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S Madsbad

Publications and source records attributed to S Madsbad.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Thiazolidinediones--a new class of oral antidiabetics].

Two members of the group, thiazolidinediones, have been approved for the treatment of type 2 diabetes mellitus. These novel oral antihyperglycaemic agents reduce insulin resistance through binding to and activation of the nuclear receptor, PPAR gamma, with subsequent effects on the glucose and lipid homoeostasis. The compounds will probably exhibit beneficial effects on other facets of the metabolic syndrome. Their effectiveness on glycaemic control appears comparable, as assessed by the literature available. HbA1c is lowered by 1.0 to 1.5%. Both drugs are approved for combination therapy with either metformin or sulphonylureas, not as monotherapy or in combination with insulin. Disturbed heart function (NYHA I-IV) is a contra-indication. In contrast to troglitazone, there is so far no evidence of liver toxicity. In spite of the limited literature, it is anticipated that the present class of oral hypoglycaemic agents will turn out to be an important contribution to improving the metabolic control of patients with type 2 diabetes, if the safety profile remains unchanged in long-term studies.

Administration, Oral↗
PubMed2001

[Jet leg].

The aim of the paper is to give a review of jet-lag (Time Zone Change Syndrome) with regard to aetiology, symptomatology and pathophysiology. Furthermore we give recommendations on treatment of jet-lag. The literature has focused intensely on the potential benefit of phototherapy and/or use of melatonin as treatment modalities for jet-lag. Both phototherapy and melatonin have the capability to accelerate reentrainment of the circadian rhythm after flights across multiple time zones, thereby reducing jet-lag. We stress the importance of correct timing of phototherapy and use of melatonin and suggest that the traveller adapts to the "social" rhythm at the flight destination as well.

Animals↗
PubMed2001

Quantification of beta-cell function during IVGTT in Type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods.

AIMS/HYPOTHESIS: We compared four methods to assess their accuracy in measuring insulin secretion during an intravenous glucose tolerance test in patients with Type II (non-insulin-dependent) diabetes mellitus and with varying beta-cell function and matched control subjects. METHODS: Eight control subjects and eight Type II diabetic patients underwent an intravenous glucose tolerance test with tolbutamide and an intravenous bolus injection of C-peptide to assess C-peptide kinetics. Insulin secretion rates were determined by the Eaton deconvolution (reference method), the Insulin SECretion method (ISEC) based on population kinetic parameters as well as one-compartment and two-compartment versions of the combined model of insulin and C-peptide kinetics. To allow a comparison of the accuracy of the four methods, fasting rates and amounts of insulin secreted during the first phase (0-10 min) and the second phase (10-180 min) were calculated. RESULTS: All secretion responses from the ISEC method were strongly correlated to those obtained by the Eaton deconvolution method (r = 0.83-0.92). The one-compartment combined model, however, showed a high correlation to the reference method only for the first-phase insulin response (r = 0.78). The two-compartment combined model failed to provide reliable estimates of insulin secretion in three of the control subjects and in two patients with Type II diabetes. The four methods were accurate with respect to mean basal and first-phase secretion response. The one-compartment and two-compartment combined models were less accurate in measuring the second-phase response. CONCLUSION/INTERPRETATION: The ISEC method can be applied to normal, obese or Type II diabetic patients. In patients with deviating kinetics of C-peptide the Eaton deconvolution method is the method of choice while the one-compartment combined model is suitable for measuring only the first-phase insulin secretion.

Adult↗
PubMed2001

No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP-1 and intravenous glucose.

AIMS: It has previously been shown that intravenous and subcutaneous administration of glucagon-like peptide (GLP)-1 concomitant with intravenous glucose results in reactive hypoglycaemia in healthy subjects. Since GLP-1 is also effective in Type 2 diabetic patients and is presently being evaluated as a therapeutic agent in this disease, it is important to investigate whether GLP-1 can cause hypoglycaemia in such patients. METHODS: Eight Type 2 diabetic patients (age 54 (49-67) years; body mass index 31 (27-38) kg/m2; HbA1c 9.4 (7.0-12.5)%) and seven matched non-diabetic subjects (HbA1c 5.5 (5.2-5.8)%, fasting plasma glucose 5.4 (5.0-5.7) mmol/l) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body weight (maximally tolerated dose), and 15 min later, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. RESULTS: Hypoglycaemia with a PG at or below 2.5 mmol/l was seen in five of the seven healthy subjects after 60-70 min, but PG spontaneously increased again, reaching 3.7 (3.3-4.0) mmol/l at 90 min. In the patients, PG fell slowly and stabilized at 8.6 (4.2-12.1) mmol/l after 80 min. In both groups, glucagon levels initially decreased, but later increased, exceeding basal levels in healthy subjects, in spite of persistent, high concentrations of GLP-1 (P < 0.02). CONCLUSIONS: Subcutaneous GLP-1 plus intravenous glucose induced reactive hypoglycaemia in healthy subjects, but not in Type 2 diabetic patients. Therefore, a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycaemia in Type 2 diabetes mellitus.

