Insulin Resistance In Subjects Research Articles

Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study

In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant.Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.

Neglected cardiometabolic risk factors and subclinical target organ damage in post-menopausal women with normal glucose tolerance.

Menopausal transition is a crucial step in the women's cardiovascular health, and the risk stratification in apparently health post-menopausal females has been rarely assessed. Heart ultrasonography, unusually performed in such subjects, would be able to detect initial signs of organ damage. We described the cardiovascular risk profile of non-diabetic post-menopausal women, evaluating how easily computed, biochemistry-derived scores were related to ultrasonographic measures of target organ damage. We analyzed the characteristics of a cohort of two-hundred and seventy-three women consecutively referring to a prevention program of Azienda Ospedaliero-Universitaria Pisana (years 2017-2022) who underwent clinical evaluation, complete routine biochemical analyses with proxies of insulin resistance, heart and carotid ultrasonography. The cohort was further divided into four groups according to presence of isolated hypercholesterolemia (HC, 37%), isolated hypertension (HT, 5%), both HC/HT (38%), or none of them. In HC and HC/HT, LDL cholesterol was sharply above the recommended values (149 [134-171] mg/dL and 141 [123-159] mg/dL, respectively). E/e' ratio and left atrium size were augmented in HT women and further worsened in HT/HC, with an independent effect of hypertension (E/e' ß=0.055, P=0.013, left atrium volume ß=0.059, P=0.003). Presence of carotid plaques was independently linked to hypertension (ß=0.474, P=0.003). In HC and HC/HT, the Triglycerides-Glucose Index, a surrogate of insulin resistance, was higher than in the other classes (P=0.0013), and it was associated with E/A in HC and HT/HC, with a significative interaction (P=0.0004) with hypertension. Past hormone replacement therapy did not influence clinical, biochemical or echocardiographic parameters. Postmenopausal women display a high cardiovascular risk burden; a simple clinical and biochemistry screening would be advisable to identify and treat those more at risk. Cardiac ultrasonographic parameters were worse in hypertensive, hypercholesterolemic and insulin-resistant subjects, who may also deserve a deep and early instrumental characterization, especially when these conditions are associated.

A Cross-Sectional Observational Study to Assess the Efficacy of Triglyceride to High-Density Lipoprotein Ratio as a Marker of Insulin Resistance in Subjects of Central Rural India.

The rising prevalence of insulin resistance (IR), obesity, and its complications in India is due to lifestyle changes, eating patterns, stress, and genetic factors. Markers for IR are often expensive, invasive, or impractical for use in economically disadvantaged or remote areas. To address this, we evaluated the efficacy of the triglyceride to high-density lipoprotein (TG/HDL) ratio as a simple, reliable, accessible, and affordable surrogate marker of IR in comparison to the homeostatic model assessment for insulin resistance (HOMA-IR). This cross-sectional observational study was performed at a tertiary care center in central India and included 815 subjects aged 18 to 60 years after excluding those with systemic diseases, drugs affecting weight, or pregnant or lactating women. Descriptive and inferential statistical analysis was done to represent the study findings. Males and obese subjects were more insulin resistant than females and non-obese subjects, respectively. The TG/HDL had a sensitivity of 91.81%, a specificity of 92.88%, a positive predictive value of 94.46%, and a negative predictive value of 89.56%, with a diagnostic accuracy of 92.27% when compared to HOMA-IR. We concluded that TG/HDL serves as a simple, affordable, and accurate marker of IR in a diverse population of central India. There is a definite scope to use the same for large-scale screening, epidemiological research, and routine clinical practice.

Role of Dietary Macronutrient Composition and Fibre Intake in Development of Double Diabetes in Indian Youth

