c-peptide and Uremia

Topics: Animals; C-Peptide; Calcitriol; Clomiphene; Dihydroxycholecalciferols; Female; Follicle Stimulating Hormone; Glomerular Filtration Rate; Glucagon; Gonadotropin-Releasing Hormone; Hormones; Humans; Insulin; Kidney; Kidney Failure, Chronic; Luteinizing Hormone; Male; Metabolic Clearance Rate; Mineralocorticoids; Parathyroid Hormone; Proinsulin; Prolactin; Sexual Dysfunction, Physiological; Thyroid Hormones; Uremia

Recent work from our laboratory on the mechanism of polypeptide hormone handling by the normal kidney and the pathogenesis of altered hormonal metabolism in renal failure is reviewed. The kidney extracts substantial amounts of low - and medium - molecular weight polypeptide hormones from the renal circulation by a process which probably involves both glomerular filtration plus luminal reabsorption and direct peritubular uptake, although the relative contribution of the two mechanisms under physiologic conditions is not known. The bulk of the extracted hormone is catabolized in the renal parenchyma since urinary excretion is negligible. Renal catabolism contributes an important fraction of the total metabolic clearance of polypeptide hormones, which accounts in part for their increased circulating levels in renal failure. Since certain hormones are heterogenous and a large proportion of their plasma immunoreactivity may consist of components of uncertain biologic activity, simple correlations between circulating hormone levels and endocrine abnormalities in uremia are hazardous.

Topics: Animals; Antigens; C-Peptide; Erythropoietin; Glucagon; Gonadotropins, Pituitary; Humans; Insulin; Kidney; Kidney Failure, Chronic; Luteinizing Hormone; Metabolic Clearance Rate; Molecular Weight; Pancreatic Hormones; Proinsulin; Prolactin; Uremia

Changes in plasma immunoreactive insulin (IRI) and connecting-peptide immunoreactivity (CPR) concentrations during hemodialysis (HD) were evaluated in diabetic HD patients with 3 different high-flux membranes. The removal properties of the membranes were compared.. In this prospective controlled study, 15 stable diabetic patients on HD were randomly selected for 6 HD sessions with 3 different membranes: polysulfone (PS), cellulose triacetate (CTA), and polymethylmethacrylate (PMMA). Blood samples were obtained from the blood tubing at the arterial (A) site at the beginning and end of the sixth HD session. At 60 minutes after dialysis initiation, blood samples were obtained from both the A and venous (V) sites of the dialyzer to investigate the clearance and removal properties of the membranes.. The plasma IRI and CPR levels decreased significantly at each time point with all 3 membranes. IRI clearance with the PS membrane was significantly higher than that with the CTA and PMMA membranes. No difference was observed in the IRI reduction rate between the 3 membranes. CPR clearance and reduction rate with the PMMA membrane were lower than with the PS and CTA membranes. No significant difference was observed in serum creatinine clearance and reduction rates between the 3 membranes; however, serum urea nitrogen clearance was significantly lower with the PMMA membrane compared with the PS and CTA membranes. A significantly high beta2-microglobulin clearance and reduction rate was achieved in the order PS > CTA > PMMA.. Plasma IRI and CPR are cleared by HD; their clearance rates differ with the dialyzer membranes. Plasma IRI clearance with the PS membrane is higher than that with the CTA and PMMA membranes.

Topics: Blood Glucose; C-Peptide; Cellulose; Creatinine; Cross-Over Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Equipment Design; Hemoglobins; Humans; Insulin; Membranes, Artificial; Polymers; Polymethyl Methacrylate; Renal Dialysis; Serum Albumin; Sulfones; Urea; Uremia

Topics: Blood Flow Velocity; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Retinopathy; Glycated Hemoglobin; Humans; Kidney Transplantation; Pancreas Transplantation; Prospective Studies; Proteinuria; Retinal Artery; Uremia

Islet transplantation can restore insulin production in type 1 diabetes patients. However, survival of the islet allografts will face rejection or recurrence of autoimmunity or a combination of both. In a study on islet-after-kidney transplants, we previously reported that islet cell recipients presented low T-cell alloresponses for HLA mismatches that were shared by the islet cell graft and the prior kidney graft, that is, repeated mismatch, while vigorous responses were measured against novel HLA mismatches.. We now investigated T-cell alloreactivity to repeated HLA-mismatches in three non-uremic type 1 diabetic patients each receiving three sequential islet cell implants.. These islet-after-islet recipients patients exhibited low or absent responses to repeated mismatches to the first graft which was accompanied by sustained graft function, and reduced responsiveness towards subsequent grafts. In one patient, T-cell responses towards these mismatches were noticed following new mismatches in subsequent grafts, with loss of graft function.. These case reports further support the view that subsequent islet implantations can reduce alloreactivity for repeated HLA mismatches. They demonstrate the usefulness of monitoring T-cell reactivity against islet allografts to correlate immune function with graft survival and to identify conditions for preservation of beta-cell function.

