Purpose: To review the medications that influence glucose metabolism and to examine the mechanisms of these medications on glucose metabolism. Data Sources: Data were obtained from a MEDLINE search...

Drug-Induced Disorders of Glucose Tolerance

Hypoglycemia may develop in patients with severe untreated malaria and can complicate the course of treatment with parenteral quinine as a result of quinine-induced hyperinsulinemia. Intravenous quinine is used increasingly as the therapy of choice in patients with severe malaria, most of whom are children. To assess the importance of both pretreatment and quinine-related hypoglycemia in children in an area in which the disease is endemic, we prospectively studied 95 Malawian children with falciparum malaria and altered consciousness who were treated with intravenous quinine. Nineteen patients had hypoglycemia before treatment. Seven (37 percent) died, and five of the survivors (26 percent) had neurologic sequelae. The corresponding values for patients who were initially normoglycemic were 4 percent and 4 percent, respectively (P less than 0.0001). Hypoglycemia was associated with low plasma insulin concentrations and with elevated plasma concentrations of lactate, alanine, and 5'-nucleotidase--a finding that suggests that impaired hepatic gluconeogenesis but not hyperinsulinemia contributes to the pathogenesis of pretreatment hypoglycemia. All patients were given quinine dihydrochloride in a 5 percent dextrose infusion, and those with hypoglycemia received 50 percent dextrose. Hypoglycemia recurred in seven of the patients with pretreatment hypoglycemia, but these episodes were also not associated with hyperinsulinemia. Of the 76 children who were initially normoglycemic, none became hypoglycemic during the course of treatment with intravenous quinine. We conclude that hypoglycemia is a frequent complication of falciparum malaria in children and that it reflects severe disease and is associated with a poor prognosis. We did not find it to be a complication of quinine treatment.

https://www.nejm.org/doi/pdf/10.1056/NEJM198810203191602?listPDF=true

Blood Glucose Levels in Malawian Children before and during the Administration of Intravenous Quinine for Severe falciparum Malaria

Drug-induced hypoglycemia.

Glucose homeostasis is maintained by a balance between the release and action of insulin, and the counterregulatory responses mediated principally by glucagon, catecholamines, growth hormone and cortisol. Hence, the effects of a drug on glucose metabolism may be mediated by any of these agents singly or in combination. Host factors, such as inherent glucoregulatory mechanisms, concurrent diseases, organ function and concomitant medications also increase the risk of drug-induced disturbances of glucose homeostasis in susceptible individuals. By far the most important agents causing hypoglycaemia are insulin and the sulphonylureas. Alcohol (ethanol), over-zealous glycaemic control, hypoglycaemic unawareness, defective counterregulation especially in insulin-dependent diabetes mellitus (IDDM), and renal and liver impairment are all important predisposing factors. Although antihyperglycaemic agents such as metformin and α-glucosidase inhibitors do not cause hypoglycaemia alone, they may enhance the hypoglycaemic effects of potent hypoglycaemic agents such as insulin and sulphonylureas. On the other hand, the potential hypoglycaemic effects of ACE inhibitors, α-blockers, lipid-lowering agents and recombinant human insulin-like growth factor demonstrated in experimental settings, are of potential therapeutic interest.

Drug-induced disorders of glucose metabolism. Mechanisms and management.

The term severe falciparum malaria implies an infection with manifestations and complications which are potentially fatal in man, the natural host for this parasite. Much that has been written on the pathophysiology of animal malarias is of doubtful relevance to the understanding of the mechanism of Plasmodium falciparum infection in man. The clinical picture of severe P. falciparum infection differs in several respects from severe animal malarias, even those of non-human primates. Cerebral dysfunction is the most common severe manifestation of falciparum malaria in man. Coma develops suddenly after a generalized convulsion or gradually towards the end of the first week of illness. There are signs of a symmetrical upper motor neurone lesion and brain-stem dysfunction, but only about 5% of survivors show persisting neurological deficit after 2 or 3 days of unconsciousness. The mortality of cerebral malaria depends on how it is defined and on the predominant age group and other factors. In patients with proved acute P. falciparum infection with unrousable coma, in whom other causes of encephalopathy have been excluded, the mortality is between 15 and 50% despite treatment with antimalarial drugs (Warrell, Looareesuwan, Warrell, Kasemsarn, Intaraprasert, Bunnag & Harinasuta, 1982).

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0031182000085826

A. R. Moore

Papers

Effectiveness of sms 201-995, a synthetic, long-acting somatostatin analogue, in treatment of quinine-induced hyperinsulinaemia