Aged↗
PubMed2001

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study.

AIMS: To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. METHODS: Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. RESULTS: Changes in fasting blood glucose (FBG) and HbA1c during the 12 months of treatment showed a significant difference in favour of repaglinide. In oral hypoglycaemic agents (OHA)-naive patients, HbA1c decreased in the repaglinide and glipizide groups by 1.5% and 0.3%, respectively (P < 0.05 between groups). Fasting blood glucose decreased in the repaglinide group by 2.4 mmol/l and increased in the glipizide group by 1.0 mmol/l (P < 0.05 between groups). In the study population as a whole, repaglinide was able to maintain glycaemic control (HbA1c level) during the 1-year study period, whereas control deteriorated significantly with glipizide. Change in HbA1c from baseline was significantly better with repaglinide than with glipizide after 12 months (P < 0.05). In addition, FBG deteriorated significantly in the glipizide group compared with the repaglinide group (P < 0.05). No patients in either group experienced a major hypoglycaemic event; the number of patients experiencing minor hypoglycaemia was similar in the repaglinide and glipizide groups (15% and 19%, respectively). CONCLUSIONS: Repaglinide, given as a prandial glucose regulator, is shown to be an effective and safe treatment of patients with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.

Adult↗
PubMed2001

Determinants of the effectiveness of glucagon-like peptide-1 in type 2 diabetes.

GLP-1 lowers blood glucose in fasting type 2 diabetic patients. To clarify the relation of the effect of GLP-1 to obesity, blood glucose, beta-cell function, and insulin sensitivity, GLP-1 (1.2 pmol/kg.min) was infused iv for 4-6 h into 50 fasting type 2 diabetic patients with a wide range of age, body mass index, HbA1c, and fasting plasma glucose. The effectiveness of GLP-1 was evaluated by calculation of a glucose disappearance constant for each individual (Kg, linear slope of log-transformed plasma glucose), and by the lowest stable glucose level (Nadir plasma glucose) obtained during the infusion. Grouped according to fasting plasma glucose (<10, 10-15, >15 mmol/liter), Kg values were 0.45 +/- 0.03, 0.38 +/- 0.04, and 0.28 +/- 0.04%/min (P = 0.005), and Nadir plasma glucose values were 4.7 +/- 0.1 (3.9-5.9), 5.8 +/- 0.4 (4.3-8.4), and 8.7 +/- 1.4 (6.2-18.7) mmol/liter (P = 0.0003). Nonresponders were not identified. Multiple regression analysis with Kg or Nadir plasma glucose as the dependent parameter and body mass index, age, gender, diabetes duration, and significantly correlated parameters (in multiple regression for Kg: fasting plasma glucose, fasting nonesterified fatty acid, dipeptidyl peptidase activity, peak insulin, and the logarithm of beta-cell function; and for Nadir plasma glucose: fasting plasma glucose, fasting nonesterified fatty acid, dipeptidyl peptidase activity, delta glucagon decrement, F-GLP-1 total, logarithm of beta-cell function, and Kg) as independent parameters resulted in fasting plasma glucose as the only significant predictor of Kg, and fasting plasma glucose and Kg as predictors of Nadir plasma glucose. Kg and Nadir plasma glucose were neither influenced by treatment nor by neuropathy per se. In conclusion, GLP-1 lowers plasma glucose in type 2 diabetes regardless of severity, but glucose elimination is faster and obtained glycemic level lower in patients with the lower fasting plasma glucose. Not all patients can be expected to reach normoglycemia.

Area Under Curve↗
PubMed2001

Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients.

To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter.240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.

Analysis of Variance↗
PubMed2001

Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected].

