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1.
Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome.
González, F, Considine, RV, Abdelhadi, OA, Acton, AJ
The Journal of clinical endocrinology and metabolism. 2019;(3):934-946
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Abstract
CONTEXT Inflammation and insulin resistance (IR) are often present in polycystic ovary syndrome (PCOS). OBJECTIVE We determined the effect of saturated fat ingestion on circulating lipopolysaccharide (LPS) and mononuclear cell (MNC) toll-like receptor-4 (TLR-4) and suppressor of cytokine signaling-3 (SOCS-3) in women with PCOS. DESIGN Cross-sectional study. SETTING Academic medical center. PATIENTS Nineteen reproductive-age women with PCOS (10 lean, 9 obese) and 19 ovulatory control subjects (10 lean, 9 obese). MAIN OUTCOME MEASURES LPS and TNFα levels were measured in plasma. TLR-4 and SOCS-3 mRNA and protein content were quantified in MNC from blood collected after fasting and 2, 3, and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood collected after fasting and 24, 48, and 72 hours after human chorionic gonadotropin (HCG) administration. RESULTS Regardless of PCOS status, subjects who were obese had lipid-induced increases in circulating LPS and TLR-4 protein content compared with subjects who were lean. Lean and obese women with PCOS had lipid-induced increases in plasma TNFα and SOCS-3 mRNA and protein content compared with lean control subjects. Both PCOS groups had lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. The LPS and SOCS-3 responses were negatively correlated with ISOGTT and positively correlated with HCG-stimulated androgen secretion. CONCLUSION In PCOS, lipid-induced LPS-mediated inflammation through TLR-4 is associated with obesity and worsened by PCOS, whereas lipid-induced increases in SOCS-3 may represent an obesity-independent, TNFα-mediated mechanism of IR.
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Targeting the Zinc Transporter ZIP7 in the Treatment of Insulin Resistance and Type 2 Diabetes.
Adulcikas, J, Sonda, S, Norouzi, S, Sohal, SS, Myers, S
Nutrients. 2019;(2)
Abstract
Type 2 diabetes mellitus (T2DM) is a disease associated with dysfunctional metabolic processes that lead to abnormally high levels of blood glucose. Preceding the development of T2DM is insulin resistance (IR), a disorder associated with suppressed or delayed responses to insulin. The effects of this response are predominately mediated through aberrant cell signalling processes and compromised glucose uptake into peripheral tissue including adipose, liver and skeletal muscle. Moreover, a major factor considered to be the cause of IR is endoplasmic reticulum (ER) stress. This subcellular organelle plays a pivotal role in protein folding and processes that increase ER stress, leads to maladaptive responses that result in cell death. Recently, zinc and the proteins that transport this metal ion have been implicated in the ER stress response. Specifically, the ER-specific zinc transporter ZIP7, coined the "gate-keeper" of zinc release from the ER into the cytosol, was shown to be essential for maintaining ER homeostasis in intestinal epithelium and myeloid leukaemia cells. Moreover, ZIP7 controls essential cell signalling pathways similar to insulin and activates glucose uptake in skeletal muscle. Accordingly, ZIP7 may be essential for the control of ER localized zinc and mechanisms that disrupt this process may lead to ER-stress and contribute to IR. Accordingly, understanding the mechanisms of ZIP7 action in the context of IR may provide opportunities to develop novel therapeutic options to target this transporter in the treatment of IR and subsequent T2DM.
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Effects of palm oil consumption on biomarkers of glucose metabolism: A systematic review.
