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Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.
Sarabhai, T, Koliaki, C, Mastrototaro, L, Kahl, S, Pesta, D, Apostolopoulou, M, Wolkersdorfer, M, Bönner, AC, Bobrov, P, Markgraf, DF, et al
Diabetologia. 2022;(2):301-314
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Abstract
AIMS/HYPOTHESIS Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION ClinicalTrials.gov .NCT01736202. FUNDING German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.
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Assessing the utility of cardiorespiratory fitness, visceral fat, and liver fat in predicting changes in insulin sensitivity beyond simple changes in body weight after exercise training in adolescents.
Kuk, JL, Lee, S
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(1):55-62
Abstract
To examine the utility of changes in cardiorespiratory fitness (CRF) and body composition in response to exercise training in adolescents with obesity beyond simple measures of body weight change. This is a secondary analysis of our previously published randomized trials of aerobic, resistance, and combined training. We included 104 adolescents (body mass index (BMI) ≥85th percentile) who had complete baseline and post-intervention data for CRF, regional body fat, insulin sensitivity, and oral glucose tolerance. Associations between changes in body composition and CRF with cardiometabolic variables were examined adjusted for age, sex, Tanner stage, race, exercise group, and weight loss. At baseline, CRF, visceral fat and liver fat were correlated with insulin sensitivity with and without adjustment for BMI percentile. Training-associated changes in CRF, visceral fat, and liver fat were also correlated with insulin sensitivity changes, but not independent of body weight change. After accounting for body weight change, none of the body composition or CRF were associated with changes in insulin sensitivity, glucose tolerance, systolic blood pressure, or high-density lipoprotein cholesterol. Although CRF and body composition were strong independent correlates of insulin sensitivity at baseline, changes in CRF and visceral fat were not associated with changes in insulin sensitivity after accounting for body weight change. Clinicaltrials.gov registration nos.: NCT00739180, NCT01323088, NCT01938950. Novelty With exercise training, changes in body weight, CRF, visceral fat, and liver fat were correlated with changes in insulin sensitivity. Changes in body composition or CRF generally did not remain significant correlates of changes in insulin sensitivity after adjusting for body weight changes.
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Effects of preoperative oral single-dose and double-dose carbohydrates on insulin resistance in patients undergoing gastrectomy:a prospective randomized controlled trial.
Chen, X, Li, K, Yang, K, Hu, J, Yang, J, Feng, J, Hu, Y, Zhang, X
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1596-1603
Abstract
BACKGROUND & AIMS Preoperative oral carbohydrates are strongly recommended for routine use before various elective procedures. The regimen mainly includes preoperative oral single-dose carbohydrate (2-3 h before surgery) and preoperative oral double-dose carbohydrates (10 h before surgery and 2-3 h before surgery). The choice between the two options is still controversial. METHODS A total of 139 patients with gastric cancer who underwent radical gastrectomy were recruited from a hospital in Sichuan Province, China. The patients were randomly assigned to a single-dose group (n = 70) or a double-dose group (n = 69). Insulin resistance indicators, subjective comfort indicators, inflammatory mediators, immunological indicators, postoperative recovery indexes, and complications were compared between the two groups. RESULTS There were no differences in insulin resistance indicators (fasting plasma glucose, fasting insulin, and homeostasis model assessment indexes), inflammatory mediators (C-reactive protein, interleukin-6, and tumor necrosis factor-α), immunological indicators (CD3+, CD4+, CD8+, and CD4+/CD8+) between the single-dose group and double-dose group (all P > 0.05) at preoperative day 1, preoperative 3 h, and postoperative day 1. There were no differences in subjective comfort indicators (thirst, hunger, anxiety, nausea, fatigue, and weakness) between the two groups (all P > 0.05) at preoperative day 1, preoperative 3 h, preoperative 1 h, and postoperative day 1. The postoperative recovery indexes and complications (exhaust time, liquid intake time, postoperative hospital stay, complication incidence, unplanned readmission rate, and unplanned reoperation rate 30 days after operation) did not significantly differ between the two groups (all P > 0.05). The number of preoperative nighttime urinations in the double-dose group was higher than that in the single-dose group (88.3% VS 48.5%, P < 0.001), and the number of hours of preoperative sleep in the double-dose group was lower than that in the single-dose group (4.56 ± 0.68 VS 5.71 ± 0.57, P < 0.001). CONCLUSION Oral carbohydrates administered the night before surgery did not enhance the effects of oral carbohydrates administered 2-3 h before surgery on insulin resistance, subjective comfort, inflammation, and immunity and might affect the patients' night rest. In making a decision between oral carbohydrate regimes, evening carbohydrates could be omitted. TRIAL REGISTRATION ChiCTR, ChiCTR1900020608. Registered January 10, 2019, http://www.chictr.org.cn: ChiCTR1900020608.
