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Biomedical subjects

L D Monti

Publications and source records attributed to L D Monti.

At least 19 recordsLinked to original sources

Gluconeogenesis in isolated rat hepatocytes evaluated by gas chromatography/mass spectrometry using deuterated water.

Tritiated water and radioactive tracers have been used to monitor glucose production by primary cultures of hepatocytes. More recently, 3H2O has been replaced for by 2H2O in 'in vivo' studies addressed at the evaluation of the relative contribution of gluconeogenesis to total glucose production. In this work, the possibility of using 2H2O to determine the ratio between the glucogenic flux and the overall flux through glucose 6-phosphate in isolated liver cells in vitro was evaluated. For this purpose, hepatocytes from either fasted or fed rats were incubated with a medium containing 6, 12 and 25% of 2H2O in the presence of either 2 or 20 mM pyruvate. Isotopomer analysis of six different mass clusters (m/z 328, 314, 242, 212, 187 and 145) was carried out by gas chromatography/mass spectrometry (GC/MS) of glucose aldonitrile pentaacetate. For each cluster, ions at m/z +1, +2, +3 and +4 were monitored. From the combination of different clusters the enrichment at C-6 and C-2 of glucose was computed and the C-6/C-2 ratio was considered to represent the contribution of gluconeogenesis to total glucose production, as suggested previously. Based on the results obtained, conditions selected to be optimum for the use of the method in studies on the modulation of gluconeogenesis were as follows: incubation of hepatocytes with 20 mM pyruvate in 12% 2H2O followed GC/electron ionization MS analysis of the clusters of ions at m/z 328, 314 and 187 of the glucose derivative to calculate enrichment at the C-2 and C-6 positions of glucose.

Animals

Long-term in vitro exposure to high glucose increases proinsulin-like-molecules release by isolated human islets.

The aim of this study was to determine the effect of long-term in vitro exposure to high glucose on the release and content of proinsulin and insulin in human islets. After 48 h culture in CMRL medium at 5.5 mM (control islets) and 16.7 mM glucose (experimental islets), islets were perifused and acutely stimulated with 16.7 mM glucose, followed by 3.3 mM glucose. Compared with control islets, experimental islets showed a higher basal release of true insulin and proinsulin-like-molecules (PLM), with no increase of true insulin and PLM release in response to 16.7 mM glucose, and a paradoxical true insulin release in response to 3.3 mM glucose; the PLM/total insulin ratio increased significantly after 16.7 mM glucose. Moreover these islets showed a decreased true insulin content and an increased PLM/total insulin ratio. Quantitative ultrastructural analysis of granules, supported by double gold immunostaining with monoclonal antibodies against proinsulin and insulin, showed an increased proinsulin to insulin ratio in beta-cells from experimental islets. These data support in vitro what was recently shown in vivo, and further confirm that culture in high glucose is a useful tool to mimic the effect of in vivo chronic hyperglycemia on human beta-cell function.

Adult

Glucose turnover and insulin clearance after growth hormone treatment in girls with Turner's syndrome.

The study was performed to elucidate, by means of a euglycemic-hyperinsulinemic clamp, whether insulin sensitivity, lipid levels, posthepatic insulin delivery, and insulin clearance are impaired in girls with Turner's syndrome in the absence of previous treatment (T0) and after 6 (T6) and 12 (T12) months of growth hormone (GH) therapy (GHT). The study was performed in six girls with Turner's syndrome and eight healthy girls. We found that previously untreated girls with Turner's syndrome had a normal insulin activity on glucose metabolism. GHT progressively and significantly decreased hepatic insulin sensitivity. In fact, residual hepatic glucose release (HGR), which was 19.6 +/- 4.7 mg/m2. min at T0, doubled at T6 (39.3 +/- 5.1 mg/m2.min) and showed a threefold increase at T12 (68.7 +/- 10.8 mg/m2.min, P < .05 v T0). On the contrary, GHT did not show an appreciable influence on peripheral insulin sensitivity. Insulin clearance was higher in girls with Turner's syndrome than in control girls at T0 (30.0 +/- 2.8 v 20.2 +/- 1.1 mL.kg-1.min-1). It decreased to normal values at T6 (18.2 +/- 2.0 mL.kg-1.min-1, P < .05 v T0) and remained at normal levels at T12 (23.8 +/- 2.9 mL.kg-1. min-1). The posthepatic insulin delivery rate significantly increased at T6 and T12, suggesting increased insulin secretion. In conclusion, we found that insulin-stimulated glucose turnover was normal in girls with Turner's syndrome before therapy. One year of GHT was successful in stimulating the growth rate, but significantly decreased the insulin suppressibility on HGR with only slight changes in peripheral insulin sensitivity. In addition, an increase in the insulin posthepatic delivery rate and a normalization of insulin clearance were present, probably to counteract hepatic insulin resistance.

