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

The authors present 21 cases of severe hypoglycaemic side effects in diabetics treated with oral sulphonylurea drugs, including two deaths. The medications involved the most frequently were glibenclamide followed by glybutamide and glicalzide. Such side effects often occur early and are unrelated to dose. The classical predisposing factors were noted : old age, renal insufficiency, hepato-cellular insufficiency, drug associations -- in particular oral anticoagulants and salicylates. The indications for such drugs in the treatment of diabetes are discussed. Their use seems doubly illogical in the case of late onset obesity diabetes since the latter is accompanied by cardiovascular complications. It is dangerous in the elderly, particularly sensitive to the risks of hypoglycaemia and in who the diagnosis of "diabetes" is too often made on inadequate grounds.
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PMID:[Hypoglycemic complications of oral drug therapy of diabetes mellitus. 21 cases]. 81 20

A pharmacokinetic model of the insulin-glucose system was used to examine the effectiveness of insulin administered by a variety of routes and regimens for diabetic ketoacidosis. The blood plasma concentration of glucose was set at 1,000 mg. per dl., and the effects of the following insulin regimens on the glucose plasma level were compared: low dose (90mU. per kg. per hr.) administered by hourly intramuscular injection, constant-rate infusion, hourly intravenous bolus, constant-rate infusion with intravenous loading dose, and high dose (2 U. per kg.) with half given as an intravenous bolus and the remainder administered subcutaneously. Computer simulations showed that the high-dose regimen reduced the plasma glucose concentration rapidly to a hypoglycemic level (less than 34 mg. per dl. at three hours postadministration). The low-dose regimens reduced the plasma glucose level more slowly than did the high-dose regimen. Differences among the low-dose regimens were noted. The initial decline of the plasma glucose level was relatively slow with both the intramuscular and constant-rate infusion regimens. An additional problem with the intramuscular regimen was the accumulation of insulin at sites of administration. This accumulation could make judgment of the appropriate time to discontinue insulin difficult. Both the hourly intravenous bolus and the constant-rate infusion with loading-dose regimens caused a prompt decline in the plasma glucose level. Their potential for causing hypoglycemia was low provided insulin was discontinued when the plasma glucose level reached 180 mg. per dl.
Diabetes 1976 Sep
PMID:Pharmacokinetic evaluation of dosing regimens for insulin in diabetic ketoacidosis. 82 5

Over the past 50 years, maternal mortality for the pregnant diabetic has been reduced by half. In the period from 1957 to 1974, 24 pregnant diabetic women died in Los Angeles County. Seven deaths were directly attributed to the metabolic complications of diabetes. Fatal ketoacidosis occurred in the second and third trimesters, while hypoglycemia led to death in the first trimester or postpartum period. Of 15 patients alive at the onset of labor, 8 were delivered by cesarean section. Four of these women died from sepsis and 3 from hemorrhage. In contrast to other reports, vascular disease contributed to only 1 fatality.
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PMID:Maternal mortality in diabetes mellitus: an 18-year survey. 82 86

The responses of glucagon, growth hormone, and insulin secretion to the oral administration of glucose and to the intravenous infusion of saline, arginine, and insulin were measured in seven patients who had stable diabetes, eight who had unstable diabetes, and seven healthy volunteers. Hyperglycemia suppressed secretion of glucagon in normal subjects but not in diabetics. The oral glucose and arginine infusion tests demonstrated partial preservation of insulin-secretory ability in stable diabetics and its virxual absence in unstable diabetics. Glucagon responses to arginine infusion were similar in all three groups. In response to hypoglycemia induced by insulin infusion, the concentrations of plasma glucagon increased in normal subjects and, to a lesser extent, in stable diabetics but increased in only two of the unstable diabetics. The impairment in glucagon response during hypoglycemia in diabetics correlated positively with the degree of diabetic instability and insulin deficiency during glucose and arginine testing. The severity of the insulin deficiency also correlated with the degree of diabetic instability. These findings support the hypothesis that inherent abnormalities of insulin and glucagon secretion may account for many of the clinical characteristics of unstable and stable diabetic patients.
Diabetes 1977 Jan
PMID:Abnormalities of endogenous glucagon and insulin in unstable diabetes. 83 May 63

The effects of cholinergic blockade on the plasma glucose and insulin responses during oral and intravenous glucose administration were studied. Propantheline (30 mg.) was given by mouth 45 minutes before standard glucose tolerance testing to produce symptomatic chollinergic blockade. In 10 normal subjects a flattening of the over-all plasma glucose response to oral glucose was observed compared with the control test, whereas insulin secretion was not different. In seven patients with repeated episodes of symptomatic reactive hypoglycemia, cholinergic blockade eliminated both symptomatic and chemical hypoglycemia in each, raising the mean nadir glucose from 44 +/- 4 mg./dl. to 84 +/- 8 mg./dl. (p less than 0.01) and significantly reducing insulin secretion. In contrast, following intravenous glucose challenge, cholinergic blockade produced no significant difference in the rate of glucose utilization or insulin secretion in either group. These results are compatible with the hypothesis that excessive vagal stimulation may contribute to the hypoglycemia seen in patients with reactive hypoglycemia but suggest that the predominant effect is on the gastrointestinal tract rather than on pancreatic islets directly. These studies confirm that anticholinergic drugs may be useful adjuvants in treating these patients.
Diabetes 1977 Feb
PMID:Cholinergic blockade in reactive hypoglycemia. 83 65

