Inverse association between diabetes and altitude: a cross-sectional study in the adult population of the United States.

ObjectiveTo determine whether geographical elevation is inversely associated with diabetes, while adjusting for multiple risk factors.MethodsThis is a cross-sectional analysis of publicly available online data from the Behavioral Risk Factor Surveillance System, 2009. Final dataset included 285,196 US adult subjects. Odds ratios were obtained from multilevel mixed-effects logistic regression analysis.ResultsAmong US adults (≥20 years old), the odds ratio for diabetes was 1.00 between 0 and 499 m of altitude (reference), 0.95 (95% confidence interval, 0.90-1.01) between 500 and 1,499 m, and 0.88 (0.81-0.96) between 1,500 and 3,500 m, adjusting for age, sex, body mass index, ethnicity, self-reported fruit and vegetable consumption, self-reported physical activity, current smoking status, level of education, income, health status, employment status, and county-level information on migration rate, urbanization, and latitude. The inverse association between altitude and diabetes in the US was found among men [0.84 (0.76-0.94)], but not women [1.09 (0.97-1.22)].ConclusionsAmong US adults, living at high altitude (1,500-3,500 m) is associated with lower odds of having diabetes than living between 0 and 499 m, while adjusting for multiple risk factors. Our findings suggest that geographical elevation may be an important factor linked to diabetes

Healthy males’ antioxidant system response in induced acute hyperglycemia

Objetivo: determinar la respuesta del sistema antioxidante en varones sanos, frente a la hiperglicemia aguda inducida. Diseño: estudio prospectivo, descriptivo, longitudinal, experimental. Lugar: Instituto Nacional de Biología Andina, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Sangre y suero de sujetos aparentemente sanos. Intervenciones: A 13 sujetos adultos clínicamente sanos, entre 20 y 41años, después de 10 horas de ayuno, se administró glucosa vía endovenosa, mediante el método de clamp hiperglicémico, a 125 mg/dL por encima del valor basal, durante 120 minutos. Se realizó mediciones de la glicemia a 0, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110 y 120 minutos. Se tomó la muestra sanguínea con anticoagulante EDTA y otra de sangre total, para obtención de suero, para las pruebas bioquímicas a los 0, 60 y 120 minutos. Principales medidas de resultados: Modificaciones de la glicemia y lipoperoxidación en suero, glutatión y actividad superóxido dismutasa en glóbulos rojos lisados e índices de estrés oxidativo. Resultados: El nivel de glucosa durante el clamp hiperglicémico, luego de alcanzar el ‘equilibrio’, fue 197±17,58 mg/dL. La lipoperoxidación aumentó de 2,54 + 0,51 a 2,90 + 0,58 umol/L, de 0 a 60 minutos, y a 2,66 + 0,55 umol/L a los 120 minutos. El glutatión se redujo en 8,10% a la hora, aumentando 7,08% a los 120 minutos. La actividad superóxido dismutasa se elevó 0,54% a los 60 minutos y 5,66% a los 120 minutos, sobre el basal. Los índices de valoración del estrés oxidativo tuvieron correlación r Pearson positiva, en nivel alto a muy alto. Conclusiones: la hiperglicemia aguda inducida hasta 2 horas elevó el estrés oxidativo, promoviendo generación de defensa antioxidante, con síntesis de glutatión reducido de novo y mayor actividad de la superóxido dismutasa.Objective: To determine healthy males’ antioxidant system response in induced acute hyperglycemia. Design: Prospective, descriptive, longitudinal, experimental study. Setting: National Institute of Andean Biology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological materials: Whole blood and serum of apparently healthy men. Interventions: After 10 hour fasting, intravenous glucose was administered to thirteen healthy 20-41 year-old adult men using the hyperglycemic clamp method at 125 mg/dL above basal value during 120 minutes. Glycemia was measured at 0, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 minutes. Blood sampling was obtained with EDTA anticoagulant and whole blood to obtain blood serum for biochemistry tests at 0, 60 and 120 minutes. Main outcome measures: Blood serum glycemia and lipoperoxidation variation, glutathione and superoxide dismutase activity in lysed red blood cells and oxidative stress index. Results: After achieving ‘balance’, glucose levels during hyperglycemic clamp was 197 ± 17,58 mg/dL. Lipoperoxidation increased from 2,54 + 0,51 to 2,90 + 0,58umol/L, from 0 to 60 minutes, and to 2,66 + 0,55 umol/L at 120 minutes. Glutathione was reduced in 8,10% at one hour, rising 7,08% at 120 minutes. Superoxide dismutase activity rose above basal 0,54% at 60 min and 5,66% at 120 min. Oxidative stress valuation index had high level to very high level positive Pearson r correlation. Conclusions: Acute induced hyperglycemia up to 2 hours increased oxidative stress, promoting generation of antioxidant defence with de novo synthesis of reduced glutathione and greater activity of superoxide dismutase

