RESUMEN
The aim of this study was to evaluate the mechanisms underlying weight gain induced by the atypical antipsychotic, olanzapine. We performed euglycemic, hyperinsulinemic clamp combined with indirect calorimetry on a 48-year-old male with antisocial personality disorder, alcohol dependence and paranoid ideation before and after one month of olanzapine (10 - 15 mg/day) therapy. The patient gave his informed, written consent for this study. The results were a weight gain of 6 kg and a decrease in both basal (from 1673 to 1613 kcal/24 h) and 3-hour (from 22.8 to 20.2 cal/kg fat free mass/min) energy expenditure. Serum thyroid hormone and high-density lipoprotein cholesterol levels decreased, and the triglyceride and low-density lipoprotein cholesterol levels increased. Insulin sensitivity did not change. We conclude that decreased basal energy expenditure may contribute to weight gain in olanzapine treatment.
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Antipsicóticos/efectos adversos , Metabolismo Energético/efectos de los fármacos , Pirenzepina/efectos adversos , Aumento de Peso/efectos de los fármacos , Benzodiazepinas , Calorimetría Indirecta , Humanos , Masculino , Persona de Mediana Edad , Olanzapina , Pirenzepina/análogos & derivados , Trastornos Psicóticos/tratamiento farmacológicoRESUMEN
OBJECTIVE: We studied the effect of weight reduction on cardiac parasympathetic activity (PSA) in obese women. We also studied the relationship between the changes of PSA, resting energy expenditure (REE), and major cardiovascular risk factors. RESEARCH METHODS AND PROCEDURES: Changes of cardiac vagal tone, an index of PSA, REE, and major cardiovascular risk factors, were measured in 52 healthy obese women after a 6-month weight reduction. Ten of the women were remeasured at 12 and 24 months. Cardiac vagal tone was assessed by a vagal tone monitor and REE by indirect calorimeter. RESULTS: Cardiac vagal tone increased significantly (p = 0.046), averaging a 9.5% weight loss in 6 months. The vagal tone increased further with weight loss during the following 6 months, and thereafter, it declined with weight regain. The increase of cardiac vagal tone correlated significantly with decreases of body weight, fat mass, waist circumference, serum insulin, and heart rate. REE adjusted for fat-free mass and age did not change with weight loss and was not related to cardiac vagal tone at any time-point. DISCUSSION: Cardiac PSA activity increases with weight loss in obese women. This increase may not be maintained long-term if body weight is regained. The rise of cardiac PSA is correlated with decreases of body fat mass, abdominal fat, serum insulin, and heart rate. Cardiac PSA is not related to REE.
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Metabolismo Basal/fisiología , Corazón/inervación , Obesidad/fisiopatología , Sistema Nervioso Parasimpático/metabolismo , Pérdida de Peso/fisiología , Adulto , Glucemia/metabolismo , Presión Sanguínea/fisiología , Constitución Corporal , Calorimetría Indirecta , Enfermedades Cardiovasculares/etiología , Método Doble Ciego , Metabolismo Energético , Femenino , Corazón/fisiopatología , Frecuencia Cardíaca/fisiología , Humanos , Insulina/sangre , Obesidad/complicaciones , Factores de RiesgoRESUMEN
OBJECTIVE: To examine the effect of orlistat (Xenical) treatment on body composition and resting energy expenditure (REE) during a 2 y weight-reduction programme in obese Finns. SUBJECTS: Of initially 96 obese subjects who participated in the weight-reduction programme, those 72 subjects (13 men, 59 women, body mass index (BMI) 35.9 +/- 3.9 kg/m2, age 43.4 +/- 6.0 y, mean +/- s.d.) with the complete set of data for 2 y were included in the study. DESIGN: After a 4-week lead-in period, subjects were randomized with either orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a mildly hypoenergetic balanced diet for 1 y. This was followed by 1 y double-blind period with the subjects within each treatment group re-assigned to receive orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a weight maintenance diet. MEASUREMENTS: Body composition and REE were measured after an overnight fast by a bioelectrical impedance method and indirect calorimeter, respectively. The measurements were performed at the beginning and at 3, 6, 12 and 24 months. RESULTS: During the first year, the orlistat-treated group had greater reduction of body weight and fat mass but not of fat-free mass or REE as compared to placebo. During the second year, orlistat treatment was associated with smaller regain of body weight and fat mass with no significant differences in the changes of fat-free mass or REE as compared to placebo. CONCLUSION: In addition to better weight loss and maintenance of reduced weight, orlistat treatment is associated with beneficial changes in body composition but with no excess decrease in resting energy expenditure as compared to that achieved during placebo with a dietary therapy alone.
