Biomedical subjects

B Ludvik

Publications and source records attributed to B Ludvik.

At least 19 recordsLinked to original sources

PubMed2006

Impact of antiretroviral therapy on visfatin and retinol-binding protein 4 in HIV-infected subjects.

To determine circulating levels of adipocytokines, especially the recently characterized visfatin, and the fat-derived factor retinol-binding protein-4 (RBP-4) in HIV-infected subjects and their respective changes following treatment with highly active antiretroviral therapy (HAART). Fourteen HIV-positive, HAART-naïve subjects were compared with 10 HIV-negative healthy controls and reassessed after a 1-year treatment with HAART. Plasma visfatin and RBP-4 were determined by ELISA, whereas leptin and adiponectin by RIA. Body composition was measured with dual X-ray absorptiometry (DXA). Homeostasis model assessment (HOMA-IR) was assessed using insulin and glucose levels. Visfatin and RBP-4 levels in HIV-positive subjects were comparable with those of HIV-negative controls before treatment with HAART. Treatment with HAART for 12 months resulted in a 6.9-fold and 7.1-fold increase of visfatin and RBP-4 levels (+54.0 +/- 9.7 ng mL(-1), P < 0.0001 and +95.3 +/- 31.7 ng mL(-1), P < 0.01), respectively. Leptin (-2.7 +/- 1.6 ng mL(-1), P = 0.054) was unchanged and adiponectin (-2.8 +/- 0.7 microg mL(-1), P < 0.01) decreased. Changes of visfatin concentrations correlated significantly with the increases of RBP-4 (r = 0.78, P = 0.001), fat-free mass (FFM, r = 0.75, P < 0.05) and change of HOMA-IR (r = 0.64, P < 0.05). Parameters of glucose metabolism and body fat mass were unchanged during the observation period. Treatment with HAART induced a pronounced increase of plasma visfatin and RBP-4 as well as a decrease of adiponectin in HIV-infected patients on HAART. Although body weight, fat mass and parameters of glucose metabolism remained stable, the changes in the adipocytokines might herald subsequent alterations of these parameters.

Adiponectin↗

PubMed2006

Insulin sensitivity during oral glucose tolerance test and its relations to parameters of glucose metabolism and endothelial function in type 2 diabetic subjects under metformin and thiazolidinedione.

AIM: This study was designed to assess the usefulness of a model-based index of insulin sensitivity during an oral glucose tolerance test (OGTT) in the identification of possible changes in this metabolic parameter produced by pharmacological agents known to be potent insulin sensitizers, that is metformin (M) and thiazolidinedione (T). The association of these agents with several other factors related to glucose metabolism was also investigated, as well as the relation of insulin sensitivity and secretion with markers of endothelial function such as different adhesion molecules (cAMs), that is vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and E-Selectin. METHODS: Twenty type 2 diabetic patients treated with diet only underwent a 3-h OGTT for measurement of plasma glucose, insulin, proinsulin, C-peptide and cAMs before and after administration of randomly given M (n = 9; 1700 mg/day) or T (n = 11; 600 mg/day). After 16 weeks of treatment, a second OGTT was performed. Insulin sensitivity was calculated with homeostasis model assessment and with oral glucose insulin sensitivity (OGIS), which quantifies dynamic glucose clearance per unit change of insulin. Insulin secretion was assessed by modelling technique. Differences in these parameters before and after treatment, as well as possible relationships with cAMs, were assessed. RESULTS: Basal and stimulated plasma glucose decreased after therapy in both the groups by approximately 20%. Basal insulin resistance also decreased. Insulin sensitivity in dynamic conditions (OGIS: ml/min/m(2)) increased with M (289.3 +/- 18.8 vs. 234.7 +/- 18.1, p < 0.02) and tended to improve with T (323.5 +/- 18.1 vs. 286.8 +/- 22.1, p = 0.09). Total insulin secretion over the OGTT [TIS: nmol/l(3 h)] tended to decrease with M (17.1 +/- 2.5 vs. 27.3 +/- 0.3, p = 0.08) but not with T (23.6 +/- 3.5 vs. 22.5 +/- 2.7). Plasma concentrations of E-Selectin decreased in T (38.0 +/- 2.3 vs. 51.2 +/- 6.1 ng/ml, p < 0.05). No correlation was found between insulin sensitivity and cAMs. CONCLUSIONS: Model-based indices of insulin sensitivity and secretion during an OGTT can be able to detect changes observed in patients under treatment with pharmacological agents such as M or T. Both the drugs improved glucose control similarly. Decreased plasma E-Selectin concentrations were seen in patients on T therapy only.