To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects before and during a euglycemic-hyperinsulinemic clamp. IGT relatives were insulin-resistant in oxidative and nonoxidative pathways for glucose metabolism. In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P < 0.02) but not in IGT relatives (NS). The incremental increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P < 0.05). The incremental defects in signal transduction noted for IRS-1 and PI 3-kinase may be attributed to elevated basal phosphorylation/activity of these parameters, because absolute phosphorylation/activity under insulin-stimulated conditions was similar between IGT relatives and control subjects. Insulin increased Akt serine phosphorylation in control subjects and IGT relatives, with a tendency for reduced phosphorylation in IGT relatives (P = 0.12). In conclusion, aberrant phosphorylation/activity of IRS-1, PI 3-kinase, and Akt is observed in skeletal muscle from relatives of patients with type 2 diabetes with IGT. However, the elevated basal activity of these signaling intermediates and the lack of a strong correlation between these parameters to glucose metabolism suggests that other defects of insulin signal transduction and/or downstream components of glucose metabolism may play a greater role in the development of insulin resistance in skeletal muscle from relatives of patients with type 2 diabetes.

Adult↗
PubMed2001

Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients.

Incretin hormones importantly enhance postprandial insulin secretion but are rapidly degraded to inactive metabolites by ubiquitous dipeptidyl peptidase IV. The concentrations of the intact biologically active hormones remain largely unknown. Using newly developed assays for intact glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP), we measured plasma concentrations after a mixed breakfast meal (566 kcal) in 12 type 2 diabetic patients (age 57 years [range 49-67], BMI 31 kg/m2 [27-38], and HbA1c 9.2% [7.0-12.5]) and 12 matched healthy subjects. The patients had fasting hyperglycemia (10.7 mmol/l [8.0-14.8]) increasing to 14.6 mmol/l (11.5-21.5) 75 min after meal ingestion. Fasting levels of insulin and C-peptide were similar to those of the healthy subjects, but the postprandial responses were reduced and delayed. Fasting levels and meal responses were similar between patients and healthy subjects for total GIP (intact + metabolite) as well as intact GIP, except for a small decrease in the patients at 120 min; integrated areas for intact hormone (area under the curve [AUC]INT) averaged 52 +/- 4% (for patients) versus 56 +/- 3% (for control subjects) of total hormone AUC (AUC(TOT)). AUC(INT) for GLP-1 averaged 48 +/- 2% (for patients) versus 51 +/- 5% (for control subjects) of AUC(TOT). AUC(TOT) for GLP-1 as well as AUC(INT) tended to be reduced in the patients (P = 0.2 and 0.07, respectively); but the profile of the intact GLP-1 response was characterized by a small early rise (30-45 min) and a significantly reduced late phase (75-150 min) (P < 0.02). The measurement of intact incretin hormones revealed that total as well as intact GIP responses were minimally decreased in patients with type 2 diabetes, whereas the late intact GLP-1 response was strongly reduced, supporting the hypothesis that an impaired function of GLP-1 as a transmitter in the enteroinsular axis contributes to the inappropriate insulin secretion in type 2 diabetes.

Aged↗
PubMed2001

Comparison of the soluble basal insulin analog insulin detemir with NPH insulin: a randomized open crossover trial in type 1 diabetic subjects on basal-bolus therapy.

OBJECTIVE: Insulin detemir (NN304) is a soluble basal insulin analog developed to cover basal insulin requirements. This trial aimed to compare the blood glucose-lowering effect of insulin detemir with that of NPH insulin (NPH) and to evaluate the two treatments with regard to intrasubject variation of fasting blood glucose, incidence of hypoglycemia, dose requirements, and safety. RESEARCH DESIGN AND METHODS: This multicenter open randomized crossover trial in 59 type 1 diabetic subjects comprised a 2-week run-in period on a basal-bolus regimen with NPH insulin once daily, followed by two 6-week periods of optimized basal-bolus therapy with either once-daily insulin detemir or NPH insulin. RESULTS: The area under the curve, in the time interval 23:00-8:00, derived from 24-h serum glucose profiles, was not statistically significantly different for the two treatment periods (insulin detemir:NPH ratio 89.2:83.5, P = 0.59). The intrasubject variation in fasting blood glucose during the last 4 days of treatment was lower for insulin detemir compared with NPH (P < 0.001). Mean dose requirements of insulin detemir were 2.35 times higher (95% CI 2.22-2.48) compared with NPH. During the last week of treatment, fewer subjects experienced hypoglycemic episodes on insulin detemir (60%) compared with NPH treatment (77%) (P = 0.049). CONCLUSIONS: Insulin detemir was as effective as NPH in maintaining glycemic control when administered at a higher molar dose. The results indicate that insulin detemir may provide more predictable fasting blood glucose with lower intrasubject variation and reduced risk of hypoglycemia compared with NPH.