Topics: Antilymphocyte Serum; Autoimmunity; C-Peptide; Diabetes Mellitus, Type 1; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Islets of Langerhans Transplantation; Isoantibodies; Postoperative Period; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Transplantation Conditioning; Transplantation, Homologous; Uremia

The potential effects of islet transplantation on the renal function of 36 patients with type I diabetes mellitus and kidney transplants were studied with 4 yr of follow-up monitoring. Kidney-islet recipients were divided into two groups, i.e., patients with successful islet transplants (SI-K group) (n = 24, fasting C-peptide levels of >0.5 ng/ml for >1 yr) and patients with unsuccessful islet transplants (UI-K group) (n = 12, fasting C-peptide levels of <0.5 ng/ml). Kidney graft survival rates and function, urinary albumin excretion rates, and sodium handling were compared. Na(+)/K(+)-ATPase activity in protocol kidney biopsies and in red blood cells was cross-sectionally analyzed. The SI-K group demonstrated better kidney graft survival rates (100, 83, and 83% at 1, 4, and 7 yr, respectively) than did the UI-K group (83, 72, and 51% at 1, 4, and 7 yr, respectively; P = 0.02). The SI-K group demonstrated reductions in exogenous insulin requirements and higher C-peptide levels, compared with the UI-K group, whereas GFR values were similar. Microalbuminuria (urinary albumin index) increased significantly in the UI-K group only (UI-K, from 92.0 +/- 64.9 to 183.8 +/- 83.8, P = 0.05; SI-K, from 108.5 +/- 53.6 to 85.0 +/- 39.0, NS). In the SI-K group, but not in the UI-K group, natriuresis decreased at 2 and 4 yr (P < 0.01). The SI-K group demonstrated greater Na(+)/K(+)-ATPase immunoreactivity in renal tubular cells (P = 0.05) and higher activity in red blood cells (P = 0.03), compared with the UI-K group. The Na(+)/K(+)-ATPase activity in red blood cells was positively correlated with circulating C-peptide levels but not with glycated hemoglobin levels. Successful islet transplantation was associated with improvements in kidney graft survival rates and function among uremic patients with type I diabetes mellitus and kidney grafts.

Topics: Albumins; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Erythrocytes; Glomerular Filtration Rate; Graft Rejection; Graft Survival; Humans; Islets of Langerhans Transplantation; Kidney; Kidney Transplantation; Renin-Angiotensin System; Sodium; Sodium-Potassium-Exchanging ATPase; Time Factors; Uremia

In order to evaluate somatostatin (SRIH) secretion in uremia, plasma SRIH concentrations were determined in basal conditions and after an oral glucose tolerance test (OGTT) in 14 non-dialysed patients with chronic renal failure (CRF), seven of whom had normal glucose tolerance (NGT) and seven impaired glucose tolerance (IGT). Plasma insulin, C-peptide and glucagon and blood glucose concentrations were also evaluated. The results were compared with those obtained in a group of age- and sex-matched normal subjects. In CRF patients, plasma SRIH fasting values (8.6 +/- 0.6 and 7.8 +/- 0.6 pmol/L in NGT and IGT patients, respectively) were comparable to those recorded in controls (7.7 +/- 0.5 pmol/L). SRIH response to OGTT, evaluated as area under curves (AUC) above basal, was similar in both groups of CRF patients (412.9 +/- 84.5 and 415.6 +/- 51.9 pmol/L per min), and significantly lower than in controls (660.1 +/- 58.5 pmol/L per min). Data indicate that chronic uremia induces a loss of SRIH secretory cell responsiveness to glucose. A possible effect of impaired SRIH secretion on glucose metabolism in CRF is discussed.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Somatostatin; Uremia

