scholarly journals C-peptide and Central Nervous System Complications in Diabetes

2004 ◽  
Vol 5 (1) ◽  
pp. 79-90 ◽  
Author(s):  
Zhen-guo Li ◽  
Anders A. F. Sima
Keyword(s):  
Type 1 Diabetes ◽  
Neuronal Apoptosis ◽  
Experimental Studies ◽  
Neuronal Loss ◽  
Diabetic Complication ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
C Peptide ◽  
Igf System

Substantial evidence collected from clinical data and experimental studies has indicated that CNS is not spared from diabetes complications. Impairments in CNS function are well documented in both type 1 and type 2 diabetic patients as well as in various animal models of diabetes, in terms of alterations in cognition, neuropsychology, neurobehavior, electrophysiology, structure, neurochemistry and apoptotic activities. These data suggest thatprimary diabetic encephalopathyexists as a definable diabetic complication. The mechanisms underlying this CNS complication are not clear. Experimental studies have suggested that neuronal apoptosis may play an important role in neuronal loss and impaired cognitive function. In diabetes multiple factors are responsible for neuronal apoptosis, such as a perturbed IGF system, hyperglycemia and the aging process itself. Recent data suggest that insulin/C-peptide deficiency may exert an eminent role. Administration of C-peptide partially corrects the perturbed IGF system in the brain and prevents neuronal apoptosis in hippocampus of type 1 diabetes. In neuroblastoma SH-SY5Y cells C-peptide provides a dose-dependent stimulation on cell proliferation and an anti-apoptotic effect as well. These studies provide a basis for administration of C-peptide as a potentially effective therapy for type 1 diabetes.

scholarly journals Type 1 Diabetic Neuropathy and C-peptide

2004 ◽  
Vol 5 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Anders A. F. Sima ◽  
Weixian Zhang ◽  
George Grunberger
Keyword(s):  
Clinical Trials ◽  
Animal Studies ◽  
Large Scale ◽  
Structural Changes ◽  
Diabetic Complication ◽  
Diabetic Patients ◽  
C Peptide ◽  
Beneficial Effects ◽  
Regulatory Effects

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucoseindependent effects. Preclinical studies have demonstrated dose-dependent effects onNa+,K+-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.

scholarly journals Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus

2010 ◽  
Vol 162 (4) ◽  
pp. 711-717 ◽  
Author(s):  
Ebru Asicioglu ◽  
Dilek Gogas Yavuz ◽  
Mehmet Koc ◽  
Beste Ozben ◽  
Dilek Yazici ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Cells ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Vascular Damage ◽  
Circulating Endothelial Cells ◽  
Diabetic Patients ◽  
Activity Levels ◽  
Type 2 Diabetic Patients

ObjectiveCirculating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population.MethodsThirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers.ResultsPatients with type 1 diabetes mellitus had higher number of CECs (7.46±5.37 vs 2.13±1.13 cells/ml,P<0.001), lower FMD (7.87±2.19 vs 12.06±2.34%,P<0.001), higher TBARS (4.94±1.20 vs 3.07±0.75 nmol/MDA,P<0.001), lower GSH (206.12±98.06 vs 353.61±68.45 μM,P<0.001), and lower PON activity levels (89.10±17.82 vs 127.65±29.01 U/l,P<0.001) as compared to controls.There was positive correlation between CEC numbers and HbAlc levels (r=0.49,P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r2=0.40,P<0.009) were associated with CEC numbers.ConclusionCECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients

2004 ◽  
Vol 286 (1) ◽  
pp. E14-E19 ◽  
Author(s):  
Bo-Lennart Johansson ◽  
Jan Sundell ◽  
Karin Ekberg ◽  
Cathrine Jonsson ◽  
Marko Seppänen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Type 1 Diabetes ◽  
Muscle Blood Flow ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Skeletal Muscle Blood Flow ◽  
C Peptide ◽  
Type 1 Diabetic Patients

Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.

scholarly journals C-Peptide Prevents Hippocampal Apoptosis in Type 1 Diabetes

2002 ◽  
Vol 3 (4) ◽  
pp. 241-245 ◽  
Author(s):  
Zhen-guo Li ◽  
Weixian Zhang ◽  
Anders A. F. Sima
Keyword(s):  
Central Nervous System ◽  
Cell Death ◽  
Type 1 Diabetes ◽  
Nervous System ◽  
Neuronal Apoptosis ◽  
C Peptide ◽  
Neuronal Density ◽  
Apoptotic Activity ◽  
Hippocampal Apoptosis