Adolescent↗
PubMed2001

Additive glucose-lowering effects of glucagon-like peptide-1 and metformin in type 2 diabetes.

OBJECTIVE: The incretin hormone glucagon-like peptide-1 (GLP-1) reduces plasma glucose in type 2 diabetic patients by stimulating insulin secretion and inhibiting glucagon secretion. The biguanide metformin is believed to lower plasma glucose without affecting insulin secretion. We conducted this study to investigate the effect of a combination therapy with GLP-1 and metformin, which could theoretically be additive, in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a semiblinded randomized crossover study, seven patients received treatment with metformin (1,500 mg daily orally) alternating with GLP-1 (continuous subcutaneous infusion of 2.4 pmol x kg(-1) x min(-1)) alternating with a combination of metformin and GLP-1 for 48 h. Under fixed energy intake, we examined the effects on plasma glucose, insulin, C-peptide, glucagon, and appetite. RESULTS: Fasting plasma glucose (day 2) decreased from 13.9 +/- 1 (no treatment) to 11.2 +/- 0.4 (metformin) and 11.5 +/- 0.5 (GLP-1) and further decreased to 9.4 +/- 0.7 (combination therapy) (P = 0.0005, no difference between monotherapy with GLP-1 and metformin). The 24-h mean plasma glucose (day 2) decreased from 11.8 +/- 0.5 (metformin) and 11.7 +/- 0.8 (GLP-1) to 9.8 +/- 0.5 (combination) (P = 0.02, no difference between GLP-1 and metformin). Insulin levels were similar between the three regimens, but glucagon levels were significantly reduced with GLP-1 compared with metformin (P = 0.0003). Combination therapy had no additional effect on appetite scores. CONCLUSIONS: Monotherapy with GLP-1 and metformin have equal effects on plasma glucose and additive effects upon combination.

Blood Glucose↗
PubMed2000

Improved postprandial glycaemic control with insulin Aspart in type 2 diabetic patients treated with insulin.

The effect on postprandial blood glucose control of an immediately pre-meal injection of the rapid acting insulin analogue Aspart (IAsp) was compared with that of human insulin Actrapid injected immediately or 30 minutes before a test meal in insulin-treated type 2 diabetic patients with residual beta-cell function. In a double-blind, double dummy crossover design, patients attended three study days where the following insulin injections in combination with placebo were given in a random order: IAsp (0.15 IU/kg body weight) immediately before the meal, or insulin Actrapid (0.15 IU/kg) immediately (Act0) or 30 minutes before (Act-30) a test meal. We studied 25 insulin-requiring type 2 diabetic patients, including 14 males and 11 females, with a mean age of 59.7 years (range, 43-71), body mass index 28.3 kg/m2 (range, 21.9-35.0), HbA1c 8.5% (range, 6.8-10.0), glucagon-stimulated C-peptide 1.0 nmol/l (range, 0.3-2.5) and diabetes duration 12.5 years (range, 3.0-26.0). Twenty-two patients completed the study. A significantly improved postprandial glucose control was demonstrated with IAsp as compared to Act0, based on a significantly smaller postprandial blood glucose excursion (IAsp, 899 +/- 609 (SD) mmol/l.min versus Act0, 1102 +/- 497 mmol/l min, p < 0.01) and supported by a significantly lower maximum serum glucose concentration (Cmax) up to 360 min after dosing (IAsp, 10.8 +/- 2.2 mmol/l vs. Act0, 12.0 +/- 2.4 mmol/l, p < 0.02). No difference was demonstrated in glucose endpoints between IAsp, administered with a meal and Actrapid injected 30 minutes before the meal (AUCglucose IAsp, 899 +/- 609 mmol/l min vs. Act-30, 868 +/- 374 mmol/l min; Cmax IAsp, 10.8 +/- 2.2 mmol/l vs. Act-30, 11.1 +/- 1.8 mmol/l). No concerns about the safety of IAsp were raised. Immediate pre-meal administration of the rapid-acting insulin analogue Aspart in patients with type 2 diabetes resulted in an improved postprandial glucose control compared to Actrapid injected immediately before the meal, but showed similar control compared to Actrapid injected 30 minutes before the meal. These results indicate that the improved glucose control previously demonstrated with insulin Aspart compared to human insulin in healthy subjects and type 1 diabetic patients also applies to insulin-treated type 2 diabetic patients.

