RESUMEN
AIM: Heat exposure has been indicated to positively affect glucose metabolism. An involvement of heat shock protein 72 (HSP72) in the enhancement of insulin sensitivity upon heat exposure has been previously suggested. Here, we performed an intervention study exploring the effect of passive heat acclimation (PHA) on glucose metabolism and intracellular (a) HSP72 concentrations in overweight humans. METHODS: Eleven non-diabetic overweight (BMI 27-35 kg/m2 ) participants underwent 10 consecutive days of PHA (4-6 h/day, 34.4 ± 0.2°C, 22.8 ± 2.7%RH). Before and after PHA, whole-body insulin sensitivity was assessed using a one-step hyperinsulinaemic-euglycaemic clamp, skeletal muscle biopsies were taken to measure intracellular iHSP72, energy expenditure and substrate oxidation were measured using indirect calorimetry and blood samples were drawn to assess markers of metabolic health. Thermophysiological adaptations were measured during a temperature ramp protocol before and after PHA. RESULTS: Despite a lack of change in iHSP72, 10 days of PHA reduced basal (9.7 ± 1.4 pre- vs 8.4 ± 2.1 µmol · kg-1 · min-1 post-PHA, P = .038) and insulin-stimulated (2.1 ± 0.9 pre- vs 1.5 ± 0.8 µmol · kg-1 · min-1 post-PHA, P = .005) endogenous glucose production (EGP) and increased insulin suppression of EGP (78.5 ± 9.7% pre- vs 83.0 ± 7.9% post-PHA, P = .028). Consistently, fasting plasma glucose (6.0 ± 0.5 pre- vs 5.8 ± 0.4 mmol/L post-PHA, P = .013) and insulin concentrations (97 ± 55 pre- vs 84 ± 49 pmol/L post-PHA, P = .026) decreased significantly. Moreover, fat oxidation increased, and free fatty acids as well as cholesterol concentrations and mean arterial pressure decreased after PHA. CONCLUSION: Our results show that PHA for 10 days improves glucose metabolism and enhances fat metabolism, without changes in iHSP72. Further exploration of the therapeutic role of heat in cardio-metabolic disorders should be considered.
Asunto(s)
Glucosa/metabolismo , Hipertermia Inducida , Resistencia a la Insulina , Anciano , Glucemia , Diabetes Mellitus Tipo 2 , Técnica de Clampeo de la Glucosa , Humanos , Insulina , Persona de Mediana Edad , SobrepesoRESUMEN
BACKGROUND: Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting. PURPOSE: This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance. DATA SOURCES AND STUDY SELECTION: PubMed, Web of Science, Embase, CINAHL, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) from 1980 until 31 December 2018 reporting treatment effects of vitamin D supplementation on insulin sensitivity. DATA EXTRACTION: The main outcome of interest was the change in insulin sensitivity, derived from the gold standard hyperinsulinemic-euglycemic clamp or the Matsuda index derived from the oral glucose tolerance test and insulin sensitivity index from intravenous glucose tolerance test. We extracted data on the standardized mean difference between the vitamin D treatment and placebo groups in change from baseline insulin sensitivity. DATA SYNTHESIS: Eighteen RCTs were included in this meta-analysis comparing vitamin D supplementation (n = 612) with placebo (n = 608). Vitamin D supplementation had no effect on insulin sensitivity (standardized mean difference -0.01, 95% CI -0.12, 0.10; P = 0.87, I 2 = 0%). Visual inspection of funnel plot symmetry did not suggest potential publication bias. LIMITATIONS: The number of individuals who participated in the included studies was relatively small, possibly due to the invasive character of the measurement (e.g., clamp). CONCLUSIONS: This meta-analysis provides no evidence that vitamin D supplementation has a beneficial effect on peripheral insulin sensitivity in people with or at risk for insulin resistance.
