c-peptide and Acute-Disease

Fulminant type 1 diabetes is defined as a subtype of type 1 diabetes with a remarkably acute onset. A nationwide survey identified that this variant accounts for approximately 20% of acute-onset type 1 diabetic patients in Japan. Recent studies indicate that this is not a minor subtype in other East Asian countries. As genetic factors, we revealed association of HLA-DR-DQ, HLA-B and CTLA-4 to fulminant type 1 diabetes. As an environmental factor, viral infection would contribute to the development of this subtype. Cellular infiltration to islets was detected soon after the onset but not observed 1 month after the onset. Macrophages and T cells were the main components of the infiltrates. Enterovirus RNA and Toll-like receptor-3 expression, a signature of viral infection, was also observed. These findings suggest that viral infection in the susceptible individual might trigger anti-viral immune response and that pancreatic beta cells are rapidly destroyed through the accelerated immune reaction.

Topics: Acute Disease; Adult; Aged; Asia, Eastern; Blood Glucose; C-Peptide; CTLA-4 Antigen; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Enterovirus Infections; Female; Glycated Hemoglobin; HLA-B Antigens; HLA-DRB1 Chains; Humans; Insulin-Secreting Cells; Japan; Male; Middle Aged; Virus Diseases

It is clinically relevant and of physiological interest to investigate whether GH-induced insulin resistance depends on the timing of GH exposure relative to when insulin sensitivity is assessed.. GH-induced insulin resistance is rapidly reversible.. Eight male GH-deficient patients underwent a 6-h euglycemic-hyperinsulinemic glucose clamp thrice in a randomized crossover design receiving either no GH (study 0), a 7-h GH infusion (0.2-0.3 mg in total) that terminated 5 h before the clamp (study 1), or a similar GH infusion timed to continue during the first hour of the clamp (study 2). A muscle biopsy was obtained 30 min into the clamp. The patients were compared with eight healthy untreated control subjects (study c).. The glucose infusion rate, indirect calorimetry, and free fatty acid metabolism were assessed. In muscle biopsies, protein phosphorylation of signal transducer and activator of transcription 5, Akt, and Akt substrate 160 (phospho-Akt substrate signal) and gene expression of IGF-I and SOCS1-3 were assessed.. Insulin sensitivity differed significantly between the GH-deficiency studies (P = 0.005) with distinct insulin resistance in study 2 and increased insulin sensitivity in study 0 [area under the glucose infusion rate curve (mg/kg · min): 1663 ± 151 (study 0) vs. 1482 ± 166 (study 1) vs. 1123 ± 136 (study 2) vs. 1492 ± 229 (control group)]. Free fatty acid levels and lipid oxidation were elevated in response to GH exposure but became suppressed during the clamp. IGF-I and SOCS3 gene expression was increased in study 2.. Very-low-dose GH exposure evokes acute insulin resistance that subsides after 5 h. This time-dependent reversibility should be considered when assessing the impact of GH on glucose homeostasis.

Topics: Acute Disease; Adult; Aged; Biopsy; Blood Glucose; C-Peptide; Calorimetry, Indirect; Cross-Over Studies; Fatty Acids, Nonesterified; Gene Expression; Glucose Clamp Technique; Glucose Intolerance; Human Growth Hormone; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Male; Middle Aged; Muscle, Skeletal; Signal Transduction; Suppressor of Cytokine Signaling Proteins

Although it is well established that severe chronic hyperglycemia is associated with microvascular disease, it is not known whether transient hyperglycemia similar to that observed with impaired glucose tolerance or early Type 2 diabetes contributes to this pathology by altering microvascular function. To test the hypothesis that acute hyperglycemia decreases microvascular vasodilator responsiveness in human skin, we measured the cutaneous vasodilator response to local warming. This response can be divided into two phases, an initial peak that relies predominantly on local sensory nerves and a second slower phase that is largely dependent on endothelial nitric oxide. We reasoned that a change in one or both phases would indicate a change in the corresponding mechanism(s) with hyperglycemia. Twenty-eight healthy volunteers (14 women, 14 men) were randomly divided into three groups, corresponding to 6 h of euglycemia (n = 8), 6 h when glucose was clamped at approximately 7 mmol/l (n = 10), or 6 h when glucose was varied to mimic a postprandial pattern (i.e., peak glucose approximately 11.1 mmol/l) commonly observed in individuals with impaired glucose tolerance (n = 10). Insulin concentrations in all instances were maintained at approximately 65 pmol/l by means of continuous infusions of somatostatin and insulin. Glucagon and growth hormone were also continuously infused to maintain their basal concentrations. Despite substantial differences in both the level and pattern of glucose concentrations, neither maximum cutaneous vasodilation nor the pattern of the vasodilator response to local warming differed over the 6 h of study. We conclude that acute hyperglycemia similar to levels commonly observed in people with either early Type 2 diabetes or impaired glucose tolerance does not alter the vasodilator response to local warming of the skin in humans.

Topics: Acute Disease; Adult; Blood Glucose; Blood Vessels; C-Peptide; Female; Glucose Intolerance; Hemodynamics; Hot Temperature; Humans; Hyperglycemia; Insulin; Male; Osmolar Concentration; Reference Values; Regional Blood Flow; Skin; Time Factors

First-phase insulin response to intravenous glucose is impaired both in type 2 diabetic patients and in subjects at risk for the disease. Hyperglycemia can modify beta-cell response by either inhibiting or potentiating both first- and second-phase insulin release. In normal subjects, the effect of acute hyperglycemia on insulin secretion is controversial. We measured (in 13 healthy volunteers) insulin secretion (by deconvolution of plasma C-peptide concentrations) during three consecutive 30-min hyperglycemic steps (2.8, 2.8, and 5.6 mmol/l), followed by an intravenous arginine bolus. First-phase insulin secretion in response to the first hyperglycemic step (456 +/- 83 pmol.min(-1).m(-2)) was significantly larger than that in response to the second step (311 +/- 37 pmol.min(-1).m(-2), P < 0.01); the subsequent increase in glycemia failed to stimulate first-phase secretion any further (377 +/- 60 pmol.min(-1).m(-2), NS vs. the previous value). This inhibition was also evident when insulin release rates were corrected for the respective increments (absolute or percentage) in plasma glucose levels and was not due to beta-cell exhaustion because the arginine bolus still elicited a large peak of insulin secretion (4,790 +/- 2,330 pmol.min(-1).m(-2)). In contrast, second-phase insulin secretion was related to the prevailing glucose levels across the three hyperglycemic steps in a direct quasilinear manner. We conclude that first-phase insulin secretion is inhibited by short-term modest hyperglycemia, whereas the second-phase insulin secretion increases linearly with hyperglycemia.