Adult↗
PubMed2000

The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults.

The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P < 0.001) and a 12% reduction of fat mass (P < 0.002); however, the glucose tolerance deteriorated significantly, and three patients developed impaired glucose tolerance. Fasting insulin level (P < 0.003) and the homeostasis model assessment insulin resistance score increased significantly, indicating a deterioration in insulin sensitivity; whereas the insulin sensitivity index, calculated from the frequently sampled iv glucose tolerance test, only decreased slightly. The clearance of C-peptide and insulin increased 100% and 60%, respectively, and the prehepatic insulin secretion was tripled during rhGH treatment; but related to the impairment in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite an increase in lean body mass and a reduction of fat mass. Therefore, rhGH treatment may precipitate diabetes in some patients already susceptible to the disorder.

Adult↗
PubMed2000

Circulating levels of incretin hormones and amylin in the fasting state and after oral glucose in GH-deficient patients before and after GH replacement: a placebo-controlled study.

OBJECTIVE: Hyperinsulinemia in association with GH excess is considered a compensatory response to insulin resistance, but the possibility of alternative insulinotropic mechanisms has not been investigated in vivo. It is also unknown how GH influences the secretion from pancreatic beta-cells of amylin, a peptide which regulates prandial glucose homeostasis and may be linked to development of beta-cell dysfunction. We therefore measured plasma concentrations of two gut insulinotropic hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin-releasing peptide (GIP), and total as well as non-glycosylated amylin, in 24 GH-deficient adults before and after 4 months of GH replacement (daily evening injections of 2 IU GH/m). DESIGN: Double-blind, placebo-controlled, parallel study. METHODS: All participants underwent an oral glucose tolerance test (OGTT) at 0 and 4 months. RESULTS: A 33% suppression of fasting GLP-1 concentrations was measured in the GH group at 4 months (P=0.02), whereas a non-significant increase occurred in the placebo group (P=0.08). Fasting levels of GIP and amylin did not change significantly after 4 months in either group. The incremental response in GLP-1 during the OGTT was significantly lower after GH treatment as compared with both baseline (P=0.02) and the response in the placebo group (P=0. 03). The stimulation of GIP secretion following OGTT was similar on all occasions. The OGTT-induced incremental response in non-glycosylated amylin was moderately elevated after GH treatment as compared with placebo (P=0.05). Plasma concentrations of glucose and insulin, both in the fasting state and after the OGTT, were higher after GH treatment, but the ratio between amylin and insulin remained unchanged. CONCLUSIONS: GH-induced hyperinsulinemia is accompanied by proportionate elevations in amylin concentrations and a blunting of gut GLP-1 secretion. The mechanisms underlying the suppression of GLP-1 remain to be elucidated.

Adult↗
PubMed2000

Validation of methods for measurement of insulin secretion in humans in vivo.

To detect and understand the changes in beta-cell function in the pathogenesis of type 2 diabetes, an accurate and precise estimation of prehepatic insulin secretion rate (ISR) is essential. There are two common methods to assess ISR, the deconvolution method (by Eaton and Polonsky)-considered the "gold standard"-and the combined model (by Vølund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity of these mathematical techniques for quantification of insulin secretion have been tested in dogs, but not in humans. In the present studies, we examined the validity of both methods to recover the known infusion rates of insulin and C-peptide mimicking ISR during an oral glucose tolerance test. ISR from both the combined model and the deconvolution method were accurate, i.e., recovery of true ISR was not significantly different from 100%. Furthermore, both maximal and total ISRs from the combined model were strongly correlated to those obtained by the deconvolution method (r = 0.89 and r = 0.82, respectively). These results indicate that both approaches provide accurate assessment of prehepatic ISRs in type 2 diabetic patients and control subjects. A simplified version of the deconvolution method based on standard kinetic parameters for C-peptide (Van Cauter et al.) was compared with the 2-day deconvolution method, and a close agreement was found for the results of an oral glucose tolerance test. We also studied whether C-peptide kinetics are influenced by somatostatin infusion. The decay curves after bolus injection of exogenous biosynthetic human C-peptide, the kinetic parameters, and the metabolic clearance rate were similar whether measured during constant peripheral somatostatin infusion or without somatostatin infusion. Assessment of C-peptide kinetics can be performed without infusion of somatostatin, because the endogenous insulin concentration remains constant. Assessment of C-peptide kinetics with and without infusion of somatostatin results in nearly identical secretion rates for insulin during an oral glucose tolerance test.

Adult↗