c-peptide and Liver-Diseases

Topics: Adult; Aged; Biomarkers; C-Peptide; Diabetes Complications; Diabetes Mellitus; Drug Administration Schedule; Female; Humans; Infections; Insulin; Kidney Diseases; Liver Diseases; Male; Middle Aged; Patient Selection; Pregnancy

Topics: C-Peptide; Gastrointestinal Diseases; Gastrointestinal Hormones; Humans; Insulin; Liver Diseases; Prostaglandins; Radioimmunoassay

Topics: C-Peptide; Carbohydrate Metabolism; Glucose Tolerance Test; Hepatitis, Viral, Human; Humans; Hypoglycemia; Insulin; Insulin Resistance; Liver Cirrhosis; Liver Diseases

Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.. Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m 2 , glucagon-stimulated C-peptide of >1.5 ng/mL, glycated hemoglobin >7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value <0.05 was defined as significant.. MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.. RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.

Topics: Adipokines; Adolescent; Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Gastric Bypass; Gastrointestinal Hormones; Glucagon; Glycated Hemoglobin; Humans; Insulin; Liver Diseases; Middle Aged; Obesity, Morbid; Prospective Studies; Sirtuin 1; Young Adult

Zinc is a trace element vital for immune function during host response to infection. The proinsulin C-peptide has been shown to exert beneficial effects through activation of the anti-inflammatory peroxisome proliferator-activated receptor γ (PPARγ) in experimental endotoxemia. Some in vitro activities of C-peptide appear dependent on the presence of zinc. We investigated the effect of zinc supplementation before onset of sepsis on the anti-inflammatory properties of C-peptide. Male C57BL/6 mice were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). Mice received zinc gluconate (1.3 mg/kg) intraperitoneally (i.p.) for 3 days before CLP. One hour after CLP, animals received C-peptide (280 nmol/kg i.p.) or the antimicrobial agent imipenem (25 mg/kg i.p.). Cecal ligation and puncture was associated with an 11% survival rate, pulmonary leukosequestration, and liver injury. Molecular analysis in lungs of septic mice showed increased nuclear activation of the proinflammatory extracellular signal-regulated kinases 1 and 2 and nuclear factor κB, but decreased PPARγ expression, when compared with sham animals. Combination of zinc supplementation with C-peptide posttreatment significantly improved survival rate (61%) similarly to antibiotic treatment (60%), ameliorated lung architecture and liver function, reduced tissue neutrophil infiltration, and increased bacterial clearance when compared with vehicle, C-peptide, or zinc treatment alone. These beneficial effects were associated with restored lung nuclear expression of PPARγ and reduction of phosphorylated extracellular signal-regulated kinases 1 and 2 and nuclear factor κB activities in comparison to vehicle or single treatment protocols. Our data demonstrate that short-term zinc prophylaxis before the infectious insult is a requisite for the anti-inflammatory properties of C-peptide by facilitating modulation of inflammatory pathways.

Topics: Acute Lung Injury; Animals; Bacterial Load; Bronchoalveolar Lavage Fluid; C-Peptide; Cytokines; Dietary Supplements; Drug Evaluation, Preclinical; Drug Therapy, Combination; Extracellular Signal-Regulated MAP Kinases; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; NF-kappa B; Sepsis; Survival Analysis; Systemic Inflammatory Response Syndrome; Zinc

The function of peroxisome proliferator-activated receptor-gamma (PPARgamma) in hepatic inflammation and injury is unclear. In this study, we sought to determine the role of PPARgamma in hepatic ischemia/reperfusion injury in mice. Male mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 8 hours of reperfusion. PPARgamma was found to be constitutively activated in hepatocytes but not in nonparenchymal cells. Upon induction of ischemia, hepatic PPARgamma activation rapidly decreased and remained suppressed throughout the 8-hour reperfusion period. This reduced activation was not a result of decreased protein availability as hepatic nuclear PPARgamma, retinoid X receptor-alpha (RXRalpha), and PPARgamma/RXRalpha heterodimer expression was maintained. Accompanying the decrease in PPARgamma activation was a decrease in the expression of the natural ligand 15-deoxy-Delta(12,14)-prostaglandin J(2). This was associated with reduced interaction of PPARgamma and the coactivator, p300. To determine whether PPARgamma activation is hepatoprotective during hepatic ischemia/reperfusion injury, mice were treated with the PPARgamma agonists, rosiglitazone and connecting peptide. These treatments increased PPARgamma activation and reduced liver injury compared to untreated mice. Furthermore, PPARgamma-deficient mice had more liver injury after ischemia/reperfusion than their wild-type counterparts.. These data suggest that PPARgamma is an important endogenous regulator of, and potential therapeutic target for, ischemic liver injury.