In order to evaluate effects of metabolic acidosis on glucose metabolism in uremia, we studied, by an intravenous glucose tolerance test (IVGTT), 46 patients with severe chronic renal failure divided into three groups according to their blood bicarbonate (BB) values: group A formed by 15 patients without or with light metabolic acidosis (BB > or = 20 mEq/1); group B formed by 18 patients with moderate metabolic acidosis (16 < or = BB < 20 mEq/1); group C formed by 13 patients with severe metabolic acidosis (BB < 16 mEq/1). In 8 patients of group B (subgroup B1) and in 8 of group C (subgroup C1), IVGTT was also repeated after adjustment of acid-base balance by intravenous or oral bicarbonate administration. Twenty-nine healthy volunteers formed the normal controls. For each test, glucose constant decay (K), immunoreactive insulin (IRI) area and C-peptide (C-p) area response, insulinogenic index (IGI) and insulin resistance index (RI) were calculated. Compared to controls, all uremic groups showed significantly lower values of K and IGI and significantly higher values of C-p area and RI. In group C, RI was significantly higher than in groups A and B. No differences were found in the other glucose metabolism parameters among the uremic groups. After bicarbonate administration, subgroup C1 showed a significant decrease in RI and a rise in K values, while subgroup B1 showed no changes in glucose metabolism parameters. From these data, we infer that abnormalities of acid-base balance do not affect insulin response but severe metabolic acidosis may play an additional role in the insulin resistance of uremic patients.

Topics: Acid-Base Equilibrium; Administration, Oral; Adult; Aged; Bicarbonates; Blood Glucose; C-Peptide; Female; Glucose; Glucose Tolerance Test; Humans; Hydrogen-Ion Concentration; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Uremia

In this study, pancreas transplantation is used as a clinical model of pancreas denervation in humans. To assess the role of innervation on the feedback autoinhibition of insulin secretion, we studied four groups of subjects--group 1: 16 patients with combined pancreas and kidney transplantation (plasma glucose = 5.1 mM, HbA1c = 6.4%, creatinine = 86 mM); group 2: 8 patients with chronic uveitis on the same immunosuppressive therapy as transplanted patients (12 mg/day prednisone, 5 mg.kg-1.day-1 CsA); group 3: 4 uremic, nondiabetic patients in chronic hemodialysis; group 4: 7 normal, nondiabetic control subjects. The following means were used to study the groups: 1) a two-step hyperinsulinemic euglycemic clamp (insulin infusion rate = 1 mU and 5 mU.kg-1.min-1); and 2) a 0.3 mU.kg-1.min-1 hypoglycemic clamp (steady-state plasma glucose = 3.1 mM). Basal plasma-free IRI (84 +/- 6, 42 +/- 12, 72 +/- 12, and 30 +/- 6 pM in groups 1, 2, 3, and 4, respectively), basal C-peptide (0.79 +/- 0.05, 0.66 +/- 0.05, 3.04 +/- 0.20, and 0.59 +/- 0.06 nM in groups 1, 2, 3, and 4, respectively), and glucagon (105 +/- 13, 69 +/- 4, 171 +/- 10, and 71 +/- 5 pg/ml in groups 1, 2, 3, and 4, respectively) were increased in groups 1 and 3 with respect to groups 2 and 4 (P < 0.01). During euglycemic hyperinsulinemia, plasma C-peptide decreased by 45, 20, and 44% in groups 2, 3, and 4, respectively, but showed no significant change from the basal in patients with transplanted pancreases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3-Hydroxybutyric Acid; Adult; Analysis of Variance; Blood Glucose; C-Peptide; Denervation; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Epinephrine; Fatty Acids, Nonesterified; Feedback; Follow-Up Studies; Glucagon; Glucose Clamp Technique; Glycated Hemoglobin; Hormones; Humans; Hydroxybutyrates; Insulin; Insulin Secretion; Kidney Transplantation; Lactates; Pancreas; Pancreas Transplantation; Pancreatic Polypeptide; Somatostatin; Uremia

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Homeostasis; Humans; Insulin; Insulin Secretion; Kidney Transplantation; Pancreas Transplantation; Uremia

Metabolic glucose control was followed in 36 patients at 12-month intervals for up to 5 years after a successful combined kidney and segmental duct-occluded pancreas transplantation. All recipients had normal blood glucose levels at each examination. HbA1 values, intravenous glucose tolerance test, C-peptide levels and C-peptide responses to glucagon stimulation were also, on average, within the normal range. Several individual patients had, however, abnormal values for these parameters. At most 46% had abnormal values for HbA1 and intravenous glucose tolerance test, up to 13% showed low C-peptide values and up to 46% of the stimulated C-peptide responses were inadequate at the different intervals. These parameters did not deteriorate with time. This was true both for the whole group of patients as well as for the 6 patients with a 5-year observation time evaluated separately. Despite these abnormalities in glucose metabolism, all patients remained normoglycaemic without need for exogenous insulin up to 5 years after transplantation. The long-term ability of duct-occluded segmental pancreatic grafts to preserve euglycaemia therefore seems to remain intact at least for 5 years.