Blood Glucose↗

PubMed2005

Continuous glucose monitoring in diabetic long distance runners.

Marathon running is growing in popularity, and many diabetic patients are participating in various marathon races all over the world each year. This study aimed to investigate the prevalence and extent of glycemic excursions (hypo- and hyperglycemic) during a marathon run in patients with well-controlled diabetes mellitus using a continuous glucose monitoring system (CGMS). Five subjects with type 1 and one patient with type 2 diabetes mellitus were monitored with the Medtronic MiniMed CGMS during the 2002 Vienna City Marathon (n = 3) or the "Fernwärme run" (n = 3) long distance runs of 42.19/15.8 km. All six patients finished their course. The CGSM system was well tolerated in all patients over an average duration of 34 +/- 4.0 hours and it did not limit the patients' activities. The mean running time for the Vienna city marathon was 257 +/- 8 min (247 to 274 min) and for the Fernwärme run 134 +/- 118 min (113 to 150 min). A total of 1470 blood glucose measurements (mean 245 readings per subject) were performed. During and after the marathons frequent hypo- and hyperglycemic episodes with and without clinical symptoms were measured. Our data confirm that the CGMS may help to identify asymptomatic hypoglycemia or hyperglycemia during and after a long distance run. The system may also be helpful to improve our understanding about the individual changes of glucose during and after a marathon and may protect hypoglycemic or hyperglycemic periods in future races.

Adult↗

PubMed2005

Improvement of glucose tolerance in type 2 diabetic patients: traditional vs. modern insulin regimens (results from the Austrian Biaspart Study).

OBJECTIVE: Major advantages of modern insulin regimens containing premixed insulin analogues in comparison to traditional insulin regimens have not been evaluated yet. The aim of the present study was to investigate whether meal-related (breakfast, lunch, dinner) application of biphasic insulin aspart 30 (BIAsp 30) provides better glycaemic control than administration of biphasic human insulin 30 (BHI 30) twice per day. RESEARCH DESIGN AND METHODS: In a multi-centre, randomized, open-label parallel trial, a total of 177 patients with type 2 diabetes mellitus were exposed to the two different insulin regimens described above over a study period of 24 weeks. HbA1c and glycemic exposure parameters were measured at predefined intervals. RESULTS: The mean difference between treatment groups in HbA1c after 24 weeks of treatment was 0.08% (p = 0.6419). Analysing the 7-point blood-glucose (BG) profiles, significant differences in BG levels were observed after lunch (156 vs. 176 mg/dl, p = 0.0289), before dinner (142 vs. 166 mg/dl p = 0.006) and after dinner (154 vs. 182 mg/dl p = 0.002) in favour of BIAsp 30 insulin. Prandial BG increment was lower in the BIAsp 30 group at breakfast (p = 0.057) and lunch (p < 0.0005). No difference was found regarding safety parameters in the two treatment groups. CONCLUSIONS: This study demonstrates that meal-related BIAsp 30-insulin maintains postprandial BG control more effectively than traditional BHI 30 insulin twice per day in type 2 diabetic patients.

Adult↗

PubMed2005

Sleeve gastrectomy and gastric banding: effects on plasma ghrelin levels.