Topics: Animals; C-Peptide; E1A-Associated p300 Protein; Gene Expression Regulation; Hepatocytes; Liver; Liver Diseases; Male; Mice; Mice, Inbred C57BL; PPAR gamma; Prostaglandin D2; Reperfusion Injury; Retinoid X Receptor alpha; Rosiglitazone; Thiazolidinediones

Controversial data exists concerning the impact of immunosuppressive therapy on the development of post-transplantation diabetes mellitus (PTDM). Therefore, we investigated glucose metabolism in healthy donors and in recipients of living-donor liver transplants (LD-LTX, n=18) without pre-existing diabetes mellitus before, on day 10, month 6, and month 12 after intervention. The computer-assisted analysis of glucose, insulin, and C-peptide profiles obtained from frequently sampled intravenous glucose tolerance tests allows to achieve an integrated view of factors controlling glucose tolerance, i.e., insulin sensitivity (SI), first and second phase insulin secretion (phi1 and phi2). SI of donors declined by day 10 after operation (SI 2.65 +/- 0.41 vs. 4.90 +/- 0.50 10(-4) minute(-1) microU ml(-1), P < 0.01) but returned to values as before after 6 months. Phi1 did not change. Phi(2), however, significantly increased by day 10 (8.57 +/- 0.82 10(9) minute(-1) to 13.77 +/- 1.53 10(9) minute(-1), P < 0.01) but was in the same range as before after 6 months. In parallel to donors SI of recipients progressively increased after LD-LTX. Phi1 did not alter in recipients. Phi2 continuously decreased and was not different from donors by month 12. The extent of liver injury assessed by liver enzyme concentrations and liver function represented by cholinesterase activity, albumin, and INR were closely related with changes of SI in donors and recipients during the first year after intervention. In conclusion, the extent of liver damage plays a predominant role in regulating glucose tolerance. No impact of immunosuppressive therapy on SI, phi1 and phi2 was detected.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Immunosuppressive Agents; Insulin; Liver Diseases; Liver Function Tests; Liver Transplantation; Living Donors; Male; Middle Aged; Treatment Outcome

Tyrosinaemia type I (TT I) (McKusick 276700) is a heterogeneous disorder with a broad spectrum of clinical phenotypes. Although histological abnormalities of the pancreas are well recognized, there are only incidental reports of pancreatic dysfunction manifested as insulin-dependent diabetes mellitus. We report three subjects with TT I and acute liver dysfunction who had hyperinsulinism in early infancy. Hypoglycaemia persisted despite dietary treatment and one patient had inadequate lipolysis at the time of hypoglycaemia. All three patients were successfully treated with diazoxide (10 mg/kg per day) and chlorthiazide (35 mg/kg per day) and treatment was gradually withdrawn after 9, 13 and 34 months, respectively. The mechanism of pancreatic dysfunction in TT I is unknown but may be related to the toxic metabolites that accumulate in this condition. We conclude that hyperinsulinism is not a rare complication in TT I. In patients with persistent hypoglycaemia, C-peptide should always be measured. Treatment with diazoxide and chlorthiazide is highly effective, appears to be safe, and does not need to be continued lifelong.

Topics: Blood Glucose; C-Peptide; Chlorothiazide; Diazoxide; Diuretics; Humans; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Liver Diseases; Pancreatic Diseases; Sodium Chloride Symporter Inhibitors; Tyrosinemias

A 45-year-old man had been complaining of thirst and polydypsia for the last 3 months and was diagnosed as having type 2 diabetes mellitus because his fasting blood glucose showed 221 mg/dl with positive urinary ketone. He was hospitalized to a private hospital and Penfil 30R was started. However, serum gamma-GTP and aminotransferases began to elevate after insulin treatment and exceeded 1000 IU/l. Insulin was discontinued and serum gamma-GTP and aminotransferases returned close to the normal range. Since his glycemic control became poor again, Penfil 30R was restarted and serum gamma-GTP and aminotransferases elevated again. Therefore, insulin was discontinued and the patient was referred to the Third Department of Internal Medicine, Yamanashi Medical University Hospital because of liver dysfunction. His plasma glucose decreased by diet therapy, and improved further by the administration of glibenclamide. After obtaining informed consent, Humalin R was challenged. Seven days after insulin injection, serum aminotransferases began to elevate again. Lymphocyte stimulation test was negative against three preparations (Penfil R, Penfil N and Humalin R). The present case suggests that human insulin itself can cause liver dysfunction and we need to pay more attention to liver function tests when we start insulin treatment.