Asunto(s)
Fármacos Antiobesidad/farmacología , Composición Corporal/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Lactonas/farmacología , Obesidad/terapia , Adulto , Fármacos Antiobesidad/administración & dosificación , Fármacos Antiobesidad/uso terapéutico , Constitución Corporal , Índice de Masa Corporal , Calorimetría Indirecta , Método Doble Ciego , Impedancia Eléctrica , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Femenino , Finlandia , Humanos , Lactonas/administración & dosificación , Lactonas/uso terapéutico , Lipasa/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Obesidad/dietoterapia , Orlistat , Placebos , Pérdida de PesoRESUMEN
OBJECTIVE: To investigate the determinants of resting energy expenditure (REE) in obese non-diabetic Caucasian women. DESIGN: A cross-sectional survey study before the beginning of a weight-reduction program. SUBJECTS: 141 obese, non-diabetic women of Caucasian origin (BMI 34.8 +/- 3.7 kg/m2, age 43.2 +/- 8.0 y, mean +/- s.d.). MEASUREMENTS: Resting energy expenditure (an indirect calorimetry), body composition (a bioelectrical impedance), fat distribution (anthropometry) and heart rate (ECG) were determined after 12 h overnight fast and apolipoprotein E phenotype was examined. RESULTS: In a linear multiple regression analysis fat-free mass, fat mass and age together with heart rate and waist-hip ratio emerged as significant determinants of REE. In the other regression model, also serum insulin emerged as a significant determinant of REE, in addition to fat-free mass, fat mass and age. There was no significant differences in REE among the different apolipoprotein E phenotype groups. CONCLUSION: Besides fat-free mass, also fat mass, age, heart rate, waist-hip-ratio, and serum insulin level make a significant contribution to REE in obese women.
Asunto(s)
Metabolismo Energético , Obesidad/metabolismo , Tejido Adiposo , Adulto , Apolipoproteínas E/sangre , Composición Corporal , Constitución Corporal , Calorimetría Indirecta , Estudios Transversales , Impedancia Eléctrica , Femenino , Frecuencia Cardíaca , Humanos , Fenotipo , Análisis de Regresión , Descanso , FumarRESUMEN
Apolipoprotein E (apo E) is a normal constituent of very-low-density lipoproteins and it participates in the metabolism of both low-density lipoproteins (LDL) and apo E-containing lipoproteins. In the present study, the aim was to examine to what extent apo E phenotypes modify central obesity-induced changes in serum lipids, insulin, and blood pressure in obese women. Altogether, 143 middle-aged obese women with a body mass index (in kg/m2) of 28.0-43.0 were examined. Twelve had apo E 3,2 phenotype, 93 had apo E 3,3 phenotype, and 38 had either apo E 4,3 or 4,4 (4,3 + 4,4 group) phenotype. Serum total and LDL cholesterol were lower in the apo E 3,2 group than in other groups, but no significant differences were observed in other lipid variables in this regard. Both systolic and diastolic blood pressure measures tended to be lowest in subjects with apo E 3,2 phenotype and highest in those with apo E 4,3 or 4,4 phenotype (P = 0.08-0.15 for trend). When serum lipids, blood pressure, and insulin were analyzed by waist circumference and apo E phenotype group, it became evident that women who had central obesity and the apo E 4 allele had the highest blood pressures, insulin-glucose ratios, and insulin concentrations. These results suggest that apo E phenotype significantly modifies the central obesity-induced changes in metabolic and hemodynamic variables characteristic of insulin resistance.