Temporal trends in obesity defined by the relative fat mass (RFM) index among adults in the United States from 1999 to 2020: a population-based study

Objectives The body mass index (BMI) largely underestimates excess body fat, suggesting that the prevalence of obesity could be underestimated. Biologically, women are known to have higher body fat than men. This study aimed to compare the temporal trends in general obesity by sex, ethnicity and age among adults in the USA using the relative fat mass (RFM), a validated surrogate for whole-body fat percentage and BMI.Design Population-based study.Setting US National Health and Nutrition Examination Survey, from 1999–2000 to 2017–March 2020.Participants A representative sample of adults 20–79 years in the USA.Main outcome measures Age-adjusted prevalence of general obesity. RFM-defined obesity was diagnosed using validated cut-offs to predict all-cause mortality: RFM≥40% for women and ≥30% for men. BMI-defined obesity was diagnosed using a cut-off of 30 kg/m2.Results Analysis included data from 47 667 adults. Among women, RFM-defined obesity prevalence was 64.7% (95% CI 62.1% to 67.3%) in 2017–2020, a linear increase of 13.9 percentage points (95% CI 9.0% to 18.9%; p<0.001) relative to 1999–2000. In contrast, the prevalence of BMI-defined obesity was 42.2% (95% CI 39.4% to 45.0%) in 2017–2020. Among men, the corresponding RFM-defined obesity prevalence was 45.8% (95% CI 42.0% to 49.7%), a linear increase of 12.0 percentage points (95% CI 6.6% to 17.3%; p<0.001). In contrast, the prevalence of BMI-defined obesity was 42.0 (95% CI 37.8% to 46.3%). The highest prevalence of RFM-defined obesity across years was observed in older adults (60–79 years) and Mexican Americans, in women and men. Conversely, the highest prevalence of BMI-defined obesity across years was observed in middle-age (40–59 years) and older adults, and in African American women.Conclusions The use of a surrogate for whole-body fat percentage revealed a much higher prevalence of general obesity in the USA from 1999 to 2020, particularly among women, than that estimated using BMI, and detected a disproportionate higher prevalence of general obesity in older adults and Mexican Americans

Renal Denervation Reverses Hepatic Insulin Resistance Induced by High-Fat Diet.

Activation of the sympathetic nervous system (SNS) constitutes a putative mechanism of obesity-induced insulin resistance. Thus, we hypothesized that inhibiting the SNS by using renal denervation (RDN) will improve insulin sensitivity (SI) in a nonhypertensive obese canine model. SI was measured using euglycemic-hyperinsulinemic clamp (EGC), before (week 0 [w0]) and after 6 weeks of high-fat diet (w6-HFD) feeding and after either RDN (HFD + RDN) or sham surgery (HFD + sham). As expected, HFD induced insulin resistance in the liver (sham 2.5 ± 0.6 vs. 0.7 ± 0.6 × 10-4 dL ⋅ kg-1 ⋅ min-1 ⋅ pmol/L-1 at w0 vs. w6-HFD [P < 0.05], respectively; HFD + RDN 1.6 ± 0.3 vs. 0.5 ± 0.3 × 10-4 dL ⋅ kg-1 ⋅ min-1 ⋅ pmol/L-1 at w0 vs. w6-HFD [P < 0.001], respectively). In sham animals, this insulin resistance persisted, yet RDN completely normalized hepatic SI in HFD-fed animals (1.8 ± 0.3 × 10-4 dL ⋅ kg-1 ⋅ min-1 ⋅ pmol/L-1 at HFD + RDN [P < 0.001] vs. w6-HFD, [P not significant] vs. w0) by reducing hepatic gluconeogenic genes, including G6Pase, PEPCK, and FOXO1. The data suggest that RDN downregulated hepatic gluconeogenesis primarily by upregulating liver X receptor α through the natriuretic peptide pathway. In conclusion, bilateral RDN completely normalizes hepatic SI in obese canines. These preclinical data implicate a novel mechanistic role for the renal nerves in the regulation of insulin action specifically at the level of the liver and show that the renal nerves constitute a new therapeutic target to counteract insulin resistance

Renal Denervation Reverses Hepatic Insulin Resistance Induced by High-Fat Diet.

