Pancreatic beta cell function and insulin resistance profiles in first-degree relatives of patients with prediabetes and type 2 diabetes.

AIMS: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes. METHODS: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups. RESULTS: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001). CONCLUSIONS: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.

Age-related differences in fluctuations in insulin resistance evaluated with HOMA-IR and triglyceride and glucose-based indices during the menstrual cycle, as determined using the NHANES cross-sectional dataset.

OBJECTIVES: To determine how age affects insulin resistance during the menstrual cycle and insulin resistance-associated indices: the Triglyceride-glucose and Triglyceride-glucose-BMI indexes. METHODS: This prospective observational study used fasting plasma glucose, fasting insulin, triglycerides, body mass index (BMI), and days since the start of the menstrual period collected from the NHANES dataset (1999-2006). Insulin resistance was determined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The participants were categorized as young (16-34 years) or older (>35 years). Rhythmicity during the menstrual cycle was analyzed using the Cosinor and Cosinor2 packages for R. MAIN OUTCOME MEASURES: Cosine fit curves for insulin resistance during the menstrual cycle and age-associated effects on rhythmicity. RESULTS: Using 1256 participants, rhythmicity was observed for fasting insulin and HOMA-IR (p < 0.05) but not for fasting plasma glucose, the Triglyceride-glucose index, or the Triglyceride-glucose-BMI index. Significant amplitudes for fasting insulin and HOMA-IR were observed when age was considered. Acrophases for fasting insulin and HOMA-IR were significant only for the younger group, and the differences between these groups were significant, suggesting that the changes in scores for insulin resistance for the younger and older groups occur at different times of their menstrual cycle. CONCLUSIONS: Insulin resistance does fluctuate during the menstrual cycle, and it is at a maximum at different times for younger and older women. Since these results are unadjusted, this study is preliminary and further investigation is required.

Adipose Tissue Insulin Resistance Correlates with Disease Severity in Pediatric Metabolic Dysfunction-Associated Steatotic Liver Disease: A Prospective Cohort Study.

OBJECTIVES: To assess the role of adipose tissue insulin resistance (Adipo-IR) in the pathogenesis of pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) and to determine Adipo-IR evolution during a lifestyle intervention program. STUDY DESIGN: In this prospective cohort study, children and adolescents with severe obesity were recruited between July 2020 and December 2022 at an inpatient pediatric rehabilitation center. Treatment consisted of dietary intervention and physical activity. Liver steatosis and fibrosis were evaluated using ultrasound examination and transient elastography with controlled attenuation parameter and liver stiffness measurement. Every 4-6 months, anthropometric measurements, serum biochemical analysis, ultrasound examination, and elastography were repeated. Adipo-IR was estimated by the product of the fasting serum insulin times the fasting free fatty acid concentration, and hepatic IR by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), respectively. RESULTS: Of 200 patients with obesity, 56% had evidence of steatosis on ultrasound examination and 26% were diagnosed with fibrosis (≥F2). Adipo-IR increased progressively from lean controls to patients with obesity to patients with MASLD and MASLD with fibrosis. Adipo-IR was already increased in patients with only mild steatosis (P = .0403). Patients with more insulin-sensitive adipose tissue exhibited a lower liver fat content (P < .05) and serum alanine transaminase levels (P = .001). Adipo-IR correlated positively with visceral adipose tissue weight, waist circumference, and the visceral adipose tissue/gynoid adipose tissue ratio (P < .001), but not with total body fat percentage (P = .263). After 4-6 months of lifestyle management, both MASLD and Adipo-IR improved. CONCLUSIONS: Our data suggest that Adipo-IR is associated with the presence of pediatric MASLD, particularly steatosis.

Assessment of Cardiometabolic Risk Factors and Insulin Sensitivity by Hyperinsulinemic-Euglycemic Clamp in Resistance to Thyroid Hormone ß Syndrome.