Asunto(s)
Apolipoproteínas E/sangre , Obesidad/sangre , Fenotipo , Adulto , Glucemia/metabolismo , Presión Sanguínea , Composición Corporal , Constitución Corporal , Índice de Masa Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Finlandia , Humanos , Insulina/sangre , Resistencia a la Insulina , Persona de Mediana EdadRESUMEN
The aim of this study was to characterize abnormalities of triglyceride-rich apolipoprotein (apo) B-containing lipoproteins in type I diabetic patients with elevated albumin excretion rates (AERs). Sixty-four patients (31 men, 33 women) with normoalbuminuria (AER <20 microg/min), 52 (35 men, 17 women) with microalbuminuria (AER 20-200 microg/min), and 37 (17 men, 20 women) with albuminuria (AER >200 microg/min) and 56 healthy control subjects matched for age and body weight were studied. The major finding was increased mass concentrations of the highly atherogenic intermediate-density lipoprotein fraction in patients with microalbuminuria (P < 0.05) and albuminuria (P < 0.05), compared with those with normoalbuminuria. Triglyceride, free cholesterol, cholesterol ester, and phospholipid concentrations in the VLDL, intermediate-density lipoprotein, and LDL (P < 0.05-0.01), as well as total cholesterol, total triglyceride, and apoB concentrations were higher in patients with renal disease than in those without. Notably, there were no differences between patients with microalbuminuria and albuminuria. Only minor compositional changes could be detected. Postheparin plasma lipoprotein lipase (LPL) activities were identical, but hepatic lipase activities were higher in microalbuminuric and albuminuric patients than in normoalbuminuric patients (P < 0.01). LPL activity and VLDL1, (Sf 60-400) (r = -0.528; P < 0.001) and VLDL2 (Sf 20-60) mass concentrations (r = -0.471; P < 0.001) were negatively related. In conclusion, in type I diabetic patients with early renal disease, there are multiple lipoprotein changes, which are potentially atherogenic and may contribute to the excess of macrovascular complications seen in such patients.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Nefropatías Diabéticas/sangre , Lipoproteínas/sangre , Adulto , Albuminuria , Análisis de Varianza , Apolipoproteínas B/sangre , Presión Sanguínea , Colesterol/sangre , Ésteres del Colesterol/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 1/orina , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Hemoglobina Glucada/análisis , Heparina , Humanos , Lipoproteína Lipasa/sangre , Lipoproteínas/aislamiento & purificación , Lipoproteínas IDL , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Fosfolípidos/sangre , Valores de Referencia , Triglicéridos/sangreRESUMEN
To examine the mechanisms by which immunosuppression by steroids impairs glycogen synthesis in human skeletal muscle, we measured glycogen synthase protein content and activity in muscle samples from 14 patients receiving corticosteroid therapy after kidney transplantation and in 20 healthy control subjects. A percutaneous muscle sample was taken before and at the end of a euglycemic hyperinsulinemic insulin clamp. Insulin-stimulated glucose disposal was reduced by 33% in kidney transplant patients compared with healthy controls (33.8 +/- 4.2 vs. 50.5 +/- 2.7 mumol (kg LBM)-1 min-1; P<0.01), primarily due to a decrease in nonoxidative glucose metabolism (14.2 +/- 3.3 vs. 32.3 +/- 2.7 mumol (kg LBM)-1 min-1; P<0.001). Glycogen synthase activity measured at both 0.1 mmol/L (17.6 +/- 2.6 vs. 24.0 +/- 2.2 nmol min-1 mg protein-1; P<0.05), and at 10 mmol/L glucose 6-phosphate (24.1 +/- 3.5 vs. 33.7 +- 2.4 nmol min-1 mg protein-1; P<0.05) and glycogen synthase protein concentrations (8.8 +/- 1.8 vs. 18.9 +/- 1.9 relative units per ng DNA; P<0.01) were lower in kidney transplant patients compared with controls. Glycogen synthase protein correlated with nonoxidative glucose metabolism (r=0.42; P=0.04). Alpha-actinin (used as a control of general protein degradation) was lower in kidney transplant patients compared with controls (4.4 +/- 0.8 vs. 9.6 +/- 1.1 cpm/ng DNA; P<0.01). In conclusion, corticosteroids cause insulin resistance, which correlates with impaired activation of glycogen synthase and decreased enzyme protein content. The decrease in glycogen synthase protein may reflect increased degradation rather than a defect in translation.
Asunto(s)
Glucógeno/metabolismo , Inmunosupresores/efectos adversos , Trasplante de Riñón , Metilprednisolona/efectos adversos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Adulto , Glucemia/metabolismo , Femenino , Glucógeno/biosíntesis , Glucógeno Sintasa/metabolismo , Humanos , Inmunosupresores/uso terapéutico , Insulina/fisiología , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Músculo Esquelético/enzimología , Factores de TiempoRESUMEN
Hypertriglyceridaemia is associated with insulin resistance of both lipid and glucose metabolism. It is not known whether the insulin resistance affects both glucose oxidation and glycogen formation. To study the oxidative and non-oxidative pathways of non-esterified fatty acids (NEFA) and glucose metabolism, eight male hypertriglyceridaemic subjects were studied during insulin infusion (75 and 340 pmol/m2.min) in combination with indirect calorimetry and infusions of [3-3H]glucose and [1-14C]palmitate before and after 4 weeks of treatment with the antilipolytic agent acipimox (250 mg three times daily). Compared with eight healthy subjects the hypertriglyceridaemic subjects were resistant to the antilipolytic effect of insulin, both in the basal state (P < 0.05) and during insulin infusion (P < 0.05). This was associated with impaired insulin-stimulated glucose uptake (P < 0.05), predominantly in the non-oxidative pathway (P < 0.05). Acipimox decreased basal NEFA concentrations (P < 0.01) and reduced lipid oxidation during low-dose insulin infusion (P < 0.05). Glucose uptake, predominantly glycogen formation, was stimulated by acipimox (P < 0.05). In conclusion, the insulin resistance of glucose metabolism associated with hypertriglyceridaemia is largely due to a defect in non-oxidative glucose metabolism. Acipimox improves glucose metabolism both by affecting glucose oxidation (low-dose insulin) and non-oxidative glucose metabolism (high-dose insulin).