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Resistance training attenuates circulating FGF-21 and myostatin and improves insulin resistance in elderly men with and without type 2 diabetes mellitus: A randomised controlled clinical trial.
Shabkhiz, F, Khalafi, M, Rosenkranz, S, Karimi, P, Moghadami, K
European journal of sport science. 2021;(4):636-645
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Abstract
Fibroblast growth factor 21 (FGF-21) and myostatin have been proposed to be potential therapeutic target for insulin resistance in age-related metabolic disorders including type 2 diabetes (T2D). Moreover, despite the potential metabolic effect of resistance training on insulin resistance, aging, and T2D; the effect of this type of exercise training on FGF-21 and myostatin in elderly men with and without T2D are unknown. Forty-four elderly men were assigned to either the RT training (RT; without T2D: 12, with TD2 = 10) or the control group (C; without T2D: 12, with TD2 = 10). The RT group performed 12-wk resistance training intervention, 3 days/wk, 10 repetitions with 70% 1RM. At the baseline, the elderly men with T2D had a higher FGF-21 (p = 0.002) and myostatin (p = 0.02) concentrations and lower muscle strength (p = 0.01) than the elderly men without T2D. RT resulted in significant decrease in FGF-21 and myostatin concentration and increase in muscle strength in both elderly men with and without T2D (P = 0.001, for all) as well as decrease in HOMA-IR in only elderly men without T2D (P = 0.001). There was no significant difference in the RT-induced FGF-21 reduction between elderly men with and without T2D (p = 0.77, p = 0.28, respectively), but, RT caused a larger reduction in circulating myostatin in elderly men without T2D than with T2D (P = 0.007). Taken together, our results demonstrated that 12 weeks of RT induced an overall significant reduction of FGF-21 and myostatin in elderly men with and without T2D; with higher reduction of myostatin in elderly men without T2D.
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Preconception insulin resistance and neonatal birth weight in women with obesity: role of bile acids.
Wang, Z, Nagy, RA, Groen, H, Cantineau, AEP, van Oers, AM, van Dammen, L, Wekker, V, Roseboom, TJ, Mol, BWJ, Tietge, UJF, et al
Reproductive biomedicine online. 2021;(5):931-939
Abstract
RESEARCH QUESTION Does maternal preconception insulin resistance affect neonatal birth weight among women with obesity? Is insulin resistance associated with circulating bile acids? Do bile acids influence the association between maternal preconception insulin resistance and neonatal birth weight? DESIGN An exploratory post-hoc analysis of the LIFEstyle randomized controlled trial comparing lifestyle intervention with conventional infertility treatment in women with a BMI of ≥29 kg/m2. Fasting blood samples were collected at randomization and after 3 and 6 months in 469 women. Insulin resistance was quantified using the homeostasis model assessment of insulin resistance (HOMA-IR). Bile acid sub-species were determined by liquid chromatography with tandem mass spectrometry. Singletons were included (n = 238). Birth weight Z-scores were adjusted for age, offspring gender and parity. Multilevel analysis and linear regressions were used. RESULTS A total of 913 pairs of simultaneous preconception HOMA-IR (median [Q25; Q75]: 2.96 [2.07; 4.16]) and total bile acid measurements (1.79 [1.10; 2.94]) µmol/l were taken. Preconception HOMA-IR was positively associated with total bile acids (adjusted B 0.15; 95% CI 0.09 to 0.22; P < 0.001) and all bile acid sub-species. At the last measurement before pregnancy, HOMA-IR (2.71 [1.91; 3.74]) was positively related to birth weight Z-score (mean ± SD 0.4 ± 1.1; adjusted B 0.08; 95% CI 0.01 to 0.14; P = 0.03). None of the preconception bile acids measured were associated with birth weight. CONCLUSION Maternal preconception insulin resistance is an important determinant of neonatal birth weight in women with obesity, whereas preconception bile acids are not.
