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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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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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Effects of Calorie Restriction on Health Span and Insulin Resistance: Classic Calorie Restriction Diet vs. Ketosis-Inducing Diet.
Napoleão, A, Fernandes, L, Miranda, C, Marum, AP
Nutrients. 2021;(4)
Abstract
As the incidence of Chronic Non-Communicable Diseases (CNCDs) increases, preventive approaches become more crucial. In this review, calorie restriction (CR) effects on human beings were evaluated, comparing the benefits and risks of different CR diets: classic CR vs. ketosis-inducing diets, including intermittent fasting (IF), classic ketogenic diet (CKD), fasting mimicking diet (FMD), very-low-calorie ketogenic Diet (VLCKD) and Spanish ketogenic Mediterranean diet (SKMD). Special emphasis on insulin resistance (IR) was placed, as it mediates metabolic syndrome (MS), a known risk factor for CNCD, and is predictive of MS diagnosis. CR is the most robust intervention known to increase lifespan and health span, with high evidence and known biochemical mechanisms. CR improves cardiometabolic risk parameters, boosts exercise insulin sensitivity response, and there may be benefits of implementing moderate CR on healthy young and middle-aged individuals. However, there is insufficient evidence to support long-term CR. CKD is effective for weight and MS management, and may have additional benefits such as prevention of muscle loss and appetite control. SKMD has extreme significance benefits for all the metabolic parameters studied. Studies show inconsistent benefits of IF compared to classic CR. More studies are required to study biochemical parameters, reinforce evidence, identify risks, and seek effective and safe nutritional CR approaches.
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Moderate-Intensity Exercise and High-Intensity Interval Training Affect Insulin Sensitivity Similarly in Obese Adults.
Ryan, BJ, Schleh, MW, Ahn, C, Ludzki, AC, Gillen, JB, Varshney, P, Van Pelt, DW, Pitchford, LM, Chenevert, TL, Gioscia-Ryan, RA, et al
The Journal of clinical endocrinology and metabolism. 2020;(8):e2941-59
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OBJECTIVE We compared the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on insulin sensitivity and other important metabolic adaptations in adults with obesity. METHODS Thirty-one inactive adults with obesity (age: 31 ± 6 years; body mass index: 33 ± 3 kg/m2) completed 12 weeks (4 sessions/week) of either HIIT (10 × 1-minute at 90%HRmax, 1-minute active recovery; n = 16) or MICT (45 minutes at 70%HRmax; n = 15). To assess the direct effects of exercise independent of weight/fat loss, participants were required to maintain body mass. RESULTS Training increased peak oxygen uptake by ~10% in both HIIT and MICT (P < 0.0001), and body weight/fat mass were unchanged. Peripheral insulin sensitivity (hyperinsulinemic-euglycemic clamp) was ~20% greater the day after the final exercise session compared to pretraining (P < 0.01), with no difference between HIIT and MICT. When trained participants abstained from exercise for 4 days, insulin sensitivity returned to pretraining levels in both groups. HIIT and MICT also induced similar increases in abundance of many skeletal muscle proteins involved in mitochondrial respiration and lipid and carbohydrate metabolism. Training-induced alterations in muscle lipid profile were also similar between groups. CONCLUSION Despite large differences in training intensity and exercise time, 12 weeks of HIIT and MICT induce similar acute improvements in peripheral insulin sensitivity the day after exercise, and similar longer term metabolic adaptations in skeletal muscle in adults with obesity. These findings support the notion that the insulin-sensitizing effects of both HIIT and MICT are mediated by factors stemming from the most recent exercise session(s) rather than adaptations that accrue with training.
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Association of rs670 variant of APOA1 gene with lipid profile and insulin resistance after 9 months of a high protein/low carbohydrate vs a standard hypocaloric diet.