Adolescent

Effects of low-dose heparin infusion on arterial endothelin-1 release in humans.

BACKGROUND: The aim of this study was to evaluate the effect of low-dose heparin infusion on arterialized endothelin-1 (ET-1) release in the presence of fasting or high insulin levels in healthy humans. METHODS AND RESULTS: Eleven normal subjects underwent two tests in random order lasting 240 minutes. A primed (250 IU), continuous heparin (600 IU/h) infusion was performed in test 1; saline was infused in test 2 as control. At 120 minutes, a euglycemic hyperinsulinemic clamp (25 mU.kg-1.h-1) was started that lasted 2 hours in both tests. Two hours after heparin infusion (test 1), ET-1 levels decreased by 32% (3.52 +/- 0.60 to 3.02 +/- 0.73 pg/mL), while nitric oxide (NO) and forearm blood flow increased by 29% and 14%, respectively. During saline infusion, ET-1, nitric oxide, and forearm blood flow remained unchanged. There was a significant interaction between the effect of decreasing ET-1 levels and the heparin treatment (F, 4.06; df, 3.30; P < .01). The decrease in ET-1 levels was significantly correlated with the increase in forearm blood flow in test 1 (r = .74; P < .01) but not in test 2. During the heparin/insulin period, ET-1 increased by 25%, returning to fasting values; nitric oxide levels increased by 12%; and forearm blood flow remained unchanged. CONCLUSIONS: The present study showed that it is possible to decrease ET-1 levels by use of low-dose heparin infusion in humans. This effect seems mediated by a simultaneous increase in nitric oxide levels and is completely reversed by a mild increase in insulin concentrations.

Adult

Effects of an acute decrease in non-esterified fatty acid levels on muscle glucose utilization and forearm indirect calorimetry in lean NIDDM patients.

The aim of the study was to evaluate an acute decrease in NEFA levels during an oral glucose tolerance test and its effects on glucose tolerance, muscle glucose uptake and muscle indirect calorimetry in ten lean non-insulin-dependent diabetic subjects. Two 75-g oral glucose tolerance tests were performed in random order. Placebo or 250 mg acipimox (to inhibit lipolysis) were administered orally 2 h before the start of the oral glucose tolerance test. Two hours after acipimox administration (time 0), non-esterified fatty acid, glycerol and 3-hydroxybutyrate levels decreased by 84, 68 and 77% respectively, compared to basal levels. Concomitantly, muscle lipid oxidation and non-oxidative glycolysis also decreased significantly. After placebo administration, non-esterified fatty acids, glycerol and 3-hydroxybutyrate and lipid oxidation increased by 29, 28, 106 and 33%, respectively (NS vs basal levels; p < 0.001 vs acipimox). There was a negative rate of net glucose storage (interpreted as glycogenolysis) during post-absorptive conditions and at time 0 after administration of both drugs. After oral glucose tolerance test, the incremental areas of blood glucose and insulin were significantly decreased by 18 and 19% after acipimox compared to placebo. In addition, the ratio between the incremental area of forearm muscle glucose uptake and the insulin levels was significantly increased by 45% during acipimox compared to placebo administration. Glucose oxidation and non-oxidative glycolysis were significantly higher while lipid oxidation was significantly lower after acipimox than after placebo. In conclusion, our study found that in lean non-insulin-dependent diabetic subjects, an acute decrease in non-esterified fatty acid levels improves glucose tolerance, muscle glucose uptake, glucose oxidation and non-oxidative glycolysis, but is unable to normalize glucose storage.

3-Hydroxybutyric Acid

Dynamics of myocardial adaptation to low-flow ischemia and hypoxemia.

