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Ocular effects of second generation oral hypoglycemic agents.

Second generation oral hypoglycemic agents, such as glyburide and glipizide, are often the treatment of choice in non-insulin dependent diabetes mellitus. These sulfonylureas are more potent osmotic agents than their predecessors and may give rise to crystalline lens changes and refractive error shifts in the absence of blood glucose variation. Such a case is presented, as is a detailed description of the mechanism of action of commonly prescribed oral hypoglycemic agents.

Administration, Oral↗

Insulinoma complicating pregnancy presenting with hypoglycemic coma after delivery: a case report and review of the literature.

The incidence of insulinoma in pregnancy is unknown. All of the eight previously reported cases presented in the first trimester with hypoglycemic episodes. We report a case of a 24-year-old multigravida who presented with hypoglycemic coma after delivery. We discuss the possible protective role of pregnancy counter-regulatory hormones in keeping the patient asymptomatic until delivery, and present the difficulties in both diagnosis and differential diagnosis of insulinoma in the peripartum period. Chronic hypoglycemia in pregnancy has been associated with intrauterine growth retardation and increased perinatal mortality. However, this infant was at the 90th percentile for body weight, suggesting that asymptomatic maternal hypoglycemia had not been present during the gestation. Insulinoma complicating pregnancy, though very rare, should now be included in the differential diagnosis of postpartum hypoglycemia.

Adenoma, Islet Cell↗

[Hypoglycemic action of different doses of nopal (Opuntia streptacantha Lemaire) in patients with type II diabetes mellitus].

To assess the relationship between the doses of O. streptacantha Lem. and its acute hypoglycemic action in diabetics, eight patients with type II diabetes mellitus were studied. Four test were performed to each patient with the intake of: (a) 400 ml of water, (b) 100 g (c) 300 g and (d) 500 g of broiled stems of O. streptacantha Lem. Serum glucose was measured at 0, 60, 120 and 180 minutes. Maximal decrease of serum glucose was noticed at 180 minutes, with a mean of 2.3, 10, 30.1 and 46.7 mg/dl less than basal value with 0, 100, 300 and 500 g respectively (P = NS, less than 0.05, less than 0.001 and less than 0.001 respectively). A significant direct correlation (r = 0.690, P less than 0.001) was noticed between the doses and the hypoglycemic effect.

Administration, Oral↗

[Hypoglycemic hemiparesis. A case report].

Hypoglycemia can result in a transient hemiplegia mimicking a minor cerebral vascular accident. With the widespread use of oral hypoglycemics and insulin this unexpected presentation of hypoglycemia is now being reported more frequently in the medical literature. This article describes a case of hypoglycemic hemiparesis and illustrates the need to consider this diagnosis, especially when the diabetic patient presents with stroke-like symptoms.

Aged↗

Investigation of the prolonged hypoglycemic effect of human proinsulin in diabetes mellitus.

Human proinsulin possesses a clear hypoglycemic effect, the extent and kinetics of which were investigated in 8 insulin dependent diabetics. In addition, to adequate therapy with a controlled-release insulin, each patient received i.v. injections of insulin (e U) and proinsulin (9 U) on separate test days. After 9 U of proinsulin, the blood glucose decrease was delayed in comparison to 3 U of insulin. However, it reached identical maximum blood glucose decrease values. The elimination kinetics of proinsulin are delayed compared to insulin. There is a linear relation between the time and the reciprocal value of the measured insulin immuno-reactivity. The hypoglycemic effect of proinsulin which is protracted for hours corresponds to that of an extreme controlled-release insulin. Under certain conditions, proinsulin might therefore prove effective in the long-term treatment of the insulin-dependent diabetes mellitus.

Adult↗

Effects of thioglucoses on sensitivity to insulin hypoglycemic convulsions.