Topics: Acute Disease; Adult; Aged; Arginine; C-Peptide; Diabetes Mellitus, Type 2; Glucose; Humans; Hyperglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Middle Aged

An extrapancreatic effect of sulfonylureas has been postulated. However, in vivo results have been disputed because the amelioration of insulin action that follows sulfonylurea may represent the relief from glucose toxicity rather than a direct effect of the drug. Therefore, we studied the hypoglycemic action of gliclazide acutely and after 2 months of therapy in seven type 2 diabetic patients. All patients received a 240-minute i.v. glucose infusion with [3-3H]glucose. In a random order, 160 mg gliclazide (study 1) or placebo (study 2) was given orally before glucose infusion. Finally, the effect of 160 mg gliclazide was reassessed after a two-month treatment with the same sulfonylurea (80 mg t.i.d.). Basal plasma glucose, insulin, C-peptide and endogenous glucose production (EGP) were similar before the two initial studies. During glucose infusion, EGP was more suppressed after gliclazide in spite of comparable increase in plasma insulin and C-peptide. After the two-month therapy, basal plasma glucose levels and HbA1c were lower while plasma insulin and C-peptide were higher with respect to baseline (p < 0.05). Gliclazide further reduced plasma glucose, the incremental area above baseline, and EGP during glucose infusion, while plasma insulin and C-peptide achieved higher plateaus (p < 0.05). When data were pooled, plasma glucose concentration and EGP correlated both in the basal state (r = 0.71) and during the last hour of glucose infusion (r = 0.84; both p < 0.05). These data suggest that gliclazide enhances the suppression of EGP induced by insulin and that this effect is greater with chronic treatment because of concomitant improvement of insulin secretion.

Topics: Acute Disease; Blood Glucose; C-Peptide; Chronic Disease; Diabetes Mellitus, Type 2; Gliclazide; Gluconeogenesis; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Kinetics; Middle Aged; Placebos; Regression Analysis; Time Factors; Tritium

Hypoxia was shown to reduce insulin concentrations at rest and during exercise. However, some studies have also demonstrated increases in the hormone associated with arterial desaturation. This study was conducted in order to decide [1] whether acute alveolar hypoxia increased or decreased the circulating insulin levels, and [2] to elucidate whether interactions of insulin with other hormones were of relevance in this respect. Glucose (GLU), insulin (INS), c-peptide (CP), adrenaline and noradrenaline (CATs), atrial natriuretic peptide (ANP) and cortisol (CORT) as well as the capillary blood gases were determined in 15 healthy fasting male volunteers (age: 26.2 +/- 2.8 years, body mass index: 22.4 +/- 2.7 kg.m-2). On two separate test days the subjects breathed, in random order, either normal air (N) or a gas mixture with reduced oxygen content (H; FIO2: 0.14). Measurements were made at rest as well as during an incremental cycle exercise in a supine position (increments of 6 min and 50 W) at 100 W and 150 W, at volitional exhaustion (N: 227 +/- 36 W; H: 200 +/- 32 W) as well as in the 5th min of recovery. Arterial desaturation was seen throughout on H-day. At rest all hormones and GLU were normal and showed no influence of H. During exercise INS remained constant on N-day, increased on H-day and was significantly higher with H than with N, most pronounced at 150 W and at volitional exhaustion with 20%, respectively. For CP and GLU no significant exercise-induced changes were seen on either test day and no influence of H was detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; C-Peptide; Exercise; Humans; Hypoxia; Insulin; Male

We report on the transition in blood glucose levels before and after the onset of fulminant type 1 diabetes mellitus in a perinatal woman. In week 38 of pregnancy, before which the patient had normal glucose tolerance, idiopathic acute pancreatitis was diagnosed. Five days thereafter, she became hypoglycemic, so we closely monitored her blood glucose levels. A total of 13 days later, she was hyperglycemic with a blood glucose level >16.0 mmol/L and glycated hemoglobin of 6.4%. Her fasting serum C-peptide reactivity level was 3.6 ng/mL on the 5th day, and 0.2 ng/mL on the 18th day. Multiple insulin injection therapy was administered since the 18th day; after that, ketoacidosis did not occur. The patient was diagnosed with fulminant type 1 diabetes mellitus based on hyperglycemia without high glycated hemoglobin levels and sudden onset insulin-dependent diabetes. Monitoring glucose levels in the case of idiopathic acute pancreatitis during pregnancy and prompt initiation of insulin therapy are important.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Pancreatitis; Pregnancy; Pregnancy Complications

Pancreatogenic diabetes mellitus has been assumed to result from non-immune beta cell destruction when the pancreas is replaced by fibrotic tissue secondary to acute and chronic pancreatitis. We hypothesize that recurrent episodes of pancreatic inflammation may increase the risk for developing β-cell autoimmunity in susceptible individuals.. We describe 11 patients who had both recurrent acute and/or chronic pancreatitis and type 1 diabetes (T1D) requiring insulin therapy.. All 11 patients had positive autoantibodies and 8 patients tested had minimal to undetectable (7/8) or moderate (1/8) stimulated C-peptide at 12 months after T1D onset. Three had biopsy confirmation of insulitis.. These cases lend support to the theory that pancreatitis may increase risk for T1D. We postulate that the pro-inflammatory conditions of pancreatitis may increase posttranslational protein modifications of β-cell antigens and neoepitope generation, which are potential initiating events for loss of β-cell self-tolerance.

Topics: Acute Disease; Adolescent; Adult; Autoantibodies; C-Peptide; Child; Child, Preschool; Chronic Disease; Diabetes Mellitus, Type 1; Humans; Infant; Inflammation; Middle Aged; Pancreatitis; Protein Processing, Post-Translational; Recurrence; Risk Factors; Young Adult

Topics: Acute Disease; Aged; Blood Glucose; C-Peptide; ChAdOx1 nCoV-19; Comorbidity; COVID-19; COVID-19 Vaccines; Emergencies; Humans; Hyperglycemia; Hypertension; Male; Metabolic Syndrome; Middle Aged; Prediabetic State; SARS-CoV-2

Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT).. Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models.. The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint.. Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.

Topics: Acute Disease; Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Metabolic Diseases; Middle Aged; Pancreatic Hormones; Pancreatitis; Prediabetic State; Prevalence

To assess the outcomes of drug therapy (DT) followed by pancreatic endotherapy for continuing painful episodes in recurrent acute pancreatitis.. DT comprised of pancreatic enzymes and anti-oxidants failing which, endotherapy (ET; pancreatic sphincterotomy and stent placement) was done. The frequency of pain, its visual analogue score (VAS), quality of life (QoL), serum C peptide and faecal elastase were compared between baseline and after 1 year of follow up in all patients and in the two subgroups on DT and ET. Response was defined as at least 50% reduction in the severity of pain to below a score of 5.. Of the thirty nine patients analysed, 21 (53.9%) responded to DT and 18 (46.1%) underwent ET. The VAS for pain (7.0 ± 2.0. A standardised protocol of DT, followed by ET decreased the intensity and frequency of pain in recurrent acute pancreatitis, enhanced QoL and improved pancreatic function.

