Assessment of beta cell function in subjects with newly diagnosed type 2 diabetes

Open access

Abstract

Objectives: The primary aim of this study was to assess residual beta cell function at diagnosis of type 2 diabetes and identify accessible laboratory markers that best estimate it. The secondary objective was to evaluate the change in beta cell function 6 months after starting different therapeutical regimens. Materials and methods: Forty seven subjects were included in the study and each performed a 75-g oral glucose tolerance test (OGTT) at baseline and after 6 months. Metabolic and immunologic parameters were determined from fasting samples. According to the degree of metabolic decompensation, specific therapy was started: metformin, metformin plus gliclazide or insulin therapy (with/out metformin). Early and total beta cell function was evaluated by the disposition index (DI) calculated for 30 minutes and 120 minutes, respectively. Results: At diagnosis, fasting blood glucose (BG) and HbA1c varied largely (129-521 mg/dl and 5.5-14%, respectively). The DI30 and DI120 decreased with more severe glycemic decompensation. For both DI30 and DI120 significant negative correlations were found for glycemic markers (HbA1c, 2-hour BG and maximal BG amplitude) and positive correlation for 2- hour C peptide (p<0.0001 for all). HbA1c value of 7% discriminated an important decrease of DI30 and DI120. Insulin and combined therapy significantly improved DI120 at 6 months (p: 0.0062 and 0.01, respectively), while DI30 was improved only with insulin therapy (p: 0.0326). Conclusions: Beta cell function at onset correlated with HbA1c, 2-hour BG and C peptide during OGTT. Thus OGTT and HbA1c are pivotal for evaluation of beta cell function. Insulin therapy improved early and total insulin secretion at 6 months.

1. Bi Y, Zhu D, Jing Y, Hu Y, Feng W, Shen S, et al. Decreased beta cell function and insulin sensitivity contributed to increasing fasting glucose in Chinese. Acta Diabetol 2012; 49 Suppl 1: S51-8.

2. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Beta-Cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 2005; 90: 493-500.

3. Kanat M, Winnier D, Norton L, Arar N, Jenkinson C, DeFronzo RA, et al. The relationship between {beta}-cell function and glycated hemoglobin: results from the veterans administration genetic epidemiology study. Diabetes Care 2011; 34: 1006-10.

4. Pfützner A, Weber MM, Forst T. A biomarker concept for assessment of insulin resistance, beta-cell function and chronic systemic inflammation in type 2 diabetes mellitus. Clin Lab 2008; 54: 485-90.

5. Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 2008; 294: E15-26.

6. Bacha F, Gungor N, Arslanian SA. Measures of betacell function during the oral glucose tolerance test, liquid mixed-meal test, and hyperglycemic clamp test. J Pediatr 2008; 152: 618-21.

7. Tripathy D, Almgren P, Tuomi T, Groop L. Contribution of insulin-stimulated glucose uptake and basal hepatic insulin sensitivity to surrogate measures of insulin sensitivity. Diabetes Care 2004; 27: 2204-10.

8. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33 Suppl 1: S62-9.

9. Mari A, Pacini G. Methods for the Assessment of β- cell Function in vivo; in “Clinical Diabetes and Research: Methods and Techniques” Editor Michael Roden; John Wiley & Sons Ltd., 2007, pg 7-27.

10. Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58: 773-95.

11. Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes 2004; 53 Suppl 3: S16-21.

12. Bi Y, Zeng L, Zhu D, Yan J, Zhang Y, Tong G, et al. Association of β-cell function and insulin sensitivity with fasting and 2-h plasma glucose in a large Chinese population. Diabetes Obes Metab 2012; 14: 174-80.

13. Abdul-Ghani MA, Matsuda M, Jani R, Jenkinson CP, Coletta DK, Kaku K, et al. The relationship between fasting hyperglycemia and insulin secretion in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab 2008; 295: E401-6.

14. Abdul-Ghani MA, DeFronzo RA. Plasma glucose concentration and prediction of future risk of type 2 diabetes. Diabetes Care 2009; 32 Suppl 2: S194-8.

15. Loopstra-Masters RC, Haffner SM, Lorenzo C, Wagenknecht LE, Hanley AJ. Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia 2011; 54: 3047-54.

16. Banu S, Jabir NR, Manjunath CN, Shakil S, Kamal MA.C-peptide and its correlation to parameters of insulin resistance in the metabolic syndrome. CNS Neurol Disord Drug Targets 2011; 10: 921-7.

17. Bergstrom RW, Newell-Morris LL, Leonetti DL, Shuman WP, Wahl PW, Fujimoto WY. Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese- American men. Diabetes 1990; 39: 104-11.

18. Pfützner A, Kunt T, Hohberg C, Mondok A, Pahler S, Konrad T, et al. Fasting intact proinsulin is a highly specific predictor of insulin resistance in type 2 diabetes. Diabetes Care 2004; 27: 682-7.

19. Hanley AJ, McKeown-Eyssen G, Harris SB, Hegele RA, Wolever TM, Kwan J, et al. Cross-sectional and prospective associations between abdominal adiposity and proinsulin concentration. J Clin Endocrinol Metab 2002; 87: 77-83.

20. Pfützner A, Forst T. Elevated intact proinsulin levels are indicative of Beta-cell dysfunction, insulin resistance, and cardiovascular risk: impact of the antidiabetic agent pioglitazone. J Diabetes Sci Technol. 2011 May;5(3):784-93.