Glucagon response to insulin hypoglycemia was tested in diabetics with autonomic neuropathy (N=9), diabetics without neuropathy (N=8), and normals (N=9). With similar levels of hypoglycemia, growth hormone and plasma cortisol increased in all groups. The glucagon response in normals (121+/-19 vs. 308+/-30 pg./ml., mean+/-S.E.M. of baseline vs. hypoglycemia peak) was significantly less in nonneuropathic diabetics than in normals (128+/-13 vs. 209+/-30) and absent in neuropathic diabetes (128+/-23 vs. 115+/-20). Arginine stimulation produced a glucagon response in the neuropathic diabetics (106+/-16 vs. 523+/-103). The data indicate that the capacity to release glucagon during hypoglycemia is lost in diabetic neuropathy while glucagon responsiveness to arginine is retained. Neuropathy in diabetes may contribute to metabolic instability.
Diabetes 1977 Mar
PMID:Lack of glucagon response to hypoglycemia in diabetic autonomic neuropathy. 83 71

To examine the role of catecholamines in glucopenia-induced glucagon secretion, urinary epinephrine and norepinephrine and plasma immunoreactive glucagon (IRG) were measured during insulin-induced hypoglycemia in normal and insulin-dependent diabetic-man. Despite equivalent levels of hypoglycemia the mean plasma IRG increment in diabetes was only 15% of normals. The increases in epinephrine and norepinephrine were comparable in diabetics and normals; thus, the blunted response in plasma IRG to the stimulus of low blood sugar in diabetics cannot be explained by a generalized defect in catecholamine secretion. It is suggested that an alpha-cell glucoreceptor defect may account for the abnormal response to glucopenia in diabetics. To evaluate the possibility that impaired sensitivity to circulating catecholamines could explain the alpha cell dysfunction in diabetics, exogenous epinephrine was infused in normals and insulin-dependent diabetics. Elevated plasma IRG during epinephrine infusion was observed in only 50% of normals. The diabetics were hyperresponsive; mean increment in plasma IRG 3 times that of normals. The data demonstrate enhanced rather than impaired sensitivity to catecholamines in diabetes mellitus.
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PMID:Glucagon and catecholamine secretion during hypoglycemia in normal and diabetic man. 83 46

Nine children were sent to the authors for hypoglycemia and familial history of diabetes mellitus. After oral glucose load abnormal responses in insulin secretion were obtained in all of them, and in one patient blood glucose curve was consistent with probable chemical diabetes.
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PMID:[Hypoglycemia. First manifestation of diabetes mellitus in children (author's transl)]. 84 74

The effect of ethanol on stimulus-induced insulin secretion was studied, and possible mechanisms were examined in fasting unanesthetized and unrestrained rats with indwelling jugular and aortic catheters. Glucose (150 mg.) or tolbutamide (10 mg.) was given rapidly, i.v., one hour after agavage of ethanol or saline (control). Acutely, ethanol treatment caused marked inhibition of glucose-induced insulin secretion and impaired glucose disappearance rate. Tolbutamide-induced insulin secretion was also significantly inhibited, and decline in glucose was significantly less in ethanol-treated rats. In response to ethanol, serum calcium concentration significantly declined for two hours. In another study, an ethanol metabolite, acetate (0.4 micronmole/min.) or vehicle (control) was infused for 60 minutes prior to 150 mg. glucose pulse. Acetate priming significantly potentiated glucose-induced insulin secretion and also improved glucose tolerance. It is proposed that (1) ethanol in vivo acutely induces hypocalcemia, which inhibits glucose- and tolbutamide-induced insulin secretion--which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycemia. (2)Acetate might be the actual petentiating influence on glucose-induced insulin secretion observed several hours after ethanol treatment.
Diabetes 1977 Apr
PMID:Effect of ethanol on stimulus-induced insulin secretion and glucose tolerance. A study of mechanisms. 84 8

The hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses was tested in five subjects following one hour of sustained hyperglycemia. Despite a rapidly falling blood glucose concentration, no increase in plasma growth hormone, cortisol, glucagon, or catecholamines occurred as long as the blood glucose concentration remained above fasting levels. Plasma growth hormone, cortisol, and catecholamines were not released until the mean blood glucose reached 28 mg./100 ml., 39 mg./100 ml., and 39 mg./100 ml., respectively, below the fasting level. Plasma glucagon was suppressed during the period of hyperglycemia. As the blood glucose concentration fell below basal levels, a progressive increase in glucagon occurred. Plasma glucagon returned to fasting values when the nadir in blood glucose was attained. During the period of rapidly falling blood glucose, only plasma insulin showed any change; its response lagged behind the decline in blood glucose. By the time the fasting glucose level was attained, the plasma insulin was still almost three times the basal level. We concluded that under our experimental conditions the rate of fall in blood glucose and the degree of hypoglycemia achieved is primarily determined by the plasma insulin concentration.
Diabetes 1977 May
PMID:A test of the hypothesis that the rate of fall in glucose concentration triggers counterregulatory hormonal responses in man. 85 48


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