Background: Resistance to thyroid hormone beta (RTHß) is a rare disease resulting from mutations in the THRB gene, characterized by reduced T3 action in tissues with high thyroid hormone receptor ß expression. Thyroid hormones regulate body composition and metabolism in general, and increased or decreased hormone levels are associated with insulin resistance. This study evaluated the presence of cardiometabolic risk factors and insulin sensitivity in patients with RTHß. Methods: In all, 16 patients, 8 adults (52.3 ± 16.3 years of age) and 8 children (10.9 ± 3.9 years of age), were compared to 28 control individuals matched for age, sex, and body mass index (BMI). Anthropometry evaluation and blood samples were collected for glycemia, lipids, insulin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, ultrasensitive C-reactive protein (CRPus), free thyroxine, total triiodothyronine, thyrotropin, and anti-thyroid peroxidase measurements. Body composition was assessed using dual-emission X-ray absorptiometry and bioimpedance. Insulin sensitivity was evaluated in adult patients and controls using the hyperinsulinemic-euglycemic clamp (HEC), whereas homeostasis model assessment of insulin resistance (HOMA-IR) was calculated in all individuals studied. Results: Patients and controls presented similar weight, BMI, abdominal perimeter, and total fat body mass. Patients with RTHß demonstrated higher total cholesterol (TC), p = 0.04, and low-density lipoprotein cholesterol (LDL-C), p = 0.03, but no alteration was observed in other parameters associated with metabolic risk, such as leptin, TNF-α, and CRPus. Two adult patients met the criteria for metabolic syndrome. There was no evidence of insulin resistance assessed by HEC or HOMA-IR. Elevated IL-6 levels were observed in patients with RTHß. Conclusion: Using HEC as the gold standard method, no evidence of reduced insulin sensitivity in skeletal muscle was documented in RTHß adult patients; however, higher levels of TC and LDL-C were observed in these patients, which suggest the need for active monitoring of this abnormality to minimize cardiometabolic risk. In addition, we demonstrated, for the first time, that the increase in IL-6 levels in patients with RTHß is probably secondary to metabolic causes as they have normal levels of TNF-α and CRPus, which may contribute to an increase in cardiovascular risk. A larger number of patients must be studied to confirm these results.

Discovery and validation of plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance and diabetes progression or regression among Puerto Rican adults.

AIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

Exploring the impact of high-energy diets on cattle: Insights into subacute rumen acidosis, insulin resistance, and hoof health.

Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows, but their correlation with high-energy diets and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high-starch diet and a conventional diet on the rumen environment, acute-phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. A total of 16 animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood analyses, rumen fluid analyses, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating SARA. The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. We found a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Because both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Moderate-intensity constant or high-intensity interval training? Metabolic effects on candidates to undergo bariatric surgery.

BACKGROUND & AIMS: Bariatric surgery is highly effective against obesity. Pre-surgical exercise programs are recommended to prepare the candidate physically and metabolically for surgery-related rapid weight loss. However, the ideal exercise prescription in this population is unknown. This study aimed to compare the metabolic effects of moderate-intensity constant (MICT) vs. a high-intensity interval training (HIIT) program in candidates to undergo bariatric surgery. METHODS AND RESULTS: Twenty-five candidates (22 women) to undergo sleeve gastrectomy aged from 18 to 60 years old were recruited. At baseline, we measured body composition, physical activity levels, grip strength, and aerobic capacity. Further, we assessed metabolic function through glycemia and insulinemia (both fasting and after oral glucose tolerance test (OGTT)), homeostatic model assessment for insulin resistance (HOMA-IR), lipid profile, glycated haemoglobin (HbA1c), transaminases, fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), apelin, and adiponectin. Afterward, participants were randomized into MICT (n = 14) or HIIT (n = 11). Both training programs consisted of 10 sessions (2-3 times/week, 30 min per session) distributed during 4 weeks before the surgery. After this, all outcomes were measured again at the end of the training programs and 1 month after the surgery (follow-up). A mixed effect with Tukey's post-hoc analysis was performed to compare values at baseline vs. post-training vs. postsurgical follow-up. Both training programs increased aerobic capacity after training (p < 0.05), but only after MICT these changes were kept at follow-up (p < 0.05). However, only MICT decreased fat mass and increased total muscle mass and physical activity levels (p < 0.05). Metabolically, MICT decreased insulinemia after OGTT (p < 0.05), whereas HIIT increased adiponectin after training and GDF15 at follow-up (both p < 0.05). CONCLUSIONS: Both MICT and HIIT conferred benefits in candidates to undergo bariatric surgery, however, several of those effects were program-specific, suggesting that exercise intensity should be considered when preparing these patients. Future studies should explore the potential benefits of prescribing MICT or HIIT in a customized fashion depending on a pretraining screening, along with possible summatory effects by combining these two exercise programs (MICT + HIIT). CLINICAL TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry, N° ISRCTN42273422.