BACKGROUND: Different changes of plasma ghrelin levels have been reported following gastric banding, Roux-en-Y gastric bypass, and biliopancreatic diversion. METHODS: This prospective study compares plasma ghrelin levels and weight loss following laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) in 20 patients. RESULTS: Patients who underwent LSG (n=10) showed a significant decrease of plasma ghrelin at day 1 compared to preoperative values (35.8 +/- 12.3 fmol/ml vs 109.6 +/- 32.6 fmol/ml, P=0.005). Plasma ghrelin remained low and stable at 1 and 6 months postoperatively. In contrast, no change of plasma ghrelin at day 1 (71.8 +/- 35.3 fmol/ml vs 73.7 +/- 24.8 fmol/ml, P=0.441) was found in patients after LAGB (n=10). Increased plasma ghrelin levels compared with the preoperative levels at 1 (101.9 +/- 30.3 fmol/ml vs 73.7 +/- 24.8 fmol/ml, P=0.028) and 6 months (104.9 +/- 51.1 fmol/ml vs 73.7 +/- 24.8 fmol/ml, P=0.012) after surgery were observed. Mean excess weight loss was higher in the LSG group at 1 (30 +/- 13% vs 17 +/- 7%, P=0.005) and 6 months (61 +/- 16% vs 29 +/- 11%, P=0.001) compared with the LAGB group. CONCLUSIONS: As a consequence of resection of the gastric fundus, the predominant area of human ghrelin production, ghrelin is significantly reduced after LSG but not after LAGB. This reduction remains stable at follow-up 6 months postoperatively, which may contribute to the superior weight loss when compared with LAGB.

Adult↗

PubMed2004

Impact of laparoscopic adjustable gastric banding on plasma ghrelin, eating behaviour and body weight.

BACKGROUND: Plasma ghrelin, an orexigenic peptide derived from the stomach and duodenum, increases following weight loss and might contribute to weight regain. The aim of the present study was to evaluate the effect of laparoscopic adjustable gastric banding (LAGB) on body weight and body composition as well as plasma ghrelin in relation to eating behaviour in morbidly obese patients. MATERIALS AND METHODS: This study was performed in 23 morbidly obese subjects who underwent standardized LAGB. Fasting plasma ghrelin was measured before and 6 months after surgery and was correlated with body weight, body composition, and eating behaviour. RESULTS: Six months after LAGB, body weight decreased significantly by -15.7 +/- 1.4 kg (mean +/- SEM, P = 0.0001) which was accompanied by an increased cognitive restraint of eating (P = 0.001), and by a decreased disinhibition of eating and susceptibility to hunger (P = 0.0001). Plasma ghrelin increased (P = 0.016) by 27.2% from 100.39 +/- 12.90 to 127.22 +/- 13.15 fmol mL(-1). The change in plasma ghrelin correlated with changes in body weight (r = -0.49, P = 0.02), BMI (r = -0.42, P = 0.048) and fat mass (r = -0.519, P = 0.013), but not with changes of fat-free mass and of the three dimensions of eating behaviour. CONCLUSION: Weight loss following LAGB leads to an increase in fasting plasma ghrelin and is accompanied by a decrease in hunger, disinhibition of eating and an increase in cognitive restraint. Thus, changes in eating behaviour, which promote reduction of food intake and not fasting ghrelin, determines weight loss achieved by LAGB.

Adolescent↗

PubMed2003

Inverse relation between amylin and glucagon secretion in healthy and diabetic human subjects.

