Alimentary Hypoglycemia Research Articles

Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia

New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention and management of insulin-induced hypoglycemia. This is applicable in type 1 diabetes, hyperinsulinism, and alimentary hypoglycemia. The aim of this review is to describe these new formulations of glucagon and to provide an overview of current and future therapeutic opportunities that these may provide. Four main categories of glucagon formulation have been studied: intranasal glucagon, biochaperone glucagon, dasiglucagon, and non-aqueous soluble glucagon. All four have demonstrated similar glycemic responses to standard glucagon formulations when administered during hypoglycemia. In addition, potential roles of these formulations in the management of congenital hyperinsulinism, alimentary hypoglycemia, and exercise-induced hypoglycemia in type 1 diabetes have been described. As our experience with newer glucagon preparations increases, the role of glucagon is likely to expand beyond the emergency use that this medication has been limited to in the past. The innovations described in this review likely represent early examples of a pending large repertoire of indications for stable glucagon.

Increased Insulin Sensitivity in Patients with Idiopathic Reactive Hypoglycemia

We performed a euglycemic hyperinsulinemic glucose clamp in 20 patients selected from a large number of subjects referred to our clinic with symptoms suggesting reactive hypoglycemia. Diagnosis was made on the basis of blood glucose measurements during symptoms in their daily life and confirmed by a 5-h oral glucose tolerance test. The patients were divided into the following groups: 8 patients with idiopathic reactive hypoglycemia (IRH), i.e. biochemical hypoglycemia associated with symptoms and plasma insulin concentrations in the normal range; 6 patients with nonhypoglycemia (NH), i.e. patients experiencing the symptoms evoking hypoglycemia at essentially normal plasma glucose levels; and 6 patients with alimentary hypoglycemia secondary to previous gastric surgery (GS). Eight normal volunteers formed the control group (N). Hypoglycemia in this study was considered to be present when plasma glucose concentrations were below 2.5 mmol/L. The peak cortisol levels after glycemic nadir were higher (2P less than 0.05) in IRH compared to GS and N. In the same group, a partially deficient glucagon response to hypoglycemia was noted. During the euglycemic clamp, the glucose uptake appeared to be significantly greater in the IRH group than in NH, GS, and N groups (8.13 +/- 0.49 vs. 7.02 +/- 0.35, 6.48 +/- 0.22, and 6.66 +/- 0.42 mg/kg.min, respectively; 2P less than 0.05). Therefore, our data suggest that increased insulin sensitivity represents a feature of idiopathic reactive hypoglycemia.

Alimentary hypoglycemia: a new appraisal

The clinical evaluation and the results of oral glucose tolerance tests in patients with alimentary hypoglycemia, reported previously or studied as part of our group of 24 patients with this disorder, suggest that alimentary hypoglycemia may differ from other reactive hypoglycemias in clinical presentation and importance. Unlike other reactive hypoglycemias, alimentary hypoglycemia may be associated with severe or permanent neuropsychiatric complications. Subtle, “neuroglycopenic” symptoms of hypoglycemia may occur, instead of “typical,” “adrenergic” symptoms. Glucose ingestion, by causing early hyperglycemia and provoking the release of insulinotropic enteric hormones appears responsible for this disorder. Therefore, therapy with diets low in simple sugar, but unrestricted in complex carbohydrate and fiber are now advocated.

Insulin release in response to calcium in the diagnosis of insulinoma

A calcium infusion (4 mg Ca ++/kg/hr) significantly increased plasma insulin levels and reduced blood glucose in 4 patients with insulin-secreting pancreatic islet cell tumors. These parameters were not altered by a similar infusion of calcium in normal volunteers, 2 patients with alimentary hypoglycemia, and 2 with functional hypoglycemia. No difference in response was observed between patients with benign and malignant β-cell tumors. Infusion of diazoxide (600 mg) with calcium blocked the stimulation of the latter on insulin secretion. The results indicate the usefulness of calcium infusion in the diagnosis of insulin-secreting tumor.