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Follow-Up Studies; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Immunosuppressive Agents; Kidney Transplantation; Pancreas Transplantation; Reference Values; Uremia

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Graft Survival; Humans; Kidney Transplantation; Middle Aged; Pancreas Transplantation; Survival Analysis; Time Factors; Uremia

To evaluate the role of calcitriol on insulin secretion in uraemia, nine patients on maintenance haemodialysis, never treated with vitamin D nor with calcium-channel blockers, were studied. Baseline glucose, insulin, C peptide, calcium, intact PTH, and calcitriol serum values were measured, and after an oral load of 75 g glucose, insulin and C peptide were also determined at 15, 30, 45, 60, and 120 min. Following 14 days of treatment with oral calcitriol (0.5 microgram/day), the same study protocol was applied. Serum calcitriol values, which were low as expected, increased after therapy, but did not reach the values observed in healthy controls. Despite no change in total serum calcium, intact PTH values decreased significantly (182 vs 88.3 ng/ml, P less than 0.003). Baseline serum insulin was significantly increased after calcitriol (7.5 vs 35 microU/ml, P less than 0.001). Similarly, an enhancement in insulin secretion following calcitriol was observed at 15 min (34 vs 70, P less than 0.01) and 30 min (57 vs 96 microU/ml, P less than 0.01). Computation of the total area under the curve confirmed these results. Changes in C peptide profile paralleled those described for insulin. These data confirm that vitamin D modulates pancreatic beta-cell secretion and suggest that calcitriol may regulate insulin release in uraemic patients.

Topics: Adult; Blood Glucose; C-Peptide; Calcitriol; Calcium; Female; Humans; Hyperparathyroidism, Secondary; Insulin; Insulin Secretion; Male; Middle Aged; Parathyroid Hormone; Uremia

Topics: Adult; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Histocompatibility Testing; Humans; Insulin; Kidney Transplantation; Male; Pancreas Transplantation; Uremia

To test secretory capacity of the beta-cell to a glucose stimulus in uremic patients on chronic dialysis, three hyperglycemic clamps (plasma glucose increments: 1, 4.5 and 11 mmol/l) were performed in 8 uremic and 8 healthy subjects. Early-phase insulin and C-peptide responses (delta I and delta C) during the initial 6 min were consistently exaggerated at all three steps in uremic patients compared with controls (delta I. 16 +/- 4 vs 4 +/- 2, 41 +/- 11 vs 15 +/- 4 and 60 +/- 12 vs 24 +/- 5 mU/l; delta C. 0.39 +/- 0.13 vs 0.07 +/- 0.02, 0.40 +/- 0.13 vs 0.16 +/- 0.02 and 0.73 +/- 0.15 vs 0.29 +/- 0.04 nmol/l, p less than 0.05 in all cases). Similarly, late-phase insulin secretion defined as the insulin increment between 90 and 120 min after initiation of the glucose challenge was enhanced in uremic patients at the two highest glycemic steps (44 +/- 10 vs 16 +/- 2 and 123 +/- 29 vs 44 +/- 5 mU/l, both p less than 0.01). The raised late-phase insulin response allowed comparable glucose disposal in the two groups (uremic patients: 9.2 +/- 1.0 and 15.5 +/- 1.6 mg.kg-1.min-1.. 9.0 +/- 1.3 and 19.9 +/- 2.4 mg.kg-1.min-1). The slopes of potentiation, i.e. the slopes of the regression lines expressing the relationship between changes in insulin increments and changes in glucose, were markedly steeper in uremic patients (0.45 +/- 0.09 and 0.66 +/- 0.20, early and late-phase respectively) than in controls (0.20 +/- 0.06 and 0.25 +/- 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Insulin Secretion; Male; Renal Dialysis; Uremia