Asunto(s)
Glucosa/metabolismo , Hipertrigliceridemia/tratamiento farmacológico , Hipertrigliceridemia/metabolismo , Hipolipemiantes/uso terapéutico , Resistencia a la Insulina , Metabolismo de los Lípidos , Pirazinas/uso terapéutico , Ácidos Grasos no Esterificados/metabolismo , Técnica de Clampeo de la Glucosa , Humanos , Insulina/administración & dosificación , Insulina/farmacología , Lipólisis , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Palmitatos/administración & dosificación , Palmitatos/farmacologíaRESUMEN
We examined whether insulin resistance, i.e. impaired insulin stimulated glucose uptake in NIDDM patients and their first-degree relatives is associated with alterations in the effect of insulin on the expression of the GLUT-4 gene in skeletal muscle in vivo. Levels of GLUT-4 mRNA and protein were measured in muscle biopsies taken before and after a euglycaemic insulin clamp from 14 NIDDM patients, 13 of their first-degree relatives and 17 control subjects. Insulin stimulated glucose uptake was decreased in the diabetic subjects (19.8 +/- 3.0 mumol.kg LBM-1.min-1, both p < 0.001) compared with control subjects (44.1 +/- 2.5 mumol.kg LBM-1.min-1) and relatives (39.9 +/- 3.3 mumol.kg LBM-1.min-1). Basal GLUT-4 mRNA levels were significantly higher in diabetic subjects and relatives compared to control subjects (99 +/- 8 and 108 +/- 9 pg/micrograms RNA vs 68 +/- 5 pg/micrograms RNA; both p < 0.01). Insulin increased GLUT-4 mRNA levels in all control subjects (from 68 +/- 5 to 92 +/- 6 pg/micrograms RNA; p < 0.0001), but not in the diabetic patients (from 99 +/- 8 to 90 +/- 8 pg/micrograms RNA, NS), or their relatives (from 94 +/- 9 to 101 +/- 11 pg/micrograms RNA, NS). In the relatives, individual basal GLUT-4 mRNA concentrations varied between 55 and 137 pg/micrograms RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Insulina/farmacología , Proteínas de Transporte de Monosacáridos/metabolismo , Músculos/metabolismo , ARN Mensajero/metabolismo , Glucemia/análisis , Diabetes Mellitus Tipo 2/genética , Femenino , Glucosa/metabolismo , Humanos , Immunoblotting , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Proteínas de Transporte de Monosacáridos/genética , Músculos/efectos de los fármacosRESUMEN
To study whether therapeutic reduction of non-esterified fatty acids (NEFA) can be used to improve glucose metabolism, we administered the antilipolytic agent, acipimox, 250 mg four times daily for 4 weeks in eight obese Type 2 diabetic patients. Glucose and NEFA metabolism were assessed before and after treatment with a two-step euglycaemic hyperinsulinaemic clamp (0.25 and 1 mU kg-1 min-1 insulin) combined with infusions of [3-3H] glucose and [1-14C] palmitate. Three days of acipimox treatment reduced 24-h serum NEFA levels by 10%, but the difference disappeared after 4 weeks of treatment mainly due to a two-fold rise in morning NEFA concentrations (p < 0.01). After 3 days of acipimox treatment, fasting and 24-h plasma glucose and serum triglyceride concentrations were significantly reduced (p < 0.05), but no longer after 4 weeks of treatment. Despite the rebound rise in NEFA, acute administration of acipimox still inhibited both oxidative and non-oxidative NEFA metabolism in the basal state (p < 0.01-0.001) and during insulin infusion (p < 0.05-0.001). Inhibition of NEFA metabolism was associated with increased insulin-stimulated glucose uptake (from 3.56 +/- 0.28 to 5.14 +/- 0.67 mumol kg-1 min-1, p < 0.05), mainly due to stimulation of non-oxidative glucose disposal (from 1.74 +/- 0.23 to 3.03 +/- 0.53 mumol kg-1 min-1, p < 0.05). In conclusion, acipimox administered acutely inhibits NEFA appearance (lipolysis), which is associated with improved glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Ácidos Grasos no Esterificados/sangre , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Pirazinas/uso terapéutico , Glucemia/efectos de los fármacos , Colesterol/sangre , HDL-Colesterol/sangre , Ritmo Circadiano , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ayuno , Femenino , Glucosa/metabolismo , Técnica de Clampeo de la Glucosa , Glicerol/sangre , Humanos , Infusiones Intravenosas , Insulina/administración & dosificación , Insulina/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Factores de Tiempo , Triglicéridos/sangreRESUMEN