Asunto(s)
Resistencia a la Insulina , Deficiencia de Vitamina D/dietoterapia , Vitamina D/administración & dosificación , Adolescente , Adulto , Anciano , Suplementos Dietéticos , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/metabolismo , Secreción de Insulina/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/fisiología , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Vitamina D/farmacología , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/metabolismo , Adulto JovenRESUMEN
Endothelial dysfunction (ED) and low-grade inflammation (LGI) have a role in the development of CVD. The two studies reported here explored the effects of dietary proteins and carbohydrates on markers of ED and LGI in overweight/obese individuals with untreated elevated blood pressure. In the first study, fifty-two participants consumed a protein mix or maltodextrin (3×20 g/d) for 4 weeks. Fasting levels and 12 h postprandial responses of markers of ED (soluble intercellular adhesion molecule 1 (sICAM), soluble vascular cell adhesion molecule 1 (sVCAM), soluble endothelial selectin and von Willebrand factor) and markers of LGI (serum amyloid A, C-reactive protein and sICAM) were evaluated before and after intervention. Biomarkers were also combined into mean Z-scores of ED and LGI. The second study compared 4 h postprandial responses of ED and LGI markers in forty-eight participants after ingestion of 0·6 g/kg pea protein, milk protein and egg-white protein. In addition, postprandial responses after maltodextrin intake were compared with a protein mix and sucrose. The first study showed significantly lower fasting ED Z-scores and sICAM after 4 weeks on the high-protein diet (P≤0·02). The postprandial studies found no clear differences of ED and LGI between test meals. However, postprandial sVCAM decreased more after the protein mix compared with maltodextrin in both studies (P≤0·04). In conclusion, dietary protein is beneficial for fasting ED, but not for fasting LGI, after 4 weeks of supplementation. On the basis of Z-scores, postprandial ED and LGI were not differentially affected by protein sources or carbohydrates.
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Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Endotelio Vascular/fisiopatología , Obesidad/dietoterapia , Sobrepeso/dietoterapia , Prehipertensión/prevención & control , Vasculitis/prevención & control , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Cruzados , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/efectos adversos , Proteínas en la Dieta/efectos adversos , Suplementos Dietéticos/efectos adversos , Endotelio Vascular/inmunología , Ayuno , Femenino , Humanos , Mediadores de Inflamación/sangre , Masculino , Obesidad/sangre , Obesidad/inmunología , Obesidad/fisiopatología , Sobrepeso/sangre , Sobrepeso/inmunología , Sobrepeso/fisiopatología , Polisacáridos/administración & dosificación , Polisacáridos/efectos adversos , Periodo Posprandial , Prehipertensión/etiología , Factores de Tiempo , Vasculitis/etiologíaRESUMEN
The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling.
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Ritmo Circadiano/genética , Ingestión de Alimentos/genética , Predisposición Genética a la Enfermedad , Variación Genética , Hipotálamo/metabolismo , Obesidad Mórbida/genética , Transducción de Señal/genética , Adulto , Alelos , Femenino , Estudios de Asociación Genética , Humanos , Mutación INDEL/genética , Masculino , Polimorfismo de Nucleótido Simple/genética , Adulto JovenRESUMEN
BACKGROUND: Dietary protein intake may help to manage blood pressure (BP) and prevent complications associated with elevated BP. OBJECTIVE: The objective of this study was to determine whether 4 wk of increased protein intake (â¼25% compared with â¼15% of energy intake that isoenergetically replaces carbohydrate intake) lowers office and daytime BP compared with increased carbohydrate intake. DESIGN: A randomized, double-blind, parallel study compared consumption of 3 × 20 g protein/d (20% pea, 20% soy, 30% egg, and 30% milk-protein isolate) with 3 × 20 g maltodextrin/d. Protein or maltodextrin were isoenergetically substituted for a sugar-sweetened drink. Primary outcomes were office and daytime BP. A total of 99 men and women [age range: 20-70 y; BMI (in kg/m²): 25-35] with untreated elevated BP (BP ≥130/85 and <160/100 mm Hg) were randomly assigned. Ninety-four completers (51 subjects in the maltodextrin group, 43 subjects in the protein group) were included in the analyses. RESULTS: Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 4.9 ± 1.7 mm Hg (P = 0.005) and 2.7 ± 1.3 mm Hg (P = 0.05) lower, respectively, in the protein group. Daytime SBP was 4.6 ± 1.7 mm Hg lower in the protein group (P = 0.006), whereas daytime DBP did not differ between groups (P = 0.37). Urinary sodium excretion was higher in the maltodextrin group (P = 0.004). CONCLUSION: Increased protein intake, at the expense of maltodextrin, lowers BP in overweight adults with upper-range prehypertension and grade 1 hypertension. This trial was registered at www.trialregister.nl as NTR 1362.