Based on the effects of gold thioglucose (GTG), we have previously proposed a regulatory center in brain which adjusts the convulsive response to insulin hypoglycemia. The sensitivity to insulin hypoglycemic convulsions is decreased 24 hr and increased 1 week after a single i.p. injection of GTG. The differences are in the brain's convulsive response to equal hypoglycemia, as the blood glucose response to insulin is unchanged. The generalized convulsive threshold, reflected in the sensitivity to nonmetabolic pentylenetetrazol (Metrazol) convulsions, is not altered. Despite its systemic administration, GTG causes lesions focused in the ventromedial hypothalamus. In the present study, this regulatory center was explored further by the ability of two thioglucoses to substitute for GTG. beta-D-Thioglucose had no effect. 5-Thioglucose simulated the early (24 hr) action of GTG but had no effect at 1 week. However, unlike GTG, 5-thioglucose did not cause the ventromedial hypothalamus lesion. The early (24 hr) and late (1 week) components are thus dissociated. The early effect on insulin hypoglycemic convulsions does not require a ventromedial hypothalamus lesion. Structure-activity relationships and relationships to glucoregulatory systems are discussed.

Animals↗

Transient hypoglycemic paraparetic syndrome in an elderly patient.

An elderly diabetic patient sustained a transient hypoglycemic paraparetic episode that was attributed to inappropriate administration of glyburide. There were no other predisposing causes to account for the transient hypoglycemia. The predominant clinical signs were paraparesis of the lower extremities, with the right side more affected than the left. The patient's paraparesis cleared within two hours after administration of 50 mL of 50 percent glucose intravenously.The management of a paraparetic syndrome should include an appraisal of all the predisposing factors and their correction. The mechanism that was deemed responsible for the patient's transient hypoglycemic paraparetic syndome was loss of cerebrovascular autoregulation in a vulnerable area (the vertebral-basilar artery distribution). In the elderly patient tight control of blood glucose levels should be avoided in view of the potential development of hypoglycemia and brain injury.

Aged↗

Reduction of severe hypoglycemic events in type I (insulin dependent) diabetic patients using continuous subcutaneous insulin infusion.

In order to evaluate the safety and effectiveness of insulin pump treatment and to establish criteria for its use, we retrospectively studied 45 patients from a referral university diabetes clinic who were treated with either intensive subcutaneous insulin injections or continuous subcutaneous insulin infusion. Hemoglobin A1C was 8.5 +/- 0.3% (SEM) before and 8.1 +/- 0.1% during continuous subcutaneous insulin infusion (p = NS), but rose to 10.0 +/- 0.2% at a 16-month post-study follow-up. The frequency of ketoacidosis was 0.17 events/year before and 0.20 during infusion pump use (p = NS) and declined to 0.10 at the follow-up (p = NS). Severe hypoglycemia was reduced from 2.73 events/year to 0.22 during continuous subcutaneous infusion treatment (p less than 0.001), and from 3.72-0.32 (p less than 0.001) in a subgroup of 23 patients who initiated insulin pump treatment because of frequent and severe hypoglycemic events during intensive insulin injection treatment. Insulin pump use, compared to intensive insulin injections in a non-research setting, (a) is equally effective for maintenance of near normal glycosylated hemoglobin levels, (b) need not result in increased ketoacidosis, and (c) is effective for reducing hypoglycemic events. Thus, insulin pump treatment can benefit larger and randomized studies are needed to confirm these results.

Adult↗

Role of cholinergic mechanism in the hypoglycemic action of B. pertussis vaccine.

The present work aims to study the role of the cholinergic mechanism in the hypoglycemic action of B. pertussis vaccine in rats. The vaccine resembles insulin in that the hypoglycemia produced is mainly due to the increase conversion of glucose to glycogen in the liver and muscle. Both the hypoglycemia as well as glycogen deposition was partially blocked by atropine. On the other hand the vaccine potentiated the fall in the blood sugar and deposition of glycogen in the tissues produced by physostigmine. This suggests the possible involvement of the cholinergic system in the hypoglycemic action of the vaccine.

Animals↗

Hypoglycemic coma with ketoacidosis in nondiabetic alcoholics.

