c-peptide and Brain-Diseases

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

Diabetic polyneuropathy (DPN) occurs more frequently in type 1 diabetes resulting in a more severe DPN. The differences in DPN between the two types of diabetes are due to differences in the availability of insulin and C-peptide. Insulin and C-peptide provide gene regulatory effects on neurotrophic factors with effects on axonal cytoskeletal proteins and nerve fiber integrity. A significant abnormality in type 1 DPN is nodal degeneration. In the type 1 BB/Wor-rat, C-peptide replacement corrects metabolic abnormalities ameliorating the acute nerve conduction defect. It corrects abnormalities of neurotrophic factors and the expression of neuroskeletal proteins with improvements of axonal size and function. C-peptide corrects the expression of nodal adhesive molecules with prevention and repair of the functionally significant nodal degeneration. Cognitive dysfunction is a recognized complication of type 1 diabetes, and is associated with impaired neurotrophic support and apoptotic neuronal loss. C-peptide prevents hippocampal apoptosis and cognitive deficits. It is therefore clear that substitution of C-peptide in type 1 diabetes has a multitude of effects on DPN and cognitive dysfunction. Here the effects of C-peptide replenishment will be extensively described as they pertain to DPN and diabetic encephalopathy, underpinning its beneficial effects on neurological complications in type 1 diabetes.

Topics: Animals; Brain Diseases; C-Peptide; Cognition Disorders; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Hyperalgesia; Rats; Rats, Inbred BB

Glycaemic status on hospital admission was compared in 97 children with severe falciparum malaria (36 with cerebral malaria) and 89 children with other serious illnesses (32 in coma; 57 with acute pneumonia, not in coma). The frequency of hypoglycaemia (blood glucose below 2.2 mmol/l) did not differ significantly between malarial and control patients (5.2% vs 11.2%) nor between the comatose (11.1% vs 18.8%) and conscious (1.6% vs 7.0%) malarial and control subgroups. Compared with normoglycaemic patients, hypoglycaemic patients had appropriately low serum insulin (3.0 vs 8.2 mU/l) and C-peptide (0.13 vs 0.42 mmol/l) and high plasma non-esterified fatty acids (1.42 vs 0.83 mmol/l). Hypoglycaemia, the level of consciousness, and death were all significantly associated with the time since the last meal. Hypoglycaemia is not a specific complication of malaria but is found in severely ill fasted children, resulting from glycogen depletion and perhaps impaired hepatic gluconeogenesis. It should be sought in all severely sick children. A single bolus dose of glucose may not be enough to correct it.

Topics: Alanine; Blood Glucose; Brain Diseases; C-Peptide; Child; Child, Preschool; Coma; Discriminant Analysis; Eating; Evaluation Studies as Topic; Fatty Acids, Nonesterified; Glasgow Coma Scale; Humans; Hypoglycemia; Infant; Infant, Newborn; Insulin; Malaria; Prognosis; Time Factors

We studied the occurrence, clinical manifestations, and mechanism of hypoglycemia in patients with falciparum malaria in eastern Thailand. Hypoglycemia, which was often severe and recurrent, occurred in 17 patients, including 12 in a series of 151 patients with cerebral malaria. Thirty episodes were investigated. Plasma concentrations of insulin and C peptide were inappropriately high, and lactate and alanine concentrations were significantly higher than in patients with falciparum malaria who were normoglycemic (P less than 0.05). Sixteen patients had received quinine; plasma quinine and insulin concentrations were correlated at the time of hypoglycemia (P = 0.007). In seven healthy fasting volunteers intravenous quinine increased the mean plasma insulin concentration (+/- S.D.) from 8.9 +/- 3.1 to 17.1 +/- 8.4 mU per liter (P = 0.02) and reduced the mean plasma glucose concentration from 88 +/- 20 to 68 +/- 23 mg per deciliter (P = 0.002). Our observations indicate that in falciparum malaria quinine-induced insulin secretion may precipitate hypoglycemia, but other factors, including the large glucose requirements of the malaria parasites may also contribute. This important complication, associated with pregnancy and severe disease, must be excluded in all patients with falciparum malaria who have impaired or deteriorating consciousness.

Topics: 3-Hydroxybutyric Acid; Adolescent; Adult; Alanine; Blood Glucose; Brain Diseases; C-Peptide; Child; Female; Humans; Hydroxybutyrates; Hypoglycemia; Insulin; Lactates; Lactic Acid; Malaria; Male; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Infectious; Quinine