c-peptide and Heart-Failure

Congestive heart failure (CHF) is a serious disease with a poor prognosis. Diabetes is an independent risk factor for CHF, probably in part due to disturbances in myocardial metabolism. Glucagon-like peptide-1 (GLP-1) causes glucose-dependent secretion of insulin, improving glycaemic control. In turn, this may improve myocardial metabolism and myocardial function. The aim of the present study was to assess the feasibility and safety of three days' infusion of recombinant GLP-1 in an open observational study in six patients with type 2 diabetes and CHF. The study included assessment of myocardial function. There were no major complications of the infusion, and all patients completed the study protocol. Some improvement was observed in glycaemic state, and there was an insignificant trend towards improved myocardial function. It is concluded that GLP-1 deserves further evaluation in such patients.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Exercise Test; Glucagon; Glucagon-Like Peptide 1; Heart; Heart Failure; Humans; Infusions, Parenteral; Injections, Subcutaneous; Insulin; Male; Myocardial Contraction; Pilot Projects; Recombinant Proteins; Time Factors

Twelve outpatients with type II diabetes mellitus and mild clinical signs and history of cardiac failure were studied to assess the effects of ibopamine on glucose and lipid metabolism. For the assessment of cardiac failure a clinical score was computed, based on the evidence of dyspnea and ankle oedema. The patients were randomly allocated to ibopamine 100 mg t.i.d. or placebo in a double-blind cross-over 3 weeks design. Daily plasma glucose profile, glycaemia and plasma insulin during glucose tolerance test, serum C-peptide, lactacidemia, free fatty acids, triglycerides, urinary glucose, diuresis and clinical evaluation were the studied parameters. During the study, a clinically favourable trend for ibopamine was observed, as far as cardiac failure was concerned. No significant differences were found between ibopamine and placebo in any of the metabolic parameters. No change in diet or in the previous dosage of the antidiabetic drugs occurred during the study in any patient. We conclude that ibopamine 100 mg t.i.d. does not affect metabolic control and lipid pattern in type II diabetic patients, therefore representing a safe tool for the treatment of chronic heart failure in these patients.

Topics: Aged; C-Peptide; Cardiotonic Agents; Deoxyepinephrine; Diabetes Mellitus, Type 2; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Heart Failure; Hemodynamics; Humans; Lactates; Lactic Acid; Male; Vasodilator Agents

Sacubitril/valsartan, a novel therapy in chronic heart failure (CHF), inhibits the breakdown of various peptides. However, whether or not sacubitril/valsartan administration affects urinary C-peptide levels is unclear. We herein report a 70-year-old man with type 2 diabetes mellitus (T2DM) and hypertension coexisting with CHF and nephrotic syndrome. The patient's urinary C-peptide levels dramatically increased after sacubitril/valsartan administration and decreased after discontinuation of the drug. Furthermore, sacubitril/valsartan administration to five other patients with hypertension and T2DM markedly increased urinary C-peptide levels. Thus, the insulin secretory capacity of patients with T2DM receiving sacubitril/valsartan may be overestimated when their urinary C-peptide level is measured.

Topics: Aged; Angiotensin Receptor Antagonists; Biphenyl Compounds; C-Peptide; Diabetes Mellitus, Type 2; Drug Combinations; Heart Failure; Humans; Hypertension; Male; Stroke Volume; Tetrazoles; Valsartan

The possible mechanism of increased urinary C-peptide due to neprilysin inhibitors is investigated. Neprilysin inhibition blocks degradation of natriuretic peptides, and elicits a natriuretic and antihypertensive effect. Neprilysin inhibition might similarly block degradation of C-peptides in the kidney and thus increase the urinary C-peptide level.

Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; C-Peptide; Diabetes Mellitus; Drug Combinations; Heart Failure; Humans; Neprilysin; Tetrazoles; Valsartan

MOTS-c, a mitochondrial-derived peptide (MDP), has been shown to have multiple biological activities such as antioxidation, anti-inflammation, and anti-apoptosis properties. In the present study, we aimed at evaluating the therapeutic effect of MOTS-c peptide in an animal model of heart failure. The heart failure mouse model was made by transverse aortic constriction (TAC) operations. The MOTS-c peptide was administrated subcutaneously by using an osmotic pump. At the end of the animal experiment, cardiac function was evaluated by echocardiography, and heart tissues were subjected to histological and molecular analysis. In vitro cultured H9C2 cells were used to test the effects of MOTS-c overexpression on cell death in response to H

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; C-Peptide; Disease Models, Animal; Heart; Heart Failure; Mice; Mice, Inbred C57BL; Peptides

The relationship between disturbances in glucose homeostasis and heart failure (HF) progression is bidirectional. However, the mechanisms by which HF intrinsically impairs glucose homeostasis remain unknown. The present study tested the hypothesis that the bioavailability of intact glucagon-like peptide-1 (GLP-1) is affected in HF, possibly contributing to disturbed glucose homeostasis. Serum concentrations of total and intact GLP-1 and insulin were measured after an overnight fast and 15 min after the ingestion of a mixed breakfast meal in 49 non-diabetic patients with severe HF and 40 healthy control subjects. Similarly, fasting and postprandial serum concentrations of these hormones were determined in sham-operated rats, and rats with HF treated with an inhibitor of the GLP-1-degrading enzyme dipeptidyl peptidase-4 (DPP4), vildagliptin, or vehicle for 4 weeks. We found that HF patients displayed a much lower increase in postprandial intact and total GLP-1 levels than controls. The increase in postprandial intact GLP-1 in HF patients correlated negatively with serum brain natriuretic peptide levels and DPP4 activity and positively with the glomerular filtration rate. Likewise, the postprandial increases in both intact and total GLP-1 were blunted in HF rats and were restored by DPP4 inhibition. Additionally, vehicle-treated HF rats displayed glucose intolerance and hyperinsulinemia, whereas normal glucose homeostasis was observed in vildagliptin-treated HF rats. We conclude that the postprandial increase in GLP-1 is blunted in non-diabetic HF. Impaired GLP-1 bioavailability after meal intake correlates with poor prognostic factors and may contribute to the establishment of a vicious cycle between glucose disturbance and HF development and progression.

Topics: Aged; Animals; Blood Glucose; C-Peptide; Female; Glucagon-Like Peptide 1; Glucose Intolerance; Heart Failure; Humans; Insulin; Male; Middle Aged; Obesity; Peptide Fragments; Postprandial Period; Rats, Wistar

Type 2 diabetes mellitus and hypertension are two major risk factors leading to heart failure and cardiovascular damage. Lowering blood sugar by the sodium-glucose co-transporter 2 inhibitor empagliflozin provides cardiac protection. We established a new rat model that develops both inducible diabetes and genetic hypertension and investigated the effect of empagliflozin treatment to test the hypothesis if empagliflozin will be protective in a heart failure model which is not based on a primary vascular event. The transgenic Tet29 rat model for inducible diabetes was crossed with the mRen27 hypertensive rat to create a novel model for heart failure with two stressors. The diabetic, hypertensive heart failure rat (mRen27/tetO-shIR) were treated with empagliflozin (10 mg/kg/d) or vehicle for 4 weeks. Cardiovascular alterations were monitored by advanced speckle tracking echocardiography, gene expression analysis and immunohistological staining. The novel model with increased blood pressure und higher blood sugar levels had a reduced survival compared to controls. The rats develop heart failure with reduced ejection fraction. Empagliflozin lowered blood sugar levels compared to vehicle treated animals (182.3 ± 10.4 mg/dl vs. 359.4 ± 35.8 mg/dl) but not blood pressure (135.7 ± 10.3 mmHg vs. 128.2 ± 3.8 mmHg). The cardiac function was improved in all three global strains (global longitudinal strain - 8.5 ± 0.5% vs. - 5.5 ± 0.6%, global radial strain 20.4 ± 2.7% vs. 8.8 ± 1.1%, global circumferential strain - 11.0 ± 0.7% vs. - 7.6 ± 0.8%) and by increased ejection fraction (42.8 ± 4.0% vs. 28.2 ± 3.0%). In addition, infiltration of macrophages was decreased by treatment (22.4 ± 1.7 vs. 32.3 ± 2.3 per field of view), despite mortality was not improved. Empagliflozin showed beneficial effects on cardiovascular dysfunction. In this novel rat model of combined hypertension and diabetes, the improvement in systolic and diastolic function was not secondary to a reduction in left ventricular mass or through modulation of the afterload, since blood pressure was not changed. The mRen27/tetO-shIR strain should provide utility in separating blood sugar from blood pressure-related treatment effects.