Abstract Introduction: Insulin resistance (IR) and obesity are common presentations of double diabetes (DD) in subjects with type-1 diabetes (T1D). There is evidence that dietary composition has an impact on developing IR. Objectives were to assess the impact of macronutrient and fibre intake on glycaemic control and the role of macronutrient composition of diet in the development of DD in subjects with T1D. Methods: This cross-sectional study included 77 young adults (10–25 years) with T1D. Data related to demography, anthropometry, biochemistry and body composition were collected. Dietary data was collected by fourteen-day food diary. IR was calculated using eGDR, SEARCH and CACTI equations, and metabolic syndrome (MS) was diagnosed using the International Diabetes Federation Consensus Definition. Results: Subjects at risk of DD had higher age, leptin levels, percentage carbohydrate consumption in diet and IR. A positive association of insulin sensitivity with fibre intake and %protein intake was noted. Poor glycaemic control, adiponectin/leptin ratio, fibre intake and insulin/carbohydrate ratio were significant negative predictors of IR. Addition of dietary factors to the regression model improved the R square and percentage of subjects identified correctly. Inclusion of dietary parameters significantly improves the prediction of the risk of development of DD in subjects with T1D. Conclusion: Good glycaemic control and increased intake of dietary fibre may prevent the development of IR in subjects with T1D and reduce the burden of DD.

D-Allulose Ameliorates Dysregulated Macrophage Function and Mitochondrial NADH Homeostasis, Mitigating Obesity-Induced Insulin Resistance.

D-allulose, a rare sugar, has been proposed to have potential benefits in addressing metabolic disorders such as obesity and type 2 diabetes (T2D). However, the precise mechanisms underlying these effects remain poorly understood. We aimed to elucidate the mechanisms by which D-allulose influences obesity-induced insulin resistance. We conducted gene set enrichment analysis on the liver and white adipose tissue of mice exposed to a high-fat diet (HFD) along with the white adipose tissue of individuals with obesity. Our study revealed that D-allulose effectively suppressed IFN-γ, restored chemokine signaling, and enhanced macrophage function in the livers of HFD-fed mice. This implies that D-allulose curtails liver inflammation, alleviating insulin resistance and subsequently impacting adipose tissue. Furthermore, D-allulose supplementation improved mitochondrial NADH homeostasis and translation in both the liver and white adipose tissue of HFD-fed mice. Notably, we observed decreased NADH homeostasis and mitochondrial translation in the omental tissue of insulin-resistant obese subjects compared to their insulin-sensitive counterparts. Taken together, these results suggest that supplementation with allulose improves obesity-induced insulin resistance by mitigating the disruptions in macrophage and mitochondrial function. Furthermore, our data reinforce the crucial role that mitochondrial energy expenditure plays in the development of insulin resistance triggered by obesity.

In praise of pioglitazone: An economically efficacious therapy for type 2 diabetes and other manifestations of the metabolic syndrome.

Pioglitazone improves glycaemic control, not only by lowering insulin resistance, but also by improving beta cell function. Because of the improved beta cell function the glycaemic control that occurs with pioglitazone is prolonged. Pioglitazone has positive effects not only on cardiac risk factors and surrogate measures of cardiovascular disease, it also lowers the incidence of cardiac events in patients with diabetes. The recurrence of transient ischaemic attack and ischaemic stroke is also reduced in non-diabetic, insulin-resistant subjects. Utilized at preclinical stages (but not later) of heart failure, pioglitazone improves diastolic function and avoids progression to heart failure. Pioglitazone, through suppression of atrial remodelling, also decreases the incidence of atrial fibrillation. The manifestations of diseases associated with insulin resistance (non-alcoholic steatohepatitis and polycystic ovary disease) are also improved with pioglitazone. Pioglitazone may possibly improve psoriasis and other dermopathies. Pioglitazone is therefore an inexpensive and efficacious drug for the insulin-resistant subject with diabetes that is underutilized because of biases that have evolved from the toxicities of other thiazolidinediones.

Poplar Propolis Improves Insulin Homeostasis in Non-Diabetic Insulin-Resistant Volunteers with Obesity: A Crossover Randomized Controlled Trial.

Propolis, a natural resinous mixture rich in polyphenols, produced by bees from a variety of plant sources, has shown significant therapeutic effects and may prevent the development of certain chronic diseases like type 2 diabetes mellitus (T2DM). The objective of this study was to evaluate the effect of supplementation with standardized poplar propolis extract powder (PPEP) on insulin homeostasis in non-diabetic insulin-resistant volunteers with obesity. In this randomized, controlled, crossover trial, nine non-diabetic insulin-resistant volunteers with obesity, aged 49 ± 7 years, were subjected to two periods of supplementation (placebo and PPEP) for 3 months. Blood samples and anthropomorphic data were collected at baseline and at the end of each phase of the intervention. PPEP supplementation improved insulin sensitivity by significantly decreasing the percentage of insulin-resistant subjects and the insulin sensitivity Matsuda index (ISI-M). According to this study, supplementation with standardized PPEP for 3 months in non-diabetic insulin-resistant volunteers with obesity led to an improvement in insulin homeostasis by its effect on insulin resistance and secretion. This study suggests that poplar propolis has a preventive effect on the physiopathological mechanisms of T2DM and, therefore, that it can help to prevent the development of the disease.

