Effect of a family and interdisciplinary intervention to prevent T2D: randomized clinical trial.

BACKGROUND: Lifestyle changes can reduce the risk of T2D; however, no study has evaluated the effect of a lifestyle intervention involving patients´ family. The aim of this study was to compare the impact of an interdisciplinary family (FI) Vs individual intervention (II) on glucose metabolism, insulin resistance (IR), pancreatic ß-cell function and cardiovascular risk markers in patients with prediabetes, as well as to measure the impact on their families' metabolic risk. METHODS: Randomized Clinical Trial (RCT) to compare the impact of FI and II on IR and pancreatic ß-cell function in subjects with prediabetes. There were 122 subjects with prediabetes (and 101 family members) randomized to FI or II. Data were collected in 2015-2016 and analyzed in 2017-2018. FI group had the support of their family members, who also received personalized diet and exercise recommendations; patients and their family members attended monthly a lifestyle enhancement program. II group received personalized diet and exercise recommendations. The follow-up was for 12 months. Glucose, IR, pancreatic ß-cell function and secondary outcomes (body composition and lipid profile) were assessed at baseline, 6 and 12 months. RESULTS: FI group improved area under the glucose curve (AUC) (from 18,597 ± 2611 to 17,237 ± 2792, p = 0.004) and the Matsuda index (from 3.5 ± 2.3 to 4.7 ± 3.5, p = 0.05) at 12 months. II group improved Disposition Index (from 1.5 ± 0.4 to 1.9 ± 0.73, p < .0001) at 12 months. The improvements achieved in weight and lipids at 6 months, were lost in II group at 12 moths, whereas in FI persisted. Adherence up to 12 months was not different between the study groups (FI 56% Vs II 60%). CONCLUSIONS: FI intervention was more effective by improving glucose AUC, insulin sensitivity and lipid profile, besides that, metabolic risk in family members of the FI group was maintained, while the risk of II group was increased. TRIAL REGISTRATION: This study was retrospectively registered at clinicaltrials.gov on December 15, 2015 (NTC026365646).

Exercise and Sirtuins: A Way to Mitochondrial Health in Skeletal Muscle.

The sirtuins form a family of evolutionarily conserved nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. Seven sirtuins (SIRT1-SIRT7) have been described in mammals, with specific intracellular localization and biological functions associated with mitochondrial energy homeostasis, antioxidant activity, proliferation and DNA repair. Physical exercise affects the expression of sirtuin in skeletal muscle, regulating changes in mitochondrial biogenesis, oxidative metabolism and the cellular antioxidant system. In this context, sirtuin 1 and sirtuin 3 have been the most studied. This review focuses on the effects of different types of exercise on these sirtuins, the molecular pathways involved and the biological effect that is caused mainly in healthy subjects. The reported findings suggest that an acute load of exercise activates SIRT1, which in turn activates biogenesis and mitochondrial oxidative capacity. Additionally, several sessions of exercise (training) activates SIRT1 and also SIRT3 that, together with the biogenesis and mitochondrial oxidative function, jointly activate ATP production and the mitochondrial antioxidant function.

Differential proteomic analysis of the pancreas of diabetic db/db mice reveals the proteins involved in the development of complications of diabetes mellitus.

Type 2 diabetes mellitus is characterized by hyperglycemia and insulin-resistance. Diabetes results from pancreatic inability to secrete the insulin needed to overcome this resistance. We analyzed the protein profile from the pancreas of ten-week old diabetic db/db and wild type mice through proteomics. Pancreatic proteins were separated in two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and significant changes in db/db mice respect to wild type mice were observed in 27 proteins. Twenty five proteins were identified by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) and their interactions were analyzed using search tool for the retrieval of interacting genes/proteins (STRING) and database for annotation, visualization and integrated discovery (DAVID). Some of these proteins were Pancreatic α-amylase, Cytochrome b5, Lithostathine-1, Lithostathine-2, Chymotrypsinogen B, Peroxiredoxin-4, Aspartyl aminopeptidase, Endoplasmin, and others, which are involved in the metabolism of carbohydrates and proteins, as well as in oxidative stress, and inflammation. Remarkably, these are mostly endoplasmic reticulum proteins related to peptidase activity, i.e., they are involved in proteolysis, glucose catabolism and in the tumor necrosis factor-mediated signaling pathway. These results suggest mechanisms for insulin resistance, and the chronic inflammatory state observed in diabetes.

A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver.

Turmeric (Curcuma longa) is a rhizomatous herbaceous perennial plant of the ginger family which has been used to treat biliary disorders, anorexia, cough, rheumatism, cancer, sinusitis, hepatic disorders, hyperglycemia, obesity, and diabetes in both Ayurvedic and Traditional Chinese Medicine. Suggested mechanisms of action include the modulation of signal transduction cascades and effects on gene expression, however they remain to be elucidated. In this study, the expression of some proteins responsible for transcription factors, inflammation, and metabolic control were evaluated by western blot in 15-week-old db/db mice livers treated with curcumin 0.75% mixed in their diet for 8 weeks. In addition, nitrosative stress was evaluated. Curcumin increased the expression of AMPK and PPARγ, and diminished NF-κB protein in db/db mice. However, it did not modify the expression of PGC-1α or SIRT1. Nitrosative stress present in db/db mice livers was determined by a unique nitrotyrosylated protein band (75 kDa) and was not reverted with curcumin. In conclusion, curcumin regulates the expression of AMPK, PPARγ, and NF-κB; suggesting a beneficial effect for treatment of T2DM complications. In order to observe best beneficial effects it is desirable to administer curcumin in the earlier states of T2DM.