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The Effect of Exercise Intensity and Volume on Metabolic Phenotype in Patients with Metabolic Syndrome: A Randomized Controlled Trial.
von Korn, P, Keating, S, Mueller, S, Haller, B, Kraenkel, N, Dinges, S, Duvinage, A, Scherr, J, Wisløff, U, Tjønna, AE, et al
Metabolic syndrome and related disorders. 2021;(2):107-114
Abstract
Background: Moderate intensity continuous training (MICT) ameliorates dysmetabolism in patients with metabolic syndrome (MetS). The impact of low- (1HIIT) versus high-volume high-intensity interval training (4HIIT) versus MICT on central adiposity, insulin resistance, and atherogenic dyslipidemia in patients with MetS has not yet been reported. Methods: Twenty-nine patients with MetS according to International Diabetes Federation criteria (nine females, age 61 ± 5 years, body mass index 31.1 ± 3.7 kg/m2, waist circumference (WC) ♀ 102.2 ± 10.6 cm, ♂ 108.5 ± 8.6 cm) were randomized (1:1:1) to 16 weeks of (1) MICT (5 × 30 min/week, 35%-50% heart rate reserve (HRR), (2) 1HIIT (3 × 17 min/week incl. 4 min @80%-90% HRR), and (3) 4HIIT (3 × 38 min/week incl. 4 × 4 min @80%-90% HRR). Peak oxygen uptake (V̇O2peak), WC and anthropometric/metabolic indices indicative of MetS, fasting glucose/insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), dyslipidemia, and respiratory exchange ratio (RER) at warm-up were quantified at baseline and study completion. Analysis of variance and paired t tests were used for statistical analysis. Analyses were performed after checking for parametric distribution. Results: There were no significant differences between groups in waist-to-height ratio (♀: Δ -0.10 ± -0.05, ♂: Δ -0.08 ± -0.06, P = 0.916), WC (♀: Δ -1.4 ± -0.1 cm, ♂: Δ 0.1 ± 0.9 cm, P = 0.590), fasting glucose (Δ -1.18 ± 16.7 μU/mL, P = 0.773), fasting insulin (Δ 0.76 ± 13.4 μU/mL, P = 0.509), HOMA-IR (Δ 0.55 ± 4.1, P = 0.158), atherogenic dyslipidemia [triglycerides (TAG) Δ -10.1 ± 46.9 mg/dL, P = 0.468, high-density lipoprotein cholesterol (HDL-C) Δ 1.5 ± 5.4, P = 0.665, TAG/HDL-C -0.19 ± 1.3, P = 0.502], V̇O2peak (P = 0.999), or RER (P = 0.842). In the entire group, waist-to-height-ratio and V̇O2peak significantly improved by a clinically meaningful amount (Δ 2.7 ± 0.9 mL/min/kg; P < 0.001) and RER at warm-up significantly decreased (Δ -0.03 ± 0.06, P = 0.039). Conclusion: In patients with MetS, there was no significant difference between HIIT, irrespective of volume, to MICT for improving exercise capacity or metabolic health.
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Branched-Chain Amino Acids in relation to food preferences and insulin resistance in obese subjects consuming walnuts: A cross-over, randomized, double-blind, placebo-controlled inpatient physiology study.