Special features on insulin resistance, metabolic syndrome and vascular complications in hypopituitary patients.

Pituitary hormone deficiency, hypopituitarism, is a dysfunction resulting from numerous etiologies, which can be complete or partial, and is therefore heterogeneous. This heterogeneity makes it difficult to interpret the results of scientific studies with these patients.Adequate treatment of etiologies and up-to-date hormone replacement have improved morbidity and mortality rates in patients with hypopituitarism. As GH replacement is not performed in a reasonable proportion of patients, especially in some countries, it is essential to understand the known consequences of GH replacement in each subgroup of patients with this heterogeneous dysfunction.In this review on hypopituitarism, we will address some particularities regarding insulin resistance, which is no longer common in these patients with hormone replacement therapy based on current guidelines, metabolic syndrome and its relationship with changes in BMI and body composition, and to vascular complications that need to be prevented taking into account the individual characteristics of each case to reduce mortality rates in these patients.

Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker-256 tumor-bearing rats.

Insulin (INS) resistance is often found in cancer-bearing, but its correlation with cachexia development is not completely established. This study investigated the temporal sequence of the development of INS resistance and cachexia to establish the relationship between these factors in Walker-256 tumor-bearing rats (TB rats). INS hepatic sensitivity and INS resistance-inducing factors, such as free fatty acids (FFA) and tumor necrosis factor-α (TNF-α), were also evaluated. Studies were carried out on Days 2, 5, 8, and/or 12 after inoculation of tumor cells in rats. The peripheral INS sensitivity was assessed by the INS tolerance test and the INS hepatic sensitivity in in situ liver perfusion. TB rats with 5, 8, and 12 days of tumor, but not 2 days, showed decreased peripheral INS sensitivity (INS resistance), retroperitoneal fat, and body weight, compared to healthy rats, which were more pronounced on Day 12. Gastrocnemius muscle wasting was observed only on Day 12 of tumor. The peripheral INS resistance was significantly correlated (r = -.81) with weight loss. Liver INS sensitivity of TB rats with 2 and 5 days of tumor was unchanged, compared to healthy rats. TB rats with 12 days of tumor showed increased plasma FFA and increased TNF-α in retroperitoneal fat and liver, but not in the gastrocnemius, compared to healthy rats. In conclusion, peripheral INS resistance is early, starts along with fat and weight loss and before muscle wasting, progressive, and correlated with cachexia, suggesting that it may play an important role in the pathogenesis of the cachectic process in TB rats. Therefore, early correction of INS resistance may be a therapeutic approach to prevent and treat cancer cachexia.

Effect of high-intensity interval training compared to moderate-intensity continuous training on body composition and insulin sensitivity in overweight and obese adults: A systematic review and meta-analysis.

Objective: To compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on adults with overweight and obesity. Outcomes, including changes in insulin sensitivity, weight, body mass index (BMI), waist circumference, and body fat, were analyzed. Methods: A systematic literature review was conducted. This review is registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the number CRD42021281899. Clinical trials involving individuals who are overweight and obese and comparing HIIT with MICT effects on insulin sensitivity, weight, BMI, body fat percentage, and waist circumference were included. PubMed, Web of Science, Embase, and Scopus databases were searched using controlled vocabulary and free-text terms related to HIIT, obesity, and overweight. The search included studies published until September 2022. The Rob2 tool was used to assess the risk of bias. The results were presented through meta-analyses that provided summary estimators and confidence intervals. Subgroup analyses were conducted to assess the effect of the risk of bias on the outcomes. This research did not receive any specific funding. Results: Of the 2534 articles, 30 met the eligibility criteria. The intervention duration ranged from 4 to 16 weeks. The observed effects for each outcome were as follows: insulin sensitivity (p = 0.02), weight (p = 0.58), BMI (p = 0.53), waist circumference (p = 0.87), body fat percentage (p = 0.07), body fat mass in kilograms (p = 0.39). The level of evidence obtained was moderate except for waist circumference, which was rated as low. Limitations included heterogeneity in training protocols, measurements, and study duration. Additionally, a risk of bias was identified in these studies. Conclusion: HIIT and MICT did not significantly differ in their effects on weight, BMI, waist circumference, or body fat mass in adults with overweight and obesity. However, a moderate beneficial effect of HIIT was observed on insulin sensitivity. Therefore, further evidence is required to confirm these findings.