Topics: Acute Disease; Adolescent; Adult; Antioxidants; C-Peptide; Child; Chronic Disease; Feces; Female; Follow-Up Studies; Humans; India; Male; Middle Aged; Pain Management; Pain Measurement; Pancreas; Pancreatitis; Prospective Studies; Quality of Life; Recurrence; Sphincterotomy, Endoscopic; Young Adult

Total pancreatectomy with islet autotransplantation is increasingly being performed remotely, that is, removing the pancreas in 1 location, isolating the islet cells in another location, then returning the islets to the original location for reimplantation into the patient. We determined the influence of extended cold ischemia time on key clinical outcomes in remote islet autotransplantation.. We evaluated patients who underwent remote islet autotransplantation at 2 centers from 2011 to 2014. Patients were divided into 2 groups: those with and those without a decrease in C-peptide greater than 50% from baseline. The primary clinical outcome was the quantity of isolated islet equivalents per kilogram body weight (IEQs/kg).. Twenty-five patients met inclusion criteria; 15 had a decrease in C-peptide greater than 50% from baseline and had lower corresponding IEQs/kg compared with those without a decrease greater than 50% (4045 vs 6654 IEQs/kg, P = 0.01). There was no difference in cold ischemia time between the 2 groups (664 vs 600 minutes, P = 0.25). Daily insulin use at 1 year nearly met statistical significance (25.3 vs 8 U, P = 0.06), as did glycated hemoglobin (8.07 vs 6.69 mmol/L, P = 0.06).. Cold ischemia time does not influence islet yield in patients undergoing pancreatectomy with remote isolation.

Topics: Acute Disease; Adult; C-Peptide; Cold Ischemia; Female; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Linear Models; Male; Middle Aged; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Retrospective Studies; Time Factors; Transplantation, Autologous; Treatment Outcome

Total pancreatectomy with islet autotransplantation (TPIAT) is increasingly performed with remote islet cell processing and preparation, i.e., with islet cell isolation performed remotely from the primary surgical site at an appropriately equipped islet isolation facility. We aimed to determine whether TPIAT using remote islet isolation results in comparable long-term glycemic outcomes compared with TPIAT performed with standard local isolation.. We performed a retrospective cohort study of adult patients who underwent TPIAT at three tertiary care centers from 2010 to 2013. Two centers performed remote isolation and one performed local isolation. Explanted pancreata in the remote cohort were transported ∼130 miles to and from islet isolation facilities. The primary outcome was insulin independence 1 year following transplant.. Baseline characteristics were similar between groups except the remote cohort had higher preoperative hemoglobin A1c (HbA1c; 5.43 vs. 5.25, P=0.02) and there were more females in the local cohort (58% vs. 76%, P=0.049). At 1 year, 27% of remote and 32% of local patients were insulin independent (P=0.48). Remote patients experienced a greater drop in fasting c-peptide (-1.66 vs. -0.64, P=0.006) and a greater rise in HbA1c (1.65 vs. 0.99, P=0.014) at 1-year follow-up. A preoperative c-peptide >2.7 (odds ratio (OR) 4.4, 95% confidence interval (CI) 1.6-14.3) and >3,000 islet equivalents/kg (OR 11.0, 95% CI 3.2-37.3) were associated with one-year insulin independence in the local group.. At 1 year after TPIAT, patients undergoing remote surgery have equivalent rates of long-term insulin independence compared with patients undergoing TPIAT locally, but metabolic control is superior with local isolation.

Topics: Acute Disease; Adult; C-Peptide; Cohort Studies; Diabetes Mellitus; Female; Glycated Hemoglobin; Health Facilities; Humans; Hypoglycemic Agents; Insulin; Islets of Langerhans Transplantation; Male; Pancreatectomy; Pancreatitis; Pancreatitis, Chronic; Postoperative Complications; Recurrence; Retrospective Studies; Transplantation, Autologous; Treatment Outcome

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

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP).. Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated.. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P < 0.01). The islet β-cell function of patients was lower than that of controls (P < 0.01), whereas insulin resistance index was higher among patients (P < 0.01). Obesity, hyperlipidemia, and diabetes-related symptoms were found to be associated with endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time.. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

Topics: Acute Disease; Aged; Analysis of Variance; Biomarkers; Blood Glucose; C-Peptide; Case-Control Studies; China; Fasting; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Logistic Models; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Predictive Value of Tests; Recovery of Function; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors

To investigate the feasibility of ABC typing to redefine the subtypes of acute-onset type 1 diabetes mellitus (DM).. Radioligand assay was used to detect glutamic acid decarboxylase-antibody (GAD-Ab) and tyrosine phosphatase autoantibody (IA-2A) in 308 patients with acute-onset type 1 DM. The patients were thus divided into 2 groups: pancreatic islet auto-antibody (demonstrated as A) positive group--positive in GAD-Ab or IA-2A--and pancreatic islet auto-antibody negative group. The clinical features and frequencies of HLA-DQ genotypes of these groups were compared. Within 24 hours after the correction of diabetic ketosis or diabetic ketoacidosis and after fasting for at least 8 h fasting and postprandial venous blood samples were collected to detect the fasting C peptide (FCP, demonstrated as B) reflecting the beta cell function, and postprandial C peptide (PCP). The patients were followed up for 2 years to know the insulin dosage (< 20 U/d or > or = 20 U/d). Receiver operating characteristic curve (ROC) was drawn to judge the values of fasting C peptide, body mass index (BMI, demonstrated as C) reflecting the central obesity, and HLA-DQ genotype in further typing among the A + and A - patients and the optimal cutoff points thereof.. Compared with the A - group, the metabolic disorders at the onset were more severe, the insulin dosage at the 2-year follow-up was higher, and the percentage of susceptible HLA-DQ genotype was higher in the A + group (P < 0.05 or < 0.01). The level of FCP (B) could be used to further subtyping in both A + and A - groups, with the optimal cutoff point of 150 pmol/L in the A + group and with the optimal cutoff point of 250 pmol/L in the A - group. BMI could be used for further classification in only A - group with the optimal cutoff point of 24 kg/m2. HLA-DQ genotypes were of little value in further classification both in A + and A - groups.. ABC typing may be used as a new way to redefine the subtypes in acute-onset type 1 DM for prognosis.

Topics: Acute Disease; Adolescent; Adult; Autoantibodies; C-Peptide; Child; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Genotype; Glutamate Decarboxylase; HLA-DQ Antigens; Humans; Male; Middle Aged; Prognosis; Protein Tyrosine Phosphatases; Radioligand Assay; Young Adult

'Fulminant diabetes' has been recognized as a super-acute onset and non-autoimmune type 1 diabetes. To evaluate autoimmunity against pancreatic beta cell in fulminant diabetes, ELISPOT assay was applied to the peripheral blood of these patients. In our ELISPOT system, GAD65-reactive and insulin B9-23-reactive IFN-gamma spots were detected in 46.3 and 26.0% of autoantibody-positive type 1 diabetes. Also, in fulminant type 1 diabetic patients, IFN-gamma spots in response to GAD65 and insulin B9-23 peptide were detected in 69.2 and 25.0%, respectively. These results suggest that anti-beta cell autoimmunity contributes to develop fulminant type 1 diabetes. Fulminant type 1 diabetes is known to have IDDM-resistant HLA DR2 with similar frequency of non-T1D subjects. In a mouse model, when islet-reactive CD8 cells are transferred to young NOD mice, the recipients develop overt diabetes within 1 week with massive insulitis. In (NOD x Balb/c) F1 mice, which hold idd-resistant genes, transfer of islet-reactive CD8 cells induced diabetes to 60% F1 recipients within 1 week with the later disappearance of insulitis. This mouse model shows very similar feathers to fulminant type 1 diabetes; idd-resistant HLA and no insulitis. These results implicated that once anti-islet immunity is optimally activated, subjects with partially resistant alleles could become overt diabetes.

