Fasting Plasma C-Peptide and Micro- and Macrovascular Complications in a Large Clinic-Based Cohort of Type 1 Diabetic Patients

Abstract

OBJECTIVE—A protective effect of residual β-cell function on microvascular complications of type 1 diabetes has been suggested. Our aim was to retrospectively evaluate the association of fasting plasma C-peptide values with micro- and macrovascular complications.RESEARCH DESIGN AND METHODS—We recruited a clinic-based cohort of 471 type 1 diabetic patients born after 1945 and cared for in the period 1994–2004. Centralized measurements and standardized procedures of ascertainment of micro- and macrovascular complications were employed. Individual cumulative averages of A1C up to 2007 were calculated.RESULTS—Residual β-cell secretion was detected even many years after diabetes diagnosis. In multivariate linear regression analysis, fasting plasma C-peptide values were positively associated with age at diagnosis (β = 0.02; P < 0.0001) and triglycerides (β = 0.20; P = 0.05) and inversely associated with diabetes duration (β = −0.03; P < 0.0001) and HDL cholesterol (β = −0.006; P = 0.03). The final model explained 21% of fasting C-peptide variability. With respect to fasting C-peptide values in the lowest tertile (<0.06 nmol/l), higher values were associated with lower prevalence of microvascular complications (odds ratio [OR] 0.59 [95% CI 0.37–0.94]) independently of age, sex, diabetes duration, individual cumulative A1C average during the study period, hypertension, and cardiovascular diseases. No association was evident with macrovascular complications (0.77 [0.38–1.58]).CONCLUSIONS—Our study shows an independent protective effect of residual β-cell function on the development of microvascular complications in type 1 diabetes, suggesting the potential beneficial effect of treatment that allows the preservation of even modest β-cell function over time.

C-peptide reduces high-glucose-induced apoptosis of endothelial cells and decreases NAD(P)H-oxidase reactive oxygen species generation in human aortic endothelial cells

“…As a consequence, individuals with type 1 diabetes have severely reduced levels or absence of C-peptide; this is considered an important factor in the pathophysiology of diabetic complications. In fact, people with type 1 diabetes who retain a low but detectable level of C-peptide are less prone to develop microvascular complications of the eyes, kidneys and peripheral nerves [24][25][26]. Moreover, pancreas or islet transplantation, with restoration of endogenous insulin and C-peptide secretion, is known to be accompanied by improvement of diabetes-induced abnormalities of nerve function, endothelial function and both structural and functional changes of the kidneys [37,38].…”

“…C-peptide, the cleavage product of the proinsulin molecule in the pancreatic beta cells, has been shown to exert insulin-independent biological effects on a number of cells, proving itself as a bioactive peptide with antiinflammatory properties [23]. As type 1 diabetes patients typically lack physiological levels of insulin and C-peptide, this is considered an important factor in the pathophysiology of diabetic complications [24][25][26]. C-peptide has been shown to improve endothelial dysfunction and systemic inflammation in several in vivo and in vitro models of inflammation-mediated vascular injury by reducing expression of genes encoding endothelial cell adhesion molecules, inflammatory cytokine production and adherence and transmigration of leucocytes [27][28][29][30].…”

Plasma C-peptide level is inversely associated with family history of type 2 diabetes in Korean type 2 diabetic patients

“…Recently, C-peptide has been suggested as a bioactive peptide in several studies, in addition to a surrogate marker of insulin release. Panero et al [34] showed the protective effect of residual fasting C-peptide levels on the development of chronic complications in type 1 diabetic patients. Bo et al [11] demonstrated that lower concentrations of fasting plasma C-peptide was associated with a greater prevalence of micorvascular complications in patients with type 2 diabetes mellitus.…”

MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison’s disease

“…This represents a parallel state of partial destruction of the target organ in an autoimmune disease process. Residual insulin secretion in Type 1 diabetes patients has been correlated with improved glycaemic control and fewer microvascular complications (110,111). Interestingly, approximately 40% of autoimmune Addison's disease patients are reported to have never been hospitalised with an adrenal crisis, and this could be owing to low-level residual adrenal function.…”