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

Abstract

Aims: To examine the relationship between parasympathetic neuropathy, hyperinsulinaemia, glycaemic control (HbA1c), and future diabetic complications. Methods: We assessed parasympathetic nerve function [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic control (HbA1c), 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. Results: High HbA1c 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 (rs = 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/1; P = 0.0015) and 5 years (1.20 + 0.44 vs. 0.82 ± 0.33 nmol/1; P < 0.0001), but not 15 years after diagnosis. Conclusion: High HbA1c 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 β-cell function is evaluated. Hyperglycaemia is an important factor for the development of complications in Type 2 diabetes.