576-P: Local Muscle Microenvironment, Instead of Training Status, Affects Resting IMTG Turnover

Intramyocellular triglyceride (IMTG) level correlates with insulin resistance. Paradoxically, trained humans and obese, sedentary, insulin-resistant humans have high IMTG levels despite discrepant clinical phenotypes. We hypothesize that higher IMTG turnover in trained humans explains this paradox. Methods: Obese, insulin-resistant subjects [n=47, mean (SD), BMI:36.2 kg/m2(5.7), VO2max 25.4 ml/kg/min (5.7)] and lean trained subjects [n=15, BMI:22.2 kg/m2(1.8), VO2max 55ml/kg/min (10.1)] were fasted overnight. Two muscle biopsies (Bx) were acquired during a pulse-chase experiment using [U-13C]palmitate and [9-2H]palmitate infusions (6 h each), overlapping by 1 hour. Bx#1 was performed during the infusion overlap [last hour of 6 h [U-13C]palmitate infusion, 1 hour after starting [9-2H]palmitate. Bx#2 was performed at study conclusion [last hour of [9-2H]palmitate infusion, 6 hours after stopping [U-13C]palmitate]. Palmitate enrichment and concentration were measured. [9-2H]palmitate IMTG incorporation at Bx#1 and [U-13C] IMTG loss at Bx#2 indicated the interplay between plasma and muscle fatty acids. Results: Palmitate IMTG incorporation positively correlated between measures of IMTG turnover and negatively with insulin sensitivity. No correlation seen for VO2max/BMI. Conclusion: Muscle-level IMTG measures dictates higher resting IMTG turnover more than training related phenotype. Disclosure L.S.Chow: Research Support; Dexcom, Inc. A.Bantle: None. A.C.Alvear: None. D.G.Mashek: None. M.D.Jensen: Other Relationship; Novo Nordisk, Elsevier. Funding National Institutes of Health (R01DK098203)

120-OR: Muscle Lipid Turnover Predicts Aerobic Training Effects on Body Composition

Aerobic exercise utilizes muscle lipid. We hypothesize that high pre-training muscle lipid turnover, suggesting high muscle lipid utilization, predicts the effects of aerobic training. Obese, insulin-resistant subjects [mean(SD), BMI:37.7 kg/m2(6.2), VO2max 25 ml/kg/min (6.3)] underwent a 16 week of supervised, weight-stable, aerobic training (n=16). Body composition (DXA), fitness level (VO2max) and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were performed at baseline and end-training. Two muscle biopsies (Bx) were acquired during a pulse-chase experiment using [U-13C]palmitate and [9-2H]palmitate infusions (6 h each), overlapping by 1 hour. Bx#1 captured muscle lipid incorporation and was performed during the infusion overlap [last hour of 6 h [U-13C]palmitate infusion, 1 hour after starting [9-2H]palmitate. Bx#2 captured muscle lipid breakdown and was performed at study conclusion [last hour of [9-2H]palmitate infusion, 6 hours after stopping [U-13C]palmitate]. As expected, aerobic training increased VO2max, fat-free mass, insulin sensitivity and hepatic insulin sensitivity while decreasing fat mass and visceral fat (Table 1). Baseline measures, especially muscle palmitate incorporation and breakdown, best predicted training effects on body composition. Muscle lipid turnover, along with other baseline measures, predicts aerobic training effects on body composition. Disclosure L.S.Chow: Research Support; Dexcom, Inc. A.Bantle: None. A.C.Alvear: None. D.G.Mashek: None. M.D.Jensen: Other Relationship; Novo Nordisk, Elsevier. Funding National Institutes of Health (R01DK098203)

