c-peptide and Stroke

With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic encephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cognitive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronal loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor (IGF) system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.

Topics: Animals; Brain Diseases; C-Peptide; Cognition Disorders; Diabetes Complications; Humans; Risk Factors; Stroke

Patients with insulin resistance and early type 2 diabetes exhibit an increased propensity to develop a diffuse and extensive pattern of arteriosclerosis. Diabetic subjects show a remarkable increase in vascular complications, including myocardial infarction and strokes. The accelerated atherosclerosis in these patients is likely to be multifactorial. In this review, we focus on the advanced glycation end product (AGE)-receptor for AGE (RAGE) axis and the role of C-peptide as a mediator of lesion development. AGEs are proteins or lipids that become glycated after exposure to sugars. By engaging the RAGEs, AGEs induce the expression of proinflammatory mediators in various vascular cell types and are involved in a variety of microvascular and macrovascular complications. In animal models, interruption of the AGE-RAGE interaction reduces lesion size and plaque development and RAGE deficiency in a RAGE(-/-)/apolipoprotein E(-/-) double knockout mouse attenuates the development of atherosclerosis in diabetes. On the other side, patients with type 2 diabetes show increased levels of C-peptide and over the last years various groups examined the effect of C-peptide in vascular cells as well as its potential role in lesion development. Recent data suggest that the proinsulin cleavage product C-peptide could play a causal role in atherogenesis by promoting monocyte and CD4-positive lymphocyte recruitment in early arteriosclerotic lesions and by inducing the proliferation of vascular smooth muscle cells. The following review will summarize these two pathophysiological aspects and discuss on the one hand the potential role of the activated AGE-RAGE axis in diabetes-accelerated atherogenesis and on the other hand the role of C-peptide as a mediator in lesion development in patients with type 2 diabetes.

Topics: Animals; Apolipoproteins E; Atherosclerosis; C-Peptide; CD4-Positive T-Lymphocytes; Cell Proliferation; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Gene Expression Regulation; Glycation End Products, Advanced; Humans; Inflammation Mediators; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases; Monocytes; Myocardial Infarction; Myocytes, Smooth Muscle; Receptor for Advanced Glycation End Products; Stroke

Pancreatic β-cell dysfunction is an important factor in the development of type 2 diabetes mellitus. This study aimed to estimate the association between β-cell dysfunction and prognosis of nondiabetic patients with ischemic stroke.. Patients with ischemic stroke without a history of diabetes mellitus in the ACROSS-China (Abnormal Glucose Regulation in Patients with Acute Stroke across China) registry were included. Disposition index was estimated as computer-based model of homeostatic model assessment 2-β%/homeostatic model assessment 2-insulin resistance based on fasting C-peptide level. Outcomes included stroke recurrence, all-cause death, and dependency (modified Rankin Scale, 3-5) at 12 months after onset.. Among 1171 patients, 37.2% were women with a mean age of 62.4 years. At 12 months, 167 (14.8%) patients had recurrent stroke, 110 (9.4%) died, and 184 (16.0%) had a dependency. The first quartile of the disposition index was associated with an increased risk of stroke recurrence (adjusted hazard ratio, 3.57; 95% confidence interval, 2.13-5.99) and dependency (adjusted hazard ratio, 2.30; 95% confidence interval, 1.21-4.38); both the first and second quartiles of the disposition index were associated with an increased risk of death (adjusted hazard ratio, 5.09; 95% confidence interval, 2.51-10.33; adjusted hazard ratio, 2.42; 95% confidence interval, 1.17-5.03) compared with the fourth quartile. Using a multivariable regression model with restricted cubic spline, we observed an L-shaped association between the disposition index and the risk of each end point.. In this large-scale registry, β-cell dysfunction was associated with an increased risk of 12-month poor prognosis in nondiabetic patients with ischemic stroke.