Suprachiasmatic nucleus promotes hyperglycemia induced by sleep delay.

Short sleep is linked to disturbances in glucose metabolism and may induce a prediabetic condition. The biological clock in the suprachiasmatic nucleus (SCN) regulates the glucose rhythm in the circulation and the sleep-wake cycle. SCN vasopressin neurons (SCNVP) control daily glycemia by regulating the entrance of glucose into the arcuate nucleus (ARC). Thus, we hypothesized that sleep delay may influence SCN neuronal activity. We, therefore, investigated the role of SCNVP when sleep is disrupted by forced locomotor activity. After 2 h of sleep delay, rats exhibited decreased SCNVP neuronal activity, a decrease in the glucose transporter GLUT1 expression in tanycytes lining the third ventricle, lowered glucose entrance into the ARC, and developed hyperglycemia. The association between reduced SCNVP neuronal activity and hyperglycemia in sleep-delayed rats was evidenced by injecting intracerebroventricular vasopressin; this increased GLUT1 immunoreactivity in tanycytes, thus promoting normoglycemia. Following sleep recovery, glucose levels decreased, whereas SCNVP neuronal activity increased. These results imply that sleep-delay-induced changes in SCNVP activity lead to glycemic impairment, inferring that disruption of biological clock function might represent a critical step in developing type 2 diabetes.

Effect of Fucoxanthin on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion.

The aim of this study was to evaluate the effect of fucoxanthin on metabolic syndrome (MetS), insulin sensitivity, and insulin secretion. A randomized, double-blind, placebo-controlled clinical trial was conducted in 28 patients diagnosed with MetS. Patients were randomly assigned to receive 12 mg of fucoxanthin or placebo once a day for 12 weeks. Before and after the intervention, the components of MetS, insulin sensitivity (Matsuda index), first phase of insulin secretion (Stumvoll index), and total insulin secretion were evaluated during a 2-h oral glucose tolerance test. After fucoxanthin administration, significant differences were observed in body weight (BW) (80.6 ± 11.2 vs. 79.16 ± 12.3 kg, P < .01), body mass index (BMI) (31.1 ± 3.6 vs. 30.3 ± 3.7 kg/m2, P < .01), waist circumference (WC) (101.2 ± 9.1 vs. 98.9 ± 9.3 cm, P < .01), systolic blood pressure (SBP) (126.1 ± 10.3 vs. 120.8 ± 9.7 mmHg, P < .01), diastolic blood pressure (DBP) (81.5 ± 6.5 vs. 78.6 ± 6.3 mmHg, P < .01), triglycerides (TG) (2.2 ± 0.7 vs. 2.1 ± 0.7 mmol/L, P < .01), Stumvoll index (2403 ± 621 vs. 2907 ± 732, P < .05), and total insulin secretion (0.84 ± 0.31 vs. 1.02 ± 0.32, P < .05). In conclusion, fucoxanthin administration leads to a decrease in BW, BMI, WC, SBP, DBP, TG, as well as increase in the first phase of insulin secretion and total insulin secretion in patients with MetS. Clinical Trial Registration number: NCT03613740.

Dietary Supplementation with Yerba Mate (Ilex paraguariensis) Infusion Increases IRS-1 and PI3K mRNA Levels and Enhances Insulin Sensitivity and Secretion in Rat Pancreatic Islets.