BACKGROUND: The storage of glucose as glycogen in skeletal muscle is frequently impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM) and their nondiabetic relatives. Despite an intensive search for candidate genes associated with NIDDM, no data have been available on the gene coding for the key enzyme of this pathway, glycogen synthase. METHODS AND RESULTS: Using a human complementary DNA probe, the restriction enzyme Xbal, and Southern blot analysis, we identified two polymorphic alleles, A1 and A2, in the glycogen synthase gene. The gene was localized to chromosome 19. The A1A2 or A2A2 genotype was found in 30 percent of 107 patients with NIDDM but in only 8 percent of 164 nondiabetic subjects without a family history of NIDDM (P < 0.001). The diabetic patients with the A2 allele had a stronger family history of NIDDM (P = 0.019), a higher prevalence of hypertension (P = 0.008), and a more severe defect in insulin-stimulated glucose storage (P = 0.001) than the diabetic patients with the A1 allele. The concentration of the glycogen synthase protein in biopsy specimens of skeletal muscle from the patients with the A2 allele was normal, however, suggesting that expression of the gene was unaltered. The Xbal polymorphism was due to a change of a single base in an intron. CONCLUSIONS: The Xbal polymorphism of the glycogen synthase gene identifies a subgroup of patients with NIDDM characterized by a strong family history of NIDDM, a high prevalence of hypertension, and marked insulin resistance.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Glucógeno Sintasa/genética , Polimorfismo Genético , Alelos , Glucemia/metabolismo , Distribución de Chi-Cuadrado , Sondas de ADN , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Glucógeno Sintasa/metabolismo , Humanos , Resistencia a la Insulina/genética , Masculino , Persona de Mediana Edad , Músculos/enzimologíaRESUMEN
Hypertriglyceridaemia, which is frequently seen in Type 2 (non-insulin-dependent) diabetes mellitus, is associated with insulin resistance. The connection between hypertriglyceridaemia and insulin resistance is not clear, but could be due to substrate competition between glucose and lipids. To address this question we measured glucose and lipid metabolism in 39 Type 2 diabetic patients with hypertriglyceridaemia, i.e. mean fasting serum triglyceride level equal to or above 2 mmol/l (age 59 +/- 1 years, BMI 27.4 +/- 0.5 kg/m2, HbA1c 8.0 +/- 0.2%, serum triglycerides 3.2 +/- 0.2 mmol/l) and 41 Type 2 diabetic patients with normotriglyceridaemia, i.e. mean fasting serum triglyceride level below 2 mmol/l (age 58 +/- 1 years, BMI 27.0 +/- 0.7 kg/m2, HbA1c 7.8 +/- 0.2%, serum triglycerides 1.4 +/- 0.1 mmol/l). Insulin sensitivity was assessed using a 340 pmol.(m2)-1 x min-1 euglycaemic insulin clamp. Substrate oxidation rates were measured with indirect calorimetry and hepatic glucose production was estimated using a primed (25 microCi)-constant (0.25 microCi/min) infusion of [3-3H]-glucose. Suppression of lipid oxidation by insulin was impaired in patients with hypertriglyceridaemia vs patients with normal triglyceride levels (3.5 +/- 0.2 vs 3.0 +/- 0.2 mumol.kg-1 x min-1; p < 0.05). Stimulation of glucose disposal by insulin was reduced in hypertriglyceridaemic vs normotriglyceridaemic patients (27.0 +/- 1.3 vs 31.9 +/- 1.6 mumol.kg-1 x min-1; p < 0.05) primarily due to impaired glucose storage (9.8 +/- 1.0 vs 14.6 +/- 1.4 mumol.kg-1 x min-1; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Hipertrigliceridemia/complicaciones , Resistencia a la Insulina , Insulina , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Ayuno , Ácidos Grasos no Esterificados/sangre , Femenino , Hemoglobina Glucada/análisis , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/fisiopatología , Masculino , Persona de Mediana Edad , Valores de Referencia , Triglicéridos/sangreRESUMEN