Zulkiply, SH, Balasubramaniam, V, Abu Bakar, NA, Abd Rashed, A, Ismail, SR
PloS one. 2019;(8):e0220877
Abstract
INTRODUCTION Vegetable oil is an important source of fatty acids, and as palm oil being the highest consumed vegetable oil in many countries, its high saturated fatty acid content has led many concerns on cardiometabolic health. Dietary fatty acids has also been linked to affect glucose metabolism and insulin sensitivity. This systematic review is aimed at critically evaluating the available evidence on the association of palm oil with the biomarkers of glucose metabolism as compared to other vegetable oils. METHODS We systemically searched PubMed, CENTRAL and Scopus up to June 2018. We searched for published interventional studies on biomarkers of glucose metabolism (defined as fasting glucose, fasting insulin, HOMA, 2-hour post prandial glucose and HbA1C) that compared palm oil- or palm olein-rich diets with other edible vegetable oils (such as olive oil, canola oil and soybean oil). Two reviewers independently extracted data and assessed study risks of bias. Mean differences of outcomes were pooled for the meta-analysis. RESULTS We identified 1921 potentially eligible articles with only eight included studies. Seven randomised cross-over trials and one parallel trial were included. Study population were among young to middle-aged, healthy, non-diabetic, and normal weight participants. Intervention duration ranged from three to seven weeks, and fat substitution ranged from 15% to 20% energy. There were insignificant differences in fasting glucose when compared to partially hydrogenated soybean oil [-0.15mmol/L (-0.46,0.16) P = 0.33, I2 = 48%], soybean oil [0.05mmol/L (-0.09,0.18) P = 0.49, I2 = 0%] and olive oil [0.04mmol/L (-0.09,0.17) P = 0.76, I2 = 0%]. Insignificant effects were also seen on fasting insulin when compared to partially hydrogenated soybean oil [1.72pmol/L (-11.39,14.84) P = 0.80, I2 = 12%] and olive oil diet [-0.14pmol/L (-4.87,4.59) P = 0.95, I2 = 0%]. CONCLUSION Current evidence on the effects of palm oil consumption on biomarkers of glucose metabolism is poor and limited to only healthy participants. We conclude that little or no additional benefit will be obtained by replacing palm oil with other oils rich in mono or polyunsaturated fatty acids for changes in glucose metabolism.
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Exercise and insulin resistance in type 2 diabetes mellitus: A systematic review and meta-analysis.
Sampath Kumar, A, Maiya, AG, Shastry, BA, Vaishali, K, Ravishankar, N, Hazari, A, Gundmi, S, Jadhav, R
Annals of physical and rehabilitation medicine. 2019;(2):98-103
Abstract
BACKGROUND Insulin resistance is a determining factor in the pathophysiology of type 2 diabetes mellitus (T2DM). Exercise is known to improve insulin resistance, but a systematic review of the literature is lacking. OBJECTIVE This systematic review and meta-analysis focused on identifying evidence for the effectiveness of a structured exercise intervention program for insulin resistance in T2DM. METHODS We searched MEDLINE via PubMed, CINHAL, Scopus and Web of Science, and the Cochrane Central Register of Controlled Trials for reports of studies on fasting insulin, homeostatic model assessment for insulin resistance (Homa-IR), fasting blood sugar, glycated hemoglobin and body mass index in patients with T2DM and healthy controls that were published between 1990 and 2017. Data are reported as the standardized mean difference or mean difference with 95% confidence intervals (CIs). RESULTS Among 2242 records retrieved, only 11 full-text articles were available for meta-analysis. Data for 846 participants were analyzed, 440 in the intervention group, and 406 in the control group. The mean difference for fasting insulin level was-1.64 (95% CI; -3.38 to 0.10), Homa-Ir 0.14 (-1.48 to 1.76), fasting blood sugar-5.12 (-7.78 to-2.45), hemoglobin A1c 0.63 (-0.82 to 2.08) and body mass index-0.36 (-1.51 to 0.79). CONCLUSION The evidence highlights the effectiveness of a structured exercise intervention program for insulin resistance in T2DM with a moderate level 2 of evidence.
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Type 2 Diabetes Mellitus, Insulin Resistance, and Vitamin D.
Sacerdote, A, Dave, P, Lokshin, V, Bahtiyar, G
Current diabetes reports. 2019;(10):101
Abstract
PURPOSE OF REVIEW There is a growing, largely inconsistent, literature on the role of vitamin D in association with type 2 diabetes, insulin resistance/insulin secretion, glycemic indices, and complications of type 2 diabetes. Pathophysiologic, bystander, preventive, and treatment roles of vitamin D have all been proposed. In this focused review, we attempt to organize and clarify our current information in this area. RECENT FINDINGS Clinical study interpretation is difficult because of variability in dosage, dosage form, study duration, and populations studied, as well as recently reported normal human polymorphisms in vitamin D synthesis and catabolism, vitamin D-binding protein, and vitamin D receptors in addition to a host of potential epigenetic confounders. Low vitamin D status appears to be associated with type 2 diabetes and most other insulin resistance disorders reported to date. The extraskeletal benefits of supplementation/repletion in these disorders in our species, with a few highlighted exceptions, remain to be established. This focused review attempts to summarize our current knowledge in this burgeoning area through a review of key meta-analyses, observational studies, randomized control trials, and Mendelian randomization studies and will hopefully serve as a guide to indicate future research directions and current best practice.