Plasma concentrations of apolipoproteins C3 and C2 do not explain differences in insulin-stimulated endothelial-bound lipoprotein lipase activity in insulin resistant humans

Elevated circulating triglycerides (i.e., dyslipidemia) is a hallmark of insulin resistance and is generally caused by decrease in lipoprotein lipase (LPL) activity. LPL hydrolyzes triglycerides (TG) into free fatty acids in plasma for use and/or storage in tissues (i.e., adipose, skeletal muscle). Plasma apolipoproteins (Apos) C3 and C2 interact with LPL to modulate its function by activating or inhibiting LPL. Previous research shows, in the metabolic environment of insulin resistance, the concentration of ApoC3 is increased in plasma while that of ApoC2 is decreased. Thus, Apos are considered key factors in regulating plasma lipid metabolism via modulation of LPL function. The purpose of this study was to investigate the concentrations of ApoC3 and ApoC2 in plasma and along endothelial-bound LPL activity in insulin resistant and healthy/non-insulin resistant individuals. We evaluated insulin resistance (IR)/insulin sensitivity (IS) using an oral glucose tolerance test (i.e., Matsuda index calculation) in subjects between ages 19 and 45 years old. Subjects were placed in the following two groups: 1) IR, if Matsuda index <4.0 (N=6; 4 males, 2 females; BMI: 23-45 kg/m2), or 2) IS, if Matsuda index >7.0 (N=11, 9 males, 2 females; BMI: 18-26 kg/m2). Subjects received an intravenous insulin infusion (0.5 mU/kg/min) for 30 minutes to resemble increased postprandial plasma insulin response. To release whole-body endothelial-bound LPL, subjects received an injection of intravenous heparin (75 UI/kg). Plasma samples were collected 10 minutes after the heparin infusion and analyzed for LPL concentration and activity, and ApoC3 and ApoC2 concentrations using ELISA. Differences between IS and IR subjects were determined using a t-test, and the P value was set at P < 0.05. Plasma LPL concentrations were not different between groups (IR = 457 ± 17 ng/ml, IS = 453 ± 27 ng/ml, P > 0.05), but plasma LPL activity was higher in the IR subjects (IR = 665 ± 113 nmol/min/ml, IS = 365 ± 59 nmol/min/ml, P = 0.02). IR subjects had higher concentrations of plasma ApoC3 (IR = 3.6 ± 0.5 mg/dl, IS = 2.7 ± 0.2 mg/dl, P=0.03) but ApoC2 was not different between groups (IR = 0.15 ± 0.03 mg/dl, IS = 0.11 ± 0.01 mg/dl, P = 0.11). The ratio of circulating LPL to circulating ApoC3 (IR = 145 ± 22, IS = 176 ± 15) or circulating ApocC2 (IR = 4104 ± 844, IS = 4391 ± 483) were not different between groups (P > 0.05). We conclude that interactions of LPL with APOC3 and ApoC2 may not be main determinants regulating differential whole-body plasma LPL activity under plasma insulin-stimulated conditions in insulin resistant humans. American Diabetes Association Grant #7-12-CT-40 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.

There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here, we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: 1), area occupied by type I fibers = 61.0 ± 11.8%; 2), type I area = 36.0 ± 4.9% (P < 0.001). Muscle biopsies and intravenous glucose tolerance tests were performed after an overnight fast and after starvation. Biopsies were analyzed for muscle fiber composition and mitochondrial respiration. Indices of glucose tolerance and insulin sensitivity were determined. Glucose tolerance was similar in both groups after an overnight fast and deteriorated to a similar degree in both groups after starvation. In contrast, whole body insulin sensitivity decreased markedly after starvation in group 1 (P < 0.01), whereas the decrease in group 2 was substantially smaller (P = 0.06). Nonesterified fatty acids and β-hydroxybutyrate levels in plasma after an overnight fast were similar between groups and increased markedly and comparably in both groups after starvation, demonstrating similar degrees of lipid load. The capacity of permeabilized muscle fibers to oxidize lipids was significantly higher in group 1 versus 2, whereas there was no significant difference in pyruvate oxidation between groups. The data demonstrate that loss of whole body insulin sensitivity after short-term starvation is a function of muscle fiber composition and is associated with an elevated rather than a diminished capacity of muscle to oxidize lipids.NEW & NOTEWORTHY Whether lipid-mediated insulin resistance occurs as a result of an increased or decreased capacity of skeletal muscle to oxidize lipids has been debated. We show that a 3-day fast results in increases in circulating lipids and insulin resistance in subjects expressing a high or low proportion of type I muscle fibers. High expression of type I is associated with a higher capacity to oxidize lipids and a greater loss of insulin sensitivity after starvation.