Tuccinardi, D, Perakakis, N, Farr, OM, Upadhyay, J, Mantzoros, CS
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3032-3036
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Abstract
BACKGROUND&AIMS: To assess whether the concentrations of circulating Branched-Chain Amino Acids (BCAAs) change after walnut consumption and, whether these changes are associated with alterations in markers of insulin resistance and food preferences. METHODS In a crossover, randomized, double-blind, placebo-controlled study, ten subjects participated in two 5-day inpatient study admissions, during which they had a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts every morning. Between the two phases there was a 1-month washout period. RESULTS Fasting valine and isoleucine levels were reduced (p = .047 and p < .001) and beta-hydroxybutyrate levels were increased after 5-days of walnut consumption compared to placebo (p = .023). Fasting valine and isoleucine correlated with HOMA-IR while on walnut (r = 0.709, p = .032 and r = 0.679, p = .044). The postprandial area under the curve (AUC) of leucine in response to the smoothie consumption on day 5 was higher after walnut vs placebo (p = .023) and correlated negatively with the percentage of Kcal from carbohydrate and protein consumed during an ad libitum buffet meal consumed the same day for lunch (r = -0.661, p = .037; r = -0.628, p = .05, respectively). CONCLUSION The fasting and postabsorptive profiles of BCAAs are differentially affected by walnut consumption. The reduction in fasting valine and isoleucine may contribute to the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality, whereas the increase in postabsorptive profiles with walnuts may influence food preference. TRIAL REGISTRATION CLINICALTRIALS.GOV: Number: NCT02673281, Website: https://clinicaltrials.gov/ct2/show/NCT02673281.
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Randomized double-blind clinical trial examining the Ellagic acid effects on glycemic status, insulin resistance, antioxidant, and inflammatory factors in patients with type 2 diabetes.
Ghadimi, M, Foroughi, F, Hashemipour, S, Rashidi Nooshabadi, M, Ahmadi, MH, Ahadi Nezhad, B, Khadem Haghighian, H
Phytotherapy research : PTR. 2021;(2):1023-1032
Abstract
Oxidative stress can worsen glycemic status. Considering the antioxidant properties of Ellagic acid (EA), this study was designed to evaluate the effect of EA on glycemic indices, lipid profile, oxidative stress, and inflammation status in type 2 diabetic patients. Overall, 44 patients were recruited and were randomly allocated consumed 180 mg of EA per day (n = 22) or placebo (n = 22) for 8 weeks. The blood sugar (BS), insulin, insulin resistance (IR), hemoglobin A1c (HbA1 c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total antioxidant capacity (TAC), malondialdehyde (MDA), the activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD), C-reactive protein (CRP), TNF-α and interleukin 6 (IL-6) were measured at the beginning and end of the study. At the end of the study, the mean of BS, insulin, IR, HbA1 c, TC, TG, LDL, MDA, CRP, TNF-α, and IL-6 were significantly decreased in the intervention group (p < .05). Also, the mean of TAC (+0.8 ± 0.01) and activity of GPx (+10.26 ± 0.22) and SOD enzymes (+459.6 ± 9.76) significantly increased in the intervention group (p < .05). EA supplementation can be helpful as a diet supplement in patients with type 2 diabetes through improvement in chronic adverse effects.
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Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome.
Kaur, V, Dimitriadis, GK, Pérez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, et al
Metabolism: clinical and experimental. 2021;:154908
Abstract
BACKGROUND Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
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Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control.
Ponirakis, G, Abdul-Ghani, MA, Jayyousi, A, Zirie, MA, Al-Mohannadi, S, Almuhannadi, H, Petropoulos, IN, Khan, A, Gad, H, Migahid, O, et al
Journal of diabetes investigation. 2021;(11):2002-2009
Abstract
AIMS/INTRODUCTION This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy. MATERIALS AND METHODS This was an exploratory substudy of an open-label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy. RESULTS A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low-density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05). CONCLUSIONS Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.