c-peptide and Peripheral-Nervous-System-Diseases

Studies have demonstrated that proinsulin C-peptide stimulates the activities of Na(+),K(+)-ATPase and endothelial nitric oxide synthase, both of which are enzyme systems of importance for nerve function and known to be deficient in type 1 diabetes. The aim of this randomized double-blind placebo-controlled study was to investigate whether C-peptide replacement improves nerve function in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-peptide (600 nmol/24 h, four doses s.c.) or placebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA(1c) 7.0%) completed the study. Neurological and neurophysiological measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduced nerve conduction velocities in the sural nerve (sensory nerve conduction velocity [SCV]: 50.9 +/- 0.70 vs. 54.2 +/- 1.2 m/s, P < 0.05) and peroneal nerve (motor nerve conduction velocity: 45.7 +/- 0.55 vs. 53.5 +/- 1.1 m/s, P < 0.001) compared with age-, height-, and sex-matched control subjects. In the C-peptide treated group there was a significant improvement in SCV amounting to 2.7 +/- 0.85 m/s (P < 0.05 compared with placebo) after 3 months of treatment, representing 80% correction of the initial reduction in SCV. The change in SCV was accompanied by an improvement in vibration perception in the patients receiving C-peptide (P < 0.05 compared with placebo), whereas no significant change was detectable in cold or heat perception. In conclusion, C-peptide administered for 3 months as replacement therapy to patients with early signs of diabetic neuropathy ameliorates nerve dysfunction.

Topics: Adult; Age of Onset; Blood Pressure; Body Weight; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Insulin; Male; Neural Conduction; Neurologic Examination; Patient Selection; Peripheral Nervous System Diseases; Placebos; Time Factors

This study was done to characterize the natural course of C-peptide levels in patients with type 1 diabetes and identify distinguishing characters among patients with lower rates of C-peptide decline. A sample of 95 children with type 1 diabetes was analyzed to retrospectively track serum levels of C-peptide, HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The clinical characteristics were compared between the patients with low and high C-peptide levels, respectively. The average C-peptide level among all patients was significantly reduced five years after diagnosis (P < 0.001). The incidence of diabetic ketoacidosis was significantly lower among the patients with high levels of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS) 15 yr after diagnosis were significantly higher among the patients with low C-peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C-peptide level was significantly decreased after 5 yr from diagnosis. Type 1 diabetes patients whose beta-cell functions were preserved might have low incidence of diabetic ketoacidosis. The declines of C-peptide level after diagnosis in type 1 diabetes may be associated with changes of body weight and BMI.

Topics: Adolescent; Body Mass Index; Body Weight; C-Peptide; Child; Child, Preschool; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diabetic Retinopathy; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Incidence; Infant; Male; Peripheral Nervous System Diseases; Retrospective Studies

To explore the risk factors of diabetic peripheral neuropathy (DPN) and the relationship between DPN and diabetic retinopathy (DR).. The data of the in-patients with type 2 diabetes mellitus (T2 DM) were retrospectively studied. A total of 200 T2 DM patients were divided into DPN group (n = 136) and non-DPN group (n = 64) according to peripheral neuropathy. The basic clinical data and the incidence rate of DR were compared between two groups. Logistic regression analysis was used to study the risk factors of DPN.. The course of disease, the level of BMI, glycosylated hemoglobin (HbA1c), 2 hour postprandial blood glucose (2 hPG), 2 hour glucose C peptide (2 hC-P) and the incidence rate of the DR were significantly different between two groups (P < 0.01). Logistic regression analysis showed that significant differences were observed in T2 DM complicated by DR (P = 0.023), the course of disease (P = 0.008), the level of HbA1c (P = 0.006), BMI (P = 0.000) and 2 hC-P (P = 0.065).. Diabetic retinopathy, the course of disease, the level of BMI,HbA1c and 2 hC-P are the risk factors for type 2 diabetic peripheral neuropathy. Diabetic peripheral neuropathy is positive correlated with diabetic retinopathy.

Topics: Adult; Aged; Aged, 80 and over; Blood Glucose; Body Mass Index; C-Peptide; China; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Risk Factors

To explore the molecular abnormalities underlying the degeneration of the node of Ranvier, a characteristic aberration of type 1 diabetic neuropathy, we examined in type 1 BB/Wor and type 2 BBZDR/Wor rats changes in expression of key molecules that make up the nodal and paranodal apparatus of peripheral nerve. Their posttranslational modifications were examined in vitro. Their responsiveness to restored insulin action was examined in type 1 animals replenished with proinsulin C-peptide. In sciatic nerve, the expression of contactin, receptor protein tyrosine phosphatase beta, and the Na(+)-channel beta(1) subunit, paranodal caspr and nodal ankyrin(G) was unaltered in 2-month type 1 diabetic BB/Wor rats but significantly decreased after 8 months of diabetes. These abnormalities were prevented by C-peptide administered to type 1 BB/Wor rats and did not occur in duration- and hyperglycemia-matched type 2 BBZDR/Wor rats. The expression of the alpha-Na(+)-channel subunit was unaltered. In SH-SY5Y cells, only the combination of insulin and C-peptide normalized posttranslational O-linked N-acetylglucosamine modifications and maximized serine phosphorylation of ankyrin(G) and p85 binding to caspr. The beneficial effects of C-peptide resulted in significant normalization of the nerve conduction deficits. These data describe for the first time the progressive molecular aberrations underlying nodal and paranodal degenerative changes in type 1 diabetic neuropathy and demonstrate that they are preventable by insulinomimetic C-peptide.

Topics: Animals; Blood Glucose; Blotting, Western; C-Peptide; Cell Line, Tumor; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Glycated Hemoglobin; Humans; Immunohistochemistry; Insulin; Nerve Degeneration; Neural Conduction; Peripheral Nervous System Diseases; Protein Processing, Post-Translational; Ranvier's Nodes; Rats; Rats, Inbred BB; Sciatic Nerve

In a study of 102 patients (64 women and 38 men; 63 whites and 39 nonwhites; 77 with adult-onset disease and 25 with juvenile-onset disease), the data, after being adjusted for age, showed that diabetic peripheral neuropathy was associated with diabetic keratopathy. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than .01); the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were reduced tear break-up time (P less than .03), the type of diabetes (P less than .01), and metabolic status, shown by fasting C-peptide levels (P less than .01). No significant relationships were found between keratopathy and tear glucose levels, endothelial cell densities, corneal thickness, or duration of disease.

Topics: Aged; C-Peptide; Corneal Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Triglycerides; Vibration