To explore mechanisms underlying central nervous system (CNS) complications in diabetes, we examined hippocampal neuronal apoptosis and loss, and the effect of C-peptide replacement in type 1 diabetic BB/W rats. Apoptosis was demonstrated after 8 months of diabetes, by DNA fragmentation, increased number of apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied by reduced neuronal density in the hippocampus. No apoptotic activity was detected and neuronal density was unchanged in 2-month diabetic hippocampus, whereas insulin-like growth factor (IGF) activities were impaired. In type 1 diabetic BB/W rats replaced with C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)- positive cells were shown and DNA laddering was not evident in hippocampus at either 2 or 8 months. C-peptide administration prevented the preceding perturbation of IGF expression and reduced the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes causes a duration-dependent programmed cell death of the hippocampus, which is partially prevented by C-peptide.

scholarly journals Residual β-Cell Function and the Insulin-Like Growth Factor System in Danish Children and Adolescents With Type 1 Diabetes

2015 ◽  
Vol 100 (3) ◽  
pp. 1053-1061 ◽  
Author(s):  
Jesper S. Sorensen ◽  
Niels H. Birkebaek ◽  
Mette Bjerre ◽  
Flemming Pociot ◽  
Kurt Kristensen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Β Cell ◽  
Cross Sectional ◽  
Prepubertal Children ◽  
C Peptide ◽  
Pubertal Status ◽  
Igf System ◽  
Β Cell Function

Context: C-peptide-positive adults with type 1 diabetes (T1D) have higher circulating total and free IGF-1 and lower IGF binding protein 1 (IGFBP-1) than C-peptide-negative patients. Whether this is also the case in children remains unknown. Objective: The objective of the study was to examine the IGF system in children/adolescents with and without residual β-cell function (RBF). Design and Patients: This was a cross-sectional study containing 136 prepubertal (hereof 15 RBF positive) and 206 pubertal (hereof 42 RBF positive) children/adolescents with T1D for 3–6 years as well as 40 prepubertal and 30 pubertal healthy controls. RBF was evaluated by meal-stimulated C-peptide. Main Outcome Measures: Fasting serum levels of bioactive IGF (ie, the ability of serum to activate the IGF-1 receptor in vitro), total IGF-1, total IGF-2, and IGFBP-1 and -3. Results: Irrespective of pubertal status, patients with T1D showed lower bioactive IGF and total IGF-1, but higher IGFBP-1 as compared with controls (P &lt; .05). When stratified according to RBF status, a positive RBF was associated with normalization of all IGF-related peptides but IGFBP-1 in prepubertal children (P &lt; .05), whereas none of the IGF components were normalized in prepubertal, RBF-negative children. In pubertal children, total IGF-1 and bioactive IGF remained subnormal and IGFBP-1 supranormal, irrespective of RBF status (P &lt; .05). Conclusion: Independent of pubertal status, T1D was associated with an abnormal IGF system. However, a positive RBF status appeared important but only in prepubertal children, in whom all IGF components but IGFBP-1 were normalized. We speculate that the pubertal GH surge induces insulin resistance, which overrides the stimulatory effect that an RBF may exert on the liver-derived IGF system.

scholarly journals C-Peptide and Its C-Terminal Fragments Improve Erythrocyte Deformability in Type 1 Diabetes Patients

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Thomas Hach ◽  
Thomas Forst ◽  
Thomas Kunt ◽  
Karin Ekberg ◽  
Andreas Pfützner ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Type 1 Diabetes ◽  
Signal Transduction Pathway ◽  
Erythrocyte Deformability ◽  
Diabetic Patients ◽  
Transduction Pathway ◽  
Stress Range ◽  
C Peptide ◽  
Type 1 Diabetic Patients

Aims/hypothesis. Data now indicate that proinsulin C-peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. This study aimed to investigate the influence of C-peptide and fragments thereof on erythrocyte deformability and to elucidate the relevant signal transduction pathway.Methods. Blood samples from 23 patients with type 1 diabetes and 15 matched healthy controls were incubated with 6.6 nM of either human C-peptide, C-terminal hexapeptide, C-terminal pentapeptide, a middle fragment comprising residues 11–19 of C-peptide, or randomly scrambled C-peptide. Furthermore, red blood cells from 7 patients were incubated with C-peptide, penta- and hexapeptides with/without addition of ouabain, EDTA, or pertussis toxin. Erythrocyte deformability was measured using a laser diffractoscope in the shear stress range 0.3–60 Pa.Results. Erythrocyte deformability was impaired by 18–25% in type 1 diabetic patients compared to matched controls in the physiological shear stress range 0.6–12 Pa(P<.01–.001). C-peptide, penta- and hexapeptide all significantly improved the impaired erythrocyte deformability of type 1 diabetic patients, while the middle fragment and scrambled C-peptide had no detectable effect. Treatment of erythrocytes with ouabain or EDTA completely abolished the C-peptide, penta- and hexapeptide effects. Pertussis toxin in itself significantly increased erythrocyte deformability.Conclusion/interpretation. C-peptide and its C-terminal fragments are equally effective in improving erythrocyte deformability in type 1 diabetes. The C-terminal residues of C-peptide are causally involved in this effect. The signal transduction pathway isCa2+-dependent and involves activation of red blood cellNa+,K+-ATPase.

