Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes
- PMID: 18594062
- PMCID: PMC2453684
- DOI: 10.2337/dc08-0575
Too much glucagon, too little insulin: time course of pancreatic islet dysfunction in new-onset type 1 diabetes
Abstract
Objective: To determine the time course of changes in glucagon and insulin secretion in children with recently diagnosed type 1 diabetes.
Research design and methods: Glucagon and C-peptide concentrations were determined in response to standard mixed meals in 23 patients with type 1 diabetes aged 9.4 +/- 4.6 years, beginning within 6 weeks of diagnosis, and every 3 months thereafter for 1 year.
Results: Glucagon secretion in response to a physiologic stimulus (mixed meal) increased by 37% over 12 months, while C-peptide secretion declined by 45%. Fasting glucagon concentrations remained within the normal (nondiabetic) reference range.
Conclusions: Postprandial hyperglucagonemia worsens significantly during the first year after diagnosis of type 1 diabetes and may represent a distinct therapeutic target. Fasting glucagon values may underestimate the severity of hyperglucagonemia. The opposing directions of abnormal glucagon and C-peptide secretion over time support the link between dysregulated glucagon secretion and declining beta-cell function.
Figures
References
-
- Gromada J, Franklin I, Wollheim CB: Alpha-cells of the endocrine pancreas: 35 years of research but the enigma remains. Endocr Rev 28:84–116, 2007 - PubMed
-
- Sperling MA, Aleck K, Voina S: Suppressibility of glucagon secretion by glucose in juvenile diabetes. J Pediatr 90:543–547, 1977 - PubMed
-
- Gerich JE, Lorenzi M, Karam JH, Schneider V, Forsham PH: Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus. JAMA 234:159–155, 1975 - PubMed
-
- Ternand C, Go VL, Gerich JE, Haymond MW: Endocrine pancreatic response of children with onset of insulin-requiring diabetes before age 3 and after age 5. J Pediatr 101:36–39, 1982 - PubMed
-
- Henkel E, Menschikowski M, Koehler C, Leonhardt W, Hanefeld M: Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus. Metabolism 54:1168–1173, 2005 - PubMed
