Proinsulin and the proinsulin/insulin ratio in overweight and obese children and adolescents: Relation to clinical parameters, insulin resistance, and impaired glucose regulation

Pediatric Diabetes

Volumn 12, Issue 3 PART 2, 2011, Pages 242-249

  von Berghes, Carlotta ^a   Brabant, Georg ^b   Biebermann, Heike ^a   Krude, Heiko ^a   Wiegand, Susanna ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Childhood obesity; Impaired glucose regulation; Insresistance; PI

Indexed keywords

CARBOHYDRATE; INSULIN; PROINSULIN;

ADOLESCENT; ARTICLE; BODY MASS; CARBOHYDRATE METABOLISM; CHILD; FEMALE; HOMEOSTASIS MODEL ASSESSMENT OF INSULIN RESISTANCE INDEX; HUMAN; IMPAIRED GLUCOSE TOLERANCE; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PANCREAS INSUFFICIENCY; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PUBERTY; SCORING SYSTEM;

ADOLESCENT; BODY WEIGHT; CHILD; CHILD, PRESCHOOL; CROSS-SECTIONAL STUDIES; FEMALE; GERMANY; GLUCOSE TOLERANCE TEST; HUMANS; INFANT; INSULIN RESISTANCE; MALE; METABOLIC SYNDROME X; OBESITY; PROINSULIN; PUBERTY; SEX CHARACTERISTICS; YOUNG ADULT;

EID: 79955471560     PISSN: 1399543X     EISSN: 13995448     Source Type: Journal    
DOI: 10.1111/j.1399-5448.2010.00734.x     Document Type: Article

References (48)