We investigated whether one or more factors control performance in O2-limited hearts. For this purpose, we measured the dynamics of myocardial adaptation to reduced O2 supply with a specially designed setup, analyzing early changes after reduction in either flow of the perfusion medium or its PO2. For 10 min, 38 isolated rat hearts underwent low-flow ischemia or hypoxemia, matched for O2 supply. Early during ischemia, developed pressure declined at a rate of 311 +/- 25 mmHg/s; lactate release increased and then leveled off to 3.4 +/- 0.7 mumol/min within 2 min. During hypoxemia, pressure dropped initially, as observed during ischemia. However, it then increased before slowly decreasing. Lactate release during hypoxemia peaked at 13.0 +/- 2.3 mumol/min after 2 min, leveling off to 3.5 +/- 1.3 mumol/min. Glycogen decreased by 52 and 81% in ischemic and hypoxemic hearts, respectively (P < 0.05). Reexposure to ischemia or hypoxemia induced comparable changes in both groups. We conclude that, at the beginning of ischemia, a single factor does limit myocardial performance. This variable, which remains undisturbed for 10 min, is presumably O2 availability. In contrast, approximately 20 s after induction of hypoxemia, glycolytic ATP production can partially override low O2 availability by providing most of the energy needed. During repeated restriction of O2 supply, O2 availability alone limits performance during both ischemia and hypoxemia.

Adaptation, Physiological

Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans.

The purpose of the study was to evaluate fasting endothelin-1 levels in subjects with syndrome X, in subjects with insulinoma, and in normal subjects. The single and synergistic contributions of insulin and triglyceride levels to endothelin-1 release were studied in normal subjects. This was achieved by the evaluation of endothelin-1 levels in response to an insulin bolus combined with a euglycemic clamp (protocol A) and during intralipid (test 1) or saline (test 2) infusions lasting 360 min (protocol B). In protocol B, a euglycemic two-step hyperinsulinemic (25 and 125 mU x kg-1 x h-1) clamp was started at 120 min. Subjects with syndrome X showed significantly higher endothelin-1 levels than normal subjects and subjects with insulinoma (7.22 +/- 0.89 vs. 2.61 +/- 0.38 and 2.49 +/- 0.24 pg/ml, P < 0.01). After an insulin bolus, endothelin-1 levels peaked at 10 min (3.71 +/- 0.96 pg/ml). The incremental area of endothelin-1 was significantly higher after insulin than after a saline bolus. In test 1, an acute increase in triglyceride levels significantly enhanced endothelin-1 levels, with were further increased by the synergistic contribution of high insulin and triglyceride levels. In test 2, endothelin-1 release was achieved at high insulin levels but remained significantly lower than in test 1. In conclusion, subjects with syndrome X showed higher endothelin-1 levels than normal subjects and subjects with insulinoma. These levels were reproduced in normal subjects by a simultaneous increase in insulin and triglyceride levels.

Adult

Insulin regulation of glucose turnover and lipid levels in obese children with fasting normoinsulinaemia.

To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion. Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels. During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.

3-Hydroxybutyric Acid

A sensitive and reliable method for assaying true human insulin without interaction with human proinsulin-like molecules.

In the present study our interests focused on the evaluation of a high capacity assay (MEIA) which allows true insulin determinations in the absence of cross-reactivity with proinsulin-like molecules. This method was compared to a commercially available radioimmunoassay (RIA) for insulin determination. As the latter gives insulin levels which represent a mixture of insulin and proinsulin-like molecules, the proinsulin-like molecules were quantitated by subtracting the true insulin levels measured using MEIA from the total insulin levels obtained using RIA. These methods were applied for the analysis of blood samples drawn in 63 normal subjects, 16 obese subjects, 3 patients submitted to islet transplantation and 4 patients with insulinoma. The MEIA was precise, fully automated and time-saving, making its application on a routine basis particularly attractive. MEIA and RIA were equally able to correctly quantify human insulin molecules. On the contrary, the antibody present in the true insulin assay did not interact with proinsulin-like molecules, which were recognized even in the presence of increasing insulin levels. In normal subjects, the true and total insulin levels in the fasting state and at the time peak after glucose- or arginine-induced endogenous insulin release were well correlated at r = 0.88 and 0.89, respectively. Interestingly, total insulin values were overestimated by 10%-16% as compared with true insulin levels, which represent proinsulin values superimposable on previously reported data. Proinsulin-like molecules made up 50% of the total insulin in obese and transplanted patients, and about 70% in patients with insulinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cephalic-phase insulin and glucagon release in normal subjects and in patients receiving pancreas transplantation.

