Early parasympathetic neuropathy associated with elevated fasting plasma C‐peptide concentrations and late parasympathetic neuropathy with hyperglycaemia and other microvascular complications

Abstract

To examine the relationship between parasympathetic neuropathy, hyperinsulinaemia, glycaemic control (HbA(1c)), and future diabetic complications. We assessed parasympathetic nerve function [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic control (HbA(1c)), fasting plasma (f-p-) C-peptide in 82 Type 2 diabetic patients (age 61 +/- 1 years) 5 and 12-15 years after diagnosis. Diabetic retinopathy was assessed 15 years after diagnosis. High HbA(1c) values in the first study were associated with retinopathy (with 8.6 +/- 2.0 vs. without retinopathy 6.2 +/- 1.9%; P < 0.0001) and disturbed parasympathetic nerve function (low E/I ratio; r(s) = -0.41; P = 0.0061) in the second study, as well as with deteriorations in GFR between the first and second study (r(s) = 0.62; P < 0.0001). Patients with parasympathetic neuropathy in the first study had significantly higher f-p-C-peptide concentrations than those without 3 years (1.20 +/- 0.43 vs. 0.86 +/- 0.40 nmol/l; P = 0.0015) and 5 years (1.20 +/- 0.44 vs. 0.82 +/- 0.33 nmol/l; P < 0.0001), but not 15 years after diagnosis. High HbA(1c) values 5 years after diagnosis of Type 2 diabetes were associated with retinopathy, disturbed parasympathetic nerve function, and deterioration in GFR 7-10 years later. Parasympathetic neuropathy 5 years after diagnosis was associated with high C-peptide concentrations. Parasympathetic nerve function has to be considered when beta-cell function is evaluated. Hyperglycaemia is an important factor for the development of complications in Type 2 diabetes.