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Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity-Breast Cancer Links.
Bustamante-Marin, XM, Merlino, JL, Devericks, E, Carson, MS, Hursting, SD, Stewart, DA
Frontiers in endocrinology. 2021;:632284
Abstract
The worldwide prevalence of overweight and obesity has tripled since 1975. In the United States, the percentage of adults who are obese exceeds 42.5%. Individuals with obesity often display multiple metabolic perturbations, such as insulin resistance and persistent inflammation, which can suppress the immune system. These alterations in homeostatic mechanisms underlie the clinical parameters of metabolic syndrome, an established risk factor for many cancers, including breast cancer. Within the growth-promoting, proinflammatory milieu of the obese state, crosstalk between adipocytes, immune cells and breast epithelial cells occurs via obesity-associated hormones, angiogenic factors, cytokines, and other mediators that can enhance breast cancer risk and/or progression. This review synthesizes evidence on the biological mechanisms underlying obesity-breast cancer links, with emphasis on emerging mechanism-based interventions in the context of nutrition, using modifiable elements of diet alone or paired with physical activity, to reduce the burden of obesity on breast cancer.
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Triglyceride/High-Density Lipoprotein Cholesterol Ratio: A Clue to Metabolic Syndrome, Insulin Resistance, and Severe Atherosclerosis.
Azarpazhooh, MR, Najafi, F, Darbandi, M, Kiarasi, S, Oduyemi, T, Spence, JD
Lipids. 2021;(4):405-412
Abstract
High serum levels of triglycerides (Tg) and low levels of high-density lipoprotein cholesterol (HDL-C) are characteristic of the Metabolic Syndrome (MetS). We assessed the ratio of Tg to HDL-C as a way to identify MetS and insulin resistance. We also evaluated its association with severity of carotid atherosclerosis. Data were analyzed from three cohorts totaling 13,908 participants. MetS was defined according to the International Diabetes Federation criteria. Optimal cut-off for Tg/HDL-C ratio was obtained using Youden's index in receiver-operating characteristic (ROC) curve analyses. The risk of MetS and IR in those with a Tg/HDL-C ratio above the optimum cutoff was evaluated by logistic regression analysis. A Tg/HDL-C ratio above the optimal cutoff level significantly increased the odds ratio for MetS in the three cohorts (OR 6.00, 4.04, and 3.50, least in the healthy population), identified insulin resistance defined by the homeostatic model of insulin resistance (HOMA-IR) (p < 0.0001), and was strongly associated with atherosclerosis severity (p = 0.0001). Tg/HDL-C ratio identifies persons with MetS, insulin resistance, and severe atherosclerosis. It should be used more widely to identify patients at high risk. This is clinically important because insulin resistance is treatable.
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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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Amino Acid-Induced Impairment of Insulin Signaling and Involvement of G-Protein Coupling Receptor.
Zakaria, NF, Hamid, M, Khayat, ME
Nutrients. 2021;(7)
Abstract
Amino acids are needed for general bodily function and well-being. Despite their importance, augmentation in their serum concentration is closely related to metabolic disorder, insulin resistance (IR), or worse, diabetes mellitus. Essential amino acids such as the branched-chain amino acids (BCAAs) have been heavily studied as a plausible biomarker or even a cause of IR. Although there is a long list of benefits, in subjects with abnormal amino acids profiles, some amino acids are correlated with a higher risk of IR. Metabolic dysfunction, upregulation of the mammalian target of the rapamycin (mTOR) pathway, the gut microbiome, 3-hydroxyisobutyrate, inflammation, and the collusion of G-protein coupled receptors (GPCRs) are among the indicators and causes of metabolic disorders generating from amino acids that contribute to IR and the onset of type 2 diabetes mellitus (T2DM). This review summarizes the current understanding of the true involvement of amino acids with IR. Additionally, the involvement of GPCRs in IR will be further discussed in this review.
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HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: A Multicenter Cohort Study.
Yamamoto, R, Jensen, MK, Aroner, S, Furtado, JD, Rosner, B, Hu, FB, Balkau, B, Natali, A, Ferrannini, E, Baldi, S, et al
The Journal of clinical endocrinology and metabolism. 2021;(8):e2928-e2940
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Abstract
CONTEXT High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. OBJECTIVE We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and cardiovascular disease (RISC) study, a multicenter European clinical investigation, whose recruitment initiated in 2002, with a follow-up of 3 years. MAIN MEASURES Insulin sensitivity was estimated from an oral glucose tolerance test at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich enzyme-linked immunosorbent assay (ELISA)-based method. RESULTS The 2 HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (P-trend = 0.01), compared to the lowest quintile. No significant association was observed for total HDL, and very low density lipoprotein (VLDL) and low density lipoprotein (LDL) containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. CONCLUSION Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.
