c-peptide and Glycogen-Storage-Disease-Type-I

We report the successful treatment of autoimmune hypoglycemia in an 82-year-old non-diabetic Caucasian male with hydrothermally modified slow release corn starch, a product which is used in other conditions associated with hypoglycemia, most typically glycogen storage disease type I. An 82-year-old-Caucasian male presented with recurrent spontaneous hypoglycemia as low as 30 mg/dl following in-patient treatment for community acquired pneumonia. During a fasting-test, symptomatic hypoglycemia occurred. Plasma concentrations of c-peptide and insulin were considerably elevated. Autoimmune hypoglycemia was confirmed by the presence of insulin autoantibodies. While dietary restriction alone did not result in sufficient glucose control in this patient with autoimmune hypoglycemia, treatment with hydrothermally modified slow release corn starch led to stable euglycemia. This easy, well tolerated and non-invasive treatment may constitute a new therapeutic option for hypoglycemia in patients with autoimmune hypoglycemia who do not achieve sufficient control of hypoglycemia by dietary restriction alone.

Topics: Aged, 80 and over; C-Peptide; Delayed-Action Preparations; Glycogen Storage Disease Type I; Humans; Hypoglycemia; Insulin; Insulin Antibodies; Male; Starch; Zea mays

The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1 would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became hypoglycemic during the fasting studies, and samples obtained at the point of hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other endocrinologic or metabolic diseases that result in fasting hypoglycemia demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an additional marker of insulin action that might help to differentiate hyperinsulinism from other hypoglycemic disorders.

Topics: Adolescent; Biomarkers; C-Peptide; Child; Child, Preschool; Fasting; Fatty Acids; Female; Glycogen Storage Disease Type I; Human Growth Hormone; Humans; Hyperinsulinism; Hypoglycemia; Hypopituitarism; Infant; Infant, Newborn; Insulin; Insulin-Like Growth Factor Binding Protein 1; Ketosis; Lipid Metabolism, Inborn Errors; Male

Renal disease is a frequent and serious complication of type I glycogen storage disease. A type I glycogen storage disease patient with focal segmental glomerulosclerosis and progressive renal insufficiency underwent a renal allograft transplantation. Despite the same cornstarch therapy, the post-transplantation course was complicated by worsening of the metabolic control manifested by exacerbated lactic acidaemia and hyperlipidaemia. This lactic acidaemia was remarkable for its association with hyperglycaemia. Hyperglycaemia accompanied by lactic acidaemia is strikingly unusual in type I glycogen storage disease, since this is a disease characterized by hypoglycaemia and an inverse relationship between blood glucose concentration and lactate levels. Both fasting insulin and C-peptide levels in the patient were greater than similar age-matched type I glycogen storage disease controls, indicating hyperinsulinaemia. The most likely mechanism responsible for the combined hyperglycaemia and lactic acidaemia was insulin resistance due to glucocorticoid treatment, instituted for immunosuppression. The hyperglycaemia associated with the lactic acidaemia was transient and resolved with steroid tapering. The exacerbated hyperlipidaemia, however, persisted after renal transplantation. Type I glycogen storage disease patients may be prone to glucocorticoid-induced insulin resistance, since the cellular metabolism in these patients may already be compromised with ineffective insulin action and/or reduced insulin output.

Topics: Acidosis, Lactic; Adolescent; Blood Glucose; C-Peptide; Creatinine; Female; Glucocorticoids; Glycogen Storage Disease Type I; Humans; Hyperglycemia; Insulin; Kidney Transplantation

Insulin and glucagon secretion was investigated in ten patients with hepatic glycogenosis, types I and III, in order to understand the relationship between hypoglycemia and pancreatic function. In all patients, both oral glucose tolerance and intravenous arginine infusion tests revealed hypoinsulinemia. Decreased urinary C-peptide levels with standard food intake also supported hypofunction of pancreatic beta cells. On the contrary, the normal secretion pattern of glucagon in both types indicated in the arginine loading test, intact alpha cells in the pancreas. Persistent hypoinsulinism, which is apparently an adaptation to hypoglycemia, could be an important cause of nutritional dwarfism in both types of glycogenosis. The usefulness of the measurement of urinary C-peptide, which evaluates the pancreatic function and provides management for normal body growth, is discussed.

Topics: Blood Glucose; C-Peptide; Child; Child, Preschool; Female; Glucagon; Glucose Tolerance Test; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type III; Humans; Infant; Insulin; Insulin Secretion; Male