BACKGROUND: The role of amylin, which is cosecreted together with insulin by the pancreatic B-cells, in the pathogenesis of type-2 diabetes is still unclear. To elucidate a possible relation between amylin and glucagon we directly evaluated the respective prehepatic secretions following administration of a 75-g oral glucose load (OGL) in humans. MATERIALS AND METHODS: We studied six healthy controls (C), six obese, insulin resistant subjects (O) and six patients with type 2 diabetes (D). Catheters were placed in the femoral artery and hepatic vein according to the hepatic vein catheterization technique. Splanchnic blood flow was assessed by infusion of indocyanine-green dye. The measured variables were analyzed by a general circulatory model for calculation of prehepatic secretion. RESULTS: The total amount of released glucagon was not different between the respective groups (20.5 +/- 2.3 in C, 27.7 +/- 5.1 in O and 27.9 +/- 5.4 micro g/4 h in D). When considered as the difference from the fasting profile, however, glucagon secretion was reduced by 3.5 +/- 14% in C, 25 +/- 12% in O and increased by 36 +/- 21% in D (P = 0.051, D vs. C). Amylin secretion was increased in O (1.10 +/- 0.15) vs. C (0.63 +/- 0.05, P < 0.05) and D (0.24 +/- 0.10 nmol, P < 0.01). Following glucose administration, glucagon secretion significantly inversely correlated with secretion of amylin (r = -0.6, P < 0.01), but not with that of insulin (r =-0.23, P = 0.36). CONCLUSIONS: The inverse correlation between amylin and glucagon secretion suggests that amylin modulates glucagon secretion following oral glucose administration. This study proves for the first time a role of endogenous amylin in the regulation of glucose homeostasis.

Adult↗

PubMed2001

Increased plasma leptin in gestational diabetes.

AIMS/HYPOTHESIS: Insulin resistance as well as marked changes in body weight and energy metabolism are associated with pregnancy. Its impact on plasma leptin is not known and was determined in this longitudinal study in both diabetic and normal pregnancy. METHODS: At 28 gestational weeks plasma concentrations of leptin and B-cell hormones were measured at fasting and after an oral glucose load (OGTT:75 g) in women with gestational diabetes and pregnant women with normal glucose tolerance and compared with women who were not pregnant (C). RESULTS: Plasma leptin (ng/ml) was higher (p < 0.001) in women with gestational diabetes (24.9 +/- 1.6) than in women with normal glucose tolerance (18.2 +/- 1.5) and increased in both groups when compared with the non-pregnant women (8.2 +/- 1.3; p < 0.0005). No change in plasma leptin concentrations was induced by OGTT in any group. Basal insulin release was higher (p < 0.05) in women with gestational diabetes compared with the pregnant women with normal glucose tolerance. Marked insulin resistance was confirmed by a 20 % lower (p < 0.05) insulin sensitivity in subgroup analysis and a decrease of almost 40% in fasting glucose/insulin ratio (p < 0.005) in women with gestational diabetes. Leptin correlated in women with gestational diabetes with basal plasma concentrations of glucose (p < 0.02), insulin (p < 0.004) and proinsulin (p < 0.01) as well as with BMI (p < 0.001) and overall pregnancy induced maternal weight gain (p < 0.009). With normalisation of blood glucose 8 weeks after delivery in women with gestational diabetes their plasma leptin decreased (p < 0.0005) to 17.3 +/- 1.9 ng/ml but did not completely normalize (p < 0.05 vs non-pregnant women). CONCLUSION/INTERPRETATION: Our data show that women with gestational diabetes without any change in plasma leptin upon oral glucose loading have increased plasma leptin concentrations during and after pregnancy, a clear association of plasma leptin with the respective concentration of glucose and insulin resistance as well as with changes in body weight, and a failure to normalize spontaneously BMI to the same extent as pregnant women with normal glucose tolerance when compared with matched control subjects.

Adult↗

PubMed2001

Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT.

To directly evaluate prehepatic secretion of pancreatic hormones during a 3-h oral glucose tolerance test (OGTT), we measured insulin and C-peptide in six healthy control, six obese, and six type 2 diabetic subjects in the femoral artery and hepatic vein by means of the hepatic catheterization technique. Hypersecretion in obesity was confirmed (309 +/- 66 nmol in obese vs. 117 +/- 22 in control and 79 +/- 13 in diabetic subjects, P </= 0.01), whereas early phase secretion was impaired in diabetes. We also measured hepatic insulin extraction (higher in diabetic than in control subjects, P = 0.03) and insulin clearance. The measured data were also used to validate a previously proposed mathematical model, developed to quantify prehepatic secretion, hepatic insulin extraction, and insulin clearance during OGTT, when C-peptide and insulin concentrations are systemically measured. We found good correspondence between experimental data and model estimates for prehepatic insulin secretion (P > 0.3, r(2) = 0.93), whereas estimation of hepatic insulin extraction and insulin clearance needs further investigation for improvement.