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Effects of Tea Consumption on Anthropometric Parameters, Metabolic Indexes and Hormone Levels of Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Shen, W, Pan, Y, Jin, B, Zhang, Z, You, T, Qu, Y, Han, M, Yuan, X, Zhang, Y
Frontiers in endocrinology. 2021;:736867
Abstract
OBJECTIVE Our aim was to conduct a systematic review and meta-analysis to assess the effectiveness and safety of tea supplements for patients with polycystic ovary syndrome (PCOS). METHODS We conducted searches of the published literature in PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), VIP database, and Wanfang Database in 1985 to September 2021. Data from randomized controlled trials (RCTs) were obtained to assess the effects of tea versus placebo in women with PCOS. Weighted mean differences (WMDs) were pooled using a random-effects model or risks ratios (RRs) using a random-effects model. RESULTS Six RCTs (235 participants) were included in our systematic review. Tea supplements as adjuvant therapy led to greater improvement in body weight (WMD -2.71, 95% CI -4.95 to -0.46, P = 0.02, I2 = 0%), fasting blood glucose (FBG: WMD -0.40, 95% CI -0.59 to -0.20, P < 0.0001, I2 = 0%) and fasting insulin (FINS: WMD -3.40, 95% CI -4.76 to -2.03, P < 0.00001, I2 = 0%) when compared with placebo. There were no significant differences of body mass index, waist circumference, hip circumference, waist-to-hip ratio (WHR), body fat rate, total testosterone, free testosterone (FT), dehydroepiandrosterone, luteinizing hormone or follicular-stimulating hormone (FSH) between the two groups. In addition, subgroup analysis suggested that green tea was effective on body weight, FINS, FBG, FT, and FSH, and herbal tea can also reduce FT levels, tea supplements had a significant impact on FBG and FSH in trials with intervention duration ≥ 3 months, and intervention lasting less than 3 months can improve FINS. Tea had significant effect on reducing WHR, FBG and FSH in Asian PCOS patients, but not in Caucasians. And there was no statistically significant effect of tea on weight and FINS in Asians, but it was effective for Caucasian participants. Compared with placebo, tea supplements did not cause significant adverse reactions (RR 1.45, 95% CI 0.30 to 6.90, P = 0.65, I2 = 0%). CONCLUSION This meta-analysis suggests that consumption of tea supplementation in women with PCOS could significantly decrease the levels of FBG and FINS as well as reduce body weight. Especially green tea, not only has the above effects, but also has a significant effect on improving a variety of reproductive hormone indexes. Furthermore, tea supplementation is a relatively safe therapy for PCOS patients. SYSTEMATIC REVIEW REGISTRATION PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=212755, identifier CRD42021249196.
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Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.
Yang, H, Lin, J, Li, H, Liu, Z, Chen, X, Chen, Q
Frontiers in endocrinology. 2021;:571229
Abstract
BACKGROUND Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS). METHODS This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects. RESULTS Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI (P < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E2), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β (HOMA-β), triglyceride (TG) and alanine aminotransferase (ALT) (P < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E2, FINS, HOMA-IR, and HOMA-β were negatively associated with serum PRL (P < 0.05). CONCLUSIONS Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.
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Insulin resistant diabetes mellitus in SHORT syndrome: case report and literature review.
Masunaga, Y, Fujisawa, Y, Muramatsu, M, Ono, H, Inoue, T, Fukami, M, Kagami, M, Saitsu, H, Ogata, T
Endocrine journal. 2021;(1):111-117
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Abstract
SHORT syndrome is a rare developmental disorder frequently associated with growth failure and insulin resistant diabetes mellitus (IRDM). Since GH has a diabetogenic effect, GH therapy has been regarded as a contraindication. We observed a Brazilian girl with SHORT syndrome who received GH therapy from 4 6/12 years of age for SGA short stature. GH dosage was increased from 0.23 to 0.36 mg/kg/week, but statural response to GH therapy remained poor. Her blood HbA1c level, though it remained 5.5-6.0% in childhood, began to elevate with puberty and increased to 9.2% at 10 6/12 years of age, despite the discontinuation of GH therapy at 9 11/12 years of age. Laboratory studies indicated antibody-negative IRDM. She was treated with metformin and canagliflozin (a sodium glucose co-transporter 2 (SGLT2) inhibitor), which ameliorated overt diurnal hyperglycemia and mild nocturnal hypoglycemia and reduced her blood HbA1c around 7%. Whole exome sequencing revealed a de novo heterozygous pathogenic variant (c.1945C>T:p.(Arg649Trp)) in PIK3R1 known as the sole causative gene for SHORT syndrome. Subsequent literature review for patients with molecularly confirmed SHORT syndrome revealed the development of IRDM in 10 of 15 GH-untreated patients aged ≥12 years but in none of three GH-treated and six GH-untreated patients aged ≤10 years. These findings imply a critical role of pubertal development and/or advanced age rather than GH therapy in the development of IRDM, and a usefulness of SGLT2 inhibitor in the treatment of IRDM.
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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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The mother relationship between insulin resistance and non-alcoholic steatohepatitis: Glucosinolates hydrolysis products as a promising insulin resistance-modulator and fatty liver-preventer.
Mohammed, ED, Abdel-Naim, AB, Kangpeng, J, Jiang, R, Wei, J, Sun, B
Life sciences. 2021;:118615
Abstract
Non-alcoholic fatty liver disease (NFLD) is one of the present public health problems which have no specific and effective treatment. The speed of the disease progression depends on the patient's lifestyle. Due to life stresses and lack of time, a high number of people depend on fast food containing a high amount of fats which one of the main causes of insulin resistance (IR). IR is one of the metabolic disorders which strongly intersected with molecular NAFLD and leading to its progression into non-alcoholic steatohepatitis (NASH). In this review, we introduced the updated statistics of NAFLD and NASH progression all over the world shows its importance, etiologies, and pathogenesis. Also, IR and its role in NASH initiation and progression explored, and current treatments with its limitations have been explained. Glucosinolates (GLS) is a group of phytochemicals which known by its potent hydrolysis products with promising anti-cancer effect. In this review, we have collected the recent experimental studies of different GLS hydrolysis products against IR and chronic liver diseases supported by our lab finding. Finally, we recommend this group of phytochemicals as promising molecules to be studied experimentally and clinically against a wide range of chronic liver diseases with an acceptable safety margin.