Novel Adiposity and Biochemical-Anthropometric Indices to Identify Cardiometabolic Risk and Metabolic Syndrome in Mexican Adults.

Although several indices used in clinical practice identify cardiometabolic risk (CR) and metabolic syndrome (MetS), it is imperative to develop indices for specific populations. Therefore, we proposed and validated sex-specific indices to identify CR associated with visceral adipose tissue (VAT) accumulation or MetS in Mexican adults. Additionally, a cut-off value for the visceral fat area (VFA) to identify CR was proposed. Clinical, anthropometric, biochemical, and body composition variables were evaluated in 904 subjects (25-45 years old) (84.4% men). Multiple and logistic regressions were used to model the indices and ROC curve analysis to determine predictive performance. An additional cohort (n = 186) was used for indices validation, and Cohen's kappa coefficient was employed for agreement analysis. The proposed sex-specific indices, called Mexican adiposity indices (MAIs) and biochemical-anthropometric indices (BAIs), were good predictors for CR and MetS. The kappa coefficients showed a moderate agreement level. The VFA cut-off value chosen to identify CR was 100.3 cm2 because it had the best combination of sensitivity (66.8%) and specificity (64.4%). MAIs and BAIs could be clinical tools to identify either CR associated to VAT accumulation or MetS, respectively. A VFA cut-off value of 100.3 cm2 could identify CR in Mexican men.

Effect of recreational physical activity on insulin levels in Mexican/Hispanic children.

The effect of increased recreational physical activity in children on insulin levels has not yet been studied. We carried out a randomized controlled trial in 76 children 6-9 years old, 32 of them increased their physical activity and 30 maintained the same level. In the intervention group, after a week of baseline, recreational activity three times/week was programmed for 12 weeks. We compared insulin, homeostatic model assessment (HOMA) index, glucose, HDL-C, LDL-C, triglycerides, and body mass index in both groups. Thereafter, we compared groups of normal weight, overweight, and with obesity in the experimental group. The group of recreational activity increased their median daily steps (15,329 to 19,910) and decreased insulin (p < 0.001) and HOMA index (4.36 vs. 2.39, p < 0.001). The diminution of insulin levels was more significant in the overweight group (p < 0.007). In conclusion, in our group, children who increased physical activity during 12 weeks decrease insulin levels and insulin resistance without change in other metabolic and anthropometric variables.

Aerobic training but no resistance training increases SIRT3 in skeletal muscle of sedentary obese male adolescents.

In recent years, prevalence of obesity in children and adolescents has increased. A strategy for prevention and management of obesity is aerobic training (AT) due to its effectiveness to decrease fat mass. AT increases the content of SIRT3, a mitochondrial protein that increases the expression of PGC-1α and NFR1, thereby enhances mitochondrial function and metabolic health. Resistance training (RT) provides metabolic benefits but its effect on SIRT3 content is unknown. To compare the effect of AT and RT on SIRT3, PGC-1α and NRF-1 protein levels in skeletal muscle of sedentary obese adolescents. Twenty-seven sedentary obese male adolescents (age: 16.7 ± 0.9 years; BMI: 33.7 ± 4.3 kg/m2) completed a 1-month control period prior to randomization to one of two supervised exercise protocols: AT (3 days/week, 40 min/day, 70-80% peak heart rate) or RT (3 days/week, 11 exercises, 2 sets/exercise, 12 repetitions/set) for 12 weeks. Biopsies were obtained from the vastus lateralis muscle before and after 12 weeks to analyse SIRT3, PGC-1α and NRF-1 proteins content. Peak oxygen consumption (VO2peak) and anthropometric variables were evaluated before and after training. AT increased SIRT3 content, which was associated with improvements in PGC-1α content and body fat percentage. RT did not affect SIRT3 or PGC-1α. VO2peak increased only in AT. The increase in muscle mitochondrial SIRT3 was observed only following AT. In contrast, RT increased muscle mass without improving SIRT3 in obese male adolescents.

Dietary advanced glycation end products and their role in health and disease.

Over the past 2 decades there has been increasing evidence supporting an important contribution from food-derived advanced glycation end products (AGEs) to the body pool of AGEs and therefore increased oxidative stress and inflammation, processes that play a major role in the causation of chronic diseases. A 3-d symposium (1st Latin American Symposium of AGEs) to discuss this subject took place in Guanajuato, Mexico, on 1-3 October 2014 with the participation of researchers from several countries. This review is a summary of the different presentations and subjects discussed, and it is divided into 4 sections. The first section deals with current general knowledge about AGEs. The second section dwells on mechanisms of action of AGEs, with special emphasis on the receptor for advanced glycation end products and the potential role of AGEs in neurodegenerative diseases. The third section discusses different approaches to decrease the AGE burden. The last section discusses current methodologic problems with measurement of AGEs in different samples. The subject under discussion is complex and extensive and cannot be completely covered in a short review. Therefore, some areas of interest have been left out because of space. However, we hope this review illustrates currently known facts about dietary AGEs as well as pointing out areas that require further research.