Fat-free mass (FFM) was measured with three different methods: near-infrared spectroscopy, bioelectrical impedance and tritiated water technique, in 76 (39 females/37 males) subjects (age 47 +/- 2 [SEM] years, BMI 26.8 +/- 0.6 kg m-2). From bioelectrical impedance measurements FFM was calculated with manufacturers formula and a formula developed by Deurenberg et al [1]. FFM estimated from tritiated water technique (51.9 +/- 1.1 kg) was significantly lower than measured with near-infrared spectroscopy (57.4 +/- 1.4 kg; p < 0.001) and bioelectrical impedance calculated with manufacturers formula (59.6 +/- 1.5 kg; p < 0.001), but did not differ from the estimation made according to Deurenberg (52.1 +/- 1.2 kg). All the methods were highly intercorrelated, although the correlation coefficients were lower in the obese than lean subjects. Obesity seems to influence the bioimpedance method more than the near-infrared spectroscopy method. The results demonstrate that the near-infrared spectroscopy and the bioelectrical impedance method are simple and reproducible techniques to estimate fat-free mass in normal weight man. Both measurements are based partly on the anthropometric measurements. However, it is necessary to use an adjusted formula to obtain reliable measures of fat-free mass with the bioimpedance method in obese subjects.
Asunto(s)
Composición Corporal , Índice de Masa Corporal , Tejido Adiposo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Impedancia Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Espectrofotometría Infrarroja , Tritio , AguaRESUMEN
To examine determinants of basal metabolic rate we studied 66 Type 2 (non-insulin-dependent) diabetic and 24 healthy age- and weight-matched control subjects with indirect calorimetry and infusion of [3H-3-] glucose. Eight Type 2 diabetic patients were re-studied after a period of insulin therapy. Basal metabolic rate was higher in Type 2 diabetic patients than in control subjects (102.8 +/- 1.9 J.kg LBM-1.min-1 vs 90.7 +/- 2.8 J.kg LBM-1.min-1; p less than 0.01) and decreased significantly with insulin therapy (p less than 0.01). The basal rate of hepatic glucose production was higher in Type 2 diabetic patients than in control subjects (1044.0 +/- 29.9 vs 789.3 +/- 41.7 mumol/min; p less than 0.001) and decreased after insulin therapy (p less than 0.01). Hepatic glucose production correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.49; p less than 0.001) and in control subjects (r = 0.50; p less than 0.05). Lipid oxidation was increased in Type 2 diabetic patients compared with control subjects (1.68 +/- 0.05 vs 1.37 +/- 0.08 mumol.kg LBM-1.min-1; p less than 0.01) and decreased significantly after insulin therapy (p less than 0.05). The rate of lipid oxidation correlated positively with basal metabolic rate both in Type 2 diabetic patients (r = 0.36; p less than 0.01) and in control subjects (r = 0.51; p less than 0.01). These data demonstrate that basal metabolic rate, rates of hepatic glucose production and lipid oxidation are interrelated in Type 2 diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Metabolismo Basal , Diabetes Mellitus Tipo 2/metabolismo , Adolescente , Adulto , Calorimetría , Niño , Preescolar , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Glucosa/administración & dosificación , Glucosa/metabolismo , Humanos , Lactante , Recién Nacido , Inyecciones Intravenosas , Insulina/uso terapéutico , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Oxidación-Reducción , TritioRESUMEN
To examine whether age-related changes in energy metabolism are influenced by gender, 20 females and 20 males varying in age from 21 to 80 yr were studied with euglycemic insulin clamp in combination with indirect calorimetry and infusion of [3-3H]glucose. Lean body mass (LBM) was measured with the tritiated water technique. Fat percentage correlated with age in males (r = 0.60; P < 0.05) but not in females. Although the rates of insulin-stimulated total glucose disposal and nonoxidative glucose metabolism were similar in females and males, nonoxidative glucose metabolism expressed per kilogram body weight (r = -0.64; P < 0.01) or per kilogram LBM (r = -0.46; P < 0.05) was inversely correlated with age only in males. Basal metabolic rate expressed per kilogram body weight decreased with age in both sexes, but no correlation with age was observed when data were expressed per kilogram LBM. The data clearly demonstrate different effects of age on energy metabolism in males and females.
