RESUMEN
OBJECTIVE: To evaluate whether the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS: EMPA treatment resulted in a placebo-corrected absolute change of -1.8% (95% CI -3.4, -0.2; P = 0.02) and relative change in LFC of -22% (-36, -7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change -2.5 kg [-3.7, -1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (-74 mol/L [-108, -42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS: EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.
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Tejido Adiposo/efectos de los fármacos , Adiposidad/efectos de los fármacos , Compuestos de Bencidrilo/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/uso terapéutico , Hígado/efectos de los fármacos , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Anciano , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Método Doble Ciego , Regulación hacia Abajo/efectos de los fármacos , Femenino , Alemania , Humanos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Placebos , Pérdida de Peso/efectos de los fármacosRESUMEN
OBJECTIVE: Overfeeding with a high-fat and/or high-carbohydrate (CHO) diet is known to increase plasma concentrations of endotoxin (lipopolysaccharide [LPS]) that may lead to metabolic disturbances like insulin resistance. The impact of CHO quality (i.e., the glycemic index [GI]) independent of fat intake on metabolic endotoxemia remains unclear. In the present study, the effects of changes in energy balance and GI on plasma endotoxin were studied. METHODS: Fifteen healthy young men overconsumed diets containing 65% CHO and 20% fat for 1 week (OF; +50% of energy requirement) followed by 3 weeks of caloric restriction (CR; -50% of energy requirement) and were then randomized to 2 weeks hypercaloric refeeding (RF, +50% of energy requirement) with either a low- or high-GI (40 vs 74) diet. RESULTS: During OF, subjects gained 1.9 ± 0.7 kg body weight (+0.6 ± 0.8% fat mass) followed by a weight loss of 6.1 ± 0.8 kg (-2.0 ± 0.6% fat mass) and weight regain of 4.0 ± 0.6 kg (0.9 ± 0.8% fat mass). Fasting insulin and homeostasis model assessment-insulin resistance (HOMAIR) increased with OF and RF and decreased with CR, MatsudaISI decreased by 37% after RF (all p < 0.05). Endotoxin significantly increased by 30.8% with OF and by 24.7% with RF (both p < 0.05), whereas CR normalized endotoxin levels. No difference in endotoxin levels was observed between refeeding a hypercaloric high- or low-GI diet. Changes in endotoxin levels with RF were not related to changes in insulin sensitivity. CONCLUSION: A hypercaloric diet (OF and RF) increased plasma endotoxin irrespective of GI, whereas a negative energy balance did not reduce endotoxemia. Impaired insulin sensitivity with hypercaloric refeeding on a high-GI diet was not explained by metabolic endotoxemia.
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Endotoxemia , Metabolismo Energético/fisiología , Índice Glucémico/fisiología , Adulto , Índice de Masa Corporal , Peso Corporal , Restricción Calórica , Dieta , Endotoxinas/sangre , Ingestión de Energía , Humanos , Hiperfagia , Resistencia a la Insulina , Lípidos/sangre , MasculinoRESUMEN
BACKGROUND: Adaptive thermogenesis (AT) is the fat-free mass (FFM)-independent reduction of resting energy expenditure (REE) to caloric restriction (CR). AT attenuates weight loss and favors weight regain. Its variance, dynamics, and control remain obscure. OBJECTIVES: Our aims were to address the variance and kinetics of AT, its associations with body composition in the context of endocrine determinants, and its effect on weight regain. DESIGN: Thirty-two nonobese men underwent sequential overfeeding (1 wk at +50% of energy needs), CR (3 wk at -50% of energy needs), and refeeding (2 wk at +50% of energy needs). AT and its determinants were measured together with body composition as assessed with the use of quantitative magnetic resonance, whole-body MRI, isotope dilution, and nitrogen and fluid balances. RESULTS: Changes in body weight were +1.8 kg (overfeeding), -6.0 kg (CR), and +3.5 kg (refeeding). CR reduced fat mass and FFM by 114 and 159 g/d, respectively. Within FFM, skeletal muscle (-5%), liver (-13%), and kidneys (-8%) decreased. CR also led to reductions in REE (-266 kcal/d), respiratory quotient (-15%), heart rate (-14%), blood pressure (-7%), creatinine clearance (-12%), energy cost of walking (-22%), activity of the sympathetic nervous system (SNS) (-38%), and plasma leptin (-44%), insulin (-54%), adiponectin (-49%), 3,5,3'-tri-iodo-thyronine (T3) (-39%), and testosterone (-11%). AT was 108 kcal/d or 48% of the decrease in REE. Changes in FFM composition explained 36 kcal, which left 72 kcal/d for true AT. The decrease in AT became significant at ≤3 d of CR and was related to decreases in insulin secretion (r = 0.92, P < 0.001), heart rate (r = 0.60, P < 0.05), creatinine clearance (r = 0.79, P < 0.05), negative fluid balance (r = 0.51, P < 0.01), and the free water clearance rate (r = -0.90, P < 0.002). SNS activity and plasma leptin, ghrelin, and T3 and their changes with CR were not related to AT. CONCLUSION: During early weight loss, AT is associated with a fall in insulin secretion and body fluid balance. This trial was registered at clinicaltrials.gov as NCT01737034.
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Adaptación Fisiológica , Restricción Calórica , Inanición/metabolismo , Adiponectina/sangre , Adulto , Metabolismo Basal , Composición Corporal , Índice de Masa Corporal , Peso Corporal , Péptido C/sangre , Creatinina/sangre , Metabolismo Energético , Ghrelina/sangre , Frecuencia Cardíaca , Humanos , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Leptina/sangre , Masculino , Minnesota , Testosterona/sangre , Termogénesis , Triyodotironina/sangre , Adulto JovenRESUMEN
OBJECTIVE: Changes in insulin sensitivity (IS) and insulin secretion occur with perturbations in energy balance and glycemic load (GL) of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear. METHODS: In a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2) followed 1wk of overfeeding (OF), 3wks of caloric restriction (CR) containing either 50% or 65% carbohydrate (CHO) and 2wks of refeeding (RF) with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI), insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose) and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion) were assessed. RESULTS: IS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05). Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05) whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05) and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only). After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant. CONCLUSION: Weight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and ghrelin seem to be the major endocrine determinants of IS, leptin/adiponectin-ratio and fT4 levels may impact changes in insulin secretion with weight cycling. TRIAL REGISTRATION: ClinicalTrials.gov NCT01737034.
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Peso Corporal , Resistencia a la Insulina , Insulina/metabolismo , Adulto , Glucemia , Composición Corporal , Dieta , Ayuno , Prueba de Tolerancia a la Glucosa , Humanos , Secreción de Insulina , Masculino , Distribución Aleatoria , Adulto JovenRESUMEN
Caloric restriction and intermittent fasting are known to improve glucose homeostasis and insulin resistance in several species including humans. The aim of this study was to unravel potential mechanisms by which these interventions improve insulin sensitivity and protect from type 2 diabetes. Diabetes-susceptible New Zealand Obese mice were either 10% calorie restricted (CR) or fasted every other day (IF), and compared to ad libitum (AL) fed control mice. AL mice showed a diabetes prevalence of 43%, whereas mice under CR and IF were completely protected against hyperglycemia. Proteomic analysis of hepatic lipid droplets revealed significantly higher levels of PSMD9 (co-activator Bridge-1), MIF (macrophage migration inhibitor factor), TCEB2 (transcription elongation factor B (SIII), polypeptide 2), ACY1 (aminoacylase 1) and FABP5 (fatty acid binding protein 5), and a marked reduction of GSTA3 (glutathione S-transferase alpha 3) in samples of CR and IF mice. In addition, accumulation of diacylglycerols (DAGs) was significantly reduced in livers of IF mice (P=0.045) while CR mice showed a similar tendency (P=0.062). In particular, 9 DAG species were significantly reduced in response to IF, of which DAG-40:4 and DAG-40:7 also showed significant effects after CR. This was associated with a decreased PKCε activation and might explain the improved insulin sensitivity. In conclusion, our data indicate that protection against diabetes upon caloric restriction and intermittent fasting associates with a modulation of lipid droplet protein composition and reduction of intracellular DAG species.