Adult↗

PubMed2001

A model-based method for assessing insulin sensitivity from the oral glucose tolerance test.

OBJECTIVE: Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data. RESEARCH DESIGN AND METHODS: OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT). RESULTS: OGIS and Cl CLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/- 11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239 +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P < 0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar. CONCLUSIONS: OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies.

Body Mass Index↗

PubMed2001

Metabolic changes in the ageing man.

The incidence of the metabolic syndrome, which is associated with visceral fat accumulation, hyperlipidaemia, hypertension, and type 2 diabetes mellitus, is raising with age. Insulin resistance and hyperinsulinaemia have been proposed as the causal link between the elements of the metabolic cluster mentioned above. The decrease in insulin action and insulin secretion can be explained by increased fat mass, decreased muscle mass, and by general endocrine changes related to ageing. Due to the increased incidence of cardiovascular diseases with the metabolic syndrome, lifestyle modifications including weight loss achieved by a low-calorie diet and physical activity should be promoted to increase insulin sensitivity and to prevent glucose intolerance and type 2 diabetes mellitus in ageing subjects.

Adult↗

PubMed2000

[Diabetes therapy related to etiology. Indications, uses and side effects of new insulin sensitizers].

Via their central point of attack on the nuclear PPAR gamma receptors, thiazolidinediones improve insulin sensitivity and thus bring lower blood sugar and insulin levels. Depending on the group of patients investigated, they reduce the HbA1c by 0.7% to 1.5%. Rosiglitazone and pioglitazone will soon be available on the European market. In contrast to troglitazone they show no signs of any hepatotoxic effect in the studies performed to date. Common to the class of insulin sensitizers is their effect in promoting the differentiation of subcutaneous adipocytes, leading to subsequent weight increase and the development of edema.

Blood Glucose↗

PubMed2000

The increased insulin sensitivity in growth hormone-deficient adults is reduced by growth hormone replacement therapy.

BACKGROUND: Growth hormone deficiency is associated with increased morbidity and mortality from cardiovascular diseases, which might be related to changes in glucose and lipid metabolism. DESIGN: To assess the influence of long-term growth hormone replacement therapy (GHRT) on glucose metabolism we examined eight growth hormone-deficient (GHD) adults (seven female/one male; age, 46 +/- 3 years; body mass index, 31 +/- 2 kg m-2) over a period of 18 months in comparison to an adequate control group consisting of eight obese subjects matched for age, sex, and body mass index. We performed frequently sampled intravenous glucose tolerance tests (FSIGT) with minimal model analysis before the study, and after 12 and 18 months. RESULTS: Following GHRT, insulin-like growth factor-1 (IGF-1) increased significantly from a basal level of 75.9 +/- 18.9 to 200.8 +/- 31.0 microg L-1 after 12 months of therapy and remained stable, thereafter. GHRT did not affect fasting blood glucose, basal insulin, cholesterol, blood pressure and body weight. However, at 12 months, HbA1c (6.0 +/- 0.1 vs. 5.6 +/- 0.1% at basal, P < 0.05) and triglyceride (2.3 +/- 0.4 vs. 1.4 +/- 0.3 mmol L-1) significantly increased but returned to pretreatment values at 18 months. Insulin sensitivity was higher in GHD (8.2 +/- 3.1) compared to controls (3. 6 +/- 0.53 x 10-4 min-1/(microU mL-1), P = 0.06) and decreased significantly after 18 months of GHRT to 5.1 +/- 2.6, P < 0.05. Basal insulin secretion was similar to that in the control group and increased significantly after 12 and 18 months, total insulin secretion only after 12 months. SG (glucose effectiveness)was lower in GHD patients (0.0095 +/- 0.001 min-1) compared to controls (0.020 +/- 0.003 min-1, P < 0.05) and increased significantly after 12 and 18 months of GHRT (0.016 +/- 0.002, and 0.015 +/- 0.001 min-1, P < 0. 05), respectively. Hepatic insulin extraction rate was similar in both groups and remained unchanged following GHRT. CONCLUSION: We conclude that long-term GHRT induces a significant decrease of the increased insulin sensitivity in GHD patients to levels observed in body mass index-matched control subjects. This is accompanied by an increase in basal and total insulin secretion as well as in glucose effectiveness as a possible compensatory mechanism.