Asunto(s)
Envejecimiento/fisiología , Resistencia a la Insulina , Caracteres Sexuales , Adulto , Anciano , Anciano de 80 o más Años , Composición Corporal , Metabolismo Energético , Femenino , Glucosa/metabolismo , Humanos , Metabolismo de los Lípidos , Masculino , Persona de Mediana EdadRESUMEN
The present study was undertaken to compare the effect of hyperglycemia and euglycemia during identical hyperinsulinemic conditions on glucose metabolism in NIDDM subjects. Eight NIDDM subjects participated in a 4 h hyperglycemic (12.1 +/- 0.7 mmol/l), hyperinsulinemic (475 +/- 43 pmol/l) and in a 4 h euglycemic (5.5 +/- 0.5 mmol/l), hyperinsulinemic (468 +/- 36 pmol/l) insulin clamp in combination with indirect calorimetry and [3H]-3-glucose. Six non-diabetic subjects were studied during euglycemia (5.1 +/- 0.2 mmol/l) and hyperinsulinemia (474 +/- 35 pmol/l) and served as controls. In NIDDM patients the rate of insulin-stimulated glucose disposal was 57% greater during hyperglycemia compared with euglycemia throughout the 4 h clamp (p less than 0.01). The major part of the increase in glucose metabolism during hyperglycemia was due to an increase in the non-oxidative glucose metabolism (89%). Whereas glucose metabolism could not be normalized during the prolonged euglycemic hyperinsulinemic clamp in NIDDM patients (49.9 +/- 6.8 vs 57.5 +/- 5.4 mumol.(kgLBM)-1.min-1 in controls) the addition of hyperglycemia resulted in complete normalization of the glucose disposal rates (78.3 +/- 5.8 mumol.(kgLBM)-1.min-1). The effect of hyperglycemia was apparent already at 60 min of the clamp. The data thus suggest that glucose metabolism in NIDDM is insulin resistant, but that the defect in insulin-stimulated glucose uptake can be overcome by increasing the glucose concentration.
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Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Hiperglucemia/fisiopatología , Hiperinsulinismo/fisiopatología , Anciano , Índice de Masa Corporal , Calorimetría , Colesterol/sangre , Humanos , Hiperglucemia/genética , Hiperglucemia/metabolismo , Hiperinsulinismo/sangre , Hiperinsulinismo/metabolismo , Insulina/farmacología , Persona de Mediana Edad , Oxidación-Reducción , Radioinmunoensayo , Factores de Tiempo , Triglicéridos/sangreRESUMEN
OBJECTIVE: To compare the effect of morning and bedtime NPH insulin combined with daytime sulfonylurea on glycemic control in non-insulin-dependent diabetes mellitus (NIDDM) patients no longer responding to treatment with sulfonylureas alone. RESEARCH DESIGN AND METHODS: Twenty-four NIDDM patients who fulfilled these criteria were randomized to treatment with Protaphan human insulin in the morning or at bedtime (22 +/- 1 IU) plus 3.5 mg glibenclamide twice a day. RESULTS: Morning and bedtime NPH insulin resulted in equal reduction of HbA1 (from 13.5 +/- 0.3 to 9.4 +/- 0.1 and 9.6 +/- 0.2%, respectively) and mean self-monitored blood glucose (9.2 +/- 0.5 vs. 10.1 +/- 0.4 mM). Bedtime insulin resulted in lower morning blood glucose (7.8 +/- 0.5 vs. 9.1 +/- 0.4 mM; P less than 0.01), whereas morning insulin resulted in lower evening blood glucose (10.1 +/- 0.6 vs 12.1 +/- 0.6 mM, P less than 0.01). CONCLUSIONS: Morning and bedtime NPH insulin combined with glibenclamide are equipotent in the treatment of NIDDM patients with secondary failure to sulfonylurea. However, this treatment regimen normalizes blood glucose only in a small group of patients. Therefore, more intensified insulin therapy seems to be required to achieve this goal.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliburida/administración & dosificación , Insulina Isófana/administración & dosificación , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Distribución Aleatoria , Factores de TiempoRESUMEN
Weight reduction improves glucose utilization, but it is not known whether this occurs primarily through the oxidative or nonoxidative pathways of glucose metabolism. We studied this question in 12 obese subjects [whose body mass index (BMI) was 33.4 +/- 1.1 kg/m2)] before and after 6 wk on a very-low-calorie diet of 1680 kJ/d with the euglycemic insulin clamp technique in combination with indirect calorimetry. The mean body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001). This was mainly due to a reduction in fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001), whereas lean body mass decreased only slightly (from 58.0 +/- 2.0 to 56.4 +/- 1.8 kg). The basal energy expenditure decreased with weight loss by 10.7%. This was associated with a reduced rate of lipid oxidation (P less than 0.05). Weight loss increased glucose utilization by 26%, primarily by enhancing insulin-stimulated glucose oxidation (P less than 0.05), whereas the effect on nonoxidative glucose metabolism was less pronounced (P greater than 0.05). Substantial weight loss increases glucose utilization by enhancing glucose oxidation.
