c-peptide and Alzheimer-Disease

The progress of metabolic syndrome (MetS) continues with the onset of type-2 diabetes mellitus (Type-2 DM) along with linkage to other disorders such as neurodegenerative, especially Alzheimer's disease (AD), via oxidative stress and low grade systemic inflammatory process. Type-2 DM and AD are health disorders of priority research. The treatment for an individual suffering with Type- 2 DM and/or AD requires monitoring by clinicians. The aim of this study was to investigate the role of C-peptide and its correlation to insulin resistance, body mass index (BMI), β cell function, insulin sensitivity, lipid profile and hemoglobin A1c (HbA1c). The study was designed to include 96 Type-2 DM individuals from India. 58.3% males and 41.7% females were selected and fasting blood samples were collected for estimation of fasting C-peptide, fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c and lipid profile. Analysis was done on Hitachi912 and Elecsys 2010 using Roche reagents and standard controls. Anthropometries to calculate BMI and β cell function, insulin sensitivity, and insulin resistance were obtained. The statistical tool ANOVA, followed by calculation of p-value and r � value were applied for investigating correlation of C-peptide levels to those of high density lipoprotein-C (HDL-C), low density lipoprotein-C (LDL-C), triglycerides (TGL), HbA1c, β cell function, insulin sensitivity and insulin resistance. Highly significant positive correlations were observed in different quantiles of C-peptide levels to the studied parameters of MetS, BMI and % β cell function. Lower HDL-C level was found to be significantly related to higher C-peptide levels. Similarly, TGL and C-peptide levels displayed a significant positive correlation. A significant negative correlation was observed between C-peptide quantiles and % sensitivity. Thus, insulin resistance showed a positive correlation until the fourth quantile. No significant correlation was observed between C-peptide and HbA1c levels. This study demonstrates that assessment of C-peptide levels is a useful tool to monitor the progress of MetS among patients suffering from Type-2 DM and AD, as these disorders are intertwined to each other by common metabolic pathways. Assessment of C-peptide levels, along with HDL-C levels, in patients can be used to monitor insulin resistance.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Body Mass Index; C-Peptide; Cholesterol, HDL; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Young Adult

Insulin degradation pathways may be related to Alzheimer's disease pathology. In preliminary analyses, we considered the relation of combined lower insulin secretion (c-peptide) and higher insulin--possibly a phenotype for impaired insulin degradation--to cognitive decline.. Fasting plasma c-peptide and insulin were measured in 1,187 non-diabetic Nurses' Health Study participants (mean age = 64 years). Cognitive testing began 10 years later. Participants completed three repeated assessments (over an average span of 4.4 years) of verbal memory, a strong predictor of Alzheimer disease development. C-peptide and insulin distributions were dichotomized at their medians to create four cross-tabulated categories. Multivariable linear mixed effects models were used to relate c-peptide/insulin categories to cognitive decline.. Compared to the lower c-peptide/lower insulin group, women with lower c-peptide/higher insulin had a significantly faster rate of verbal memory decline: the mean difference was -0.05 units/year (95% CI -0.09,-0.01). This mean difference was similar to that which we found for women 5 years apart in age, indicating that having a profile of lower c-peptide/higher insulin appeared cognitively equivalent to aging by five years on tests of verbal memory. For women with higher c-peptide/higher insulin, the estimated mean difference in decline compared to those in the lower c-peptide/lower insulin group was statistically significant, but slightly lower, at -0.04 units/year (95% CI: -0.07,-0.02).. These preliminary analyses of a possible phenotype of impaired insulin degradation provide supportive evidence that deficits in insulin degradation may be related to late-life verbal memory decline.

Topics: Aged; Aging; Alzheimer Disease; C-Peptide; Cognition; Cognition Disorders; Female; Humans; Insulin; Male; Memory; Middle Aged; Multivariate Analysis; Phenotype

Ginkgo biloba extract is ingested on a chronic basis for enhancing mental focus and improving cognitive function in the elderly. This study was undertaken to determine the effect of Ginkgo biloba extract on glucose-stimulated pancreatic beta-cell function in normal glucose-tolerant individuals. Twenty individuals (14 females and 6 males, ages 21-57 years) underwent a 2-hour 75 g oral glucose tolerance test (OGTT) before and after ingestion of Ginkgo biloba extract (120 mg/day at bedtime) for 3 months. Ginkgo biloba extract ingestion caused a decrease in systolic blood pressure from 125 +/- 15 to 118 +/- 12 mmHg (p < 0.05) and in diastolic blood pressure from 86 +/- 10 to 68 +/- 10 (p < 0.01). Fasting plasma insulin and C-peptide were increased, and the insulin and C-peptide areas under the curve during the OGTT changed from 136 +/- 55 to 162 +/- 94 microU/ml/h (p = 0.1232) and 9.67 +/- 5.34 to 16.88 +/- 5.20 ng/ml/h (p < 0.001), respectively. The observed dissimilar insulin/C-peptide response curves may be due to Ginkgo biloba-induced increase of the rate of insulin metabolic clearance.

Topics: Adult; Alzheimer Disease; C-Peptide; Female; Ginkgo biloba; Glucose; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Middle Aged; Plant Extracts; Plants, Medicinal

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Aging; Alzheimer Disease; Brain; C-Peptide; Frontal Lobe; Humans; Insulin; Middle Aged; Neurons; Occipital Lobe; Parietal Lobe; Receptor, Insulin; Reference Values; Temporal Lobe