The Role of Advanced Glycation End Products on Dyslipidemia.

Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs' production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.

Insulin Resistance and Hypertension among Type 2 Diabetes Subjects in a Tertiary Institution in South East Nigeria

Background: Type 2 diabetes mellitus (T2DM) is frequently associated with hypertension (HTN), adding significantly to its overall morbidity and mortality. Aim: This study aimed to investigate the relationship between insulin resistance (IR) and blood pressure and other factors associated with both conditions. Patients, Materials and Methods: A case–control study of 180 subjects consisting of 60 with T2DM and HTN, 60 with T2DM and normal blood pressure, and 60 without T2DM or HTN (control). Sociodemographic, anthropometric, and clinical parameters were obtained from each subject and control. IR was derived from homeostasis model assessment (HOMA)-IR index calculated from fasting blood glucose and insulin. Results: The mean age of subjects with T2DM and HTN was 49.58 ± 10.50 years, that of subjects with T2DM and normotension was 48.50 ± 10.44 years, while that of controls was 48.85 ± 10.15 years. IR (HOMA-IR ≥2) was found in 96.7% of subjects with T2DM and HTN, 88.3% of those with T2DM and normotension, and 1.7% of subjects with neither of both conditions. Central obesity (Waist circumference “WC”), overweight, and obesity (BMI) significantly related to IR in subjects with T2DM and HTN (p = 0.020, 0.021 and 0.016 respectively) while only WC and obesity (BMI) significantly related to IR in subjects with T2DM and normotension (p = 0.001 and 0.036 respectively). Conclusions: There is a high prevalence of IR in T2DM subjects which is heightened by the presence of HTN.

Associations of Betatrophin/ANGPTL8 with Septic Dyslipidemia in Human Peritonitis: An Explorative Analysis.

Sepsis is defined by life-threatening organ dysfunction mediated by the host's response to infection. This can result in septic dyslipidemia, which is involved in the neutralization of pathogen-related lipids. Knowledge of the regulatory mechanisms of septic dyslipidemia is incomplete. The cytokine betatrophin/Angiopoietin-like protein 8 (ANGPTL8) plays a role in the regulation of triacylglyceride metabolism, though its function in septic dyslipidemia remains unknown. Sixty-six patients were enrolled in a cross-sectional study. Circulating concentrations and adipose tissue (AT) mRNA expression of betatrophin/ANGPTL8 were studied in patients suffering from peritoneal sepsis. Insulin-resistant individuals and subjects without metabolic derangement/systemic inflammation were enrolled as controls. All underwent open abdominal surgery. Circulating betatrophin/ANGPTL8 was analyzed by an enzyme-linked immunosorbent assay and AT mRNA expression levels were assessed by real-time PCR. Standard laboratory analyses including lipid electrophoresis were evaluated. Sepsis patients showed pronounced septic dyslipidemia (p &lt; 0.05 for all major lipid classes). Despite comparable betatrophin/ANGPTL8 mRNA expression in AT (p = 0.24), we found significantly increased circulating betatrophin/ANGPTL8 with septic dyslipidemia (p = 0.009). Expression levels of betatrophin/ANGPTL8 in AT correlated with circulating concentrations in both control groups (r = 0.61; p = 0.008 and r = 0.43; p = 0.034), while this association was undetectable in sepsis. After stratification, betatrophin/ANGPTL8 remained associated with hypertriacylglyceridemia (p &lt; 0.05).

Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study.