The aim of the study was to evaluate whether the cephalic phase of insulin release is still present in patients submitted to simultaneous kidney and pancreas transplantation. Subjects were five kidney-pancreas-transplanted patients (group P) and five control (group C). The experimental protocol lasted 30 minutes, and blood samples were collected at 1-minute intervals. After a 20-minute period of steady-state fasting (premeal period), subjects received a palatable standard meal (pizza). Samples were collected over the subsequent 10 minutes (meal period). No evidence of an increase in serum free insulin, serum C-peptide, and plasma glucagon during food ingestion was observed in group P whereas the test was effective in eliciting cephalic-phase insulin and glucagon release in group C. Gastric inhibitory polypeptide and somatostatin did not show any variation during the test in both groups. In conclusion, the absence of cephalic-phase insulin and glucagon release in group P could be explained by denervation of the grafted pancreas. This early alteration could contribute to the impairment in glucose tolerance frequently observed in successfully pancreas-transplanted patients.

Adult

Effects of an acute increase in plasma triglyceride levels on glucose metabolism in man.

The aim of the study was to evaluate the effects of an acute increase in triglyceride levels induced by Intralipid (Kabivitrum, Stockholm, Sweden) infusion on forearm glucose uptake, glucose oxidative metabolism, and hepatic glucose production independent of circulating free fatty acid (FFA) levels in man. Six normal subjects underwent three different tests in random order. Each test consisted of a control period of 120 minutes followed by a euglycemic, hyperinsulinemic clamp lasting 120 minutes. In test 1, a high-dose intravenous Intralipid infusion was performed to increase triglyceride and FFA levels. In test 2, heparin (30 U/min) plus low-dose Intralipid infusions were performed to maintain triglyceride at normal levels and increase only FFA levels. Test 3 was performed as a control study. During the 120-minute control period, forearm glucose uptake and hepatic glucose production were not affected by increasing only FFA levels (test 2) or FFA and triglyceride levels (test 1) as compared with the control study. On the contrary, glucose oxidation was significantly decreased as compared with the control study during tests 1 and 2, without a further significant decrease during simultaneously increased FFA and triglyceride levels. Concomitantly, lipid oxidation was similar in tests 1 and 2, at values significantly greater than in test 3. During the euglycemic clamp, forearm glucose uptake and glucose oxidation were significantly lower during tests 1 and 2 than test 3. At variance with the control period, the increase of triglyceride levels during test 1 caused a significant 30% to 40% decrease of both parameters as compared with test 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The continuous low dose insulin and glucose infusion test: a simplified and accurate method for the evaluation of insulin sensitivity and insulin secretion in population studies.

In this study we investigated a simple nonlabor-intensive method to evaluate insulin sensitivity and beta-cell function which is suitable for application in population studies. The method is a refinement of the modified Harano test and consists of a continuous low dose insulin (25 mU/kg.h) and glucose (4 mg/kg.min) infusion test (LDIGIT) lasting 150 min. Insulin sensitivity was evaluated as the MCR of glucose divided by the steady state serum insulin level achieved at the end of the test. Insulin secretion was expressed as the incremental area for C-peptide concentration during the first 15 min of the test. We compared the indices of insulin sensitivity and insulin secretion yielded by LDIGIT with those derived from the euglycemic clamp and the hyperglycemic clamp, respectively. Fifty-four subjects underwent a LDIGIT (33 with normal glucose tolerance and 21 with impaired glucose tolerance); of the 54, 19 were submitted to a euglycemic clamp, 18 to a hyperglycemic clamp, and 10 to a modified Harano test (insulin infusion, 50 mU/kg.h; glucose infusion, 6 mg/kg.min). LDIGIT overcame the drawbacks associated with the modified Harano test because it resulted in more stable final glucose levels and prevented the occurrence of hypoglycemic episodes. No significant differences were found between the insulin sensitivity index (ISI) of the LDIGIT and that of the euglycemic clamp for each group of subjects. Moreover, there was a strong correlation between the ISI determined by LDIGIT and the ISI determined by clamp (r = 0.90; P < 0.0001), and the best regression line was not different from the identity line, suggesting that the two indices are equivalent. The index of insulin secretion provided by LDIGIT correlated well with that of the hyperglycemic clamp (r = 0.82; P < 0.001) and was significantly higher in overweight subjects than in normal weight subjects. In conclusion, LDIGIT is a simple and accurate method to assess insulin sensitivity and secretion. It can be useful in population studies and in situations when more complex techniques are not feasible.