Five nondiabetic, chronically alcoholic patients presented in a comatose state during a two month prospective study and were found to be ketoacidotic. All of the patients were men, 28 to 59 years old. The usual history was one of chronic heavy, daily alcohol consumption until one to three days before presentation, when persistent anorexia, abdominal distress, nausea and vomiting commenced, with abstention from food thereafter. The patients were found to be in hypoglycemic coma, with diaphoresis, tachypnea and tachycardia, and immediately awoke when intravenous infusion of glucose was started. Serum glucose ranged between 19 and 27 mg per dl, the average arterial pH was 7.19 and the mean anion gap was 25 mEq per liter. Reaction with Acetest tablets was positive for ketones in both serum and urine in three of the patients. Serum beta-hydroxybutyrate was elevated in the four patients in whom it was measured. Lactic acidosis was not present. All patients were managed with prolonged intravenous infusions of glucose and saline solutions, and within 12 to 18 hours they were feeling well and findings on serum chemistry studies were normal. Follow-up after three months showed no repeated difficulties. The combination of alcoholic ketoacidosis and hypoglycemic coma in nondiabetic persons has not been described in the literature as a clinical entity; it may, however, represent a common but unrecognized syndrome. Therefore, because of its potentially serious consequences and because treatment is simple and effective, this entity must be thought of in alcoholic patients with altered mental status.

Acidosis↗

[Successful resection of giant hepatocellular carcinoma with hypoglycemic attack].

We experienced a 68 years-old male who had frequent hypoglycemic attacks. The diagnosis of a giant hepatoma associated with hypoglycemia was established by oral glucose tolerance test (O-GTT), angiography and computed tomography. The cavography demonstrated the invasion or depression of the tumor. It was ascertained by an operative exploration that the tumor occupied most of the right trisegments of the liver and infiltrated into a part of the left lateral segment. The right hepatic trisegmentectomy along 1.5cm left side line apart from the falciform ligament was performed. Resected tumor showed 11 X 13 X 10cm in size and 1200g in weight. Microscopic findings demonstrated hepatocellular carcinoma as Edmondson's Type II. After the operation, this patient became free from the hypoglycemic attack. A fasting blood sugar became within normal limits and O-GTT demonstrated a normal blood sugar level and insulin response. No concentration of immuno-reactive insulin was found in the resected tumor, however, the blood sugar in rats which received the intravenous injection of the tumor extracts was remarkably decreased in 20 minutes. From these observation, hypoglycemia in this patient seemed to depend mainly on the factor of insulin-like activity of the tumor. In the literature, the hepatocellular carcinoma associated with paraneoplastic phenomenon, e.g. hypoglycemia, has rarely been resected because of accompanied liver cirrhosis or giant size of the tumor. This is the second patient in our country in whom the tumor was fortunately resected and the paraneoplastic syndrome disappeared postoperatively.

Aged↗

A preliminary study of the mechanism of the hypoglycemic effect of polymeric prostaglandin PGBx in hereditary diabetic mice. Insulin response curves.

Polymeric prostaglandin PGBx normalizes the high blood sugar seen in hereditary diabetic mice. PGBx does not enhance the sensitivity of these mice to the hypoglycemic effect of insulin. It is therefore proposed that the hypoglycemic effect of PGBx may be an indirect consequence of induction of increased consumption by genetically defective mitochondria of two and three carbon fragments produced at the bottom of the glycolysis chain.

Animals↗

Change in sensitivity to insulin hypoglycemic convulsions after gold thioglucose treatment: time course of development.

The sensitivity to insulin hypoglycemic convulsions has been shown to decrease at early times (16 and 24 hr) and increase at later times (1 week) after gold thioglucose (GTG) treatment. Systemically administered GTG is well known to produce hyperphagia, resulting in obesity, and cytological damage focused relatively selectively in the ventromedial hypothalamic area (VMH). Both of these effects on insulin hypoglycemic convulsions occur before the weight gain, but at a time when histological damage visible with cresyl violet stain has already appeared. Both of these changes reflect a difference in the convulsive response to hypoglycemia, rather than a differences in the degree of hypoglycemia in response to insulin. No functional change in the convulsive sensitivity was found at still earlier times during the latency in establishing the histological damage visible with cresyl violet. These results suggest that GTG lesions a relatively discrete brain region involved in adjusting the functional response of the brain to hypoglycemia, including a composite of two opposite regulatory components. The significance of such a control center in relation to energy metabolism in brain is discussed. Moreover, it has been postulated that the glucose moiety of GTG binds to glucoreceptors in the VMH to focus the cytoxicity of the gold thioportion at that site. These results are also discussed in relation to this proposed mechanism for concentration and hence localization of GTG toxicity in the VMH.

Animals↗

Ophthalmic timolol treatment causing altered hypoglycemic response in a diabetic patient.