"Yerba mate" (YM), an aqueous extract of Ilex paraguariensis, has antioxidant, diuretic, cardio-protective and hypoglycaemic properties. Since its effect on the pancreatic islets remains unclear, we evaluated insulin sensitivity and glucose-stimulated insulin secretion (GSIS) in rats consuming YM or tap water (C) for 21 days. Glucose tolerance, glycemia, triglyceridemia, insulinemia, TBARS and FRAP serum levels were evaluated. GSIS and mRNA levels of insulin signaling pathway and inflammatory markers were measured in isolated pancreatic islets from both groups. In C rats, islets were incubated with YM extract or its phenolic components to measure GSIS. YM improved glucose tolerance, enhanced GSIS, increased FRAP plasma levels and islet mRNA levels of IRS-1 and PI3K (p110), and decreased TBARS plasma levels and islet gene expression of TNF-α and PAI-1. Islets from C rats incubated with 100 µg/mL dry YM extract, 1 µM chlorogenic acid, 0.1 and 1 µM rutin, 1 µM caffeic acid or 1 µM quercetin showed an increase in GSIS. Our results suggest that YM enhances glucose tolerance because of its positive effects on GSIS, oxidative stress rate and insulin sensitivity in rat islets, suggesting that long-term dietary supplementation with YM may improve glucose homeostasis in pre-diabetes or type 2 diabetes.

Arsenic metabolism, diabetes prevalence, and insulin resistance among Mexican Americans: A mendelian randomization approach.

Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas. Methods: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014. A Mendelian randomization approach was utilized to evaluate the associations between arsenic metabolism and type 2 diabetes prevalence using the intronic variant in the arsenic methylating gene, rs9527, as the instrumental variable for arsenic metabolism. To further assess mechanisms for diabetes pathogenesis, proportions of the urinary arsenic metabolites were employed to assess the association between arsenic metabolism and insulin resistance among participants without diabetes. Urinary biomarkers of arsenic metabolites were modeled as individual proportions of the total. Arsenic metabolism was evaluated both with a static outcome of insulin resistance, homeostatic measure of assessment (HOMA-IR), and a dynamic measure of insulin sensitivity, Matsuda Index. Results: Among 475 Mexican American participants from Starr County, higher metabolism capacity for arsenic is associated with higher diabetes prevalence driven by worse insulin resistance. Presence of the minor T allele of rs9527 is independently associated with an increase in the proportion of monomethylated arsenic (MMA%) and is associated with an odds ratio of 0.50 (95% CI: 0.24, 0.90) for type 2 diabetes. This association was conserved after potential covariate adjustment. Furthermore, among participants without type 2 diabetes, the highest quartile of MMA% was associated with 22% (95% CI: -33.5%, -9.07%) lower HOMA-IR and 56% (95% CI: 28.3%, 91.3%) higher Matsuda Index for insulin sensitivity. Conclusions: Arsenic metabolism capacity, indicated by a lower proportion of monomethylated arsenic, is associated with increased diabetes prevalence driven by an insulin resistant phenotype among Mexican Americans living in Starr County, Texas.

A Single-Point Insulin Sensitivity Estimator (SPISE) of 5.4 is a good predictor of both metabolic syndrome and insulin resistance in adolescents with obesity.