Topics: Acute Disease; Animals; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Disease Models, Animal; Humans; Insulin-Secreting Cells; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; T-Lymphocytes

Hepatitis C virus (HCV) has been associated with Type 2 diabetes mellitus, and many other viral infections have been associated with Type 1 diabetes mellitus (Type 1 DM). An association between HCV and Type 1 DM, however, has never been reported. We report the case of a 66-year-old man who developed Type 1 DM 1 year after a blood transfusion-related HCV infection. Testing of serum specimens obtained in the weeks following blood transfusion demonstrated evidence of both acute HCV infection and development of Type 1 DM-related autoantibodies.. A 66-year-old Taiwanese male received blood transfusions during coronary artery bypass surgery in 1987. Serum specimens, obtained as part of a study on post-transfusion hepatitis, demonstrated that the patient had no evidence of hepatitis C prior to transfusion, but developed acute HCV infection after transfusion. One year later, the patient, who had no personal or family history of diabetes, presented with diabetic ketoacidosis, and tests for C-peptide confirmed that he had Type 1 DM. Testing of pre- and post-operative serum specimens demonstrated that the patient developed positive tests for islet cell and glutamic acid decarboxylase antibodies 4 weeks after transfusion, concurrent with the development of acute HCV infection.. The simultaneous development of HCV infection and diabetes-related autoantibodies suggest a relationship between HCV and Type 1 DM.

Topics: Acute Disease; Aged; Autoantibodies; C-Peptide; Diabetes Mellitus, Type 1; Glutamate Decarboxylase; Hepacivirus; Hepatitis C; Humans; Islets of Langerhans; Male; Taiwan; Transfusion Reaction

Topics: Acute Disease; Adolescent; Adult; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Male; Trauma Severity Indices; Wounds and Injuries

Adult spontaneous hypoglycaemia is not a diagnosis per se but a manifestation of a disease. Although rare, it is important to identify spontaneous hypoglycaemia and its causes because treatment may be preventative or curative. Hypoglycaemia can occur as an epiphenomenon in many serious diseases. It is sufficient to recognise the disease's association with hypoglycaemia and then take appropriate action to prevent the recurrence of hypoglycaemia. In investigating apparently healthy individuals, common pitfalls to avoid are: failure to recognise subacute neuroglycopenia clinically; failure to document hypoglycaemia adequately during symptoms; failure to measure pancreatic hormones, counter-regulatory hormones, and ketones in hypoglycaemic samples; failure to recognise pre-analytical and analytical limitations of laboratory assays; and failure to abandon obsolete and inappropriate investigations. Providing these caveats are met, appropriate laboratory and radiological investigations will almost always uncover the cause of spontaneous hypoglycaemia.

Topics: Acute Disease; Adult; Autoantibodies; Blood Glucose; C-Peptide; Clinical Laboratory Techniques; Diagnosis, Differential; Exercise Test; Fasting; Homeostasis; Humans; Hypoglycemia; Insulin; Insulinoma; Pancreatic Neoplasms; Postprandial Period; Proinsulin; Receptor, Insulin

We aimed to characterize a cohort of 'atypical' diabetic patients of sub-Saharan African origin and to analyse possible determinants of long-term remission.. Over 6 years, we studied the clinical and therapeutic profile of 42 consecutive patients undiagnosed or untreated prior to inclusion presenting with cardinal features of diabetes mellitus. We measured insulin secretion and sensitivity at inclusion. Immunogenetic (anti-GAD, anti-ICA and HLA class II) markers of Type 1 diabetes were compared with a 90-non-diabetic unrelated adult African population.. Twenty-one ketonuric patients (age 42 +/- 9 (sd) years; body mass index (BMI) 26 +/- 3 kg/m2) were initially insulin-treated (IT), and 21 non-ketonuric patients (age 38 +/- 8 years; BMI 26 +/- 5 kg/m2) had oral and/or diet therapy (NIT). Insulin could be discontinued in 47.6% (10/21) IT with adequate glycaemic control (HbA1c 6.7 +/- 1.3%), while insulin was secondarily started in 38.1% (8/21) NIT in expectation of better control. The initial basal (odds ratio (OR) 9.1, 95% confidence interval (CI) 1.3-64.4) and stimulated C-peptide (OR 8.17, 95% CI 1.5-44.1) were independently associated with remission. Insulin resistance was present in all the groups, more marked in the insulin-treated NIT. Anti-GAD antibodies and ICA were rare, but 38.1% IT vs. 1.1% controls had Type 1 diabetes HLA susceptibility haplotypes (P < 0.001) without significant difference between the subgroups.. Prolonged discontinuation of insulin is frequent in African diabetic patients initially presenting with signs of insulinopenia. In our patients, long-term insulin therapy was not associated with immunogenetic markers of Type 1 diabetes. The initial measure of insulin secretion seemed a good predictor of long-term remission.

Topics: Acute Disease; Adult; Africa South of the Sahara; Autoantibodies; C-Peptide; Diabetes Mellitus; Drug Administration Schedule; Follow-Up Studies; Genetic Predisposition to Disease; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Insulin; Insulin Resistance; Islets of Langerhans; Logistic Models; Middle Aged; Remission Induction; Time Factors

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Liver Failure; Liver Transplantation; Male; Reference Values

Topics: Acute Disease; Animals; C-Peptide; Chronic Disease; Diabetic Neuropathies; Disease Models, Animal; Insulin; Neural Conduction; Ranvier's Nodes; Rats; Sodium Channels

Infected pancreatic necrosis (IPN) is the main cause of death in patients with severe acute pancreatitis. Therefore an early prediction of IPN is of utmost importance.. Analysis of new blood variables as potential early predictors to differentiate between IPN and sterile pancreatic necrosis (SPN).. 64 consecutive patients with acute pancreatitis were enrolled in this prospective study; 29 were suffering from acute oedematous pancreatitis (AIP), and 35 from necrotising disease (NP) as diagnosed by contrast enhanced computed tomography.. Procalcitonin (PCT) and granulocyte colony stimulating factor (G-CSF) in the serum were examined and compared with C reactive protein (CRP). CRP was measured with a turbidimetric immunoassay (Autokit CRP; Wako, Osaka, Japan), and PCT and G-CSF by ELISA (Lumitest PCT; Brahms Diagnostica, Berlin, Germany; G-CSF-Elisa; R&D Systems, Abingdon, Oxon, UK). Monitoring was performed daily and related to the onset of symptoms.. Within the first week, all three variables (CRP, PCT, and G-CSF) were significantly higher in patients with NP than in those with AIP (CRP, p<0.001; G-CSF, p<0. 001; PCT, p<0.001). During the course of the study, 12 of the 35 patients with NP developed late IPN after a median of 20.5 (range 3-49) days. Neither the peak nor the lowest concentrations during the monitoring period were of any value for predicting IPN (median peak values in SPN v IPN: PCT, 0.93 v 1.93 ng/ml; G-CSF, 347 v 421 pg/ml; CRP, 270 v 325 mg/l).. Serum PCT, G-CSF, and CRP concentrations are of similar value for early differentiation between mild and severe acute pancreatitis. However, these variables are not suitable for the early prediction of IPN.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; C-Peptide; Calcitonin; Calcitonin Gene-Related Peptide; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Necrosis; Pancreatitis, Acute Necrotizing; Protein Precursors