Topics: Alanine Transaminase; Alkaline Phosphatase; Antibodies, Viral; Aspartate Aminotransferases; Bilirubin; C-Peptide; Diabetes Mellitus, Type 2; gamma-Glutamyltransferase; Glyburide; Hepatitis B Surface Antigens; Humans; Hypoglycemic Agents; Immunoglobulin M; Insulin; Insulin Antibodies; Ketone Bodies; L-Lactate Dehydrogenase; Liver Diseases; Lymphocyte Activation; Male; Middle Aged; Thirst

The liver is the major source of circulating insulinlike growth factor-I (IGF-I) and has been suggested as a major source of at least two of the major binding proteins that modify its bioavailability. We aimed to assess the direct effects of liver dysfunction on serum levels of IGF-1 and its major binding proteins by measuring fasting levels of growth hormone, IGF-1, IGFBP-1, IGFBP-3, insulin, C peptide, and glucose in 35 patients with cirrhosis and during an oral glucose tolerance test in 16 of those patients. Serum levels of growth hormone (GH) were high in the patients: median, 12.0 mU/L (range, 1 to 87) compared with normals, 0.95 mU/L (0.1 to 20) (P < .0005) and serum IGF-1 levels were low: 81 ng/mL (38 to 153) versus 193 ng/mL (151 to 235) (P < .0001). Serum IGFBP-3 levels were low in the patients: 1.59 mg/L (0.46 to 4.43) compared with normals, 5.41 (4.34 to 6.11) (P < .0001), and there was a significant negative correlation between IGFBP-3 levels and Childs Pugh score (r = .63 P < .0001). Fasting IGFBP-1 levels were significantly higher in the patients 31 ng/mL (11 to 92) than normals, 14 (7 to 20) (P < .0001). There was no correlation between fasting insulin and IGFBP-1 levels despite high fasting insulin levels. A decrease in IGFBP-1 levels was seen during the glucose tolerance test (GTT) in all patients. In conclusion, there are significant changes in the levels of two of the major IGF-1 binding proteins that may further limit the bioavailability of already low circulating IGF-1 levels. Substrate availability appears to be a stronger influence on fasting IGFBP-1 levels than does insulin, and the close correlation of IGFBP-3 with liver function indicates a dominant regulatory role of the hepatocyte.

Topics: Adult; Blood Glucose; C-Peptide; Carrier Proteins; Chronic Disease; Fasting; Female; Glucose Tolerance Test; Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Liver Diseases; Male; Middle Aged; Somatomedins

Topics: C-Peptide; Diabetes Mellitus, Type 1; Follow-Up Studies; Glycated Hemoglobin; Graft Rejection; Humans; Islets of Langerhans Transplantation; Kidney Transplantation; Liver Diseases; Liver Transplantation; Tissue Donors

The behavior of insulin and glucagon and related metabolic substrates was assayed in plasma of patients with fulminant hepatic failure. All 12 subjects were provided the same nutritional support. High levels of insulin and glucagon were present at all times and no difference was observed between surviving patients (four) and those who died (8). Elevated values for branched-chain and aromatic amino acids as well as alanine were present. Statistically significant lower levels of aromatic amino acids and consequently a greater branched chain-aromatic amino acid ratio was found in surviving vs nonsurviving patients. A significantly greater level of alpha-fetoprotein was found in patients who survived as compared to those who died.