Activation of the sympathetic nervous system (SNS) constitutes a putative mechanism of obesity-induced insulin resistance. Thus, we hypothesized that inhibiting the SNS by using renal denervation (RDN) will improve insulin sensitivity (SI) in a nonhypertensive obese canine model. SI was measured using euglycemic-hyperinsulinemic clamp (EGC), before (week 0 [w0]) and after 6 weeks of high-fat diet (w6-HFD) feeding and after either RDN (HFD + RDN) or sham surgery (HFD + sham). As expected, HFD induced insulin resistance in the liver (sham 2.5 ± 0.6 vs. 0.7 ± 0.6 × 10-4 dL ⋅ kg-1 ⋅ min-1 ⋅ pmol/L-1 at w0 vs. w6-HFD [P < 0.05], respectively; HFD + RDN 1.6 ± 0.3 vs. 0.5 ± 0.3 × 10-4 dL ⋅ kg-1 ⋅ min-1 ⋅ pmol/L-1 at w0 vs. w6-HFD [P < 0.001], respectively). In sham animals, this insulin resistance persisted, yet RDN completely normalized hepatic SI in HFD-fed animals (1.8 ± 0.3 × 10-4 dL ⋅ kg-1 ⋅ min-1 ⋅ pmol/L-1 at HFD + RDN [P < 0.001] vs. w6-HFD, [P not significant] vs. w0) by reducing hepatic gluconeogenic genes, including G6Pase, PEPCK, and FOXO1. The data suggest that RDN downregulated hepatic gluconeogenesis primarily by upregulating liver X receptor α through the natriuretic peptide pathway. In conclusion, bilateral RDN completely normalizes hepatic SI in obese canines. These preclinical data implicate a novel mechanistic role for the renal nerves in the regulation of insulin action specifically at the level of the liver and show that the renal nerves constitute a new therapeutic target to counteract insulin resistance

Renal Denervation Reverses Hepatic Insulin Resistance Induced by High-Fat Diet

Activation of the sympathetic nervous system (SNS) constitutes a putative mechanism of obesity-induced insulin resistance. Thus, we hypothesized that inhibiting the SNS by using renal denervation (RDN) will improve insulin sensitivity (S(I)) in a nonhypertensive obese canine model. S(I) was measured using euglycemic-hyperinsulinemic clamp (EGC), before (week 0 [w0]) and after 6 weeks of high-fat diet (w6-HFD) feeding and after either RDN (HFD + RDN) or sham surgery (HFD + sham). As expected, HFD induced insulin resistance in the liver (sham 2.5 ± 0.6 vs. 0.7 ± 0.6 × 10(−4) dL ⋅ kg(−1) ⋅ min(−1) ⋅ pmol/L(−)(1) at w0 vs. w6-HFD [P < 0.05], respectively; HFD + RDN 1.6 ± 0.3 vs. 0.5 ± 0.3 × 10(−4) dL ⋅ kg(−1) ⋅ min(−1) ⋅ pmol/L(−1) at w0 vs. w6-HFD [P < 0.001], respectively). In sham animals, this insulin resistance persisted, yet RDN completely normalized hepatic S(I) in HFD-fed animals (1.8 ± 0.3 × 10(−4) dL ⋅ kg(−1) ⋅ min(−1) ⋅ pmol/L(−1) at HFD + RDN [P < 0.001] vs. w6-HFD, [P not significant] vs. w0) by reducing hepatic gluconeogenic genes, including G6Pase, PEPCK, and FOXO1. The data suggest that RDN downregulated hepatic gluconeogenesis primarily by upregulating liver X receptor α through the natriuretic peptide pathway. In conclusion, bilateral RDN completely normalizes hepatic S(I) in obese canines. These preclinical data implicate a novel mechanistic role for the renal nerves in the regulation of insulin action specifically at the level of the liver and show that the renal nerves constitute a new therapeutic target to counteract insulin resistance