifest diabetes.
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PMID:[The effect of chlorpropamide on the course of latent insular insufficiency in rats under conditions favorable for its transition to patent diabetes]. 125 24

In clinical practice of hypoglycemic therapy of diabetes mellitus the problem of the optimal selection of oral hypoglycemic agent, corresponding to the individual patterns of regulatory and metabolic disturbances is of primary importance. The individual, pathophysiological basis should be met as much as possible by the pharmacodynamic properties of the selected, hypoglycemic drug. For this reason group of 23 diabetics type II underwent a prolonged, open trial of controlled pharmacotherapy with 4 sulphonylurea derivatives. Pertinent clinical and metabolic parameters were assessed before, during and after planned periods of therapy with Tolbutamide or Chlorpropamide to Gliclazide and Gliclazide to Glibenclamide. In the same time the levels of serum insulin fasting and after breakfast were determined. Also the comparative efficacy of the exchange of the drug in a subgroup of diabetics with fasting glycemia below and above 160 mg% was assessed. It was shown, that the change of Tolbutamide or Chlorpropamide to Gliclazide or Glibenclamide improved the therapeutical effectiveness in general. The individual responses to such a change were however individually differentiated. The change of Tolbutamide or Chlorpropamide to Gliclazide increased the therapeutical efficacy only in these patients, in whom such a change was associated with an increase of prandial, reactive serum insulin level (IRI). In practice they were patients with the fasting glycemia lower than 160 mg%. In patients with fasting glycemia higher than 160 mg% the change of oral compounds under study was not connected with an increase of prandial serum insulin. The metabolic parameters have not improved either. Perhaps they were patients with diabetes mellitus type II, who should be primarily qualified to insulin.
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PMID:[Relative effectiveness of tolbutamide, chlorpropamide and gliclazide]. 140 40

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.
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PMID:Use of sulfonylurea agents in older diabetic patients. 222 54

Although either insulin or oral hypoglycemics may be used in conjunction with diet and exercise in the management of type II diabetes, drug therapy for type I diabetes involves only insulin. C-peptide levels can be tested to assess whether the patient has remaining pancreatic endocrine function. Patients being started on insulin for the first time should receive a single injection of an intermediate-acting insulin of "human" origin at a dose of approximately 0.5 U/kg. Thereafter, fasting, mid-morning, mid-afternoon, bedtime, and possibly early morning blood sugars should be examined periodically to determine if the insulin dose needs to be increased, decreased, split, or if the patient needs to be on a two-insulin regimen. Intensive insulin therapy has become commonplace to control plasma glucose levels in the majority of patients receiving insulin therapy. Proper patient education regarding the insulin regimen, injection techniques, blood glucose monitoring, as well as diet, exercise, and foot care are essential if the patient's diabetes is to be controlled adequately. Guidelines for "adequate" glycemic control are outlined in Table 6. Recent evidence suggests that tight control of plasma glucose levels may decrease the macrovascular complications of diabetes. Although there is also evidence to suggest that the onset of microvascular complications might be delayed with strict glycemic control, the data are conflicting. The benefits of strict control must be weighted against the problems of hypoglycemia experienced by many patients who attempt tight control of their blood glucose levels. Biguanide compounds are available in Europe, but the sulfonylureas comprise the only class of oral agents in the United States commercially available for the treatment of type II diabetes. The two generations of these drugs reflect their potency and possible side-effect profiles. Of the first-generation agents, tolbutamide and chlorpropamide are the most widely prescribed. Tolbutamide is the weakest of the sulfonylureas, possibly making it a good drug for initiating oral therapy in the elderly. Chlorpropamide is becoming a less popular agent because of its long duration of action and its increased incidence of side effects. Of the second-generation agents, glyburide offers a better dosing schedule (once daily compared with twice daily for glipizide); however, glyburide may produce a greater incidence of hypoglycemia, particularly in the elderly or in patients with significant renal impairment. There are few good studies comparing these two drugs so that recommending one over the other is difficult. Drug interactions are numerous with the first-generation drugs, but less so with the newer second-generation agents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antidiabetic agents. 223 34

Changes in serum lipids and lipoproteins were examined during eight weeks chlorpropamide therapy in eight C-peptide negative, insulin-dependent diabetic patients (mean age 40 years, mean onset of diabetes 20 years). Chlorpropamide was found to have a generalized cholesterol lowering effect (progressive significant fall in mean total cholesterol, LDL-C, HDL-C, and HDL3-C) with no significant change in the ratio of high-density lipoprotein to low-density lipoprotein cholesterol which was independent of insulin secretion.
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PMID:Chlorpropamide lowers serum and lipoprotein cholesterol in insulin-dependent diabetes. 295 Nov 57


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