Background: The Single-Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity estimated using BMI and triglycerides and high-density lipoprotein cholesterol. We assessed the accuracy of SPISE to screen obesity-related cardiometabolic risk in children and adolescents. Method: Cross-sectional validation study for a screening test in a sample of n=725 children and adolescents from an obesity clinic. Weight, height, waist circumference, blood arterial pressure, lipid profile, glucose, insulin and Tanner stage were measured. BMI, BMI for-age-and sex (BAZ), and HOMA-IR were estimated. HOMA-IR values ≥2.1 and ≥3.3 were considered IR in Tanner I-II, ≥3.3 for Tanner III-IV and ≥2.6 for Tanner V, respectively. Metabolic Syndrome (MetS) was diagnosed with the Cook phenotype. SPISE was estimated according to the following algorithm: [600* HDL^0.185/(TG^0.2* BMI^1.338)]. The optimal SPISE cut points for IR and MetS prediction were determined by ROC curve analysis. Results: In prepubertal obese patients (9.2 ± 2.1y; 18.4% males), the prevalence of IR and MetS was 28.2% y 46.9%, respectively; 58% had severe obesity (BAZ ≥4 SD). In pubertal obese patients (12.6 ± 1.8y; 57% males), the prevalence of IR and MetS was 34.1% and 55.3%, respectively; 34% had severe obesity. In prepubertal children, a SPISE of 6.3 showed the highest sensitivity (73.2%) and specificity (80%) to screen individuals with IR (AUC: 0.80; LR +: 3.3). Likewise, a SPISE of 5.7 got the highest sensitivity (82.6%) and specificity (86.1%) to screen patients with MetS (AUC: 0.87; LR +: 5.4). In pubertal patients, a SPISE of 5.4 showed the highest sensitivity and specificity to screen children and adolescents with both IR (Sn: 76.1%; Sp: 77.5%; AUC: 0.8; LR +: 3.1) and MetS (Sn: 90.4%; Sp: 76.1%; AUC: 0.90; LR +: 3.5). Conclusion: In children and adolescents with obesity, SPISE has good or very good performance in predicting IR and MetS. SPISE may be considered a relatively simple and low-cost diagnosis tool that can be helpful to identify patients with greater biological risk. In adolescents with obesity, the same cut point allows identification of those at higher risk of both IR and MetS.

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

Ellagic Acid Effect on the Components of Metabolic Syndrome, Insulin Sensitivity and Insulin Secretion: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, usually with a common pathophysiological origin in insulin resistance and abdominal obesity. Considering the reported effects of ellagic acid (EA) on insulin resistance and abdominal obesity, the aim of this study was to evaluate the effect of EA on the components of MetS, insulin sensitivity and insulin secretion by conducting a randomized, double-blind, placebo-controlled, clinical trial with 32 volunteers diagnosed with MetS. Sixteen patients were randomly allocated, received 500 mg of EA orally twice a day for 12 weeks, and the other 16 received a placebo. Clinical and laboratory determinations were obtained at baseline and at the end of the study. After EA administration, patients reduced their waist circumference (females: 102.2 ± 4.2 to 99.5 ± 3.2 cm (p < 0.05); males: 99.8 ± 6.7 to 96.0 ± 4.7 cm (p < 0.01)), systolic blood pressure (118.1 ± 10.1 to 113.7 ± 7.8 mmHg (p < 0.01)), diastolic blood pressure (118.1 ± 10.1 to 113.7 ± 7.8 mmHg (p < 0.01)), triglycerides (2.8 ± 1.1 to 2.1 ± 0.7 mmol/L (p < 0.01)), fasting plasma glucose (6.5 ± 0.5 to 5.7 ± 0.6 mmol/L (p < 0.01)), fasting plasma insulin (p < 0.01), and insulin secretion (p < 0.05), with an increase of insulin sensitivity (p < 0.01). In male patients, high-density lipoprotein cholesterol increased (p < 0.05). In conclusion, EA improved the components of MetS, reduced hyperinsulinemia, and improved insulin sensitivity.

FOXO1 is downregulated in obese mice subjected to short-term strength training.

Obesity is a worldwide health problem and is directly associated with insulin resistance and type 2 diabetes. The liver is an important organ for the control of healthy glycemic levels, since insulin resistance in this organ reduces phosphorylation of forkhead box protein 1 (FOXO1) protein, leading to higher hepatic glucose production (HGP) and fasting hyperglycemia. Aerobic physical training is known as an important strategy in increasing the insulin action in the liver by increasing FOXO1 phosphorylation and reducing gluconeogenesis. However, little is known about the effects of strength training in this context. This study aimed to investigate the effects of short-term strength training on hepatic insulin sensitivity and glycogen synthase kinase-3ß (GSK3ß) and FOXO1 phosphorylation in obese (OB) mice. To achieve this goal, OB Swiss mice performed the strength training protocol (one daily session for 15 days). Short-term strength training increased the phosphorylation of protein kinase B and GSK3ß in the liver after insulin stimulus and improved the control of HGP during the pyruvate tolerance test. On the other hand, sedentary OB animals reduced FOXO1 phosphorylation and increased the levels of nuclear FOXO1 in the liver, increasing the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) content. The bioinformatics analysis also showed positive correlations between hepatic FOXO1 levels and gluconeogenic genes, reinforcing our findings. However, strength-trained animals reverted to this scenario, regardless of body adiposity changes. In conclusion, short-term strength training is an efficient strategy to enhance the insulin action in the liver of OB mice, contributing to glycemic control by reducing the activity of hepatic FOXO1 and lowering PEPCK and G6Pase contents.