Topics: Animals; Benzhydryl Compounds; C-Peptide; Cardiotonic Agents; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucosides; Heart Failure; Humans; Hyperinsulinism; Hypertension; Male; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Sodium-Glucose Transporter 2 Inhibitors

No data is so far available on the relation between glucose values and insulin resistance and mortality, both at short- and long-term, in patients with acute heart failure syndromes (AHF). We prospectively assessed in 100 consecutive non-diabetic AHF patients whether acute glucose metabolism, as indicated by fasting glycemia and insulin resistance (HOMA index) was able to affect short- and long-term mortality. In the overall population, 51 patients showed admission glucose values >140 mg/dl. No significant difference was observed in admission and peak glycemia, insulin and C-peptide values and in HOMA-index between dead and survived patients. At multivariate logistic backward stepwise analysis the following variables were independent predictors for in-ICCU mortality (when adjusted for left ventricular ejection fraction): Fibrinogen (1 mg/dl increase) [OR (95% CI) 0.991 (0.984-0.997); p = 0.004]; NT-pro BNP (100 UI increase) [OR (95%CI) 1.005 (1.002-1.009); p = 0.004]; leukocyte count (1,000/μl increase) [OR (95%CI) 1.252 (1.070-1.464); p = 0.005]. eGFR was independently correlated with long-term mortality (HR 0.96, 95%CI 0.94-0.98, p < 0.001). In consecutive patients with acute heart failure without previously known diabetes, we documented, for the first time, that fasting glucose and insulin values and insulin resistance do not affect mortality at short- and long-term. Inflammatory activation (as indicated by the leukocyte count and the fibrinogen) and NT-pro BNP levels are independent predictors for early death while the eGFR affects the long-term mortality.

Topics: Acute Disease; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Diabetes Mellitus; Female; Glomerular Filtration Rate; Heart Failure; Humans; Hyperglycemia; Insulin; Insulin Resistance; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies

To assess relations between severity of chronic cardiac failure (CCF) and a course of comorbid type 2 diabetes mellitus (DM).. Time course changes of cerebral natriuretic peptide (CNUP) were used as a criterion of CCF severity in 81 patients with mild and moderate CCF (NYHA functional class II-III), left ventricular ejection fraction (LVEF) < 45% and type 2 DM. Of them, two groups of 19 patients each were compiled--with the highest and lowest CNUP levels. Also, patients with a rising CNUP level and CCF FC (n = 5) and those with decreasing CNUP and FC improvement (n = 33) were analysed. The following parameters were studied at baseline and 6 months later: clinicofunctional status, glomerular filtration rate (GFR), neurohormonal profile (CNUP), noradrenalin and angiotensin II, the level of HbA1c, baseline and postprandial plasma glucose, serum insulin and C-peptide.. Insignificant changes in glycemia in low C-peptide were found in groups with mild CCF. In patients with high CNUP and CCF FC there was a positive correlation between high CNUP, noradrenalin and fasting glucose. With growing severity of CCF clinicofunctional status of the patients was deteriorating while levels of noradrenalin and angiotensin II tended to rise.. Moderate decompensation of CCF had no effect on the course of associated DM. More severe and long-term decompensation may be accompanied with noticeable changes in glycemia.

Topics: Aged; Angiotensin II; C-Peptide; Comorbidity; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Retrospective Studies; Severity of Illness Index

Topics: Amine Oxidase (Copper-Containing); C-Peptide; Diabetes Mellitus; Heart Failure; Humans; Insulin; Kinetics; Reference Values

The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Chronic Disease; Heart Failure; Humans; Insulin; Insulin Resistance; Male; Oxygen Consumption; Stroke Volume