α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal, glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, and urinary AGEs using the UPLC/MS-MS method; soluble receptors for AGEs (sRAGE), and cardiometabolic risk markers in 142 (49% females) insulin resistant (Quantitative Insulin Sensitivity Check Index (QUICKI) ≤ 0.319) and 167 (47% females) age-, and waist-to-height ratio-matched insulin-sensitive controls aged 16-to-22 years. The between-group comparison was performed using the two-factor (sex, presence/absence of insulin resistance) analysis of variance; multiple regression via the orthogonal projection to latent structures model. In comparison with their insulin-sensitive peers, young healthy insulin-resistant individuals without diabetes manifest alterations throughout the α-dicarbonyls-AGEs-sRAGE axis, dominated by higher 3-deoxyglucosone levels. Variables of α-dicarbonyls-AGEs-sRAGE axis were associated with insulin sensitivity independently from cardiometabolic risk markers, and sex-specifically. Cleaved RAGE associates with QUICKI only in males; while multiple α-dicarbonyls and AGEs independently associate with QUICKI particularly in females, who displayed a more advantageous cardiometabolic profile compared with males. Further studies are needed to elucidate whether interventions alleviating dicarbonyl stress ameliorate insulin resistance.

Moderate intensity continuous and interval training affect visceral fat and insulin resistance model in female rat exposed high calorie diet

Chronic high-calorie diet (HCD) combined with physical inactivity promotes obesity and insulin resistance (IR). This study aimed to analyse the comparable effect of moderate-intensity continuous training (MICT) and moderate-intensity interval training (MIIT) on visceral fat weight and IR in subjects exposed to HCD. This randomised post-test research used only a control group design with female rats (Wistar norvegicus), 8 weeks old and 100-200 g of bodyweight. They were randomly divided into four groups: standard diet group (C), HCD group (C1), HCD combined with MICT group (C2) and HCD combined with MIIT group (C3). Each group consisted of six rats. HCD consisted of ad libitum standard diet plus dextrose solution by oral gavage for 4 weeks. The MICT was conducted by swimming plus 6% load of body weight for 10 min in the first week, for 20 min in the second week and 30 min in the third and fourth week. The MIIT was conducted by swimming in a ratio between swimming and rest time at 2:1 plus 6% load of BW, performed 5×/week for 4 weeks, and increased progressively. The mean body weight pre-intervention was 152.79±13.280 g and 150.12±9.195 g post-intervention (P=0.115). The mean fasting blood glucose pre-intervention was 79±8.668 mg/dl, and post-intervention 86.29±12.142 mg/dl (P=0.142). The mean visceral fat weight between C (1.94±0.66 g), C1 (1.45±0.47 g), C2 (1.41±0.44 g), and C3 (1.22±0.59 g) was not significant (P=0.179). The mean triglyceride level for C (173.33±30.30 mg/dl), C1 (157.16±47.32 mg/dl), C2 (112.83±25.49 mg/dl), and C3 (80.33±23.47 mg/dl) was significant (P=0.000). The mean IR model for C (4.796±0.070), C1 (4.728±0.125), C2 (4.620±0.123), C3 (4.360±0.143) was significant (P=0.000). In conclusion, both MICT and MIIT have an effect to improve IR and TG. The MIIT was more effective to improve IR compared to MICT in the female rats exposed to an HCD.

Low miR-222 expression in human visceral adipose tissue is associated with insulin resistance and PTEN and p53 mRNA levels.

The aim of this is study was to analyse the expression of miR-193b, miR-378, miR-Let7-d, and miR-222 in human visceral adipose tissue (VAT), as well as their association with obesity, insulin resistance (IR), and their role in the regulation of genes controlling adipose tissue homeostasis, including adipocytokines, the phosphatase and tension homologue (PTEN), and tumour protein 53 (p53). VAT was obtained from normal-weight (NW), overweight, and obese (OW/OB) subjects with and without IR. Stem-loop RT-qPCR was used to evaluate miRNA expression levels. miRTarBase 4.0, miRWalk, and DIANA-TarBase v8 were used for prediction of validated target gene of the miRNA analysed. A qPCR was used to evaluate PTEN, p53, leptin (LEP), and adiponectin (ADIPOQ) mRNA. miR-222 was lower in IR subjects, and miR-222 and miR-378 negatively correlated with HOMA-IR. PTEN and p53 are miR-222 direct targets according to databases. mRNA expression of PTEN and p53 was lower in OW/OB subjects with and without IR, compared to NW group and its levels positively associated with miR-222. Additionally, p53 and PTEN are positively associated with serum leptin levels. On the other hand, miR-193b and miR-378 negatively correlated with serum leptin but not with mRNA levels. Moreover, miR-Let-7d negatively correlated with serum adiponectin but not with adiponectin mRNA levels. Lower miR-222 levels are associated with IR, and PTEN and p53 expression; the implication of these genes in adipose tissue homeostasis needs more research.