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Restricción Calórica , Diabetes Mellitus Tipo 2/prevención & control , Diglicéridos/metabolismo , Ayuno , Privación de Alimentos , Gotas Lipídicas/metabolismo , Hígado/metabolismo , Obesidad/dietoterapia , Proteoma/metabolismo , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Modelos Animales de Enfermedad , Ácidos Grasos/metabolismo , Insulina/sangre , Resistencia a la Insulina , Masculino , Ratones Obesos , Músculo Esquelético/metabolismo , Obesidad/sangre , Obesidad/complicaciones , Oxidación-Reducción , Proteína Quinasa C-epsilon/metabolismo , Factores de TiempoRESUMEN
The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1(liv-/-)) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1(liv-/-) mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1(liv-/-) liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles.
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Factores de Ribosilacion-ADP/fisiología , Lipoproteínas VLDL/metabolismo , Hígado/metabolismo , Procesamiento Proteico-Postraduccional , Red trans-Golgi/enzimología , Red trans-Golgi/metabolismo , Animales , Apolipoproteína A-I/metabolismo , Retículo Endoplásmico , Lipogénesis , Lipoproteínas HDL/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Triglicéridos/metabolismoRESUMEN
In this controlled, parallel-group feeding trial, we examined the impact of carbohydrate (CHO) intake and glycemic index (GI) on glucose and lipid metabolism during refeeding after weight loss. Healthy men (n = 32 total, age: 25.5 ± 3.9 y, BMI: 23.5 ± 2.0 kg/m2) overconsumed diets containing either 50% or 65% CHO for 1 wk (+50% of energy requirements) and then underwent 3 wk of calorie restriction (CR; -50%) followed by 2 wk of overconsuming (refeeding, +50%) the same diet but with either a low or high GI (40 vs.70 during CR, 41 vs.74 during refeeding) so that glycemic load (GL; dietary CHO content x GI) differed between groups during all phases. Glucose profiles were assessed by continuous interstitial glucose monitoring, insulin sensitivity (IS) by fasting blood sampling, oral glucose tolerance test (OGTT) and hyperinsulinemic-euglycemic clamp, and liver fat by MRI. Daytime area under the curve-glucose during refeeding was higher with high compared with low GI (P = 0.01) and 65% compared with 50% CHO intake (P = 0.05) and correlated with dietary GL (r = 0.71; P < 0.001). IS increased with CR and decreased again with refeeding in all groups. The decrease in OGTT-derived IS was greater with high- than with low-GI diets (-41 vs. -15%; P-interaction = 0.01) and correlated with dietary GL during refeeding (r = -0.51; P < 0.01). Serum triglycerides (TGs) and liver fat also improved with CR (-17 ± 38 mg/dL and -1.1 ± 1.3%; P < 0.05 and <0.001) and increased again with refeeding (+48 ± 48 mg/dL and +2.2 ± 1.6%; P < 0.001). After refeeding, serum TGs and liver fat were elevated above baseline values with 65% CHO intake only (+59.9 ± 37.5 mg/dL and +1.1 ± 1.7%, P-interaction <0.001 and <0.05). In conclusion, a diet low in GI and moderate in CHO content (i.e., low GL) may have health benefits by positively affecting daylong glycemia, IS, and liver fat.