To characterize endogenous glucose production in uraemia, nondialyzed uraemic patients and controls were exposed to two major modulating hormones, insulin and glucagon. Nineteen uraemic and 15 healthy subjects underwent either a 2-step (insulin infusion rates: 0.45 and 1.0 mU.kg-1.min-1) or a 3-step (insulin infusion rates: 0.1, 0.2 and 0.3 mU.kg-1.min-1) sequential euglycaemic insulin clamp. Average steady state serum insulin concentrations were almost identical during all five infusion rates in uraemic patients (16, 22, 26, 31 and 66 mU/l) and controls (15, 19, 24, 33 and 68 mU/l). At all steps, insulin infusion was accompanied by significantly lower glucose disposal rates [( 3(-3)H]glucose) in uraemic patients compared with controls (P less than 0.05 or less). Moreover, the restraining potency of insulin on endogenous glucose production was much more prominent in healthy than in uraemic subjects at the lowest three infusion rates (0.6 +/- 1.0 versus 1.4 +/- 0.3 (mean +/- 1 SD), -0.3 +/- 0.7 versus 0.7 +/- 0.3, and -1.1 +/- 0.7 versus 0.2 +/- 0.6 mg.kg-1.min-1; P less than 0.05, P less than 0.01 and P less than 0.01, respectively), implying a shift to the right of the dose-response curve in uraemia. In contrast, basal values were comparable (2.4 +/- 0.3 versus 2.2 +/- 0.6 mg.kg-1.min-1) as the difference vanished at higher infusion rates, i.e. peripheral insulinaemia above approximately equal to 30 mU/l. Another 7 uraemic patients and 7 controls were infused with glucagon at constant rates of 4 or 6 ng.kg-1.min-1, respectively, for 210 min concomitant with somatostatin (125 micrograms/h) and tritiated glucose. The ability of glucagon to elevate plasma glucose was markedly attenuated in uraemic patients compared with controls during the initial 60 min of glucagon exposure. This difference was entirely due to diminished hepatic glucose production (3.5 +/- 0.8 versus 4.8 +/- 1.0 mg.kg-1.min-1; P less than 0.05). In conclusion, in addition to insulin resistance in peripheral tissues, uraemia is also associated with hepatic insulin resistance. Furthermore, glucagon challenge implies impaired early endogenous glucose release in uraemia suggesting a superimposed hepatic resistance to glucagon.

Topics: Adult; Aged; C-Peptide; Female; Glucagon; Glucose; Humans; Insulin; Insulin Resistance; Kinetics; Liver; Male; Middle Aged; Somatostatin; Uremia

To determine whether the deranged glucose metabolism in uremia, in addition to insulin resistance can be attributed also to reduced glucose-induced glucose uptake, a two-step sequential hyperglycemic clamp (plasma glucose: 120 and 300 mg/dl) was performed in 6 non-dialyzed uremic and 8 healthy subjects. A constant infusion of somatostatin (300 micrograms/h) and soluble insulin (0.2 mU/kg/min) resulted in peripheral serum insulin slightly higher than basal in both uremics (16 +/- 3 and 22 +/- 3 microU/ml; step 1 and 2, respectively) and controls (20 +/- 2 and 22 +/- 1 microU/ml). The glucose-induced glucose uptake (3-3H-glucose) assessed as the difference between step 2 and 1 glucose disposal at the final 30 min of each step was markedly reduced in uremics (3.2 +/- 0.5 mg/kg/min) compared to healthy subjects (5.7 +/- 0.8 mg/kg/min; p less than 0.03). However, the percentage increment in glucose uptake from step 1 to step 2 hyperglycemia was comparable in the two groups (134 +/- 27 and 148 +/- 17%). Modest hyperglycemia (120 mg/dl) and slightly raised insulinemia resulted in comparable suppression of the endogenous (hepatic) glucose production (EGP) in healthy (1.6 +/- 0.2 mg/kg/min) and uremic subjects (1.5 +/- 0.3 mg/kg/min). In controls, pronounced hyperglycemia (300 mg/dl) further reduced EGP (0.6 +/- 0.3 mg/kg/min; p less than 0.01) while EGP in uremics on the contrary tended to rise (2.0 +/- 0.4 mg/kg/min; p = 0.09), thus indicating an abnormal reaction of the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose; Humans; Hyperglycemia; Insulin; Insulin Resistance; Liver; Male; Middle Aged; Renal Dialysis; Somatostatin; Uremia