Izaola, O, Primo, D, Gomez Hoyos, E, Lopez Gomez, JJ, Ortola, A, de Luis, D
Clinical nutrition (Edinburgh, Scotland). 2020;(4):988-993
Abstract
BACKGROUND & AIMS A common G-to-A transition (rs670) in the APOA1 gene has been related with metabolism. We evaluate the association of this SNP with changes in lipid profile and insulin resistance in response to two diets. METHODS 268 obese patients were randomly allocated to a high protein/low carbohydrate -Diet HP- vs. a standard hypocaloric diet -Diet S- for 9 months. Anthropometric and biochemical status were evaluated at 3 and 9 months. RESULTS 179 subjects (66.8%) had the genotype GG, 79 patients GA (29.4%) and 10 subjects AA (3,8%). With both diets: the decrease of BMI, weight, waist circumference, fat mass was higher in A allele carriers than non-carriers. Also on both diets A allele carriers showed greater improvements in total cholesterol (-19.0 ± 2.5 mg/dl (non-A allele carriers -12.1 ± 2.0 mg/dl:p = 0.02 after Diet HP) and -13.1 ± 2.1 mg/dl (non-A allele carriers -8.9 ± 1.1 mg/dl:p = 0.02 after Diet S)), LDL-cholesterol (-18.0 ± 2.1 mg/dl (non-A allele carriers -8.3 ± 2.2 mg/dl:p = 0.01 after Diet HP) and -12.0 ± 1.5 mg/dl (non-A allele carriers -6.3 ± 2.3 mg/dl:p = 0.01 after Diet S)), insulin (-2.5 ± 0.2 mUI/L (in non A allele -1.8 ± 0.2 mUI/L:p = 0.01 after Diet HP) and -2.1 ± 0.1 mUI/L (non A allele carriers -1.2 ± 0.3 mUI/L:p = 0.01 after Diet S)), HOMA-IR (-1.3 ± 0.3 units (non A allele group -0.8 ± 0.2:p = 0.03 after Diet HP) and -1.1 ± 0.1 units (non A allele carriers -0.3 ± 0.2 mg/dl:p = 0.01 after Diet S)) than non-A allele carriers. CONCLUSIONS A allele carriers of rs670 ApoA1 polymorphism showed a higher decrease of insulin resistance, LDL cholesterol and adiposity induced by two different hypocaloric diet than non A allele carriers.
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Copeptin and Estimated Insulin Sensitivity in Adults With and Without Type 1 Diabetes: The CACTI Study.
Jensen, T, Bjornstad, P, Johnson, RJ, Sippl, R, Rewers, M, Snell-Bergeon, JK
Canadian journal of diabetes. 2019;(1):34-39
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OBJECTIVES Copeptin, a surrogate marker for vasopressin, is elevated in participants with insulin resistance (IR) and type 2 diabetes. Whereas adults with type 1 diabetes also demonstrate elevated copeptin concentrations and IR compared to controls without diabetes, the relationship between copeptin and IR in type 1 diabetes is unclear. METHODS Participants with (n=209) and without (n=244) type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were assessed for serum copeptin, vitals, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, glycated hemoglobin and lipid panels. Estimated insulin sensitivity (eIS) was calculated by validated equations in participants with and without type 1 diabetes. The relationships among copeptin, IR, waist circumference (WC) and body mass index (BMI) were examined with unadjusted and adjusted linear regression models. RESULTS Copeptin was correlated with eIS (R=-0.17, R2=0.029), WC (R=0.16, R2=0.026) and BMI (R=0.22, R2=0.048) for type 1 diabetes and with eIS (R=-0.37, R2=0.14), WC (R=0.40, R2=0.16) and BMI (R=0.25, R2=0.063) in non-type 1 diabetes. In multivariable analysis, copeptin correlated with total cholesterol (beta±SE: -0.12±0.04, p=0.008) and low-density lipoprotein (beta±SE: -0.11±0.04, p=0.01) in type 1 diabetes. In non-type 1 diabetes, copeptin was associated with WC (beta±SE: 0.14±0.04, p=0.0024), BMI (beta±SE: 0.13±0.04, p=0.007) and eIS (beta±SE: -0.14±0.04, p=0.0013). CONCLUSIONS Copeptin does not correlate with markers of IR in type 1 diabetes but strongly correlates in non-type 1 diabetes. Thus, elevated vasopressin activity and IR appear to be independent risk factors for vascular complications in type 1 diabetes.
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Contribution of lower physical activity levels to higher risk of insulin resistance and associated metabolic disturbances in South Asians compared to Europeans.
