OJEMD  Vol.5 No.9 , September 2015
Idiopathic Reactive Hypoglycemia: Mechanisms of Onset and Remission with High Protein Low Carbohydrate Diet
Abstract: Objective: Idiopathic reactive hypoglycemia is defined as early postprandial hypoglycemia occurring on ingestion of high carbohydrate containing meal. Remission ensues with high protein low carbohydrate diet. This study assessed roles of insulin and glucagon in its onset and remission. Methods: Plasma glucose, insulin and glucagon were determined after an overnight fast and repeatedly until 180 minutes on ingestion of 3 meals; 100 g glucose; 100 g pure protein liquid and mixture of 50 g each at 14 days’ interval. Five adults with IRH and 6 age matched healthy volunteers participated. Results: In IRH, glucose ingestion induced prompt rise in glucose (5.1 ± 0.8 to10.5 ± 1.2 mM/L) followed later by hypoglycemia (2.6 ± 0.4 mM/L). Insulin rose from 7 ± 2 to 90 ± 18 mU/L. Glucagon rose initially (10% ± 2%) from elevated basal concentration (373 ± 57 mU/L) followed by later decline (-43% ± 12%). On protein ingestion, glucose declined followed by a restoration to basal level while both insulin and glucagon rose (28 ± 6 mU/L; 148% ± 38%, p < 0.01). However, insulin response was lower and glucagon rise was greater when compared to responses on glucose ingestion (p < 0.01). With mixed meal, glucose (8.2 ± 0.6 mM/L), insulin (65 ± 12 mU/L) and glucagon (48% ± 7%) responses were lesser than rises following glucose ingestion (p < 0.05) and hypoglycemia did not occur. Conclusion: In IRH, initial hyperglycemia on glucose ingestion may be exacerbated by paradoxical glucagon rise and hypoglycemia may be induced by increased insulin and declining glucagon responses. Resolution of hypoglycemia with high protein low carbohydrate diet may be attributed to blunting of insulin response and concurrent glucagon rise.
Cite this paper: Prakash, K. , Kabadi, M. and Kabadi, U. (2015) Idiopathic Reactive Hypoglycemia: Mechanisms of Onset and Remission with High Protein Low Carbohydrate Diet. Open Journal of Endocrine and Metabolic Diseases, 5, 117-123. doi: 10.4236/ojemd.2015.59015.

[1]   (1971) Medical Staff Conference Reactive Hypoglycemia Mechanisms and Management California Medicine. The Western Journal of Medicine, 114, 64-70.

[2]   Betteridge, D.J. (1987) Reactive Hypoglycemia. British Medical Journal (Clinical Research Ed.), 295, 286-287.

[3]   Hofeldt, F.D. (1989) Reactive Hypoglycemia. Endocrinology Metabolism Clinics of North America, 18, 185-201.

[4]   Brun, J.F., Fedou, C. and Mercier, J. (2000) Postprandial Reactive Hypoglycemia. Diabetes & Metabolism, 26, 337-351.

[5]   Scheen, A.J. and Lefèbvre, P.J. (2004) Reactive Hypoglycemia, a Mysterious, Insidious but Non Dangerous Critical Phenomenon. Revue Medicale de Liege, 59, 237-242.

[6]   Khan, M. and Kabadi, U.M. (2011) Postprandial Hypoglycemia in “Diabetes-Damages and Treatments”. Tech Publisher, Chapter 6, 117-126.

[7]   Kabadi, U.M. (1991) Dose-Kinetics of Pancreatic Alpha- and Beta-Cell Responses to a Protein Meal in Normal Subjects. Metabolism, 40, 236-240.

[8]   Ahmadpour, S. and Kabadi, U.M. (1997) Pancreatic Alpha-Cell Function in Idiopathic Reactive Hypoglycemia. Metabolism, 46, 639-643.

[9]   Marks, V. and Teale, J.D. (1993) Hypoglycemia in the Adult. Baillière’s Clinical Endocrinology and Metabolism, 7, 705-729.

[10]   Service, F.J. (1995) Hypoglycemic Disorders. The New England Journal of Medicine, 332, 1144-1152.

[11]   Middleton, S.J. and Balan, K. (2011) Post-Prandial Reactive Hypoglycaemia and Diarrhea Caused by Idiopathic Accelerated Gastric Emptying: A Case Report. Journal of Medical Case Reports, 5, 177.

[12]   Service, G.J., Thompson, G.B., Service, F.J., Andrews, J.C., Collazo-Clavell, M.L. and Lloyd, R.V. (2005) Hyperinsulinemic Hypoglycemia with Nesidioblastosis after Gastric-Bypass Surgery. New England Journal of Medicine, 353, 249-254.

[13]   Tamburrano, G., Leonetti, F., Sbraccia, P., et al. (1989) Increased Insulin Sensitivity in Patients with Idiopathic Reactive Hypoglycemia. The Journal of Clinical Endocrinology and Metabolism, 69, 885-890.

[14]   Leonetti, F., Morviducci, L., Giaccari, A., et al. (1992) Idiopathic Reactive Hypoglycemia: A Role for Glucagon? Journal of Endocrinological Investigation, 15, 273-278.

[15]   Cavaco, B., Uchigata, Y., Porto, T., Amparo-Santos, M., Sobrinho, L. and Leite, V. (2001) Hypoglycemia Due to Insulin Autoimmune Syndrome: Report of Two Cases with Characterization of HLA Alleles and Insulin Autoantibodies. European Journal of Endocrinology, 145, 311-316.

[16]   Kim, C.H., Park, J.H., Park, T.S. and Baek, H.S. (2004) Autoimmune Hypoglycemia in a Type 2 Diabetic Patient with Anti-Insulin and Insulin Receptor Antibodies. Diabetes Care, 27, 288-289.

[17]   Hizuka, N., Fukuda, I., Takano, K., Okubo, Y., Asakawa-Yasumoto, K. and Demura, H. (1998) Serum Insulin-Like Growth Factor II in 44 Patients with Non-Islet Cell Tumor Hypoglycemia. Endocrine Journal, 45, S61-S65.

[18]   Richard, J.L., Rodier, M., Monnier, L., Orsetti, A. and Mirouze, J. (1988) Effect of Acarbose on Glucose and Insulin Response to Sucrose Load in Reactive Hypoglycemia. Diabetes & Metabolism, 14, 114-118.

[19]   Arii, K., Ota, K., Suehiro, T., Ikeda, Y., Nishimura, K., Kumon, Y. and Hashimoto, K. (2005) Pioglitazone Prevents Reactive Hypoglycemia in Impaired Glucose Tolerance. Diabetes Research and Clinical Practice, 69, 305-308.

[20]   Sorensen, M. and Johansen, O.E. (2010) Idiopathic Reactive Hypoglycemia—Prevalence and Effect of Fibre on Glucose Excursions. Scandinavian Journal of Clinical and Laboratory Investigation, 70, 385-391.

[21]   Keller, D. and Santiago, J. (1967) Cholinergic Blockade in Reactive Hypoglycemia. Diabetes, 26, 121-127.

[22]   Kabadi, U.M. (1993) Hepatic Regulation of Pancreatic Alpha-Cell Function. Metabolism, 42, 535-543.

[23]   Kabadi, U.M. (1992) Is Hepatic Glycogen Content a Regulator of Glucagon Secretion? Metabolism, 41, 113-115

[24]   Kabadi, U.M. (1987) The Association of Hepatic Glycogen Depletion with Hyperammonemia in Cirrhosis. Hepatology, 7, 821-824.

[25]   Kabadi, U.M., Eisenstein, A.B. and Konda, J. (1985) Elevated Plasma Ammonia Level in Hepatic Cirrhosis: Role of Glucagon. Gastroenterology, 88, 750-756.

[26]   Kabadi, U.M., Eisenstein, A.B., Tucci, J. and Pellicone, J. (1984) Hyperglucagonemia in Hepatic Cirrhosis: Its Relation to Hepatocellular Dysfunction and Normalization on Recovery. American Journal of Gastroenterology, 79, 143-149.