Download PDF
Exp Clin Endocrinol Diabetes 2020; 128(09): 607-614
DOI: 10.1055/a-1017-3048
Article

Association Between Serum C-Peptide Level and Cardiovascular Autonomic Neuropathy According to Estimated Glomerular Filtration Rate in Individuals with Type 2 Diabetes

Jin Ook Chung
1   Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Republic of Korea
,
Seon-Young Park
2   Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chonnam National University Medical School, Republic of Korea
,
Dong Hyeok Cho
1   Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Republic of Korea
,
Dong Jin Chung
1   Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Republic of Korea
,
Min Young Chung
1   Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonnam National University Medical School, Republic of Korea
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective To investigate the association between serum C-peptide level and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (DM) according to estimated glomerular filtration rate (eGFR)

Methods In a cross-sectional study, we examined 939 individuals with type 2 DM. We measured fasting C-peptide, 2-hour postprandial C-peptide, and ΔC-peptide (postprandial C-peptide minus fasting C-peptide) levels. The individuals were classified into 2 groups based on eGFR: individuals without impaired renal function (eGFR ≥60 ml∙min−1 1.73m−2) and those with impaired renal function (eGFR <60 ml∙min−1 1.73m−2).

Results Individuals with CAN had lower fasting C-peptide, postprandial C-peptide, and ΔC-peptide levels in patients both with and without impaired renal function. Multivariate logistic regression analyses adjusted for gender, age, and other confounders, including eGFR, showed that serum C-peptide level was significantly associated with CAN (odds ratio [OR] per standard deviation increase in the log-transformed value, 0.67; 95% confidence interval [CI], 0.52–0.87 for fasting C-peptide, P < 0.01; OR, 0.62; 95% CI, 0.47–0.83 for postprandial C-peptide, P < 0.01; OR, 0.71; 95% CI, 0.54–0.93 for ΔC-peptide, P < 0.05).

Conclusions Serum C-peptide level was negatively associated with CAN in individuals with type 2 DM independent of eGFR.

Key words

C-peptide - diabetes mellitus, type 2 - diabetic neuropathies - glomerular filtration rate

Supplementary Material

    Supplementary Material for this article is available online at http://www.thieme-connect.de/products.
  • Supplementary Material