Adult↗

PubMed1998

Distribution and kinetics of amylin in humans.

The aim of the study was to determine the apparent volume of distribution (VTOT), total body clearance (CL), fractional clearance, and mean residence time (MRT) of the beta-cell hormone amylin. We therefore performed an intravenous injection of 50 micrograms of human synthetic amylin (amlintide) in nine healthy male subjects during suppression of endogenous amylin release by intravenous somatostatin (0.06 microgram.kg-1.min-1). The plasma levels of amylin concentrations over time were analyzed using three-exponential curves. VTOT was 173 +/- 16 ml/kg and was not different from that of insulin reported in the literature (157 ml/kg). MRT was 27.7 +/- 2.1 min and thus two times the reported value for insulin (14.1 min) and C-peptide (16.4 min). CL and fractional CL were 6.2 +/- 0.2 ml.kg-1.min-1 and 0.038 +/- 0.003 min-1, respectively. Fractional CL is therefore definitely lower than that reported for insulin (0.12-0.2 min-1) but is, however, in the range of that of C-peptide (0.05 min-1). In conclusion, clearance of amylin is similar to that reported for C-peptide and much slower than insulin, indicating that the commonly used molar insulin-to-amylin ratio does not reflect the correct relationship of the two peptides.

Adult↗

PubMed1998

[Weight loss by increasing energy consumption and thermogenesis].

Obesity is caused by a chronic imbalance between energy intake and energy expenditure. The increasing incidence of obesity over the last years is partly caused by the decreased physical activity following industrialization. Weight reduction can be achieved by decreasing energy intake and increasing energy expenditure. The fat loss induced by physical activity, however, is relatively small. Exercise helps to prevent the otherwise inevitable loss of muscle during caloric restriction. Due to the low success rate of conventional weight loss programs, the development of drugs to increase thermogenesis is subject to worldwide research. While in animal experiments stimulation of beta-3 adrenergic receptors leads to a significant weight loss, in humans these drugs fail to stimulate energy expenditure probably due to the lack of significant amounts of brown adipose tissue. The recently identified uncoupling proteins (UCP) 2 and 3 dissipate the protone gradient, thereby releasing stored energy as heat. These proteins might therefore act as potential targets for antiobesity drugs.

Animals↗

PubMed1997

Evidence for decreased splanchnic glucose uptake after oral glucose administration in non-insulin-dependent diabetes mellitus.