21. Røder ME, Kahn SE. Suppression of Beta-cell secretion by somatostatin does not fully reverse the disproportionate proinsulinemia of type 2 diabetes. Diabetes 2004; 53 Suppl 3: S22-5.

22. Grill V, Dinesen B, Carlsson S, Efendic S, Pedersen O, Ostenson CG. Hyperproinsulinemia and proinsulin- to-insulin ratios in Swedish middle-aged men: association with glycemia and insulin resistance but not with family history of diabetes. Am J Epidemiol 2002; 155: 834-41.

23. Ilkova H, Glaser B, Tunçkale A, Bagriaçik N, Cerasi E. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment. Diabetes Care 1997; 20: 1353-6.

24. Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care 2004; 27: 1028-32.

25. Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008; 371: 1753-60.

26. Bhattacharya S, Ammini AC, Jyotsna V, Gupta N, Dwivedi S. Recovery of β-cell functions with low-dose insulin therapy: study in newly diagnosed type 2 diabetes mellitus patients. Diabetes Technol Ther 2011; 13: 461-5.

27. Chen HS, Wu TE, Jap TS, Hsiao LC, Lee SH, Lin HD. Beneficial effects of insulin on glycemic control and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. Diabetes Care 2008; 31: 1927-32.

28. Alvarsson M, Berntorp K, Fernqvist-Forbes E, Lager I, Steen L, Orn T, et al. Effects of insulin versus sulphonylurea on beta-cell secretion in recently diagnosed type 2 diabetes patients: a 6-year follow-up study. Rev Diabet Stud 2010; 7: 225-32.

29. Harrison LB, Adams-Huet B, Raskin P, Lingvay I. β- cell function preservation after 3.5 years of intensive diabetes therapy. Diabetes Care 2012; 35: 1406-12.

30. Pennartz C, Schenker N, Menge BA, Schmidt WE, Nauck MA, Meier JJ. Chronic reduction of fasting glycemia with insulin glargine improves first- and secondphase insulin secretion in patients with type 2 diabetes. Diabetes Care 2011; 34: 2048-53.

31. ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, Díaz R, Jung H, Maggioni AP, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367: 319-28.

32. Brown RJ, Rother KI. Effects of beta-cell rest on beta-cell function: a review of clinical and preclinical data. Pediatr Diabetes 2008; 9: 14-22.

33. Absood A, Gandomani B, Zaki A, Nasta V, Michail A, Habib PM, et al. Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding. PLoS One 2013; 8: e54351.

34. Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, DonathMY. Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab 2005; 90: 501-6.

35. Irwin N, McKinney JM, Bailey CJ, Flatt PR, McClenaghan NH. Effects of metformin on BRIN-BD11 betacell insulin secretory desensitization induced by prolonged exposure to sulphonylureas. Diabetes Obes Metab 2010; 12: 1066-71.

36. Shin MS, Yu JH, Jung CH, Hwang JY, Lee WJ, Kim MS, et al. The duration of sulfonylurea treatment is associated with β-cell dysfunction in patients with type 2 diabetes mellitus. Diabetes Technol Ther 2012; 14: 1033-42.

37. Del Guerra S, Grupillo M, Masini M, Lupi R, Bugliani M, Torri S, et al. Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose. Diabetes Metab Res Rev 2007; 23: 234-8.

38. Magnusson NE, Dyrskjøt L, Grimm D, Wehland M, Pietsch J, Rungby J. Gene networks modified by sulphonylureas in beta cells: a pathway-based analysis of insulin secretion and cell death. Basic Clin Pharmacol Toxicol 2012; 111: 254-61.

39. Alvarsson M, Sundkvist G, Lager I, Henricsson M, Berntorp K, Fernqvist-Forbes E, et al. Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care 2003; 26: 2231-7.

40. Lablanche S, Cottet-Rousselle C, Lamarche F, Benhamou PY, Halimi S, Leverve X, et al. Protection of pancreatic INS-1 β-cells from glucose- and fructose-induced cell death by inhibiting mitochondrial permeability transition with cyclosporin A or metformin. Cell Death Dis 2011; 2:e134.

41. DeFronzo RA, Abdul-Ghani MA. Preservation of β- cell function: the key to diabetes prevention. J Clin Endocrinol Metab 2011; 96: 2354-66.

42. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2012; 55: 1577-96.

43. Forst T, Dworak M, Berndt-Zipfel C, Löffler A, Klamp I, Mitry M, et al. Effect of vildagliptin compared to glimepiride on postprandial proinsulin processing in the β cell of patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2013 Jun;15(6):576-9.

44. Lopez X, Cypess A, Manning R, O'Shea S, Kulkarni RN, Goldfine AB. Exogenous insulin enhances glucose- stimulated insulin response in healthy humans independent of changes in free fatty acids. J Clin Endocrinol Metab 2011; 96: 3811-21.

45. Halperin F, Lopez X, Manning R, Kahn CR, Kulkarni RN, Goldfine AB. Insulin augmentation of glucose- stimulated insulin secretion is impaired in insulin-resistant humans. Diabetes 2012; 61: 301-9.

Revista Romana de Medicina de Laborator

Romanian Journal of Laboratory Medicine

Journal Information


IMPACT FACTOR 2017: 0.400
5-year IMPACT FACTOR: 0.320



CiteScore 2017: 0.31

SCImago Journal Rank (SJR) 2017: 0.144
Source Normalized Impact per Paper (SNIP) 2017: 0.195

Cited By

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 185 185 23
PDF Downloads 50 50 7