Publication History

Received: 26 April 2019
Received: 02 September 2019

Accepted: 23 September 2019

Article published online:
14 October 2019

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Pop-Busui R, Boulton AJ, Feldman EL. et al. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care 2017; 40: 136-154
    Google Scholar
  • 2 Pop-Busui R. Cardiac autonomic neuropathy in diabetes: A clinical perspective. Diabetes Care 2010; 33: 434-441
    CrossrefPubMedGoogle Scholar
  • 3 Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med 2013; 30: 803-817
    CrossrefPubMedGoogle Scholar
  • 4 Wahren J, Kallas A, Sima AA. The clinical potential of C-peptide replacement in type 1 diabetes. Diabetes 2012; 61: 761-772
    CrossrefPubMedGoogle Scholar
  • 5 Kim BY, Jung CH, Mok JO. et al. Association between serum C-peptide levels and chronic microvascular complications in Korean type 2 diabetic patients. Acta Diabetol 2012; 49: 9-15
    CrossrefPubMedGoogle Scholar
  • 6 Panero F, Novelli G, Zucco C. et al. Fasting plasma C-peptide and micro- and macrovascular complications in a large clinic-based cohort of type 1 diabetic patients. Diabetes Care 2009; 32: 301-305
    CrossrefPubMedGoogle Scholar
  • 7 Qiao X, Zheng H, Zhang S. et al. C-peptide is independent associated with diabetic peripheral neuropathy: A community-based study. Diabetol Metab Syndr 2017; 9: 12
    CrossrefPubMedGoogle Scholar
  • 8 Yang X, Xu W, Zhu Y. et al. Decreased beta-cell function is associated with cardiovascular autonomic neuropathy in chinese patients newly diagnosed with type 2 diabetes. Neurosci Bull 2019; 35: 25-33
    CrossrefPubMedGoogle Scholar
  • 9 Brier ME, Bays H, Sloan R. et al. Pharmacokinetics of oral glyburide in subjects with non-insulin-dependent diabetes mellitus and renal failure. Am J Kidney Dis 1997; 29: 907-911
    CrossrefPubMedGoogle Scholar
  • 10 Regeur L, Faber OK, Binder C. Plasma C-peptide in uraemic patients. Scand J Clin Lab Invest 1978; 38: 771-775
    CrossrefPubMedGoogle Scholar
  • 11 Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2003; 26 Suppl 1 S5-S20
    CrossrefPubMedGoogle Scholar
  • 12 Ahn HJ, Han KA, Kwon HR. et al. Small rice bowl-based meal plan versus food exchange-based meal plan for weight, glucose and lipid control in obese type 2 diabetic patients. Korean. Diabetes J 2010; 34: 86-94
    PubMedGoogle Scholar
  • 13 Levey AS, Stevens LA, Schmid CH. et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-612
    CrossrefPubMedGoogle Scholar
  • 14 Ewing DJ, Martyn CN, Young RJ. et al. The value of cardiovascular autonomic function tests: 10 years experience in diabetes. Diabetes Care 1985; 8: 491-498
    CrossrefPubMedGoogle Scholar
  • 15 Vinik AI, Maser RE, Mitchell BD. et al. Diabetic autonomic neuropathy. Diabetes Care 2003; 26: 1553-1579
    CrossrefPubMedGoogle Scholar
  • 16 Tesfaye S, Boulton AJ, Dyck PJ. et al. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010; 33: 2285-2293
    Google Scholar
  • 17 Chung JO, Cho DH, Chung DJ. et al. Relationship between serum C-peptide level and diabetic retinopathy according to estimated glomerular filtration rate in patients with type 2 diabetes. J Diabetes Complications 2015; 29: 350-355
    CrossrefPubMedGoogle Scholar
  • 18 Wahren J, Foyt H, Daniels M. et al. long-acting c-peptide and neuropathy in type 1 diabetes: A 12-month clinical trial. Diabetes Care 2016; 39: 596-602
    CrossrefPubMedGoogle Scholar
  • 19 Johansson BL, Borg K, Fernqvist-Forbes E. et al. C-peptide improves autonomic nerve function in IDDM patients. Diabetologia 1996; 39: 687-695
    CrossrefPubMedGoogle Scholar
  • 20 Johansson BL, Borg K, Fernqvist-Forbes E. et al. Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus. Diabet Med 2000; 17: 181-189
    CrossrefPubMedGoogle Scholar
  • 21 Tuttle KR, Bakris GL, Bilous RW. et al. Diabetic kidney disease: A report from an ADA Consensus Conference. Diabetes Care 2014; 37: 2864-2883
    Google Scholar
  • 22 Dowse GK, Humphrey AR, Collins VR. et al. Prevalence and risk factors for diabetic retinopathy in the multiethnic population of Mauritius. Am J Epidemiol 1998; 147: 448-457
    CrossrefPubMedGoogle Scholar
  • 23 Funakoshi S, Fujimoto S, Hamasaki A. et al. Analysis of factors influencing pancreatic beta-cell function in Japanese patients with type 2 diabetes: association with body mass index and duration of diabetic exposure. Diabetes Res Clin Pract 2008; 82: 353-358
    CrossrefPubMedGoogle Scholar
  • 24 Chung JO, Cho DH, Chung DJ. et al. Plasma C-peptide level is inversely associated with family history of type 2 diabetes in Korean type 2 diabetic patients. Endocr J 2010; 57: 931-938
    CrossrefPubMedGoogle Scholar
  • 25 Funakoshi S, Fujimoto S, Hamasaki A. et al. Analysis of factors influencing postprandial C-peptide levels in Japanese patients with type 2 diabetes: Comparison with C-peptide levels after glucagon load. J Diabetes Investig 2011; 2: 429-434
    CrossrefPubMedGoogle Scholar
  • 26 Rigler R, Pramanik A, Jonasson P. et al. Specific binding of proinsulin C-peptide to human cell membranes. Proc Natl Acad Sci USA 1999; 96: 13318-13323
    CrossrefPubMedGoogle Scholar
  • 27 Kuehl M, Stevens MJ. Cardiovascular autonomic neuropathies as complications of diabetes mellitus. Nat Rev Endocrinol 2012; 8: 405-416
    CrossrefPubMedGoogle Scholar
  • 28 Pop-Busui R, Roberts L, Pennathur S. et al. The management of diabetic neuropathy in CKD. Am J Kidney Dis 2010; 55: 365-385
    CrossrefPubMedGoogle Scholar
  • 29 Ido Y, Vindigni A, Chang K. et al. Prevention of vascular and neural dysfunction in diabetic rats by C-peptide. Science 1997; 277: 563-566
    CrossrefPubMedGoogle Scholar
  • 30 Forst T, Kunt T, Wilhelm B. et al. Role of C-Peptide in the regulation of microvascular blood flow. Exp Diabetes Res 2008; 2008: 176245
    CrossrefPubMedGoogle Scholar
  • 31 Bhatt MP, Lim YC, Hwang J. et al. C-peptide prevents hyperglycemia-induced endothelial apoptosis through inhibition of reactive oxygen species-mediated transglutaminase 2 activation. Diabetes 2013; 62: 243-253
    CrossrefPubMedGoogle Scholar
  • 32 Hsieh SD, Iwamoto Y, Matsuda A. et al. 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
    CrossrefPubMedGoogle Scholar