Topics: Adult; Alanine; alpha-Fetoproteins; Amino Acids, Branched-Chain; Blood Glucose; C-Peptide; Female; Glucagon; Hepatic Encephalopathy; Humans; Insulin; Liver Diseases; Male

The urinary excretion of chromium, copper and manganese was determined in 185 diabetics and in an equal number of control subjects by measuring the concentration of each of these metals using electrothermal atomic spectrophotometry and dividing the values by the urinary concentration of creatinine (creat) in each subject. The mean (SEM) values for the overall diabetics and the control group were 2.32 (0.17) and 2.62 (0.22) mumol Cr/mole of creat, 76.5 (5.5) and 73.9 (6.1) mumol Cu/mole of creat, and 3.56 (0.44) and 2.66 (0.3) mumol Mn/mole of creat, respectively. There was no correlation between the urinary excretion of any of the metals examined and age or sex of either group. While the cardiovascular or ophthalmologic diseases associated with diabetes did not influence the excretion of any of these metals, significantly higher urinary excretion of Cu was exhibited by diabetics with neuropathy (p < 0.0027) or infections (p < 0.014) than by those without. Also, diabetics with liver disorders or those who were not treated with insulin excreted significantly more Mn than did their diabetic counterparts.

Topics: C-Peptide; Chromium; Copper; Creatinine; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Liver Diseases; Male; Manganese; Middle Aged; Reference Values; Spectrophotometry, Atomic; Trace Elements

Topics: C-Peptide; Diabetes Mellitus; Diabetic Retinopathy; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Liver; Liver Diseases

Topics: Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Kinetics; Liver Diseases; Male; Middle Aged

Five patients with fatal acute liver failure, given 5 g h-1 of glucose for the previous 12 h, were investigated by the hyper- and euglycaemic glucose 'clamp' technique, and the results compared with reported control values. Initial average blood glucose concentration was normal (6.0 mmol l-1, range 5.0-8.8). Plasma insulin and C-peptide concentrations were increased about tenfold (1450 pmol l-1, range 330-4021, and 3000 pmol l-1, range 670-7650, respectively). The whole body glucose metabolic rate was decreased to about half control values (21 mumol min-1 kg-1, range 6-28) and the insulin sensitivity of the glucose metabolism was decreased to about 15% (9.4 m3 min-1 kg-1, range 3.6-14.4). The calculated metabolic clearance of insulin was normal (520 ml min-1 (m2)-1, range 305-1027) and the calculated systemic delivery rate of insulin was about sixfold increased (1135 pmol min-1 (m2)-1, range 474-2010). The initial glucagon concentrations were fifty-fold increased (550 pmol 1, range 72-1309) and not suppressible by glucose and insulin. The patients thus exhibited pronounced insulin insensitivity and hyperinsulinaemia, attributable primarily to pancreatic hypersecretion. The reason for the relation between, and the pathogenetic importance of, these findings is not known.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose; Humans; Insulin; Insulin Resistance; Liver; Liver Diseases; Male; Middle Aged

Levels of plasma cyclic AMP, serum immunoreactive insulin (IRI), serum c-peptide immunoreactivity (CPR) and blood sugar (BS) were determined 0, 15, 30, 45 and 60 min after a glucagon injection (0.01 mg per kg body weight) in normal controls, patients with acute hepatitis and liver cirrhosis. Plasma cyclic AMP responses to glucagon in liver disease patients varied widely in peak value, and only in patients with fulminant hepatitis and decompensated liver cirrhosis with poor prognosis was the response suppressed. The peak response of BS was found significantly later in liver cirrhosis patients than in normal controls. IRI and CPR responses to glucagon were lower in acute hepatitis patients than in normal controls and liver cirrhosis patients. IRI levels and their sum were also lower in acute hepatitis patients, although CPR levels were not significantly different. Thus, the ratio of the sum of CPR from 0 to 60 min to that of IRI was significantly higher in acute hepatitis, indicating impaired pancreatic secretion of insulin to glucagon stimulation as well as increased uptake of insulin by the liver in acute hepatitis.

Topics: Adult; Blood Glucose; C-Peptide; Cyclic AMP; Female; Glucagon; Hepatitis, Viral, Human; Humans; Insulin; Kinetics; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

Topics: Adult; C-Peptide; Chronic Disease; Fatty Acids, Nonesterified; Female; Glucagon; Growth Hormone; Humans; Insulin; Insulin Antagonists; Insulin Resistance; Liver Diseases; Male; Middle Aged