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Glucemia/metabolismo , Restricción Calórica , Carbohidratos de la Dieta/farmacología , Índice Glucémico , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Aumento de Peso , Adulto , Índice de Masa Corporal , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/normas , Prueba de Tolerancia a la Glucosa , Humanos , Hiperfagia , Hígado/metabolismo , Masculino , Triglicéridos/sangre , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
Previous studies suggest that a low-glycaemic index (LGI) diet may improve insulin sensitivity (IS). As IS has been shown to decrease during refeeding, we hypothesised that an LGI- v. high-GI (HGI) diet might have favourable effects during this phase. In a controlled nutritional intervention study, sixteen healthy men (aged 26·8 (SD 4·1) years, BMI 23·0 (SD 1·7) kg/m2) followed 1 week of overfeeding, 3 weeks of energy restriction and of 2 weeks refeeding at ^50% energy requirement (50% carbohydrates, 35% fat and 15% protein). During refeeding, subjects were divided into two matched groups receiving either high-fibre LGI or lower-fibre HGI foods (GI 40 v. 74, fibre intake 65 (SD 6) v. 27 (SD 4) g/d). Body weight was equally regained in both groups with refeeding (mean regain 70·5 (SD 28·0)% of loss). IS was improved by energy restriction and decreased with refeeding. The decreases in IS were greater in the HGI than in the LGIgroup (group £ time interactions for insulin, homeostasis model assessment of insulin resistance (HOMAIR), Matsuda IS index (MatsudaISI);all P,0·05). Mean interstitial glucose profiles during the day were also higher in the HGI group (DAUCHGI-LGI of continuous interstitial glucose monitoring: 6·6 mmol/l per 14 h, P»0·04). At the end of refeeding, parameters of IS did not differ from baseline values in either diet group (adiponectin, insulin, HOMAIR, Matsuda ISI, M-value; all P.0·05). In conclusion, nutritional stress imposed by dietary restriction and refeeding reveals a GI/fibre effect in healthy non-obese subjects. LGI foods rich in fibre may improve glucose metabolism during the vulnerable refeeding phase of a weight cycle.
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Fibras de la Dieta/administración & dosificación , Ingestión de Alimentos , Índice Glucémico , Resistencia a la Insulina , Adulto , Humanos , Masculino , Valores de Referencia , Adulto JovenRESUMEN
Balance methods reveal changes in body energy, nitrogen, macro- and micronutrients as well as fluid in response to different feeding regimens. Under metabolic ward conditions, where physical activity is restricted and activity and food intake are controlled, the errors of estimates of energy intake, energy expenditure, and energy losses are about 2, 4, and 2%, respectively. Balance techniques can be used to validate techniques of in vivo body composition analysis (BCA). This is necessary since immediate and transient changes in body composition in response to a change in diet adversely affect the validity of techniques by violating the assumptions underlying standard methods (i.e., a constant composition or hydration of lean mass). Using two compartment reference methods, like densitometry, dual X-ray absorptiometry (DXA) or deuterium dilution, changes in fat mass with caloric restriction and overfeeding can be measured with a minimal detectable change (MDC) of 1.0-2.0 kg. However, when compared against balance data, the validity of these techniques to measure short-term changes in body composition is poor. The noninvasive and rapid new quantitative magnetic resonance (QMR) technique has a high precision with a MDC of 0.18 kg of fat mass. The validity of QMR to assess short-term changes in fat mass is challenged by comparison to balance data. Today, techniques used for in vivo BCA should be related to steady state conditions only, while in the nonsteady state, the use of balance methods is recommended to assess short-term changes in body composition.
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Absorciometría de Fotón , Composición Corporal , Ingestión de Energía , Metabolismo Energético , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Dieta , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Reproducibilidad de los ResultadosRESUMEN
Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.