Pancreatic beta-cell function was evaluated in uraemic patients by measuring beta-cell peptides in the peripheral blood after intravenous glucagon (1 mg) stimulation. Patients in chronic renal failure, patients on haemodialysis, and both new and established subjects on continuous ambulatory peritoneal dialysis (CAPD) (10 in each group) were studied and compared to 8 healthy controls. Fasting glucose (3.6-4.4 mmol/l) and insulin concentrations (9.5-11.7 mU/l) were normal and did not differ between the uraemic groups, but c-peptide concentrations were markedly increased in uremia (1.84-2.38 nmol/l) compared to controls (0.48 nmol/l). Following glucagon stimulation an exaggerated blood glucose response with delayed glucose peak was observed, while the peak insulin response to glucagon was normal; however, the return to basal concentrations was delayed in uraemia. The c-peptide response was also exaggerated and peak concentrations in uraemic subjects (3.0-4.3 nmol/l) were significantly greater than controls (1.5 nmol/l). The response of CAPD patients was similar to those on haemodialysis and non-dialysed uraemic patients. The abnormalities seen were due to uraemia, and CAPD treatment had no specific adverse effect on beta-cell function. Thus, from this data there was no evidence that CAPD per se is detrimental to beta-cell integrity.

Topics: C-Peptide; Cross Reactions; Glucagon; Humans; Insulin; Islets of Langerhans; Peritoneal Dialysis, Continuous Ambulatory; Proinsulin; Uremia

Glucose intolerance is a common concomitant of untreated chronic renal failure, but the effect of long-term treatment on the insulin resistance believed to be behind it is as yet not clarified. Peripheral tissue sensitivity to insulin was therefore examined in 7 dialyzed uraemic patients, 8 undialyzed uraemic and 8 matched healthy subjects using the hyperinsulinaemic euglycaemic clamp technique. The dialyzed subjects had been on maintenance haemodialysis for a mean of 4 yr (range, 3-131 months) and were studied both before and after a single random dialysis. The clamping was performed during 150 min using a glucose controlled insulin infusion system (Biostator). Insulin was infused at a rate of 2.0 mU/kg/min. Tissue sensitivity to insulin was expressed as glucose uptake (M) at steady state (90-150 min) over steady state serum insulin concentration (I). While M was significantly greater in healthy subjects (12.52 +/- 1.02 mg/kg/min, mean +/- 1 SEM) than in dialyzed uraemics (9.59 +/- 0.78 mg/kg/min and 9.36 +/- 0.70 mg/kg/min, both p less than 0.05), M/I was similar in chronically dialyzed patients (before and after dialysis: 0.098 +/- 0.017 mg/kg/min per microU/ml vs 0.104 +/- 0.020 mg/kg/min per microU/ml) and in controls (0.111 +/- 0.015 mg/kg/min per microU/ml; p greater than 0.20). In contrast M/I ratio of uraemic subjects who had never been dialyzed (0.062 +/- mg/kg/min per microU/ml) was significantly reduced (both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; C-Peptide; Constriction; Female; Glucagon; Growth Hormone; Humans; Insulin Resistance; Male; Middle Aged; Renal Dialysis; Uremia

Clinical pancreas transplantation at the University of Minnesota began in 1966. An initial series of 14 whole pancreas grafts was reported in part to the American Surgical Association in 1970. Only one patient survived for more than 1 year with a functioning graft. Twenty attempts at islet allotransplantation in the mid-1970s were unsuccessful. In 1978 we resumed performing pancreas transplants by the segmental technique, allowing the use of related donors. The current series (July 25, 1978 to December 20, 1983) includes 86 pancreas transplants (51 cadaver, 35 related) in 75 patients (41 with and 34 without previous kidney grafts). Variations in management of the pancreatic duct include three ligated, 15 duct-open, 39 duct-injected, and 29 pancreaticojejunostomies. The latter technique is currently preferred. Currently (April 1984) 61 patients are alive (81%), 24 have functioning grafts (32%), and 21 are insulin-independent (28%), three with open-duct grafts for 4.4 to 5.7 years, seven with silicone-injected grafts from 10 to 39 months, and 14 with pancreaticojejunostomies for 3 to 31 months; 15 of the grafts have functioned for greater than 1 year. Twenty-two of the grafts (25%) failed for technical reasons (thrombosis, infection, or ascites); 35 grafts functioned for 1 to 13 months before totally failing from either rejection, fibrosis, or recurrent disease; five patients died with functioning grafts. The graft survival rate has been higher for pancreases from related (15/35, 43% functioning) than from cadaver (9/51, 18% functioning) donors. The success rate has increased, e.g., 11/22 recipients of pancreas transplants in 1983 currently have functioning grafts (50%). Metabolic studies show most patients with functioning grafts to be euglycemic; however, three of 24 have chronic hyperglycemia unless supplemented with insulin, but they are no longer ketosis-prone. Glucose tolerance test results are normal or nearly normal in 12 and abnormal in 12 of the recipients with currently functioning grafts. Regression of diabetic nephropathy has been documented in two long-term recipients. Pancreas transplantation is currently applicable as treatment for selected diabetics who have demonstrated their propensity to develop serious secondary complications.