Effects of the association of different volumes of strength training with photobiomodulation therapy on insulin resistance: A protocol for a randomized, triple-blind, placebo-controlled trial.

Background: Insulin resistance (IR) is the main risk factor for developing type 2 diabetes. Both strength training (ST) and photobiomodulation therapy (PBMt) reduce IR, but the effect of combining different volumes of ST with PBMt is unknown. Methods: Overweight/obese individuals will be assigned to 4 groups (n = 12/group): ST with volume following international guidelines (3 sets per exercise - high volume) or one-third of this volume (1 set per exercise - low volume), combined with PBMt or placebo. ST will be performed for 20 sessions over 10 weeks and will consist of 7 exercises. The PBMt will be applied after training sessions using blankets with light emitters (LEDs) placed over the skin on the frontal and the posterior region of the body, following the parameters recommended by the literature. The placebo group will undergo an identical procedure, but blankets will emit insignificant light. To measure plasma glucose and insulin concentrations, oral glucose tolerance tests (OGTT) will be performed before and after the training period. Thereafter, IR, the area under the curve of glucose and insulin, and OGTT-derived indices of insulin sensitivity/resistance will be calculated. Expected impact on the field: This study will determine the effects of different ST volumes on IR and whether the addition of PBMt potentiates the effects of ST. Because previously sedentary, obese, insulin-resistant individuals might not comply with recommended volumes of exercise, the possibility that adding PBMt to low-volume ST enhances ST effects on IR bears practical significance.

Moderate Exercise Training Combined With a High-Fat and Sucrose Diet Protects Pancreatic Islet Function in Male C57BL/6J Mice.

Obesity is mainly caused by excess energy intake and physical inactivity, and the number of overweight/obese individuals has been steadily increasing for decades. Previous studies showed that rodents fed westernized diets exhibit endocrine pancreas deterioration and a range of metabolic disorders. This study evaluated the effects of moderated aerobic treadmill exercise training on pancreatic islet cell viability and function in mice consuming a high-fat and sucrose diet. In the present study, 60-day-old male C57BL/6J mice were divided into four groups: control (C), fed a standard diet AIN-93M (3.83 kcal/g; 70% carbohydrate (cornstarch and dextrinized starch were chosen as the major source of carbohydrate for the AIN-93 diet. In addition, a small amount of sucrose), 20% protein (casein), and 10% fat (soybean) with no training (i.e., sedentary); C + training (CTR, fed the standard diet with eight weeks of exercise; high-fat diet + sucrose (HFDS), fed a high fat and sucrose diet (5.2 kcal/g; 20% carbohydrate (cornstarch and dextrinized starch were chosen as the major source of carbohydrate), 20% protein (casein), 60% fat (Lard was chosen as the major source of fat and a small amount of soybean) + 20% sucrose diluted in drinking water with no training; and HFDS + training (HFDSTR). After eight weeks, the HFDS mice displayed increased body weight (P<0.001) and epididymal, inguinal and retroperitoneal adipose tissue mass (P<0.01). These mice also presented insulin resistance (P<0.01), glucose intolerance (P<0.001), impaired glucose-stimulated insulin secretion (GSIS) and were less responsive to the physiological net ROS production induced by glucose stimulus. The HFDS group's pancreatic islet cells were 38% less viable and 59% more apoptotic than those from the C group (P<0.05). The HFDSTR improved glucose tolerance, body mass, insulin sensitivity and GSIS (P<0.05). Furthermore, HFDSTR mice had 53% more viable isolated pancreatic islets cells and 29% fewer apoptotic cells than the HFDS group (P<0.01). Thus, exercise training may slow down and/or prevent adverse metabolic effects associated with consuming a westernized diet.