1. Weiss R, Caprio S. Development of type 2 diabetes in children and adolescents. Minerva Medica 2006: 97: 263-269.
2. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia 2003: 46: 3-19.
3. Guillausseau PJ, Meas T, Virally M, LaloiMichelin M, Medeau V, Kevorkian JP. Abnormalities in insulin secretion in type 2 diabetes mellitus. Diabetes Metab 2008: 34(Suppl. 2): S43-S48.
4. Mykkänen L, Haffner SM, Hales CN, Rönnemaa T, Laakso M. The relation of proinsulin, insulin, and proinsulin-to-insulin ratio to insulin sensitivity and acute insulin response in normoglycemic subjects. Diabetes 1997: 46: 1990-1995.
5. Pfützner A, Kunt T, Hohberg C et al. Fasting intact proinsulin is a highly specific predictor of insulin resistance in type 2 diabetes. Diabetes Care 2004: 27: 682-687.
6. Pfützner A, Standl E, Hohberg C et al. IRIS II study: intact proinsulin is confirmed as a highly specific indicator for insulin resistance in a large cross-sectional study design. Diabetes Technol Ther 2005: 7: 478-486.
7. Hanley AJG, D'Agostino R Jr, Wagenknecht LE et al. Increased proinsulin levels and decreased acute insulin response independently predict the incidence of type 2 diabetes in the insulin resistance atherosclerosis study. Diabetes 2002: 51: 1263-1270.
8. Zethelius B, Byberg L, Hales CN, Lithell H, Berne C. Proinsulin and acute insulin response independently predict type 2 diabetes mellitus in men - report from 27 years of follow-up study. Diabetologia 2003: 46: 20-26.
9. Pfützner A, Pfutzner AH, Larbig M, Forst T. Role of intact proinsulin in diagnosis and treatment of type 2 diabetes mellitus. Diabetes Technol Ther 2004: 6: 405-412.
10. Kahn SE, Leonetti DL, Prigeon RL, Boyko EJ, Bergstom RW, Fujimoto WY. Proinsulin levels predict the development of non-insulin-dependent diabetes mellitus (NIDDM) in Japanese-American men. Diabetes Med 1996: 13: 63.
11. Roder ME, Porte D Jr, Schwartz RS, Kahn SE. Disproportionately elevated proinsulin levels reflect the degree of impaired β-cell secretory capacity in patients with non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998: 83: 604-608.
12. Saad MF, Kahn SE, Nelson R et al. Disproportionately elevated proinsulin in Pima Indians with non-insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1990: 70: 1247-1253.
13. Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D Jr. Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 1987: 30: 698-702.
14. Krentz AJ, Clark PM, Cox L, Nattrass M. Hyperproinsulinaemia in impaired glucose tolerance. Clin Sci 1993: 85: 97-100.
15. Larsson H, Ahren B. Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. J Clin Endocrinol Metab 1999: 84: 2068-2074.
16. Elder DA, Prigeon RL, Wadwa RP, Dolan LM, D'Alessio DA. β-cell function, insulin sensitivity, and glucose tolerance in obese diabetic and nondiabetic adolescents and young adults. J Clin Endocrinol Metab 2006: 91: 185-191.
17. Gungor N, Bacha F, Saad R, Janosky J, Arslanian S. Youth type 2 diabetes: insulin resistance, ß-cell failure, or both? Diabetes Care 2005: 28: 638-644.
18. Sinha R, Fisch G, Teague B et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002: 346: 802-810.
19. Weiss R, Caprio S, Trombetta M, Taksali SE, Tamborlane WV, Bonadonna R. β-cell function across the spectrum of glucose tolerance in obese youth. Diabetes 2005: 54: 1735-1743.
20. Kromeyer-Hauschild K, Wabitsch M, Kunze D, Geller F. Perzentile für den body-mass-index für das kindes-und jugendalter unter heranziehung verschiedener deutscher stichproben. Monatsschr Kinderheilkd 2001: 149: 807-818.
21. Cole TJ. The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990: 44: 45-60.
22. Task Force on Blood Pressure Control in Children. Report of the second task force on blood pressure control in children - 1987. Pediatrics. Bethesda, MA: National Heart, Lung, and Blood Institute.
23. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969: 44: 291-303.
24. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970: 45: 13-23.
25. Allard P, Delvin EE, Paradis G et al. Distribution of fasting plasma insulin, free fatty acids, and glucose concentrations and of homeostasis model assessment of insulin resistance in a representative sample of Quebec children and adolescents. Clin Chem 2003: 49: 644-649.
26. World Health Organization. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Report of a WHO consultation: Part 1 Diagnosis and Definition of Diabetes Mellitus. Geneva: World Health Organization, 1999.
27. American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000: 23: 381-389.
28. Alberti Z. New diagnostic criteria and classification of diabetes-again? Diabetes Med 1998: 15: 535-536.
29. Möhlig M, Flöter A, Spranger J. Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling. Diabetologia 2006: 49: 2572-2579.
30. Forst T, Pfützner A. Moderne laborparameter in der differentialdiagnostik des diabetes mellitus typ 2. Dtsch Med Wochenschr 2006: 131: 268-273.
31. Pfützner A, Kann PH, Pfützner AH et al. Intact and total proinsulin: new aspects for diagnosis and treatment of type 2 diabetes mellitus and insulin resistance. Clin Lab 2004: 50: 567-573.
32. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985: 28: 412-419.
33. Bonora E, Targher G, Alberiche M et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care 2000: 23: 57-63.
34. Kahn SE. The importance of β-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab 2001: 86: 4047-4058.
35. Stumvoll M, Fritsche A, Stefan N, Hardt E, Haring H. Evidence against a rate-limiting role of proinsulin processing for maximal insulin secretion in subjects with impaired glucose tolerance and β-cell dysfunction. J Clin Endocrinol Metab 2001: 86: 1235-1239.
36. Rhodes CJ, Alarcón C. What beta-cell defect could lead to hyperproinsulinemia in NIDDM? Some clues from recent advances made in understanding the proinsulin-processing mechanism. Diabetes 1994: 43: 511-517.
37. Alarcón C, Leahy JL, Schuppin GT, Rhodes CJ. Increased secretory demand rather than a defect in the proinsulin conversion mechanism causes hyperproinsulinemia in a glucose-infusion rat model of non-insulin-dependent diabetes mellitus. J Clin Invest 1995: 95: 1032-1039.
38. Ferrannini E, Muscelli E, Natali A et al. The relationship between insulin sensitivity and cardiovascular disease risk (risc) project investigators- association of fasting glucagon and proinsulin concentrations with insulin resistance. Diabetologia 2007: 50: 2342-2347.
39. Chin D, Oberfield SE, Silfen ME et al. Proinsulin in girls: relationship to obesity, hyperinsulinemia, and puberty. J Clin Endocrinol Metab 2002: 87: 4673-4677.
40. Fritsche A, Madaus A, Stefan N et al. Relationships among age, proinsulin conversion, and ß-cell function in nondiabetic humans. Diabetes 2002: 51: S234-S239.
41. Shimizu M, Kawazu S, Tomono S et al. Age-related alteration of pancreatic beta-cell function. Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese, subjects without glucose intolerance. Diabetes Care 1996: 19: 8-11.
42. Kahn SE, McCulloch D, Schwartz M, Palmer J, Porte D Jr. Effect of insulin resistance and hyperglycemia on proinsulin release in a primate model of diabetes mellitus. J Clin Endocrinol Metab 1992: 74: 192-197.
43. Ward WK, Paquette T, Frank B, Porte D Jr. A sensitive radioimmunoassay for human proinsulin, with sequential use of antisera to C-peptide and insulin. Clin Chem 1986: 32: 728-733.
44. Stefan N, Fritsche A, Madaus A, Häring H, Stumvoll M. Stimulatory effect of increased non-esterified fatty acid concentrations on proinsulin processing in healthy humans. Diabetologia 2000: 43: 1368-1373.
45. Thomas L. Insulin, C-peptid, proinsulin. In: Thomas L, ed. Labor und Diagnose Indikation und Bewertung von Laborbefunden für die medizinische Diagnostik. 2008 (7 Auflage): 214-224.
46. Burghen GA, Etteldorf JN, Trouy RL, Kitabchi AE. Insulin and proinsulin in normal and chemical diabetic children. J Pediatr 1976: 89: 48-53.
47. Rosenbloom AL, Starr JI, Juhn D, Rubenstein AH. Serum proinsulin in children and adolescents with chemical diabetes. Diabetes 1975: 24: 753-757.
48. Gonzalez-Sanchez JL, Martinez-Larrad MT, Zabena C, Perez-Barba M, Serrano-Rios M. Association of variants of the TCF7L2 gene with increases in the risk of type 2 diabetes and the proinsulin:insulin ratio in the Spanish population. Diabetologia 2008: 51: 1993-1997.