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; C-Peptide; Fasting; Female; Follow-Up Studies; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Middle Aged; Models, Cardiovascular; Prognosis; Registries; Stroke

Fasting C-peptide (FCP) has been shown to play an important role in the pathophysiology of mood disorders including depression and schizophrenia, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between FCP and PSD at 6 months after acute ischemic-stroke onset among Chinese subjects.. A total of 656 stroke patients were consecutively recruited from three hospitals of Wuhan city, Hubei province. Clinical and laboratory data were collected on admission. PSD status was evaluated by DSM-V criteria and 17-item Hamilton Rating Scale for Depression (HAMD-17) at 6 months after acute ischemic stroke. The χ2-test, Mann-Whitney U-test, and t-test were used to check for statistical significance. Multivariate logistic regression model was used to explore independent predictor of PSD.. In the univariate analysis, significant differences were found between the PSD and non-PSD groups in terms of FCP level (p = 0.009). After multivariate adjustments, FCP remained a significant independent predictor of PSD, with an adjusted odds ratio of 1.179 (95%CI: 1.040-1.337, p = 0.010).. Higher FCP levels on admission were found to be associated with PSD at 6 months after acute ischemic-stroke onset. For stroke patients, doctors should pay attention to the baseline FCP for screening high-risk PSD in clinical practice.

Topics: Brain Ischemia; C-Peptide; Depression; Fasting; Humans; Prospective Studies; Stroke

To study the association between baseline level of C-peptide and all-cause death, cardiovascular death and cardiovascular complications among persons with newly diagnosed type 2 diabetes.. The Skaraborg Diabetes Register contains data on baseline C-peptide concentrations among 398 persons <65 years with newly diagnosed type 2 diabetes 1996-1998. National registries were used to determine all-cause death, cardiovascular death and incidence of myocardial infarction and ischemic stroke until 31 December 2014. The association between baseline C-peptide and outcomes were evaluated with adjustment for multiple confounders by Cox regression analysis. Missing data were handled by multiple imputation.. In the imputed and fully adjusted model there was a significant association between 1 nmol/l increase in C-peptide concentration and all-cause death (HR 2.20, 95% CI 1.49-3.25, p < 0.001, number of events = 104), underlying cardiovascular death (HR 2.69, 1.49-4.85, p = 0.001, n = 35) and the composite outcome of underlying cardiovascular death, myocardial infarction or ischemic stroke (HR 1.61, 1.06-2.45, p = 0.027, n = 90).. Elevated C-peptide levels at baseline in persons with newly diagnosed type 2 diabetes are associated with increased risk of all-cause and cardiovascular mortality. C-peptide might be used to identify persons at high risk of cardiovascular complications and premature death.

Topics: Biomarkers; C-Peptide; Cardiovascular Diseases; Cause of Death; Cohort Studies; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Registries; Stroke; Sweden; Time Factors

Although elevated serum C-peptide level as an indicator of insulin resistance increases the obesity-associated risk of cardiovascular disease among diabetic patients, evidence indicating that serum C-peptide level is associated with stroke in nondiabetic subjects is limited. The aim of this study is to evaluate the association between serum C-peptide level and ever stroke in nondiabetic subjects and investigated the associations of serum C-peptide level with body fat distribution and stroke events among nondiabetic subjects.. This study was a population-based cross-sectional study that included 7030 participants aged 12-85 years. Body fat distribution was determined by dual-energy X-ray absorptiometry. Serum C-peptide level was measured using the radioimmunoassay method. The association between serum C-peptide level and body fat distribution was evaluated by multiple linear regression models. Logistic regression analysis was performed to calculate the odds ratio (OR) of serum C-peptide level being associated with ever stroke.. A total of 103 nondiabetic subjects reported having a stroke. Logistic regression analysis revealed a high-serum C-peptide level significantly associated with ever stroke among nondiabetic subjects (OR: 3.71, 95% confidence interval: 1.78-7.75). Meanwhile, in multiple linear regression analysis, serum C-peptide level was positively associated with total and regional fat distribution among nondiabetic subjects.. The serum C-peptide level is strongly associated with the ever stroke in nondiabetic subjects and significantly associated with total and regional body fat distribution.

Topics: Absorptiometry, Photon; Adiposity; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; C-Peptide; Child; Cross-Sectional Studies; Female; Humans; Linear Models; Logistic Models; Male; Middle Aged; Nutrition Surveys; Obesity; Odds Ratio; Radioimmunoassay; Risk Factors; Stroke; United States; Up-Regulation; Young Adult