Superior mesenteric artery blood flow (SMABF) increases significantly during and after the hypoglycaemia reaction in healthy humans. To investigate the mechanisms controlling this phenomenon, SMABF and plasma catecholamines were measured in healthy human volunteers. In 10 controls, hypoglycaemia was induced by insulin infusion (2.5 m-units.min-1.kg-1). In six subjects, beta-blockade by propranolol infusion (0.7 microgram.min-1.kg-1) preceded insulin infusion and was continued throughout the study. Following the hypoglycaemia reaction, the glucose nadir was similar in both groups. In controls, increases in SMABF [42.4+/-6.1% (mean+/-S.E.M.); P<0. 001], cardiac output (34.3+/-2.3%; P<0.001) and pulse rate (from 63. 9+/-2.7 to 82.5+/-3.1 beats/min; P<0.001) occurred. Superior mesenteric artery resistance fell by 32.4+/-3.3% (P<0.001). Under beta-blockade, decreases in SMABF (34.8+/-2.9%; P<0.001) and pulse rate (from 59.5+/-0.2 to 51.8+/-2.2 beats/min; P<0.001) occurred. Superior mesenteric artery resistance increased (peak +30.8+/-12.3%; not significant). Subjects showed greater increases in adrenaline (P<0.006) and noradrenaline (P<0.022) concentrations than controls. Mesenteric hyperaemia associated with hypoglycaemia in man appears to be mediated by a beta-adrenergic mechanism that is activated by increased circulating levels of adrenaline.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Epinephrine; Hemodynamics; Humans; Hypoglycemia; Insulin; Mesenteric Artery, Superior; Norepinephrine; Splanchnic Circulation

The authors compared in seven patients with acute pancreatitis the levels of endogenous somatostatin, insulin and C-peptide to assess their mutual correlation and relation to the development of the disease and serum amalyse levels. The results were compared with values recorded in 11 healthy volunteers. The levels of endogenous somatostatin were in patients with acute pancreatitis significantly higher (p < 0.05) than in the control group. The authors found an inverse relationship between the somatostatin and amylase level (correlation coefficient 0.75). They did not observe a significant correlation between somatostatin and insulin levels nor between somatostatin and C-peptide levels. The elevated somatostatin level may be due to the counteregulatory reaction during secretion, stimulated by endogenous or exogenous factors (cholecystokinin, alcohol, food).

Topics: Acute Disease; Adult; Amylases; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Pancreatitis; Somatostatin

To clarify which endocrine modifications can be observed in acute hypoxaemic respiratory failure, 15 severely ill male patients [PAT; median age: 61 (range: 48 years); median height: 173 (range: 12) cm; median mass: 73 (range 31) kg] were investigated immediately upon admission to an intensive care unit (ICU) for this clinical disorder. Before starting treatment, the blood gases were measured and a number of selected hormones with special relevance for an ICU setting were determined. These are known to be modified by acute hypoxaemia in healthy subjects and to possess glucoregulatory properties, or an influence upon cardiocirculation or the vascular volume regulation: insulin, cortisol, adrenaline, noradrenaline, atrial natriuretic peptide, renin, aldosterone, angiotensin converting enzyme, and endothelin-I (ET). To elucidate whether potential endocrine changes resulted from acute hypoxaemia alone, the underlying disease, or unspecific influences connected with the ICU setting, all measurements were compared to those of a completely healthy reference group (REF) with comparable acute experimental hypoxaemia. The latter state was achieved by having the REF breathe a gas mixture with the oxygen content reduced to 14% (H). In the REF, neither the medians nor the distribution of endocrinologic measurements were modified significantly by acute hypoxaemia. In the PAT, the medians were increased considerably, yet with a slight diminution of ET. The distribution of individual values was considerably broader than in the REF with H. In conclusion, considerable increases in the means of the above hormones, with the exception of ET, can be registered in severely ill patients admitted to ICUs with acute hypoxaemic failure. However, such modifications cannot be considered attributable exclusively to acute arterial hypoxaemia. The underlying clinical disorders, such as septicaemia or an unspecific endocrine epiphenomenon, including severe and not only hypoxaemic stress, seem to be predominant.

Topics: Acute Disease; Adult; Aged; Aldosterone; Atrial Natriuretic Factor; C-Peptide; Critical Care; Endocrine Glands; Endothelins; Epinephrine; Humans; Hydrocortisone; Hypoxia; Insulin; Male; Middle Aged; Norepinephrine; Peptidyl-Dipeptidase A; Pneumonia; Renin; Respiratory Insufficiency

The acute effects of hyperinsulinemia on androgen homeostasis and a possible association of androgens to insulin sensitivity, serum lipids and lipoproteins and to lipid oxidation were examined in 19 healthy males (27 +/- 1 yrs, body mass index 24 +/- 1 kg/m2). In each subject, a 240 min euglycemic hyperinsulinemic clamp was performed and glucose and lipid oxidation were determined by indirect calorimetry. During hyperinsulinemia serum sex hormone-binding globulin (SHBG) concentration decreased by 5% (P < 0.01), insulin-like growth factor binding protein (IGFBP-1) by 88% (P < 0.001) and dehydroepiandrosterone sulphate (DHEAS) by 12% (P < 0.001), with no change in total or free testosterone concentrations. In the basal state, IGFBP-1 and C-peptide were inversely related (r = -0.54, P < 0.05). Fasting concentrations of serum free testosterone (r = 0.59, P < 0.01) and DHEAS (r = 0.47, P < 0.05) correlated positively with serum free fatty acid (FFA) concentrations during hyperinsulinemia, but not with fasting FFA level. Lipid oxidation rate in the basal state correlated positively to the decline in SHBG (r = 0.61, P < 0.01) and DHEAS concentrations (r = 0.62, P < 0.01) during hyperinsulinemia. While the fasting serum high density lipoprotein cholesterol level correlated positively with the insulin-induced decline in DHEAS level (r = 0.58, P < 0.01), no associations were found between serum androgens and total cholesterol, low density lipoprotein cholesterol or triglyceride concentrations. Insulin sensitivity was not related to SHBG, IGFBP-1, DHEAS or testosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Androgens; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Homeostasis; Humans; Hyperinsulinism; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Lipid Peroxidation; Male; Sex Hormone-Binding Globulin; Somatomedins; Testosterone