Orange juice intake by obese and insulin-resistant subjects lowers specific plasma triglycerides: A randomized clinical trial.

Dyslipidaemia is usually common in obesity, insulin resistance, and type 2 diabetes mellitus. Clinical trials suggest that orange juice may have a positive impact on lipid metabolism and blood lipid profiles; however conflicting results have been reported. Here, we applied a combined untargeted/targeted lipidomic analysis of plasma to examine the impact of orange (Citrus sinensis) juice intake on the lipidome profile of obese and insulin-resistant subjects. Twenty-five participants, both sexes, aged 40-60 years, with obesity and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) index >2.71) ingested 400mL of orange juice 'Pera' (C.sinensis) for 15d. Cardiometabolic biomarkers, anthropometric parameters, blood pressure, and plasma lipidomic analysis results were assessed at the beginning and end of the intervention. After the 15-d intervention, a significant decrease was observed in the diastolic blood pressure and blood lipid profile. Among plasma lipidomes, 316 lipid molecules were identified, with the triglycerides (TGs) subclass being the most abundant (n=106). Plasma lipidome profiling revealed a major signature of the intervention; with concentrations of 37TG species decreasing after intervention. Qualitatively, oleic and linoleic acids were among the most prevalent fatty acids linked to the altered TG species, representing 50% of TG chains. Modulated TG species were positively correlated with total TG and very low-density lipoprotein levels, as well as systolic and diastolic blood pressure. A strong inter-individual trend was observed, wherein, compared with less responsive subjects, the high responsive subjects displayed the highest decrease in the concentrations of altered TG species, as as well as systolic blood pressure (decrease of 10.3±6.8mmHg) and body weight (decrease of 0.67±0.71kg). These findings suggest that orange juice has a positive impact on lipid metabolism, mainly regarding the composition of TG-specific fatty acid chains and cholesterol esters, protecting against insulin resistance. Furthermore, lipidomics may help clarify alterations at the molecular level after an intervention, contributing to improve the evaluation of the link between dyslipidaemia, insulin resistance, and nutrition.

Tart Cherry Juice Reduces Plasma Triglycerides and CVD Risk Factor, But Does not Affect Indirect Measures of Insulin Resistance, in Overweight and Obese Subjects: A Randomized, Crossover Pilot Study

Tart Cherry Juice Reduces Plasma Triglycerides and CVD Risk Factor, But Does not Affect Indirect Measures of Insulin Resistance, in Overweight and Obese Subjects: A Randomized, Crossover Pilot Study

Association between sarcopenic obesity with insulin resistance and metabolic syndrome

BackgroundThere is a debate as to whether sarcopenic obesity leads to an increased risk of metabolic syndrome in young adults. ObjectiveTo determine the association between sarcopenic obesity with metabolic syndrome (MS) and insulin resistance (IR). MethodsA 5-year retrospective cross-sectional study. Subjects of the specialty consultation between 18 and 55 years old, with BMI≥35 with comorbidity or BMI≥40 with and without comorbidity were included. The association was calculated using an odds ratio with 95% confidence intervals. Results254 subjects were analyzed, 76.4% were women and average age was 38.36±8.78 years. The OR of IR in subjects with or without sarcopenic obesity was 2224 (95% CI, 1127 to 4389, p=0.02). The OR of MS in subjects with or without sarcopenia was 1.045 (95% CI, 0.624–1.748, p=0.868). A difference was found between the fat mass in the group with IR vs without IR of 60.58±14.4kg vs 53.98±12.2kg (p<0.001); likewise, between the BMI and muscle mass of 46.15±6.78 kg/m2 vs 43.51±6.11kg/m2 (p<0.05) and 30.05±7.48kg vs 27.86±5.91kg (<0.05) respectively. ConclusionThe association between sarcopenic obesity with IR in young adults was significant, but not with MS. Our findings emphasize the need to become aware of the importance of maintaining lean mass in obese subjects.