The clinical utility of C‐peptide measurement in the care of patients with diabetes

Abstract

C‐peptide is produced in equal amounts to insulin and is the best measure of endogenous insulin secretion in patients with diabetes. Measurement of insulin secretion using C‐peptide can be helpful in clinical practice: differences in insulin secretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This article reviews the use of C‐peptide measurement in the clinical management of patients with diabetes, including the interpretation and choice of C‐peptide test and its use to assist diabetes classification and choice of treatment. We provide recommendations for where C‐peptide should be used, choice of test and interpretation of results. With the rising incidence of Type 2 diabetes in younger patients, the discovery of monogenic diabetes and development of new therapies aimed at preserving insulin secretion, the direct measurement of insulin secretion may be increasingly important. Advances in assays have made C‐peptide measurement both more reliable and inexpensive. In addition, recent work has demonstrated that C‐peptide is more stable in blood than previously suggested or can be reliably measured on a spot urine sample (urine C‐peptide:creatinine ratio), facilitating measurement in routine clinical practice. The key current clinical role of C‐peptide is to assist classification and management of insulin‐treated patients. Utility is greatest after 3–5 years from diagnosis when persistence of substantial insulin secretion suggests Type 2 or monogenic diabetes. Absent C‐peptide at any time confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.

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References 132

1. 1.

   Wahren J, Kallas A, Sima AA. The clinical potential of C-peptide replacement in type 1 diabetes. Diabetes. 2012;61:761-772.

   Not in our library10.2337/db11-1423

2. 2.

   Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94:709-728.

   Not in our library10.1210/jc.2008-1410

3. 3.

   Brandenburg D. History and diagnostic significance of C-peptide. Exp Diabetes Res. 2008;2008:576862.

   Not in our library10.1155/2008/576862

4. 4.

   Clark PM. Assays for insulin, proinsulin(s) and C-peptide. Ann Clin Biochem. 1999;36:541-564.

   Not in our library10.1177/000456329903600501

5. 5.

   Polonsky KS, Licinio-Paixao J, Given BD, Pugh W, Rue P, Galloway J, et al. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest. 1986;77:98-105.

   Not in our library10.1172/jci112308

6. 6.

   Licinio-Paixao J, Polonsky KS, Given BD, Pugh W, Ostrega D, Frank BF, et al. Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide. J Clin Endocrinol Metab. 1986;63:401-403.

   Not in our library10.1210/jcem-63-2-401

7. 7.

   Field JB. Extraction of insulin by liver. Annu Rev Med. 1973;24:309-314.

   Not in our library10.1146/annurev.me.24.020173.001521

8. 8.

   Brundin T. Splanchnic and extrasplanchnic extraction of insulin following oral and intravenous glucose loads. Clin Sci (Lond). 1999;97:429-436.

   Not in our library

9. 9.

   Shapiro ET, Tillil H, Rubenstein AH, Polonsky KS. Peripheral insulin parallels changes in insulin secretion more closely than C-peptide after bolus intravenous glucose administration. J Clin Endocrinol Metab. 1988;67:1094-1099.

   Not in our library10.1210/jcem-67-5-1094

10. 10.

    Eaton RP, Allen RC, Schade DS, Erickson KM, Standefer J. Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J Clin Endocrinol Metab. 1980;51:520-528.

    Not in our library10.1210/jcem-51-3-520

11. 11.

    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.

    Not in our library10.2337/diab.41.3.368

12. 12.

    Henriksen JH, Tronier B, Bulow JB. Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man. Metabolism. 1987;36:463-468.

    Not in our library10.1016/0026-0495(87)90044-8

13. 13.

    Zavaroni I, Deferrari G, Lugari R, Bonora E, Garibotto G, Dall'Aglio E, et al. Renal metabolism of C-peptide in man. J Clin Endocrinol Metab. 1987;65:494-498.

    Not in our library10.1210/jcem-65-3-494

14. 14.

    Covic AM, Schelling JR, Constantiner M, Iyengar SK, Sedor JR. Serum C-peptide concentrations poorly phenotype type 2 diabetic end-stage renal disease patients. Kidney Int. 2000;58:1742-1750.

    Not in our library10.1046/j.1523-1755.2000.00335.x

15. 15.

    Abe M, Okada K, Matsumoto K. Plasma insulin and C-peptide concentrations in diabetic patients undergoing hemodialysis: comparison with five types of high-flux dialyzer membranes. Diabetes Res Clin Pract. 2008;82:e17-19.

    Not in our library10.1016/j.diabres.2008.07.020

16. 16.

    Faradji RN, Monroy K, Messinger S, Pileggi A, Froud T, Baidal DA, et al. Simple measures to monitor beta-cell mass and assess islet graft dysfunction. Am J Transplant. 2007;7:303-308.

    Not in our library10.1111/j.1600-6143.2006.01620.x

17. 17.

    Gale EA. Latent autoimmune diabetes in adults: a guide for the perplexed. Diabetologia. 2005;48:2195-2199.

    Not in our library10.1007/s00125-005-1954-5

18. 18.

    Thunander M, Torn C, Petersson C, Ossiansson B, Fornander J, Landin-Olsson M. Levels of C-peptide, BMI, and age, and their utility for classification of diabetes in relation to autoimmunity, in adults with newly diagnosed diabetes in Kronoberg, Sweden. Eur J Endocrinol. 2012;166:1021-1029.

    Not in our library10.1530/eje-11-0797

19. 19.

    Redondo MJ, Rodriguez LM, Escalante M, O'Brian Smith E, Balasubramanyam A, Haymond MW. Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes. Pediatr Diabetes. 2012;13:564-571.