Adult

Myocardial glucose uptake evaluated by positron emission tomography and fluorodeoxyglucose during hyperglycemic clamp in IDDM patients. Role of free fatty acid and insulin levels.

Myocardial and whole-body glucose metabolism was assessed in 19 insulin-dependent diabetes mellitus (IDDM) patients. A hyperglycemic clamp was performed 1) in the absence of insulin at free fatty acid (FFA) levels of 1.0 mmol/l (test 1); 2) in the absence of insulin at low FFA levels (0.1 mmol/l) by means of a lipid-lowering drug, acipimox (test 2); 3) during insulin infusion to achieve systemic levels of 400 pmol/l and FFA levels of 0.1 mmol/l (test 3); and 4) at the insulin levels of test 3 but increasing FFA to 1.0 mmol/l by means of heparin and intralipid infusion (test 4). Myocardial glucose uptake was measured by positron emission tomography (PET) and 2-[18F]fluoro-2-deoxy-D-glucose. Whole-body glucose uptake was measured in the four conditions by the glucose infusion rate during the PET scanning period. Myocardial glucose uptakes were 40.3 +/- 18.0, 395.5 +/- 139.6, 852.2 +/- 99.1, and 1,388.4 +/- 199.1 mumol.kg tissue-1.min-1 (mean +/- SD) and whole-body glucose uptakes were 10.1 +/- 2.3, 10.1 +/- 3.4, 42.8 +/- 5.8, and 30.5 +/- 5.6 mumol.kg body wt-1.min-1 during tests 1, 2, 3, and 4, respectively. Thus, in IDDM patients without coronary artery disease under the condition of hyperglycemia, an increase of myocardial glucose uptake was obtained either by lowering of FFA levels during hypoinsulinemia or by an increase in FFA levels during hyperinsulinemia. In both conditions no significant changes of whole-body glucose uptake were demonstrated.

Adult

Fast gas chromatographic-mass spectrometric method for the evaluation of plasma fatty acid turnover using [1-13C]palmitate.

Turnover of plasma free fatty acids (FFAs) can be determined from the palmitate enrichment of plasma after administration of analogues labeled with stable isotopes. We studied the conditions to measure both the concentration and the 13C enrichment of plasma palmitate by gas chromatography-mass spectrometry (GC-MS) using crude extracts. The method used plasma extraction after addition of heptadecanoic acid as internal standard and methylation with diazomethane. Subsequently the samples were analyzed by GC-MS. Plasma palmitate levels determined with this simplified method did not differ statistically from those obtained by a more "classical" procedure using FFA separation from other plasma lipids. Palmitic acid turnover rates (Ra) were evaluated in the steady-state period, in two normal subjects after 90 min infusion with [1-13C]palmitate bound to human albumin. The rate of appearance (Ra) was found to be 0.92 and 1.08 mmol kg-1 min-1, which is in good agreement with the turnover rate previously reported for normal subjects. Sample preparation and GC-MS analysis by the proposed procedure are simple and rapid and thus the method appears to be particularly useful in clinical studies where numerous samples have to be analyzed.

Adult

Hyperinsulinemia decreases second-phase but not first-phase arginine-induced insulin release in humans.