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Médula Ósea/patología , Resorción Ósea/complicaciones , Huesos/patología , Sobrepeso/dietoterapia , Sobrepeso/patología , Aumento de Peso , Pérdida de Peso , Absorciometría de Fotón , Tejido Adiposo Blanco/patología , Adulto , Composición Corporal , Densidad Ósea , Médula Ósea/diagnóstico por imagen , Resorción Ósea/diagnóstico por imagen , Huesos/diagnóstico por imagen , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Sobrepeso/complicaciones , Recurrencia , Caracteres Sexuales , Imagen de Cuerpo Entero , Adulto JovenRESUMEN
Pericardial adipose tissue (PAT) is positively associated with fatty liver and obesity-related insulin resistance. Because PAT is a well-known marker of visceral adiposity, we investigated the impact of weight loss on PAT and its relationship with liver fat and insulin sensitivity independently of body fat distribution. Thirty overweight nondiabetic women (BMI 28.2-46.8 kg/m(2), 22-41 years) followed a 14.2 ± 4-weeks low-calorie diet. PAT, abdominal subcutaneous (SAT), and visceral fat volumes (VAT) were measured by magnetic resonance imaging (MRI), total fat mass, trunk, and leg fat by dual-energy X-ray absorptiometry and intrahepatocellular lipids (IHCL) by ((1))H-magnetic resonance spectroscopy. Euglycemic hyperinsulinemic clamp (M) and homeostasis model assessment of insulin resistance (HOMA(IR)) were used to assess insulin sensitivity or insulin resistance. At baseline, PAT correlated with VAT (r = 0.82; P < 0.001), IHCL (r = 0.46), HOMA(IR) (r = 0.46), and M value (r = -0.40; all P < 0.05). During intervention, body weight decreased by -8.5%, accompanied by decreases of -12% PAT, -13% VAT, -44% IHCL, -10% HOMA2-%B, and +24% as well as +15% increases in HOMA2-%S and M, respectively. Decreases in PAT were only correlated with baseline PAT and the loss in VAT (r = -0.56; P < 0.01; r = 0.42; P < 0.05) but no associations with liver fat or indexes of insulin sensitivity were observed. Improvements in HOMA(IR) and HOMA2-%B were only related to the decrease in IHCL (r = 0.62, P < 0.01; r = 0.65, P = 0.002) and decreases in IHCL only correlated with the decrease in VAT (r = 0.61, P = 0.004). In conclusion, cross-sectionally PAT is correlated with VAT, liver fat, and insulin resistance. Longitudinally, the association between PAT and insulin resistance was lost suggesting no causal relationship between the two.
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Hígado Graso/metabolismo , Resistencia a la Insulina , Grasa Intraabdominal , Obesidad/patología , Pericardio/patología , Pérdida de Peso/fisiología , Adiposidad , Adulto , Estudios Transversales , Dieta Reductora , Femenino , Humanos , Metabolismo de los Lípidos , Estudios Longitudinales , Obesidad/dietoterapia , Obesidad/metabolismoRESUMEN
BACKGROUND: There is a difference between measured and predicted weight loss in obese patients. This might be explained by the composition of weight loss, adaptive thermogenesis, or poor compliance. PATIENTS AND METHODS: 48 overweight and obese female patients (31.5 +/- 6.1 years; BMI 35.4 +/- 4.4 kg/m(2)) were investigated before and 13.9 +/- 2.4 weeks after dietary treatment (1,000 kcal/day). Body composition was measured by air-displacement plethysmography and resting energy expenditure (REE) by indirect calorimetry. Physical activity was assessed using electronic pedometers in order to calculate total energy expenditure from REE and physical activity level (PAL). Fat mass (FM) and fat-free mass (FFM) were converted into caloric equivalents using 9.45 kcal/g FM and 1.13 kcal/g FFM. Predicted weight loss was calculated by Wishnofsky's '7,700 kcal/kg rule'. RESULTS: Weight (-8.4 +/- 3.9 kg; p < 0.001), FM (-7.8 +/- 3.6 kg; p < 0.001), and FFM (-0.6 +/- 2.0 kg; p < 0.05) decreased with caloric restriction. Measured weight loss was only 44% of the predicted value. Since FM contributed to 87% of weight loss, the energy deficit/kg weight loss was considerably higher (9,098 +/- 2,349 kcal/kg) than the assumed 7,700 kcal/kg. Adaptive thermogenesis after weight loss was significant in 26 of 48 women (-3.2 +/- 1.2 kcal per kg FFM; p < 0.001). CONCLUSION: 14% of the difference between measured and predicted weight loss was explained by the higher proportion of FM in weight loss and 38% by adaptive thermogenesis (in 54% of the women). Thus, poor compliance was responsible for about 50% of the difference between measured and predicted weight loss only.