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Microbes: possible link between modern lifestyle transition and the rise of metabolic syndrome.
Moossavi, S, Bishehsari, F
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2019;(3):407-419
Abstract
The rapid decrease in infectious diseases globally has coincided with an increase in the prevalence of obesity and other components of metabolic syndrome. Insulin resistance is a common feature of metabolic syndrome and can be influenced by genetic and non-genetic/environmental factors. The emergence of metabolic syndrome epidemics over only a few decades suggests a more prominent role of the latter. Changes in our environment and lifestyle have indeed paralleled the rise in metabolic syndrome. Gastrointestinal tract microbiota, the composition of which plays a significant role in host physiology, including metabolism and energy homeostasis, are distinctly different within the context of metabolic syndrome. Among humans, recent lifestyle-related changes could be linked to changes in diversity and composition of 'ancient' microbiota. Given the co-adaptation and co-evolution of microbiota with the immune system over a long period of time, it is plausible that such lifestyle-related microbiota changes could trigger aberrant immune responses, thereby predisposing an individual to a variety of diseases. Here, we review current evidence supporting a role for gut microbiota in the ongoing rise of metabolic syndrome. We conclude that population-level shifts in microbiota can play a mediatory role between lifestyle factors and pathogenesis of insulin resistance and metabolic syndrome.
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Does food insulin index in the context of mixed meals affect postprandial metabolic responses and appetite in obese adolescents with insulin resistance? A randomised cross-over trial.
Caferoglu, Z, Hatipoglu, N, Gokmen Ozel, H
The British journal of nutrition. 2019;(8):942-950
Abstract
The food insulin index (II) is a novel classification to rank foods based on their physiological insulin demand relative to an isoenergetic reference food and may be a valid predictor of postprandial insulin responses and appetite. The present study aimed to compare the postprandial metabolic responses and appetite sensations to two macronutrient- and glycaemic index-matched meals with either high or low II in obese adolescents with insulin resistance (IR). A randomised, single-blind and cross-over trial included fifteen obese adolescents aged 12-18 years with IR. All participants were provided with two different breakfasts: low glycaemic index, low insulin index (LGI-LII) and low glycaemic index, high insulin index (LGI-HII), with a 1-week washout period between meals. At time 0 (just before breakfast), 15, 30, 45, 60, 90, 120, 180 and 240 min after the meal, serum glucose, insulin and C-peptide levels and appetite scores were measured. At the end of 4 h, participants were served ad libitum lunch. Early (0-30 min), late (45-240 min) and total (0-240 min) postprandial insulin responses were lowered by 56·1, 34·6 and 35·6 % after the LGI-LII meal v. LGI-HII meal (P < 0·05). The feeling of hunger was also decreased by 25·8 and 27·5 % after the LGI-LII meal v. LGI-HII meal during the late and total responses (P < 0·05). The calculation II of meals or diets may be a useful dietary approach to reduce postprandial hyperinsulinaemia and the perceived hunger in obese adolescents with IR.
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Indirect insulin resistance detection: Current clinical trends and laboratory limitations.
Placzkowska, S, Pawlik-Sobecka, L, Kokot, I, Piwowar, A
Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2019;(3):187-199
Abstract
There is a steady increase in the number of overweight and obese people worldwide and increasingly, younger people. Excess adipose tissue impairs the action of insulin, leading to insulin resistance (IR). Tissue IR is a major factor in relation to cardiovascular disease, metabolic syndrome and diabetes. Thus, it is important to recognize at the pre-disease stage with the possibility of therapeutic intervention. IR is assessed using indicators of epidemiological significance, most often calculated from fasting and postprandial glucose and insulin values, so-called indirect indicators of insulin resistance. The most commonly used parameter is the Homeostatic Model Assessment (HOMA). Although the Quantitative Insulin Sensitivity Check Index (QUICKI), Matsuda Index and the Insulin Secretion-Sensitivity Index-2 (ISSI-2) are also used, the values of these indices established for IR vary for different age, sex, populations and ethnic groups. Thus, appropriate reference values of indirect indices should be determined for such groups, and when this is precluded, data from published studies carried out on the most ethnically, socio-economically and age-matched populations should be applied.