Afaq, S, Kooner, AS, Loh, M, Kooner, JS, Chambers, JC
PloS one. 2019;(5):e0216354
Abstract
BACKGROUND Insulin resistance and related metabolic disturbances are major risk factors for the higher T2D risk and associated morbidity and mortality amongst South Asians. The contribution of physical activity to the increased prevalence of insulin resistance and related disturbances amongst South Asians is unknown. METHODS We recruited 902 South Asian and European men and women, aged 35-85 years from the ongoing LOLIPOP study. Clinical characterisation comprised standardised questionnaire and measurement of height, weight, waist and hip circumference and blood pressure. Fasting bloods were taken for assessment of glucose, insulin, lipids and HbA1c. Physical activity was quantified using a validated accelerometer, Actigraph GT3X+, worn for 7 days. Univariate and multivariate approaches were used to investigate the relationship between ethnicity, physical activity, insulin resistance and related metabolic disturbances. RESULTS Total physical activity was ~31% (P = 0.01) lower amongst South Asians compared to Europeans (Mean MET.minutes [SD]: 1505.2 [52] vs. 2050.9 [86.6], P<0.001). After adjusting for age and sex, total physical activity had a negative association with HOMA-IR (B [SE]: -0.18 [0.08], P = 0.04) and fasting glucose levels (B[SE]: -0.11 [0.04], P = 0.02). There was no association between physical activity and other glycemic and lipid parameters. Total physical activity per week contributed towards the differences in insulin resistance and associated metabolic disturbances between South Asians and Europeans. CONCLUSION Lower levels of physical activity may contribute to the increased insulin resistance in South Asians compared to Europeans. Our results suggest that lifestyle modification through increased physical activity may help to improve glucose metabolism and reduce the burden of excess T2D and related complications amongst South Asians.
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Performance of individually measured vs population-based C-peptide kinetics to assess β-cell function in the presence and absence of acute insulin resistance.
Varghese, RT, Dalla Man, C, Laurenti, MC, Piccinini, F, Sharma, A, Shah, M, Bailey, KR, Rizza, RA, Cobelli, C, Vella, A
Diabetes, obesity & metabolism. 2018;(3):549-555
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AIMS: To compare the performance of population-based kinetics with that of directly measured C-peptide kinetics when used to calculate β-cell responsivity indices, and to study people with and without acute insulin resistance to ensure that population-based kinetics apply to all conditions where β-cell function is measured. METHODS Somatostatin was used to inhibit endogenous insulin secretion in 56 people without diabetes. Subsequently, a C-peptide bolus was administered and the changing concentrations were used to calculate individual kinetic measures of C-peptide clearance. In addition, the participants were studied on 2 occasions in random order using an oral glucose tolerance test (OGTT). On one occasion, free fatty acid elevation, to cause insulin resistance, was achieved by infusion of Intralipid + heparin. The Disposition Index (DI) was then estimated by the oral minimal model using either population-based or individual C-peptide kinetics. RESULTS There were marked differences in the exchange variables (k 12 and k 21 ) of the model describing C-peptide kinetics, but smaller differences in the fractional clearance; that is, the irreversible loss from the accessible compartment (k 01 ), obtained from population-based estimates compared with experimental measurement. Because it is predominantly influenced by k 01 , DI estimated using individual kinetics correlated well with DI estimated using population-based kinetics. CONCLUSIONS These data support the use of population-based measures of C-peptide kinetics to estimate β-cell function during an OGTT.
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Homeostasis Model Assessment-Adiponectin: the role of different types of physical exercise in obese adolescents.
da Silveira Campos, RM, Landi Masquio, DC, Campos Corgosinho, F, de Lima Sanches, P, de Piano, A, Carnier, J, Leão da Silva, P, Grotti Clemente, AP, de Castro Ferreira Vicente, SE, Oyama, LM, et al
The Journal of sports medicine and physical fitness. 2017;(6):831-838
Abstract
BACKGROUND Homeostasis Model Assessment-Adiponectin (HOMA-AD) is suggesting a new biomarker of insulin resistance in obese population. In this way, the purpose of this study was to investigate the effects of different kinds of exercise in the sensitive index predictor of insulin resistance. METHODS A total of 148 obese adolescents were enrolled in the program. They aged 15-19 y, with Body Mass Index (BMI) ≥P95th and were submitted to 1 year of interdisciplinary weight loss therapy, randomized in two groups, aerobic training (AT) (N.=51) and aerobic plus resistance training (N.=97). Blood samples were collected to analyze adiponectin, glucose and insulin concentrations. The insulin resistance was measured by HOMA-AD and Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR). RESULTS Both kinds of exercise training promoted a decrease in body mass, body mass index, fat mass, visceral and subcutaneous fat. However, only aerobic plus resistance training was effective to reduce HOMA-AD, insulin and glucose concentration; and increase insulin sensibility and adiponectin concentration. CONCLUSIONS The aerobic plus resistance training was more effective than AT alone to improve the HOMA-AD, suggesting clinical application on obesity, diabetes, atherosclerosis and metabolic syndrome control in the pediatric population.