A diabetic patient experienced a dangerous alteration in hypoglycemic symptoms during treatment with ophthalmic timolol maleate. Before and after timolol therapy, hypoglycemic reactions were characterized by sweating, uneasiness, and prompt resolution with glucose treatment. During timolol therapy, reactions were characterized by a changed mental status (including seizures on occasion) and a relative resistance to glucose treatment. Caution must be exercised in the use of even topically applied beta-adrenergic blockers in diabetic patients who are prone to hypoglycemia.

Aged↗

Hypoglycemic depression of hepatic phagocytosis in vivo and in the in situ perfused rat liver.

Depression of the phagocytic function of the reticuloendothelial system (RES) during endotoxic hypoglycemia has been implicated in the pathogenesis of endotoxin shock. The present study evaluated the in vivo effects of hypoglycemia on RES function and assessed the effects of an vivo bout of hypoglycemia on phagocytosis in the in situ perfused rat liver. Hypoglycemia was produced in male Holtzman rats using either 1 U of regular insulin (RI) (ILETIN, Lilly) or 0.75 U of long-acting insulin (LAI) (85% LENTE/15% ULTRALENTE, Lilly). RES function was quantitated by intravascular clearance of 8 mg/100 gm body weight colloidal carbon (CC). Two hr after RI and 2.5 hr after LAI, the intravascular halftimes of CC clearance were 19 +/- 2 min (N = 22) and 18 +/- 1 min (N = 19), respectively, as compared to control, 11.3 +/- 0.4 min (N = 53, P less than 0.001). The corresponding plasma glucose (PG) levels were 95 +/- 2 mg/dl in control, 14.4 +/- 0.9 for the RI group, and 17 +/- 1 for LAI. Two hr after RI, livers were perfused for 10 min in situ with 50 mg/liter CC in saline 5% rat serum. PG for control liver donors were 90 +/- 3 mg/dl, while those for hypoglycemic liver donors were 15 +/- 2. CC uptake was decreased from 22 micrograms/min/gm liver in the control (+ serum, n = 19) to 11 +/- 2 in hypoglycemia livers (N = 6); no effect of serum on hypoglycemic depression of the RES was seen. There were no differences in flow rates in the 2 groups. These results indicate that hypoglycemia directly impairs RES function and that the in vivo depression of intravascular clearance is not related to either the presence or absence of serum factors or total hepatic blood flow. Thus, the characteristic hypoglycemia of endotoxin shock may contribute to RES depression and the lethal shock syndrome.

Animals↗

Synthesis and in vivo hypoglycemic screening studies on some life essential metal complexes of oral antidiabetic [N-(p-tolylsulphonyl)-N'-n butyl-urea] (tolbutamide).

Present communication deals with the synthesis of complexes of [N-(p-tolylsulphonyl)-N'-n butyl-urea], with certain transition metals viz. Cu(II), Zn(II), Fe(II) and Cd(II). Structures of all the complexes have been established on the basis of their consistent elemental and spectral analysis. Also, it reports their in vivo hypoglycemic screening on albino rats. Out of all the complexes studied, Zn-Tolbutamide complex could be recommended as more potent hypoglycemic agent in lieu of tolbutamide alone.

Administration, Oral↗

[Hypoglycemic mediastinal tumor].

A very rarely met case of extrapancreatic hypoglycemic tumor is described, localized in the anterior mediastinum, histologically- a reticulosarcoma. The tumor advanced very rapidly till the exitus. The frequent hypoglycemic crises and comae, when the blood sugar reached to 50 mg% mere overcome by glucose solutions.

Bulgaria↗

[Intensity of glycolysis and activity of energy metabolism enzymes in rat brain after multiple exposures to hypoglycemic doses of insulin].

Changes in the rates of glycolysis, glycogenolysis, activities of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, serum glutamic pyruvic and oxaloacetic transaminases in the brain hemispheres and stem of rats exposed to 5-7 hypoglycemic comas were studied. No noticeable changes were detected in glycolysis intensity or activities of Krebs' cycle enzymes in the large hemispheres. The intensity of glycogenolysis and activities of transaminases in the brain stem reduce on day 2 of repair period after the last hypoglycemic coma. The detected changes result from multiple exposures of the brain to hypoglycemia and may be important in the development of posthypoglycemic encephalopathy.

Alanine Transaminase↗