Topics: Adult; C-Peptide; Cadaver; Diabetes Mellitus; Diabetic Nephropathies; Female; Graft Rejection; Graft Survival; Histocompatibility Testing; Humans; Immunosuppressive Agents; Insulin; Jejunum; Kidney Transplantation; Male; Middle Aged; Organ Preservation; Pancreas; Pancreas Transplantation; Pancreatic Ducts; Postoperative Care; Tissue Donors; Uremia

The effect of an oral glucose tolerance test (oGTT) on serum levels of branched-chain keto acids (BCKA), i.e. alpha-keto-isocaproic acid (KICA), alpha-keto-isovaleric acid (KIVA) and alpha-keto-beta methyl-n-valeric acid (KMVA) as well as on serum insulin, C-peptide and blood glucose levels was determined in uremic patients and in healthy control subjects. In controls, blood levels of KICA, KMVA and KIVA declined significantly following oral administration of 100 glucose. In uremic patients no decline of KICA was observed. The fall of KMVA was diminished, while suppression of KIVA blood levels in response to the oGGT remained unimpaired. Although serum insulin and C-peptide levels in uremic patients were not significantly different from the controls before and throughout the oGTT, six out of eight displayed abnormal glucose tolerance. It is suggested that the response of blood BCKA levels to an oGTT is altered in uremia, an abnormality restricted primarily to KICA and possibly explained by insulin antagonism and/or by insufficient insulin secretion.

Topics: Adult; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Hemiterpenes; Humans; Insulin; Keto Acids; Kidney Failure, Chronic; Male; Middle Aged; Uremia

Topics: Adult; Amino Acids, Branched-Chain; Blood Glucose; C-Peptide; Diet; Dietary Proteins; Female; Humans; Insulin; Keto Acids; Kidney Failure, Chronic; Male; Middle Aged; Urea; Uremia

The kidney has been suggested as the main organ for the degradation of C-peptide. This hypothesis was tested in subjects with normal fasting blood glucose concentration and varying degrees of renal failure. Forty-nine subjects with endogenous creatinine clearance ranging from 0--25 ml/min were studied. The basal steady state concentrations of C-peptide (CP) and the immunoreactivity of insulin (IRI) were determined in plasma from fasting patients. The average IRI was similar to that found in normal subjects while a higher CP was found in all patients but two. The average CP in the nephrectomized patients was six times higher than the mean CP in normal subjects (0.35 pmol/ml). There was a significant inverse correlation between clearance and CP (r = 0.51, P less than 0.001) with the highest CP in nephrectomized patients. It is concluded that the increased CP in renal failure, and especially the markedly increased CP in the nephrectomized group supports the hypothesis of the kidney being the organ mainly responsible for the degradation of C-peptide also in man.

Topics: Adult; C-Peptide; Fasting; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nephrectomy; Peptides; Uremia

Fifty grams of glucose were administered orally to twelve cirrhotics, twelve uremics and ten normal controls and the plasma insulin and C-peptide responses were measured and expressed as molar concentration. Glucose intolerance, hyperinsulinemia and elevated C-peptide levels were found in cirrhotics after glucose loading and in uremics during the later part of the glucose response. The molar ratio of C-peptide to insulin was lower in cirrhotics and higher in uremics than in controls. It is suggested that insulin is mainly degraded by the liver and C-peptide by the kidneys, and that C-peptide is not affected by the liver damage but is present in raised concentration in subjects with injured kidneys. Elevated C-peptide level in cirrhotics is consistent with hyperfunction of pancreatic B-cells.

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