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PCSK7 genotype modifies effect of a weight-loss diet on 2-year changes of insulin resistance: the POUNDS LOST trial.
Huang, T, Huang, J, Qi, Q, Li, Y, Bray, GA, Rood, J, Sacks, FM, Qi, L
Diabetes care. 2015;(3):439-44
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OBJECTIVE A common variant rs236918 in the PCSK7 gene has the strongest association with iron homeostasis and is related to insulin resistance. Dietary carbohydrate (CHO) modulates the genetic effect on insulin resistance. We examined whether 2-year weight-loss diets modify the effect of PCSK7 genetic variants on changes in fasting insulin levels and insulin resistance in a randomized, controlled trial. RESEARCH DESIGN AND METHODS Data were analyzed in the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial, which is a randomized, controlled 2-year weight-loss trial using diets that differed in macronutrient proportions. PCSK7 rs236918 was genotyped in 730 overweight or obese adults (80% whites) in this trial. We assessed the progression in fasting insulin and glucose levels, and insulin resistance by genotypes. RESULTS During the 6-month weight-loss phase, the PCSK7 rs236918 G allele was significantly associated with greater decreases in fasting insulin levels in the high-dietary CHO group (P for interaction = 0.04), while the interaction for changes in HOMA-insulin resistance (HOMA-IR) (P for interaction = 0.06) did not reach significant levels in white subjects. The G allele was significantly associated with a greater decrease in fasting insulin levels and HOMA-IR in response to high dietary CHO levels (P = 0.02 and P = 0.03, respectively). From 6 months to 2 years (weight-regain phase), the interactions became attenuated due to the regaining of weight (P for interactions = 0.08 and 0.06, respectively). In addition, we observed similar and even stronger results in the whole-study samples from the trial. CONCLUSIONS Our data suggest that PCSK7 genotypes may interact with dietary CHO intake on changes in insulin sensitivity in the white Americans.
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Effects of a high-protein/low carbohydrate versus a standard hypocaloric diet on adipocytokine levels and insulin resistance in obese patients along 9 months.
de Luis, DA, Izaola, O, Aller, R, de la Fuente, B, Bachiller, R, Romero, E
Journal of diabetes and its complications. 2015;(7):950-4
Abstract
OBJECTIVE Recent dietary trials and observational studies have focused on the effects of diet on health outcomes such as improvement in levels of surrogate biomarkers. The aim of our study was to examine the changes in weight, adipocytokines levels and insulin resistance after a high-protein/low carbohydrate hypocaloric diet vs. a standard hypocaloric diet during an intervention of 9 months. SUBJECTS AND METHODS 331 obese subjects were randomly allocated to one of two diets for a period of 9 months. Diet HP (n=168) (high-protein hypocaloric diet) consisted in a diet of 1050 cal/day, 33% of carbohydrates, 33% of fats and 34% of proteins. Diet S (n=163) (standard protein hypocaloric diet) consisted in a diet of 1093 cal/day, 53% carbohydrates, 27%fats, and 20% proteins. RESULTS With the diets HP and S, BMI, weight, fat mass, waist circumference, waist-to-hip ratio, systolic blood pressure, total cholesterol, LDL-cholesterol, insulin and HOMA decreased. The decrease at 9 months of (BMI: -2.6±1.3kg/m(2) vs. -2.1±1.2kg/m(2):p<0.05), weight (-8.4±4.2kg vs. -5.0±4.1kg: p<0.05), fat mass (-5.1±4.1kg vs. -3.4±4.2kg: p<0.05), systolic blood pressure (-5.1±7.1mmHg vs. -3.1±2.1mmHg: p<0.05), (insulin levels -4.0±4.8 UI/L vs. -2.2±2.4 UI/L; p<0.05) and HOMA (-0.8±1.0 units vs. -0.3±1.0 units; p<0.05) was higher in diet HP than Diet S. With both diets, leptin levels decreased. CONCLUSION A high-protein/low carbohydrate hypocaloric diet shows a higher weight loss, insulin and HOMA-R decreased after 9 months than a standard hypocaloric diet. The improvement in adipokine levels was similar with both diets.