In 14 patients with acute pancreatitis during 16 episodes of the disease the concentrations of blood glucose, serum insulin (IRI), C-peptide (CP), and proinsulin (Pro) were determined in the fasting state on d 1, 2, 3, 5, and 10 after the attack. The peptides were measured using RIAs, and for determination of CP two antibodies: Byk-Mallinckrodt's and more specific M-1221 Novo antibodies were used. Apart from sporadic rises in the initial period of the disease, the blood glucose level did not change significantly and had a decreasing trend. On d 1 the mean serum IRI level was 0.17 +/- 0.04 (SD) nM, and it decreased on d 5 to 0.06 +/- 0.04 nM, rising again to 0.11 +/- 0.15 nM on d 10. The serum Pro concentration was on the same days: 11.1 +/- 12.6, 4.2 +/- 2.4 and 7.5 +/- 10.8 pM, whereas the serum CP values determined with M-1221 antibodies were 0.48 +/- 0.50, 0.34 +/- 0.19, and 0.52 +/- 0.25 nM, respectively. However, when serum CP was determined using Byk-Mallinckrodt kits, the concentration on d 1 was 1.90 +/- 1.12 nM and over the following days it decreased to 1.08 +/- 0.98 nM on d 5 and on d 10 it was 1.11 +/- 0.46 nM.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; Blood Chemical Analysis; Blood Glucose; Blood Proteins; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Pancreatitis; Proinsulin; Time Factors

Insulin and glucagon are thought to play important roles as hepatotrophic factors in acute viral hepatitis (AVH); however, few reports have investigated the responses and relationships of each of these hormones to liver damage in detail. We studied insulin and glucagon responses during the acute and recovery phases of AVH. We performed a glucose tolerance test (GTT) and an insulin sensitivity test (IST) in each phase in 11 patients with AVH. In 8 additional patients in the acute phase (total n = 19), were compared immunoreactive insulin (IRI) and C-peptide immunoreactivity (CPR) levels with transaminase levels. In the acute phase, IRI concentrations were normal from fasting to 60 min, despite an increased CPR level. In the recovery phase, IRI and CPR levels increased significantly. Immunoreactive glucagon levels in both phases did not differ significantly from those in controls. During the IST, the insulin sensitivity index in both phases was significantly lower than that in the controls. Fasting IRI and sigma IRI showed significant negative correlations with transaminase levels. We found enhanced insulin secretion and a decrease in plasma insulin in the acute phase of AVH. The discrepancy between IRI and CPR responses in the acute phase suggests an increase in the degradation or consumption of insulin in the liver.

Topics: Acute Disease; Adolescent; Adult; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Hepatitis, Viral, Human; Humans; Insulin; Male; Middle Aged; Transaminases

Recent animal studies have suggested that insulin-like growth factor binding protein (IGFBP)-1 may regulate the insulin-like actions of the circulating IGFs. In man, IGFBP-1 levels change rapidly with nutritional status and are inversely related to changes in insulin. In-vitro studies have shown that both insulin and glucose independently regulate IGFBP-1 secretion in an inverse manner. A rapid rise of serum IGFBP-1 levels following insulin-induced hypoglycaemia suggested that glucose or glucose availability, rather than insulin, may be the major regulator of IGFBP-1.. Three separate experiments both in patients and in normal volunteers were designed to examine the possibility that in these extreme circumstances glucose rather than insulin was the predominant regulator of IGFBP-1.. Insulin tolerance tests (ITT) were performed during the routine assessment of pituitary function in seven patients, four female and three male (mean age +/- SEM 36.8 +/- 6.3 years, range 20.7-69.3 years) with pituitary disease. Hypoglycaemic glucose clamp studies (insulin 2 mU/kg/min for 180 minutes) were performed in five normal volunteers, two female and three male (mean age 33.6 +/- 2.2 years, range 23.5-42.0 years). A three-part infusion study was performed in five volunteers, three female and two male (mean age 22.9 +/- 0.9 years, range 20.8-25.0 years) who received for 45 minutes on three occasions separated by at least 7 days either octreotide (long-acting somatostatin analogue) (1 microgram/min), adrenaline (3 micrograms/min) or control.. Serum levels of IGFBP-1, insulin, glucose, C-peptide and cortisol were measured at varying intervals during the three studies by radioimmunoassay (RIA).. Symptomatic hypoglycaemia (1.0 +/- 0.1 mmol/l) occurred at 30 minutes in all patients during the ITT. Serum IGFBP-1 levels rose from 28 +/- 7 to 86 +/- 15 micrograms/l at 180 minutes. During the hypoglycaemic glucose clamp study plasma glucose fell from 4.8 +/- 0.3 to 2.2 +/- 0.3 mmol/l. In contrast to the response observed during ITT, IGFBP-1 levels fell from 22 +/- 6 to 10 +/- 1 microgram/l by 180 minutes. During the octreotide infusion study there was no change in plasma glucose and plasma insulin levels fell from 5.8 +/- 1.9 to < 2.0 mU/l. Serum IGFBP-1 levels rose from 21 +/- 2 to 68 +/- 5 micrograms/l by 180 minutes. There was no change in IGFBP-1 during either the adrenaline infusion or the control study. The rise in IGFBP-1 following the octreotide infusion (68 +/- 5 micrograms/l) was similar to that in the patients undergoing the ITT (86 +/- 15 micrograms/l) (P = 0.3).. The rapid rise of serum IGFBP-1 levels induced by acute hypoglycaemia could be reproduced in euglycaemic conditions with octreotide when insulin secretion was suppressed, whereas IGFBP-1 levels did not rise with hypoglycaemia induced by a prolonged insulin infusion. These findings suggest that the surprising rise of IGFBP-1 levels observed during ITT is not secondary to changes in glucose. The rapid removal from the portal circulation of endogenous insulin with its inhibitory effect on IGFBP-1 secretion therefore appears to be the likely cause for the rapid rise of IGFBP-1 following an ITT. This conclusion supports the hypothesis that IGFBP-1 may inhibit the insulin-like actions of 'free' IGF when insulin secretion is low and so directly link the availability and hence actions of IGFs to acute but temporary changes in nutritional status.

Topics: Acute Disease; Adult; Aged; C-Peptide; Carrier Proteins; Female; Glucose Clamp Technique; Humans; Hydrocortisone; Hypoglycemia; Insulin; Insulin Secretion; Insulin-Like Growth Factor Binding Protein 1; Male; Middle Aged; Octreotide; Pituitary Gland; Somatomedins

14 patients with acute pancreatitis during 16 episodes of the disease were studied. The concentration was measured of blood glucose, serum insulin (IRI), serum C-peptide (CP) using two methods: with Byk-Mallinckrodt kits and with more specific M-1221 antibodies Novo, and of serum proinsulin (Pro) in fasting state on days 1, 2, 3, 5 and 10 after the acute onset. Apart from some sporadic rises in the initial period of the disease, the blood glucose level did not change significantly, and had rather a decreasing trend. The mean serum IRI concentration was 0.17 +/- 0.17 (SD) nmol/l, and it decreased on the 5th day to 0.06 nmol/l 0.04 nmol/l, rising again to 0.11 +/- 0.15 nmol/l on the 10th day. The serum Pro concentration was on the same days: 11.1 +/- 12.6, 4.2 +/- 2.4 and 7.5 +/- 10.8 pmol/l, while the serum CP concentration determined with M-1221 antibodies was 0.48 +/- 0.50, 0.34 +/- 0.19 and 0.52 +/- 0.25 nmol/l respectively. However, when for serum CP determinations the Byk-Mallinckrodt kits were used, the concentration of this peptide was on the 1st day 1.90 +/- 1.12 nmol/l, and it decreased over the following days to 1.08 +/- 0.98 on the 5th day, but remained on the same level on the 10th day (1.11 +/- 0.46 nmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adult; Aged; C-Peptide; Female; Humans; Insulin; Male; Middle Aged; Pancreatitis; Proinsulin