Organic brain dysfunction as a possible consequence of postgastrectomy hypoglycemia.

Unlike the fasting hypoglycemias, the reactive hypoglycemias, including postgastrectomy hypoglycemia, are generally not believed to result in serious neuropsychiatric dysfunction. The authors describe two patients with progressive mental deterioration and alimentary hypoglycemia and suggest that clinicians should recognize the possibility of serious neuropsychiatric sequelae of postgastrectomy hypoglycemia.

Alimentary hypoglycemia in the absence of gastrointestinal surgery.

Abstract In three patients who had repeated episodes of symptomatic postprandial hypoglycemia, oral glucose tolerance testing demonstrated normal initial insulin response but subsequent hyperinsulinemia and hypoglycemia. Intravenous glucose and tolbutamide provoked normal glucose and insulin responses, suggesting normal beta-cell function. Evidence that the hyperinsulinism and hypoglycemia provoked by oral glucose was due to alimentary factors included hyperglycemia, hyperinsulinism, and subsequent hypoglycemia after duodenal glucose infusions, normal gastric emptying as measured by a radioisotopic method, and control of the hyperglycemic, hyperinsulinemic responses and of hypoglycemic symptoms in these patients by phenformin, a drug reported to impede glucose absorption from the gut. We conclude that alimentary hypoglycemia may occur in the absence of gastrointestinal surgery, and can be distinguished from the hypoglycemia of early diabetes by normal to increased initial insulin secretion after the inges...

Alimentary hypoglycemia associated with the Zollinger-Ellison syndrome

The patient described had clinical and laboratory evidence of Zollinger-Ellison syndrome, hyperparathyroidism and reactive hypoglycemia. From the findings of an “endocrine-like” tumor in the duodenal wall (with diminished plasma gastrin levels after its resection) and chief cell hyperplasia of the parathyroids, she was considered to have multiple endocrine adenomatosis. Excessive insulin release coincided with peak glucose concentrations in plasma after the oral administration of glucose with hypoglycemic episodes at two to three hours. The presence of a pancreatic neoplasm or hyperplasia as a cause of the hyperinsulinism in this patient with multiple endocrine adenomatosis was excluded by normal beta cell responses to the intravenous administration of glucose, tolbutamide and glucagon and the absence of pancreatic disease at laparotomy. The exaggerated insulin secretion and hypoglycemia were attenuated by the intragastric administration of sodium bicarbonate and the oral administration of methscopolamine bromide, both of which delay gastric emptying. Although the factors responsible for the hyperinsulinism cannot be absolutely resolved, from the excessive acid production and hypergastrinemia in this patient, it is inferred that increased gastric emptying may have contributed significantly to her alimentary hypoglycemia. The possible roles of enteric hormones in the postprandial hypoglycemia in this patient are discussed.

Alimentary (postgastrectomy) hypoglycemia. A remediable cause of recurrent seizures.

ALIMENTARY hypoglycemia generally denotes the occurrence of low blood glucose levels 11/2 to 3 hours postprandially in a patient who has undergone gastrectomy. While seizures are a well-known manifestation of hypoglycemia due to pancreatic adenoma, it has remained unclear whether the postprandial hypoglycemias are ever sufficiently profound or rapid in evolution to compromise cerebral function.^1-3Two patients are presented whose alimentary hypoglycemic disorders have been thoroughly documented; a recurrent seizure disorder was the presenting manifestation of hypoglycemia in each case, and both patients have responded to dietary treatment. Because there are simple and often effective modes of therapy for this disorder which may resemble idiopathic epilepsy, it is important that physicians be alerted to this possibility in evaluating patients with recurrent seizures. <h3>Report of Cases</h3> Case1.—A 49-year-old white male merchant marine was in good health until 1960, at which time he developed symptoms of duodenal ulcer;