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Dieta Reductora , Ingestión de Energía/fisiología , Metabolismo Energético , Glucosa/metabolismo , Obesidad/dietoterapia , Adulto , Humanos , Insulina/metabolismo , Metabolismo de los Lípidos , Persona de Mediana Edad , Obesidad/metabolismo , Oxidación-ReducciónRESUMEN
To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity we studied 12 obese subjects (body mass index 33.4 +/- 1.1) before and after 6 wk of a very-low-calorie diet (VLCD) with euglycemic insulin clamp in combination with indirect calorimetry. Body weight decreased from 105.3 +/- 4.6 to 94.1 +/- 4.0 kg (P less than 0.001) and fat mass from 47.2 +/- 3.6 to 37.7 +/- 3.0 kg (P less than 0.001). Total glucose disposal during insulin clamp increased from 30.4 +/- 4.3 to 38.4 +/- 4.4 mumol.kg lean body mass (LBM)-1.min-1 (P less than 0.05), insulin-stimulated glucose oxidation from 14.3 +/- 4.6 to 19.1 +/- 1.4 mumol.kg LBM-1.min-1 (P less than 0.05), and non-oxidative glucose metabolism from 16.0 +/- 3.8 to 19.3 +/- 3.6 mumol.kg LBM-1.min-1 (NS). Lipid oxidation decreased in the basal state (P less than 0.05) and during the insulin clamp (P less than 0.01). The basal rate of energy expenditure decreased from 99.1 +/- 4.6 to 88.5 +/- 2.7 kJ.kg LBM-1.min-1 (P less than 0.05) after weight reduction. A reduction in fat mass achieved by VLCD is associated with reduced lipid oxidation and, because of substrate competition, enhanced glucose oxidation. The physiological consequence is improved insulin sensitivity.
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Peso Corporal , Metabolismo Energético , Insulina/farmacología , Obesidad/metabolismo , Adulto , Glucemia/análisis , Dieta Reductora , Ayuno , Femenino , Glucosa/metabolismo , Humanos , Metabolismo de los Lípidos , Masculino , Obesidad/patología , Oxidación-ReducciónRESUMEN
To examine insulin sensitivity and the relative contribution of different fuels to energy metabolism in anorexia nervosa and obesity, we measured oxidation (indirect calorimetry) of glucose, lipids, and proteins in the basal state and during an insulin clamp (+45 mU/m2.min) in 11 women with anorexia nervosa (age, 25 +/- 3 years; body mass index [BMI], 13.6 +/- 0.4 kg/m2; fat mass, 15.7% +/- 1.6%), eight obese women (age, 31 +/- 3; BMI 36.0 +/- 1.5; fat mass, 47.1% +/- 1.9%), and eight controls (age, 26 +/- 3; BMI, 21.8 +/- 0.9; fat mass, 25.7% +/- 3.6%). Expressed per lean body mass, (LBM), glucose disposal was equally reduced in anorectics (7.53 +/- 0.62 mg/kg LBM.min) and obese (6.80 +/- 1.07 mg/kg LBM.min) compared with controls (10.64 +/- 0.69 mg/kg LBM.min; P less than .01). The reduction in glucose disposal in anorectics was primarily due to a significant (P less than .01) reduction in glucose storage, while glucose oxidation was normal. In obese women, both storage and oxidation of glucose were reduced compared with controls (P less than .01). Basal energy expenditure was similar in anorectic, obese, and control subjects (20.6 +/- 1.00, 23.7 +/- 0.56, 23.2 +/- 1.36 cal/kg LBM.min, respectively). However, the contribution of glucose, lipids, and proteins to basal energy expenditure differed between anorectic (62%, 16%, 22%), obese (26%, 58%, 16%), and control (30%, 54%, 16%) subjects (P less than .05 v all). In conclusion, in anorexia nervosa, insulin stimulates glucose oxidation more than storage. In obesity, both components of insulin-stimulated glucose metabolism are impaired.(ABSTRACT TRUNCATED AT 250 WORDS)