Twelve weeks' treatment with diazoxide without insulin supplementation in Type 2 diabetes is feasible but does not improve insulin secretion

Diabetic Medicine

Volumn 24, Issue 2, 2007, Pages 172-177

  Radtke, M ^a,b   Kollind, M ^c   Qvigstad, E ^a,b   Grill, V ^a,b  

^a NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^b TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^c Levanger Hospital   (Norway)

Author keywords

cell function; Diazoxide; Insulin secretion; K ATP channel openers; Type 2 diabetes

Indexed keywords

C PEPTIDE; DIAZOXIDE; FATTY ACID; GLUCAGON; GLUCOSE; HEMOGLOBIN A1C; INSULIN; METFORMIN; REPAGLINIDE;

ADULT; ARTICLE; BLOOD GLUCOSE MONITORING; CELL FUNCTION; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG ERUPTION; DRUG SAFETY; FATTY ACID BLOOD LEVEL; FEMALE; GLUCAGON BLOOD LEVEL; GLUCOSE BLOOD LEVEL; GLYCEMIC CONTROL; HEMOGLOBIN BLOOD LEVEL; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RELEASE; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; PANCREAS ISLET BETA CELL; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

CARBAMATES; DIABETES MELLITUS, TYPE 2; DIAZOXIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; HYPOGLYCEMIC AGENTS; INSULIN; INSULIN-SECRETING CELLS; MALE; METFORMIN; MIDDLE AGED; PIPERIDINES; TREATMENT OUTCOME;

EID: 33846609221     PISSN: 07423071     EISSN: 14645491     Source Type: Journal    
DOI: 10.1111/j.1464-5491.2006.02056.x     Document Type: Article

References (24)

1. Clauson P, Linnarsson R, Gottsäter A, Sundkvist G, Grill V. Relationships between diabetes duration, metabolic control and beta-cell function in a representative population of type 2 diabetic patients in Sweden. Diabet Med 1994; 11: 794-801.
2. Coordt MC, Ruhe RC, McDonald RB. Aging and insulin secretion. Proc Soc Exp Biol Med 1995; 209: 213-222.
3. Grill V, Björklund A. Overstimulation and beta-cell function. Diabetes 2001; 50: S122-S124.
4. Grill V, Björklund A. Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities. Cell Mol Life Sci 2000; 57: 429-440.
5. Hansen JB, Arkhammar PO, Bodvarsdottir TB, Wahl P. Inhibition of insulin secretion as a new drug target in the treatment of metabolic disorders. Curr Med Chem 2004; 11: 1595-1615.
6. 2+]i abnormalities in human pancreatic islets: important role of overstimulation. Diabetes 2000; 49: 1840-1848.
7. Björklund A, Grill V. Enhancing effects of long-term elevated glucose and palmitate on stored and secreted proinsulin-to-insulin ratios in human pancreatic islets. Diabetes 1999; 48: 1409-1414.
8. Leahy JL, Bumbalo LM, Chen C. Diazoxide causes recovery of beta-cell glucose responsiveness in 90% pancreatectomized diabetic rats. Diabetes 1994; 43: 173-179.
9. Sako Y, Grill VE. Coupling of beta-cell desensitization by hyperglycemia to excessive stimulation and circulating insulin in glucose-infused rats. Diabetes 1990; 39: 1580-1583.
10. Greenwood RH, Mahler RF, Hales CN. Improvement in insulin secretion in diabetes after diazoxide. Lancet 1976; 1: 444-447.
11. Ashcroft FM, Gribble FM. ATP-sensitive K+ channels and insulin secretion: their role in health and disease. Diabetologia 1999; 42: 903-919.
12. Grimmsmann T, Rustenbeck I. Direct effects of diazoxide on mitochondria in pancreatic B-cells and on isolated liver mitochondria. Br J Pharmacol 1998; 123: 781-788.
13. MacDonald MJ. High content of mitochondrial glycerol-3-phosphate dehydrogenase in pancreatic islets and its inhibition by diazoxide. J Biol Chem 1981; 256: 8287-8290.
14. Trube G, Rorsman P, Ohno-Shosaku T. Opposite effects of tolbutamide and diazoxide on the ATP-dependent K+ channel in mouse pancreatic beta-cells. Pflugers Arch 1986; 407: 493-499.
15. Björk E, Berne C, Kampe O, Wibell L, Oskarsson P, Karlsson FA, et al. Diazoxide treatment at onset preserves residual insulin secretion in adults with autoimmune diabetes. Diabetes 1996; 45: 1427-1430.
16. Ǒrtqvist E, Björk E, Wallensteen M, Ludwigsson J, Amen J, Johansson C, et al. Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes. Diabetes Care 2004; 27: 2191-2197.
17. Qvigstad E, Kollind M, Grill V. Nine weeks of bedtime diazoxide is well tolerated and improves beta-cell function in subjects with Type 2 diabetes. Diabet Med 2004; 21: 73-76.
18. Alemzadeh R, Slonim AE, Zdanowicz MM, Maturo J. Modification of insulin resistance by diazoxide in obese Zucker rats. Endocrinology 1993; 133: 705-712.
19. Sebastian-Gambaro MA, Liron-Hernandez FJ, Fuentes-Arderiu X. Intra- and inter-individual biological variability data bank. Eur J Clin Chem Clin Biochem 1997; 35: 845-852.
20. Jorde R, Sundsfjord J. Intra-individual variability and longitudinal changes in glycaemic control in patients with Type 1 diabetes mellitus. Diabet Med 2000; 17: 451-456.
21. Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther 1974; 15: 443-453.
22. Scheen AJ, Castillo MJ, Lefebvre PJ. Assessment of residual insulin secretion in diabetic patients using the intravenous glucagon stimulatory test: methodological aspects and clinical applications. Diabetes Metab 1996; 22: 397-406.
23. Faber OK, Binder C. C-peptide response to glucagon. A test for the residual beta-cell function in diabetes mellitus. Diabetes 1977; 26: 605-610.
24. Clauson P, Alvarsson M, Grill V. Enhancement of B-cell secretion by blood glucose normalization in type 2 diabetes is associated with fasting C-peptide levels. J Intern Med 1997; 241: 493-500.