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six weight-matched control subjects by means of the hepatic vein catheterization (HVC) technique. In a second part, we examined the applicability of the recently developed OG-CLAMP technique in NIDDM by comparing SGU and first-pass SGU during HVC with SGU during the OG-CLAMP experiment. The OG-CLAMP method combines a euglycemic, hyperinsulinemic clamp and an oral glucose tolerance test (75 g) during steady state glucose infusion (GINF). During HVC, SGU equals the splanchnic fractional extraction times the total (oral and arterial) glucose load presented to the liver. For OG-CLAMP, SGU was calculated as first-pass SGU by subtracting the integrated decrease in GINF over 180 min from 75 g. Cumulative splanchnic glucose output after oral glucose correlated significantly between both methods and was increased significantly in NIDDM patients (73.1+/-5.1 g for HVC, 76.5+/-5.5 for OG-CLAMP) compared with nondiabetic patients (46.7+/-4.4 g for HVC, 57.5+/-1.9 for OG-CLAMP). Thus, in NIDDM patients, SGU (7.4+/-2.1 vs. 37.8+/-5.9% in nondiabetic patients, P < 0.001) and first-pass SGU (4.7+/-1.7 vs. 26.5+/-5.1% in nondiabetic patients, P < 0.01) were decreased significantly during HVC, as was SGU during OG-CLAMP (3.9+/-1.7 vs. 23.4+/-2.5% in nondiabetic patients, P < 0.0001). SGU measured during OG-CLAMP correlated significantly with SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.94, P < 0.01 for nondiabetic patients) and first-pass SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.84, P < 0.05 for nondiabetic patients) during HVC. In conclusion, (a) SGU after oral glucose administration is decreased in NIDDM as measured by both methods, and (b) SGU during the OG-CLAMP is well-correlated to SGU and first-pass SGU during HVC in NIDDM. The decrease in SGU in NIDDM might contribute to postprandial hyperglycemia in diabetic subjects.

Administration, Oral↗

PubMed1997

[Amylin/IAPP (islet amyloid polypeptide)--physiology and clinical significance].

Amylin or islet amyloid polypeptide (IAPP) is the protein component of amyloid deposits commonly seen in pancreatic islets of patients with type 2 diabetes mellitus. In in vitro and in animal studies amylin has been shown to decrease insulin secretion and induce insulin resistance. Amylin is stored in the beta-cells and released together with insulin. Circulating amylin is increased in obesity, hypertension and pregnancy, while it is absent in type 1 diabetes mellitus. In type 2 diabetes mellitus the secretion of amylin is impaired prior to that of insulin. Infusion of amylin in man in doses leading to pharmacological levels did not cause any decrease of insulin sensitivity but an impairment of insulin secretion occurred. The recent availability of an amylin antagonist confirmed the effect of amylin on the decrease of insulin secretion in man. The kinetic pattern of amylin, which is presumably excreted by the kidneys, closely resembles that of C-peptide. Subcutaneous administration of the amylin agonist, pramlintide, delays gastric emptying in patients with type 1 diabetes mellitus and, thus, reduces postprandial hyperglycemia. In summary, there is evidence that amylin is able to regulate insulin secretion and gastric emptying in man, but further proof is required.

Amyloid↗

PubMed1997

Amylin: history and overview.

The presence of amyloid deposits in the pancreas was first described at the beginning of the 20th century. However, it was not until 1987 that the structure of the amylin molecule was identified. Amylin is a 37-amino-acid peptide hormone that is co-secreted with insulin by the pancreatic beta-cells in response to a nutrient stimulus. It is deficient in patients with Type 1 diabetes and elevated in patients in the early stages of Type 2 diabetes, a condition which is characterized by hyperinsulinaemia. Elevation of plasma amylin levels has also been described in patients with impaired glucose tolerance, obese subjects and in pregnant women with both normal glucose tolerance and gestational diabetes mellitus. However, it appears that deficiencies of amylin secretion appear before those of insulin in patients in the later stages of Type 2 diabetes. Early experimental studies suggested that amylin inhibits basal insulin secretion, and induces insulin resistance in skeletal muscle, leading to the hypothesis that it has a role in the aetiology of Type 2 diabetes. However, a number of more recent experimental studies have indicated that amylin is a third active pancreatic islet hormone that works with insulin and glucagon to maintain glucose homeostasis. Amylin appears to regulate glucose inflow to the circulation by influencing the rate of gastric emptying, and thus the rate at which meal-derived glucose enters the system, and also by inhibiting glucose release and hepatic glucose production in the postprandial period.

Amyloid↗