    Not in our library10.1111/j.1399-5448.2012.00875.x

20. 20.

    Winter WE, Schatz DA. Autoimmune markers in diabetes. Clin Chem. 2011;57:168-175.

    Not in our library10.1373/clinchem.2010.148205

21. 21.

    Ashby JP, Frier BM. Circulating C peptide: measurement and clinical application. Ann Clin Biochem. 1981;18:125-130.

    Not in our library10.1177/000456328101800301

22. 22.

    Koskinen P. Nontransferability of C-peptide measurements with various commercial radioimmunoassay reagents. Clin Chem. 1988;34:1575-1578.

    Not in our library

23. 23.

    Palmer JP, Fleming GA, Greenbaum CJ, Herold KC, Jansa LD, Kolb H, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21–22 October 2001. Diabetes. 2004;53:250-264.

    Not in our library10.2337/diabetes.53.1.250

24. 24.

    Little RR, Rohlfing CL, Tennill AL, Madsen RW, Polonsky KS, Myers GL, et al. Standardization of C-peptide measurements. Clin Chem. 2008;54:1023-1026.

    Not in our library10.1373/clinchem.2007.101287

25. 25.

    Wiedmeyer HM, Polonsky KS, Myers GL, Little RR, Greenbaum CJ, Goldstein DE, et al. International comparison of C-peptide measurements. Clin Chem. 2007;53:784-787.

    Not in our library10.1373/clinchem.2006.081570

26. 26.

    Bolner A, Lomeo L, Lomeo AM. ‘Method-specific’ stability of serum C-peptide in a multicenter clinical study. Clin Lab. 2005;51:153-155.

    Not in our library

27. 27.

    McDonald TJ, Perry MH, Peake RW, Pullan NJ, O'Connor J, Shields BM, et al. EDTA improves stability of whole blood C-Peptide and insulin to over 24 hours at room temperature. PLoS One. 2012;7:e42084.

    Not in our library10.1371/journal.pone.0042084

28. 28.

    Oddoze C, Lombard E, Portugal H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin Biochem. 2012;45:464-469.

    Not in our library10.1016/j.clinbiochem.2012.01.012

29. 29.

    Jane Ellis M, Livesey JH, Evans MJ. Hormone stability in human whole blood. Clin Biochem. 2003;36:109-112.

    Not in our library10.1016/s0009-9120(02)00440-x

30. 30.

    Albareda M, Rigla M, Rodriguez-Espinosa J, Caballero A, Chico A, Cabezas R, et al. Influence of exogenous insulin on C-peptide levels in subjects with type 2 diabetes. Diabetes Res Clin Pract. 2005;68:202-206.

    Not in our library10.1016/j.diabres.2004.10.005

31. 31.

    Nosari I, Lepore G, Maglio ML, Cortinovis F, Pagani G. The effect of various blood glucose levels on post-glucagon C-peptide secretion in type 2 (non insulin-dependent) diabetes. J Endocrinol Invest. 1992;15:143-146.

    Not in our library10.1007/bf03348682

32. 32.

    Hsieh SD, Iwamoto Y, Matsuda A, Kuzuya T. Pancreatic B-cell function in non-insulin-dependent diabetes mellitus during successive periods of sulfonylurea and insulin treatment: serum C-peptide response to glucagon and urine C-peptide excretion. Endocrinol Jpn. 1987;34:561-567.

    Not in our library10.1507/endocrj1954.34.561

33. 33.

    Aoki Y. Variation of endogenous insulin secretion in association with treatment status: assessment by serum C-peptide and modified urinary C-peptide. Diabetes Res Clin Pract. 1991;14:165-173.

    Not in our library10.1016/0168-8227(91)90017-8

34. 34.

    Greenbaum CJ, Mandrup-Poulsen T, McGee PF, Battelino T, Haastert B, Ludvigsson J, et al. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care. 2008;31:1966-1971.

    Not in our library10.2337/dc07-2451

35. 35.

    Gjessing HJ, Matzen LE, Froland A, Faber OK. Correlations between fasting plasma C-peptide, glucagon-stimulated plasma C-peptide, and urinary C-peptide in insulin-treated diabetics. Diabetes Care. 1987;10:487-490.

    Not in our library10.2337/diacare.10.4.487

36. 36.

    Laakso M, Ronnemaa T, Sarlund H, Pyorala K, Kallio V. Factors associated with fasting and postglucagon plasma C-peptide levels in middle-aged insulin-treated diabetic patients. Diabetes Care. 1989;12:83-88.

    Not in our library10.2337/diacare.12.2.83

37. 37.

    Besser RE, Jones AG, McDonald TJ, Shields BM, Knight BA, Hattersley AT. The impact of insulin administration during the mixed meal tolerance test. Diabet Med. 2012;29:1279-1284.

    Not in our library10.1111/j.1464-5491.2012.03649.x

38. 38.

    Torn C L-OM, Schersten B. Predictability of C-peptide for autoimmune diabetes in young adult diabetic patients. Pract Diabetes Int. 2001;18:83-88.

    Not in our library

39. 39.

    Berger B, Stenstrom G, Sundkvist G. Random C-peptide in the classification of diabetes. Scand J Clin Lab Invest. 2000;60:687-693.

    Not in our library10.1080/00365510050216411

40. 40.

    Lee A, Morley J. Classification of type 2 diabetes by clinical response to metformin–troglitazone combination and C-peptide criteria. Endocr Pract. 1999;5:305-313.

    Not in our library10.4158/ep.5.6.305

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