The aim of this study was to investigate the effect of hyperinsulinemia on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 min): a control study using saline infusion and two euglycemic clamps using a low-dose (0.33 mU.kg-1.min-1) and a high-dose (1.20 mU.kg-1.min-1) insulin infusion. After a 3-h equilibration period, arginine (25 g) was infused for 30 min, and insulin and C-peptide responses to arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels were (means +/- SE) 60.0 +/- 2.4, 165.6 +/- 1.8, and 455.4 +/- 7.8 pmol/l during saline, low-dose, and high-dose insulin infusions, respectively. The time course of insulin release during the arginine test was calculated from C-peptide concentrations by using C-peptide kinetic modeling and deconvolution. In particular, first-phase and second-phase insulin response was obtained by integrating the time course of the insulin release during either the first 5 min or the following 40 min of the arginine test, respectively. Whereas first-phase insulin release was independent of any effect induced by either insulin infusion, second-phase insulin release was reduced in a similar degree by both insulin infusion doses. First phase was 75.5 +/- 10.1, 73.7 +/- 12.8, and 73.4 +/- 10.3 pmol/kg, whereas second phase was 266.1 +/- 46.0, 143.1 +/- 33.5, and 133.0 +/- 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Metabolic effects of graded glucagon infusions in man: inhibition of glucagon, insulin, and somatostatin response to arginine.

Insulin inhibits its own release (autofeedback), and growth hormone (GH) inhibits the GH response to a variety of stimuli. The aim of this study was to evaluate whether glucagon (G) can modify pancreatic G (IRG) release in humans. Seven healthy men received intravenous (i.v.) arginine (30 g in 30 minutes) 240 minutes after the beginning of a 0.9% NaCI saline infusion and a 2.5-, 4.0-, and 8.0-ng/kg.min-1 porcine G infusion, with each infusion lasting 360 minutes. All G infusions yielded stable and dose-related plasma IRG levels, and the 4.0- and 8.0-ng/kg.min-1 G infusions decreased plasma free fatty acids (FFA) and blood glycerol and beta-OH-butyrate levels and elicited insulin (IRI) release, and the 8.0-ng/kg.min-1 G infusion elicited GH release and increased blood glucose (BG) levels; somatostatin (SRIF) levels were not affected by G infusions. At 240 minutes, plasma IRG levels were higher during G infusion than during saline infusion, whereas serum IRI and BG levels had returned to preinfusion levels. At this point, G infusions decreased the integrated (240 to 300 minutes) IRG, IRI, BG, and SRIF responses, but not the GH response to arginine. These data indicate that prolonged G infusions decrease the IRG response to arginine; in addition, G decreases plasma FFA levels, and higher G doses stimulate IRI release and exert a self-limited hyperglycemic effect. The fact that the IRI response to arginine was decreased by G could be due to a refractoriness of beta cells to subsequent stimuli; the decreased SRIF response to arginine is likely due to G itself or to a decrease of plasma FFA levels.

3-Hydroxybutyric Acid

Insulin sensitivity and lipid levels in obese subjects after slimming diets with different complex and simple carbohydrate content.

The ideal hypocaloric diet should reduce body weight, decrease fat more than muscle tissue, and ameliorate insulin sensitivity and lipid levels. The aim of this study was to investigate the effect of three hypocaloric diets with different carbohydrate (CHO) and fat contents on body weight reduction, insulin release and sensitivity, and lipid levels in patients with simple obesity. Twenty-five obese subjects with normal glucose tolerance were randomly allocated to three hypocaloric (800 kcal) diets containing: 60% high complex/high starch and fibre (HC/HSF-CHO) and 20% fat (group 1;11 subjects); 60% high simple/high natural fibre (HS/HNF-CHO) and 20% fat (group 2; 7 subjects); or 20% CHO (L-CHO) and 60% fat (group 3; 7 subjects). The remaining 20% of the diet was protein. In all cases the duration of the diet was 21 days. Before and after the diet, seven subjects from each group underwent a hyperglycemic clamp, and the other four subjects of group 1 underwent a euglycemic-hyperinsulinemic clamp, combined with a glucose turnover study. A similar decrease in body weight, fat-free mass, fat mass, total cholesterol, LDL cholesterol and apo B levels was observed in the three groups. The M/I ratio during hyperglycemic and euglycemic-hyperinsulinemic clamp and the glucose turnover rate during euglycemic-hyperinsulinemic clamp significantly decreased, and FFA levels significantly increased only after the HC/HSF-CHO diet. HDL cholesterol and apo A1 significantly increased only during the HS/HNF-CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult