Decreased β-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes

Abstract

The influence of β-cell function on cardiovascular autonomic neuropathy (CAN), an important diabetes-related complication, is still unclear. In this study, we aimed to investigate the association between residual β-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN+ group (diabetic patients with CAN, n = 20) and a CAN− group (diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured. Homeostasis model assessment-beta cells (HOMA-B) and HOMA-insulin resistance (IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN− group, the CAN+ group had significantly lower fasting plasma insulin (6.60 ± 4.39 vs 10.45 ± 7.82 μ/L, P = 0.029), fasting C-peptide (0.51 ± 0.20 vs 0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B (21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio (r = 0.24, P = 0.043) and the 30:15 test (r = 0.26, P = 0.023). Further analysis showed that fasting C-peptide (OR: 0.041, 95% CI 0.003–0.501, P = 0.012) and HOMA-B (OR: 0.965, 95% CI 0.934–0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values < 0.67 nmol/L were more likely to have CAN than those with C-peptide levels ≥0.67 nmol/L (OR: 6.00, 95% CI 1.815–19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased β-cell function was closely associated with CAN in this population.

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

“…Furthermore, associations between C-peptide and CAN in individuals with type 2 DM and renal impairment have not been addressed to date. In the present study, we observed that CAN was associated with lower C-peptide level in individuals without impaired renal function, in line with the previous findings by Yang et al [8]. In addition, in individuals with impaired renal function, Cpeptide level in the bloodstream might be out of proportion to re-duced beta cell function, because approximately half of the C-peptide level is removed by the kidney [3,9,10].…”

“…In individuals with type 1 DM who lack C-peptide, C-peptide replacement has been reported to increase HR variability during deep breathing, suggesting positive effects of C-peptide on autonomic nerve function [19,20]. However, relationships between C-peptide and CAN in type 2 DM has not been fully explored, although Yang et al [8] recently reported that C-peptide levels were negatively associated with CAN in 90 newly diagnosed Chinese patients with type 2 DM. Furthermore, associations between C-peptide and CAN in individuals with type 2 DM and renal impairment have not been addressed to date.…”

“…In addition, experimental studies have suggested the protective effects of C-peptide on diabetes-related structural and functional abnormalities of the central and peripheral nervous systems [4]. However, the effects of C-peptide on cardiovascular autonomic function in type 2 DM have not been fully explored, and most studies of the physiologic effects of C-peptide have been limited to subjects without impaired renal function [5,7,8].…”

Downregulation of glucose-6-phosphate dehydrogenase contributes to diabetic neuropathic pain through upregulation of toll-like receptor 4 in rats

“…According to the latest epidemiological survey from China, the prevalence of diabetes is 10.9% in China, 26 and following lots of refractory complications, which has become a public health problem that threatens human health. [27][28][29] Diabetic neuropathic pain refers to symptoms and/or signs associated with peripheral neurological dysfunction in diabetic patients, except for other reasons, manifested mainly as symmetric multiple sensory neuropathy, characterized by burning or needleor knife-like abnormal pain in feet, lower legs, and upper limbs. These complications seriously affect patients' quality of life.…”

Autonomic Regulation of the Cardiovascular System: Diseases, Treatments, and Novel Approaches

“…Weng and colleagues demonstrate that decreased b-cell function is associated with CAN in newly-diagnosed type 2 diabetic patients. Importantly, they found that parasympathetic nerves are more commonly and severely impaired than sympathetic nerves at the early stage of type 2 diabetes [14]. Cerebral stroke not only affects sensory and motor function, but also often causes autonomic disturbances in patients due to damage of the central autonomic network.…”