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Effect of a Fucoidan Extract on Insulin Resistance and Cardiometabolic Markers in Obese, Nondiabetic Subjects: A Randomized, Controlled Trial.
Wright, CM, Bezabhe, W, Fitton, JH, Stringer, DN, Bereznicki, LRE, Peterson, GM
Journal of alternative and complementary medicine (New York, N.Y.). 2019;(3):346-352
Abstract
OBJECTIVES To determine whether a fucoidan extract reduced insulin resistance and/or altered other cardiometabolic markers in an obese, nondiabetic population. DESIGN Single-site, double-blinded, placebo-controlled, randomized controlled trial. SETTING/LOCATION Hobart, Tasmania, Australia. SUBJECTS Eligible subjects were obese, with no history of diabetes, and ages between 18 and 65 years. INTERVENTIONS Subjects were randomly assigned, in even blocks of 10, to either active fucoidan 500 mg or placebo capsules twice daily for 90 days, with identical measurements performed at baseline and follow-up. OUTCOME MEASURES The primary outcome was insulin resistance, defined by the homeostasis model of assessment (HOMA) values. Secondary outcomes were lipid profile, glycosylated hemoglobin, urea electrolytes and creatinine, liver function tests, full/complete blood count, fasting insulin, fasting glucose, quantitative insulin sensitivity check index, glucose area under the curve, weight, body mass index, waist circumference, and systolic and diastolic blood pressure. The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12614000495628) and the Therapeutic Goods Administration (2014/0348), and was funded by Marinova Pty. Ltd. RESULTS There were no differences in the 90-day outcome measures between placebo and active treatment in the intention-to-treat-analysis (n = 35 for active, n = 37 for placebo). The mean change in HOMA scores was 0 for the placebo and -0.1 for the active groups (p = 0.73). Self-reported adherence was high, consistent with capsule counting at the conclusion of the trial. CONCLUSIONS Fucoidan taken twice daily for a period of 90 days did not markedly affect insulin resistance or other measured parameters of cardiometabolic health in an obese, nondiabetic cohort. This could be due to an intrinsic lack of efficacy, lower than measured adherence, or because longer therapy and/or higher baseline insulin resistance are required to exert a significant effect.
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Interplay between the Adaptive Immune System and Insulin Resistance in Weight Loss Induced by Bariatric Surgery.
Villarreal-Calderón, JR, Cuéllar, RX, Ramos-González, MR, Rubio-Infante, N, Castillo, EC, Elizondo-Montemayor, L, García-Rivas, G
Oxidative medicine and cellular longevity. 2019;:3940739
Abstract
Low-grade chronic inflammation plays a pivotal role among other pathophysiological mechanisms involved in obesity. Innate and adaptive immune cells undergo systemic proinflammatory polarization that gives rise to an increased secretion of proinflammatory cytokines, which in turn leads to insulin resistance. Bariatric surgery is currently the most effective treatment for obesity, as it brings on significant weight loss, glucose metabolism improvement, and a decrease in systemic inflammation biomarkers. After bariatric surgery, several changes have been reported to occur in adaptive immunity, including reduction in CD4+ and CD8+ T cell counts, a decrease in the Th1/Th2 ratio, an increase in B regulatory cells, and reduction in proinflammatory cytokine secretion. Overall, there seems to be a major shift in several lymphocyte populations from a proinflammatory to an anti-inflammatory phenotype. Furthermore, increased antioxidant activity and reduced lipid and DNA oxidation products have been reported after bariatric surgery in circulating mononuclear cells. This paper highlights the shift in the adaptive immune system in response to weight loss and improved insulin sensitivity, as well as the interplay between immunological and metabolic adaptations as a result of bariatric surgery. Finally, based on data from research, we propose several mechanisms such as changes in adaptive immune cell phenotypes and their by-products, recruitment in adipose tissue, reduced oxidative stress, and modification in metabolic substrate availability as drivers to reduce low-grade chronic inflammation after bariatric surgery in severe obesity.