Endocrinol Metab.  2016 Jun;31(2):320-327. 10.3803/EnM.2016.31.2.320.

C-Peptide-Based Index Is More Related to Incident Type 2 Diabetes in Non-Diabetic Subjects than Insulin-Based Index

• Kim JD
• Kang SJ
• Lee MK
• Park SE
• Rhee EJ
• Park CY
• Oh KW
• Park SW
• Lee WY

• KMID: 2308863
• DOI: http://doi.org/10.3803/EnM.2016.31.2.320

Abstract

BACKGROUND
Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans.
METHODS
This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline.
RESULTS
Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014).
CONCLUSION
C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

Keyword

Glucose tolerance test; C-peptide; Insulin secretion and incident diabetes

MeSH Terms

C-Peptide
Follow-Up Studies
Glucose
Glucose Tolerance Test
Insulin
Life Style
Longitudinal Studies
Prediabetic State
Retrospective Studies
ROC Curve
C-Peptide
Glucose
Insulin

Reference

1. International Diabetes Federation. IDF diabetes atlas. 6th ed. Brussels: International Diabetes Federation;2013.

2. Jeon JY, Ko SH, Kwon HS, Kim NH, Kim JH, Kim CS, et al. Prevalence of diabetes and prediabetes according to fasting plasma glucose and HbA1c. Diabetes Metab J. 2013; 37:349–357.

3. Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract. 2007; 78:305–312.

4. Laakso M. Epidemiology of diabetic dyslipidemia. Diabetes Rev. 1995; 3:408–422.

5. Bagust A, Beale S. Deteriorating beta-cell function in type 2 diabetes: a long-term model. QJM. 2003; 96:281–288.

6. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002; 287:2563–2569.

7. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002; 346:393–403.

8. Abdul-Ghani MA, Williams K, DeFronzo RA, Stern M. What is the best predictor of future type 2 diabetes? Diabetes Care. 2007; 30:1544–1548.

9. Grunberger G, Qiang X, Li Z, Mathews ST, Sbrissa D, Shisheva A, et al. Molecular basis for the insulinomimetic effects of C-peptide. Diabetologia. 2001; 44:1247–1257.

10. 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.

11. Seltzer HS, Allen EW, Herron AL Jr, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967; 46:323–335.

12. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988; 44:837–845.

13. Ohkura T, Shiochi H, Fujioka Y, Sumi K, Yamamoto N, Matsuzawa K, et al. 20/(fasting C-peptide × fasting plasma glucose) is a simple and effective index of insulin resistance in patients with type 2 diabetes mellitus: a preliminary report. Cardiovasc Diabetol. 2013; 12:21.

14. Meier JJ, Menge BA, Breuer TG, Muller CA, Tannapfel A, Uhl W, et al. Functional assessment of pancreatic beta-cell area in humans. Diabetes. 2009; 58:1595–1603.

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; 54:3047–3054.

16. Van Cauter E, Mestrez F, Sturis J, Polonsky KS. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes. 1992; 41:368–377.

17. Breda E, Cobelli C. Insulin secretion rate during glucose stimuli: alternative analyses of C-peptide data. Ann Biomed Eng. 2001; 29:692–700.

18. Hsieh SD, Kanazawa Y, Akanuma Y. Serum free C-peptide response to oral glucose loading as a parameter for the monitoring of pancreatic B-cell function in diabetic patients. Diabetes Res Clin Pract. 1985; 1:109–114.

19. Gottsater A, Landin-Olsson M, Fernlund P, Gullberg B, Lernmark A, Sundkvist G. Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and C-peptide to measure insulin secretion. Scand J Clin Lab Invest. 1992; 52:631–639.

20. Utzschneider KM, Prigeon RL, Tong J, Gerchman F, Carr DB, Zraika S, et al. Within-subject variability of measures of beta cell function derived from a 2 h OGTT: implications for research studies. Diabetologia. 2007; 50:2516–2525.

21. Luppi P, Cifarelli V, Tse H, Piganelli J, Trucco M. Human C-peptide antagonises high glucose-induced endothelial dysfunction through the nuclear factor-kappaB pathway. Diabetologia. 2008; 51:1534–1543.

22. Cifarelli V, Geng X, Styche A, Lakomy R, Trucco M, Luppi P. C-peptide reduces high-glucose-induced apoptosis of endothelial cells and decreases NAD(P)H-oxidase reactive oxygen species generation in human aortic endothelial cells. Diabetologia. 2011; 54:2702–2712.

23. Bhatt MP, Lim YC, Hwang J, Na S, Kim YM, Ha KS. C-peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation. Diabetes. 2013; 62:243–253.

24. Bhatt MP, Lim YC, Kim YM, Ha KS. C-peptide activates AMPKα and prevents ROS-mediated mitochondrial fission and endothelial apoptosis in diabetes. Diabetes. 2013; 62:3851–3862.

25. Kubota M, Sato Y, Khookhor O, Ekberg K, Chibalin AV, Wahren J. Enhanced insulin action following subcutaneous co-administration of insulin and C-peptide in rats. Diabetes Metab Res Rev. 2014; 30:124–131.

26. Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009; 32:335–341.

27. Morimoto A, Tatsumi Y, Deura K, Mizuno S, Ohno Y, Miyamatsu N, et al. Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study. Diabetologia. 2013; 56:1671–1679.