RIA was used to measure the content of insulin, C-peptide and glucagon in blood plasma of 84 patients with acute dysentery and food toxicoinfections. The studies were carried out in the acute disease period and before the discharge from hospital. The data obtained indicate that despite the appreciable differences in the disease pathogenesis, the pathophysiological mechanisms influencing pancreatic function are similar in many respects. The changes are characterized by an increase in plasma insulin and a reduction in C-peptide and glucagon. The content of hormones in the peripheral blood is dependent on the disease period. In the authors' opinion, despite the high insulin content, the reduced level of C-peptide attests to hypofunction of beta-cells in acute intestinal infection, since it reflects their function more precisely. The reduced content of plasma glucagon points to hypofunction of alpha-cells.

Topics: Acute Disease; C-Peptide; Dysentery, Bacillary; Foodborne Diseases; Glucagon; Humans; Insulin; Intestinal Diseases; Islets of Langerhans; Shigella boydii; Shigella flexneri; Shigella sonnei

The dose-response relationships between prestimulatory blood glucose concentration and the plasma C-peptide responses to stimulation with 1 mg of glucagon iv or a standard mixed meal were studied in 8 C-peptide positive patients with insulin-dependent diabetes mellitus. Hyperglycemia was maintained for 90 min before stimulation using a hyperglycemic clamp technique. Each test was performed at the steady state blood glucose levels approximately 5, approximately 12, and approximately 20 mmol/l. The glucose potentiation of the incremental plasma C-peptide area under the curve at the two levels of hyperglycemia in percent of the area at normoglycemia (median and range) was 343% (53-1053) (p less than 0.05) and 341% (267-1027) (p less than 0.05) after glucagon and 140% (76-227) (NS) and 251% (95-1700) (p less than 0.05) after the meal. The corresponding relative glucose potentiation of plasma C-peptide 6 min after stimulation with glucagon was 124% (100-427) (p less than 0.02) and 144% (100-209) (p less than 0.05). There was no significant difference in the degree of glucose potentiation at approximately 12 or approximately 20 mmol/l. Furthermore, there was no significant difference in the degree of glucose potentiation of the different estimated values of B-cell function. In conclusion, the plasma C-peptide responses to iv glucagon or to a standard test meal were markedly potentiated by acute hyperglycemia in insulin-dependent diabetes mellitus. No further potentiation was, however, obtained when the prestimulatory blood glucose concentration was raised above 12 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Food; Glucagon; Humans; Hyperglycemia; Injections, Intravenous; Islets of Langerhans; Male

To investigate host and drug effects on glucose metabolism in acute falciparum malaria, 10 previously untreated, fasting Thai males with uncomplicated infections were given a 2-h intravenous glucose infusion (5 mg/kg ideal body weight min) with an infusion of quinine dihydrochloride (10 mg/kg body weight) during the second hour. Eight patients were restudied in convalescence. Fasting plasma glucose (mean +/- SD) and insulin (geometric mean (-SD to + SD] were higher during acute illness (5.5 +/- 1.0 mmol/l and 6.2 (5.0-7.7) mU/l) than in convalescence (4.2 +/- 0.25 mmol/l and 3.7 (2.1-6.7) mU/l; P less than 0.001 and P = 0.058 respectively). After 1 h, both plasma glucose (9.3 +/- 1.4 vs 7.5 +/- 0.8 mmol/l, P less than 0.001) and insulin (21.2 (13.8-32.5) vs 15.2 (11.2-20.8) mU/l, P = 0.089) remained higher during acute illness; mathematical model (CIGMA) assessment of these values indicated lower tissue insulin sensitivity on admission (97% (71-134] than in convalescence (139% (109-178), P less than 0.025) but normal beta-cell function on both occasions. Two-hour plasma glucose (9.5 +/- 2.0 mmol/l) and insulin (81.8 (51.5-129.9) mU/l) concentrations during acute illness were also significantly higher than in convalescence (7.2 +/- 1.2 mmol/l and 40.1 (23.5-68.4) mU/l, P less than or equal to 0.025) despite similar end-infusion free plasma quinine concentrations (P greater than 0.5). Basal plasma free fatty acid concentrations were increased in acute illness (0.68 +/- 0.24 vs 0.21 +/- 0.12 mmol/l, P less than 0.001) but fell to low levels at 2 h in both studies. These data suggest tissue insulin resistance and augmented quinine-stimulated insulin secretion in acute falciparum malaria, factors which are likely to influence the clinical situation in which malaria-associated hypoglycaemia occurs.

Topics: Acute Disease; Adolescent; Adult; Animals; Blood Glucose; C-Peptide; Fasting; Fatty Acids, Nonesterified; Glucose Clamp Technique; Homeostasis; Humans; Insulin; Insulin Resistance; Malaria; Male; Middle Aged; Plasmodium falciparum; Quinine

In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Pancreatitis; Time Factors

Homoharringtonine (HHT) has been reported to induce hyperglycemia. This report describes a study conducted to characterize the effect of HHT on insulin production and action. Our data indicate that HHT-induced hyperglycemia results from the development of insulin resistance. A review of the literature suggests that patients receiving HHT continuous infusions of 5 mg/m2/d or greater and patients greater than 10 years of age may be at increased risk for the development of HHT-induced hyperglycemia. We recommend that patients with these risk factors, as well as diabetic patients and patients concurrently receiving asparaginase and/or prednisone, have their blood glucoses routinely monitored for hyperglycemia.

Topics: Acute Disease; Alkaloids; Antineoplastic Agents, Phytogenic; Blood Glucose; C-Peptide; Drug Evaluation; Harringtonines; Homoharringtonine; Humans; Hyperglycemia; Infusions, Intravenous; Insulin; Insulin Resistance; Leukemia; Risk Factors; Time Factors

The content of fibrin fibrinogen splitting products (FSP), radioimmune trypsin, C-peptide and carbohydrate antigen (CA) 19-9 in the blood of 82 patients with acute pancreatitis (edematous and hemorrhagic), and chronic recurrent pancreatitis at the stage of exacerbation, 42 patients with chronic pancreatitis, 34 patients with cancer of the pancreas (stages III-IV) and 22 healthy persons were studied. Results indicate a high diagnostic value of determination FSP, trypsin and C-peptide in patients with acute pancreatitis and chronic recurring pancreatitis at the stage of exacerbation, trypsin and C-peptide in patients with chronic pancreatitis associated with severe exocrine insufficiency of the pancreas, KA 19-9 in patients with cancer of the pancreas.