Insulin and C-peptide in venous blood were determined during oral glucose tolerance testing in 59 non-manifest diabetics with histologically established chronic liver disease (fatty degeneration, chronic aggressive hepatitis, cirrhosis). Glucose tolerance was pathologic in 60-80% of patients. When compared to a control group patients with chronic liver disease showed significantly increased values of blood glucose (after glucose intake), of insulin and of C-peptide (fasting and after glucose intake). The C-peptide/insulin ratio, a measure of hepatic insulin degradation, was significantly decreased after glucose uptake. There were no significant differences of blood sugar, insulin and C-peptide among the various liver diseases. In chronic aggressive hepatitis and in cirrhosis the C-peptide/insulin ratio was partly significantly lower than in fatty degeneration. From the increased C-peptide values increased insulin secretion in chronic liver diseases can be deducted. In addition, the decreased C-peptide/insulin ratios show an impairment of insulin degradation in liver cirrhosis and other chronic hepatic diseases. However, in fatty liver degeneration this is clearly less pronounced than in more serious liver diseases.

Topics: C-Peptide; Chronic Disease; Fatty Liver; Female; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Insulin; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

The influence of two sulfonylureas on blood glucose and plasma immunoreactive insulin (IRI) and C-peptide responses to a standardized meal was investigated in a patient with type 2 diabetes and a liver disease with enhanced peripheral levels of liver enzymes. The very high fasting values of plasma IRI and C-peptide were further elevated by the meal. This response to the meal was markedly enhanced by both sulfonylureas, glipizide and glibenclamide. The blood glucose increment after the meal was diminished by sulfonylureas. Sulfonylureas thus seem to have beneficial effects in this diabetic patient, who had a liver disease and markedly elevated basal levels of plasma IRI and C-peptide concentrations.

Topics: Aged; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Fasting; Female; Food; Glipizide; Glyburide; Humans; Insulin; Liver Diseases; Liver Neoplasms; Sulfonylurea Compounds

Topics: Adult; Aged; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Liver Diseases; Male; Middle Aged; Peptides

Topics: C-Peptide; Chronic Disease; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Liver Diseases; Peptides

Topics: C-Peptide; Diabetes Mellitus; Humans; Liver Diseases; Peptides; Radioimmunoassay; Reagent Kits, Diagnostic

Topics: C-Peptide; Catheterization; Female; Humans; Insulin; Liver Diseases; Male; Middle Aged; Portal Vein; Skin; Venous Pressure

The correlation between plasma C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) was investigated during the oral glucose tolerance test in 20 normals, 127 diabetics, and 39 non-diabetics with chronic liver or renal disorders. When all subjects were included, the increment of CPR 30 minutes after glucose load (deltaCPR) correlated well with that of IRI (deltaIRI) (r = 0.66, p less than 0.001), but the return of CPR towards the basal level was delayed as compared with IRI. The positive correlation was also observed between the sum of 6 IRI and that of 6 CPR values during the glucose tolerance test in diabetics and controls (r = 0.53, p less than 0.001). deltaCPR/deltaBS (30 min.) was also well correlated with deltaIRI/deltaBS (30 min.), and was specifically low in diabetics. Insulin-treated maturity-onset diabetics showed low but considerable CPR responses while no CPR responses were observed in insulin-treated juvenile diabetics. In each plasma sample, CPR always exceeded IRI on the molar basis. At fasting CPR/IRI ratio was 15.6 +/- 1.7 (mean +/- SE) in normals and 14.9 +/- 1.3 approximately 16.9 +/- 1.0 in diabetics. In chronic liver diseases IRI response was augmented while CPR response was not different from that of controls, and the molar ratio of CPR/IRI was significantly low (9.5 +/- 1.1). On the contrary, it exceeded that of normals in chronic renal diseases (35.7 +/- 14.9). It is concluded that, first, the plasma CPR response appears to be a valuable indicator of pancreatic B-cell function, and second, it is, nevertheless, modified in chronic liver or renal disorders.

Topics: Adolescent; Adult; Antigens; C-Peptide; Child; Chronic Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Humans; Insulin; Kidney Diseases; Liver Diseases; Male; Middle Aged; Obesity; Peptides

Topics: C-Peptide; Chronic Disease; Humans; Insulin; Liver Diseases; Pancreatitis; Peptides; Radioimmunoassay

Topics: Acute Disease; C-Peptide; Hepatic Encephalopathy; Hepatitis; Hepatitis, Viral, Human; Humans; Insulin; Liver; Liver Cirrhosis; Liver Diseases; Peptides