Survival in Type 1 and Type 2 Diabetes in a Population Referred for Invasive Evaluation of Coronary Disease

Cardiology ◽  
2017 ◽  
Vol 139 (1) ◽  
pp. 43-52 ◽  
Author(s):  
Per Mølstad ◽  
Olaf Rødevand
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Coronary Disease ◽  
Cox Regression ◽  
Diabetic Patients ◽  
Invasive Treatment ◽  
Type 2 Diabetic Patients

Objectives: To evaluate long-term and time trends of survival in patients with a clinical diagnosis of type 1 and type 2 diabetes compared to patients without diabetes in a population referred for invasive treatment of coronary disease. Methods: Patients examined for heart disease at the Feiring LHL Clinics from March 1999 until December 2014 were followed for survival until 20 September, 2015. This yielded 43,872 patients with a known survival status including 1,326 (3.0%) patients with type 1 diabetes and 4,564 (10.9%) with type 2 diabetes. Results: Cox regression revealed a hazard ratio (HR) in type 1 and type 2 diabetes, respectively, of 1.78 (95% confidence interval [CI] 1.60-1.99) and 1.29 (95% CI 1.21-1.37). Comparing survival in the treatment periods before and after 2007, patients without diabetes and with type 2 diabetes had a reduced HR of 0.78 (95% CI 0.72-0.84) and 0.76 (95% CI 0.63-0.91), respectively, but there was no reduction in type 1 diabetes (HR 1.03; 95% CI 0.74-1.42). Conclusions: Type 1 and type 2 diabetes have excess long-term mortality. In the nondiabetic and type 2 diabetic patients, a reduction in mortality has been noted in recent years, but has not been observed in type 1 diabetic patients.

scholarly journals The Effects of C-peptide on Type 1 Diabetic Polyneuropathies and Encephalopathy in the BB/Wor-rat

2008 ◽  
Vol 2008 ◽  
pp. 1-13 ◽  
Author(s):  
Anders A. F. Sima ◽  
Weixian Zhang ◽  
Zhen-guo Li ◽  
Hideki Kamiya
Keyword(s):  
Type 1 Diabetes ◽  
Cognitive Dysfunction ◽  
Neurotrophic Factors ◽  
Neuronal Loss ◽  
Diabetic Polyneuropathy ◽  
Neurological Complications ◽  
Cytoskeletal Proteins ◽  
C Peptide ◽  
Beneficial Effects

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.

scholarly journals Inverse Levels of Adiponectin in Type 1 and Type 2 Diabetes Are in Accordance with the State of Albuminuria

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Spomenka Ljubic ◽  
Anamarija Jazbec ◽  
Martina Tomic ◽  
Ante Piljac ◽  
Dubravka Jurisic Erzen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Albumin Excretion Rate ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
The Metabolic Syndrome ◽  
Definition Of ◽  
Type 2 Diabetic

Aims.To investigate the behaviour of adiponectin (ApN) in patients with type 1 and type 2 diabetic nephropathy.Methods.ApN and inflammatory and other markers of the metabolic syndrome were compared across diabetes types, albumin excretion rate (AER), and creatinine clearance (CrCl) categories in 219 type 1 and type 2 diabetic patients.Results.Significant differences among ApN levels according to AER were found in both types of diabetes (F=8.45,df=2,P<0.001). With the progression of albuminuria, ApN increased in type 1 and decreased in type 2 diabetes. Patients with decreased CrCl had higher ApN levels than those with normal CrCl in either type of diabetes (F=12.7,df=1,P<0.001). The best model for ApN (R2=0.9002) obtained from stepwise regression in type 1 diabetes included CrCl, BMI, WBC, CRP, and age, while in type 2 diabetes (R2=0.2882) it included ppPG, LDL, and UA.Conclusion.ApN behaved differently in relation to albuminuria, increasing with its progression in type 1 diabetes and decreasing in type 2 diabetes. It was however increased in the subgroups with decreased CrCl in both types of diabetes. Albuminuria seems to be more important than renal insufficiency in the definition of ApN levels in type 1 and type 2 diabetes.

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