Role of a Novel Insulin Resistance Index based on Combined Levels of C-peptide and Insulin in Assessment of the Heterogeneity of Diabetes Mellitus

Abstract

Background The C-peptide-to-insulin ratio (C/I) is associated with hepatic insulin clearance and insulin resistance. We established a novel C-peptide-to-insulin ratio index (CPIRI) and explored its application in the heterogeneity of non-autoimmune diabetes.Methods A total of 865 adults diagnosed with new-onset diabetes mellitus (DM) within 1 year and 54 healthy controls (HC) were recruited. Our CPIRI model was established with fasting C/I as the independent variable and homeostasis model assessment of insulin resistance (HOMA-IR) as the dependent variable. Patients with negative-autoantibodies against pancreatic islets were subclassified according to CPIRI, age of onset , hemoglobin A1c (HbA1c), body mass index (BMI) and homeostatic model assessment of β-cell function (HOMA-β) via cluster analysis.Results Fasting C/I and HOMA-IR in both diabetic and healthy subjects were hyperbolically correlated, and log(C/I) and log(HOMA-IR) were linearly and negatively correlated; the correlation coefficient was −0.83 (P = 0.000) and −0.76 (P = 0.000), respectively. Finally, we obtained the equations CPIRI(DM) = 670/(C/I) 2.24 + 0.25 and CPIRI(HC) = 670/(C/I) 2.24 − 1 (F = 1904.39, P = 0.000). Pancreatic islet autoantibody-negative patients were further subclassified into three subtypes; subtype 1 (13.8%) had severe insulin resistance, subtype 2 (42.1%) suffered elderly-onset DM with slight symptoms, and subtype 3 (44.1%) suffered severe dysfunction of pancreatic islets. Each subtype exhibited different clinical characteristics and complications.Conclusions CPIRI can be used to effectively evaluate insulin resistance. Adult-onset non-autoimmune diabetes can be subclassified into 3 subtypes according to CPIRI along with other symptom-based characteristics of diabetic progression.