Topics: Acute Disease; Antigens, Tumor-Associated, Carbohydrate; C-Peptide; Chronic Disease; Diagnosis, Differential; Fibrin Fibrinogen Degradation Products; Humans; Pancreatic Neoplasms; Pancreatitis; Recurrence; Trypsin

Mumps epidemics are followed by sporadic cases of insulin dependent diabetes mellitus (IDDM). We have studied beta-cell function in 11 subjects who had had a mumps infection. They had no clinical pancreatitis but were selected as they had abnormal pancreas iso-amylase values and/or glucosuria during the mumps virus infection. At the follow-up some years later the subjects were healthy. A few HbA1-values were noted in the upper part of the normal range. Total serum insulin values were normal, but the C-peptide values were low at first follow-up 1-3 years after infection in all but two patients. These values increased in 4/7 patients during the follow-up period but were subnormal in five subjects still 3-6 years after the infection. All five patients had HLA-DR 3 and/or 4. In 7 out of 11 patients islet cell surface antibodies could be demonstrated. Our results indicate that subclinical mumps pancreatitis may initiate a reaction towards the beta-cells recognized as subnormal C-peptide levels several years later in certain patients. This might contribute to manifest IDDM many years after infection.

Topics: Acute Disease; Adult; Autoantibodies; C-Peptide; Follow-Up Studies; HLA-DR Antigens; Humans; Insulin; Islets of Langerhans; Male; Mumps; Pancreatitis

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

This study was designed to investigate the long-term effects of early pancreatic resection for acute necrotizing pancreatitis. During 1973-1978 40 resections were performed in our clinic. Eleven patients died initially (28 per cent). None of the four further deaths was due to pancreatitis or associated disorders. Twenty-four patients were re-examined 5-11 years after resection--one patient refused to participate. Five had not been able to return to work because of severe polyneuropathy; one more had retired because of chronic pancreatitis in the pancreatic remnant. Polyneuropathy was found in five further patients. The reason for this high incidence of polyneuropathy (42 per cent) remains unknown. Eight patients still drank excessive alcohol; three of them had had recurrent pancreatitis and dyspepsia, and insulin requiring diabetes. All but 2 (92 per cent) had diabetes, 14 needing insulin--half of them at 6 months to 6 years after the resection. Moreover, 11 patients (46 per cent) suffered from dyspeptic symptoms. The results suggest that because of the high frequency of late complications, in addition to the early complications, early resection of pancreas should be critically re-evaluated as the treatment for acute necrotizing pancreatitis. If resection is used in patients with extreme pancreatic necrosis, careful and continuous postoperative follow-up will be needed.

Topics: Acute Disease; Adult; Aged; C-Peptide; Follow-Up Studies; Humans; Middle Aged; Necrosis; Pancreas; Pancreatectomy; Pancreatitis; Postoperative Complications; Time Factors

Topics: Acute Disease; Adult; Aged; C-Peptide; Female; Glucose Tolerance Test; Hepatitis; Humans; Insulin; Male; Middle Aged; Pancreas

Diabetic hyperosmolar coma is a syndrome of marked hyperglycemia and minimal ketoacidosis. In general, the serum glucose concentrations are not predictive of the serum ketoacid concentrations in acutely decompensated diabetes. The endocrine factors that modulate glucose concentrations may be different from those that modulate ketoacid concentrations in patients with acutely decompensated diabetes. To test this hypothesis, regression analysis was used to determine the endocrine and metabolic characteristics that correlated with serum concentrations of glucose and ketoacids in 26 diabetic patients with spontaneous, acute hyperglycemia. All patients had a serum glucose level greater than 390 mg/dl, and ketoacid levels were from 0.17 to 25.5 mM. Multiple regression analysis showed that increased serum glucose concentrations correlated with increased plasma glucagon levels (p = 0.0007, r2 = 0.45), but with no other factors. Increased total ketoacid levels (acetoacetate plus 3-hydroxybutyrate) correlated with increased free fatty acid levels (p = 0.0001), decreased C-peptide levels (p = 0.002), and increased body mass index (p = 0.002) (r2 = 0.72). Body mass index only correlated with ketoacid levels, when it was analyzed with C-peptide and free fatty acid levels. A model is proposed that predicts the serum glucose and ketoacid concentrations in patients with acutely decompensated diabetes. Glucagon modulates the serum glucose concentration in these patients with an absolute or relative insulin deficiency. Total serum ketoacid levels are determined by the serum free fatty acid concentration, residual pancreatic insulin secretion (as reflected by C-peptide), and the patient's body habitus. This model allows for the marked hyperglycemia and minimal ketosis of diabetic nonketotic hyperosmolar coma, as well as the glucose and ketoacid concentrations in other presentations of acutely decompensated diabetes.

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Diabetes Mellitus; Diabetic Coma; Diabetic Ketoacidosis; Fatty Acids, Nonesterified; Female; Glucagon; Growth Hormone; Humans; Hyperglycemia; Hyperglycemic Hyperosmolar Nonketotic Coma; Keto Acids; Male; Middle Aged; Models, Biological; Regression Analysis

Topics: Abdomen, Acute; Acute Disease; Adult; Aged; C-Peptide; Female; Glucagon; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Pancreatitis; Peptides

On 35 patients with acute hepatitis had been carried out intravenous glucose-tolerance-tests (0,5 g glucose/kg). The assimilation coefficient of glucose and the level of insulin were determined during the acute phase of illness and the recovery phase. In 8 cases additionally C-peptide was determined to interpret the regulation of insulin-secretion and hepatic reduction. During the acute phase of illness the glucose-tolerance-test proofed 15 x clearly and 13 x limiting pathological. Except one patient all cases showed an improvement during recovery and 21 x a normalisation of glucose-tolerance. The serum-insulin-analysis gave 28 x lower figures during the acute phase compared to the healing-phase, whereas the determination of the C-peptide showed higher figures matching the enhanced glucose concentrations, which proves a normal regulation of insulin-secretion during the acute phase of disease in hepatitis. Because of the enhanced C-peptide/insulin-index our results support that in the early state of hepatitis the lower insulin figures are caused through a higher insulin clearance of the acute inflamed liver.

Topics: Acute Disease; Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Hepatitis B; Hepatitis, Viral, Human; Humans; Insulin; Male; Middle Aged; Peptides

Intravenous glucose tolerance tests were performed in 10 patients with acute virus hepatitis. The assimilation coefficient of glucose and the level of insulin and C-peptide in serum were determined before and in the course of the glucose tolerance tests. In comparison to healthy normal weight persons C-peptide concentration in patients with acute hepatitis increased twice as high whereas the pattern of insulin secretion did not differ significantly. The higher levels of C-peptide indicate an increase of the beta-cell secretion in acute hepatitis. One could suppose an increased hepatic destruction of insulin in acute hepatitis, because there is no significant difference among the insulin levels. More likely, there is a reactive increase of secretion of the beta-cell due to a reduction of insulin sensitivity and this is indicated much better by C-peptide- than insulin levels because of the longer half live of the the C-peptide molecule.

Topics: Acute Disease; C-Peptide; Glucose Tolerance Test; Hepatitis, Viral, Human; Humans; Insulin; Islets of Langerhans; Peptides

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

Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.

Topics: Acute Disease; Adolescent; Adult; C-Peptide; Diabetes Mellitus, Type 1; Humans; Insulin; Monitoring, Physiologic; Pancreas; Remission, Spontaneous; Time Factors