Uric Acid Metabolic Disorders in Pituitary-Target Gland Axis.

Uric acid (UA) is the end product of purine metabolism in the human, and the imbalance between production and excretion results in the disturbance of serum uric acid (SUA). There is evidence suggesting that pituitary-target gland hormones can affect UA metabolism through regulating the activity of xanthine oxidase and UA transporters. Related endocrine diseases including thyroid dysfunction, polycystic ovary syndrome, acromegaly and Cushing's syndrome are often accompanied by elevated UA levels. In addition to the direct influence of abnormal hormones, obesity and insulin resistant play a pivotal role. Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion also present with abnormal SUA levels due to the action of antidiuretic hormone. However, certain evidence within the population is disputed. This review summarized the effects of pituitary-target gland hormones on UA metabolism, and preliminarily described the related mechanisms, offering a theoretical foundation for assessing SUA in endocrine disorders as well as guiding its management.

Triglyceride-glucose index predicts future chronic kidney disease development in all populations, including normotensive and isolated diastolic hypertension.

Hypertension and insulin resistance are established risk factors for chronic kidney disease. However, the association between chronic kidney disease and insulin resistance in detailed hypertension pattern groups such as isolated diastolic hypertension remains unclear. Triglyceride-glucose index has been noted as an indicator of insulin resistance. This study investigated the association between the triglyceride-glucose index and chronic kidney disease in four blood pressure groups: isolated diastolic hypertension, isolated systolic hypertension, systolic diastolic hypertension, and normotension. Using a database of 41,811 middle-aged men who had two or more annual health checkups from 2007 to 2019, those with chronic kidney disease at the first visit, antihypertensive/diabetes/dyslipidemia medication users, and incomplete data were excluded. Four groups were categorized using the 140/90 mmHg threshold. A COX proportional hazards model was used to assess the triglyceride-glucose index with incident chronic kidney disease. Participants were divided: isolated diastolic hypertension: 2207 (6.72%), isolated systolic hypertension: 2316 (7.06%), systolic-diastolic hypertension: 3299 (10.05%), normal: 24,996 (76.17%). The follow-up period was 6.78 years. Adjusted hazard ratios (HRs) and 95% CIs per unit increase in triglyceride-glucose index: isolated diastolic hypertension (HR = 1.31, 95% CI (1.06-1.62)), isolated systolic hypertension (HR = 1.36, 95% CI (1.12-1.64)), systolic-diastolic hypertension (HR = 1.40, 95% CI (1.19-1.64)), normal (HR = 1.18, 95% CI (1.09-1.28)). Triglyceride-glucose index is relevant for predicting chronic kidney disease development in all subtypes of hypertension. The results may lead to early prediction and prevention of the development of chronic kidney disease.

Flavonoid from Moringa oleifera leaves revisited: A review article on in vitro, in vivo, and in silico studies of antidiabetic insulin-resistant activity.

Diabetes mellitus (DM) occurs when the body experiences insulin deficiency or is unable to use insulin appropriately, which increases the blood glucose levels over the threshold. Moringa oleifera leaf is a widely used and scientifically proven herbal medicine to treat DM. The demand for the development of new drugs has prompted in vitro, in vivo, and in silico studies of antidiabetic insulin-resistant activity. This study aims to conduct a comprehensive study of the types of flavonoid and nonflavonoid compounds that have antidiabetic activity in insulin resistance mellitus using in vitro, in vivo, and in silico approaches. The literature review was conducted in accordance with the offered reporting items for systematic review. Major bibliographic databases, i.e. Scopus, PubMed, and DOAJ, covering original articles about the aforementioned issues between January 1, 2011 and December 31, 2021 were used. In this study, 274 articles were retrieved, of which 4 were duplicates, and after the titles were read, only 108 were left for analysis. After the abstract screening, 32 articles were eligible for the literature review. The results exhibit that flavonoids, including quercetin and kaempferol, and nonflavonoids, including anthraquinone, cytogluside (glycoside), hemlock tannin, phenolic steroid, and 2-phenylchromenylium (anthocyanins), have potential insulin-resistant antidiabetic activity in vitro, in vivo, and in silico. This has broadened the research into the development of new drugs.

Lactoferrin decorated bilosomes for the oral delivery of quercetin in type 2 diabetes: In vitro and in vivo appraisal.

Despite its tremendous potential for type 2 diabetes management, quercetin (QRC) suffers poor gastric stability, poor bioavailability, and extensive first pass metabolism. Drug encapsulation into bilosomes (BSL) has proven enhanced properties in-vitro and in-vivo. Herein, this work endeavoured to evaluate efficacy of QRC-encapsulated bilosomes capped with lactoferrin (LF); a milk protein with antidiabetic potential, for type 2 diabetes oral treatment. The optimized formulation (LF-QRC-BSL) was evaluated in-vitro on α-amylase enzyme inhibition and insulin resistant HepG2 cell model and in vivo on streptozocin/high fat diet induced diabetes in rats. LF-QRC-BSL showed a small size (68.1 nm), a narrow PDI (0.18) and a -25.5 mV zeta potential. A high entrapment efficiency (94 %) with sustained release were also observed. LF-QRC-BSL displayed 100 % permeation through excised diabetic rat intestines after 6 h, 70.2 % inhibition of α-amylase enzyme in-vitro and an augmented recovery of glucose uptake in insulin resistant cells. In diabetic rats, LF-QRC-BSL resulted in significant decrease in blood glucose level, improved lipid profile and tissue injury markers with reduced oxidative stress and inflammatory markers. Further, histopathological examination of the kidneys, liver and pancreas revealed an almost restored normal condition comparable to the negative control. Overall, LF-QRC-BSL have proven to be a promising therapy for type 2 diabetes.

Biological Potential of Kakkalide in medicine for the Treatment of Human disorders: An Overview of Pharmacological aspects.

BACKGROUND: Pueraria lobata is an important herbal medicine of Fabaceae family that has been clinically used in Traditional Chinese Medicine to counteract human disorders and associated secondary complications. Kakkalide also called irisolidone 7-xylosylglucoside is an isoflavonoid of Puerariae flos, Pueraria lobata and Flos Puerariae. Moreover, Kakkalide has a wide range of bioactivities in medicine. METHODS: Biological potential of kakkalide was investigated in the present work through scientific data analysis of different scientific research work on kakkalide in order to know its therapeutic potential in medicine. Scientific data on Pueraria lobata were collected and analyzed in the present work. All the scientific data were collected from Google, Google Scholar, Scopus, and Science Direct in the present work. RESULTS: Scientific data analysis of kakkalide revealed its biological importance and therapeutic potential in medicine. The present investigation signified kakkalide's effectiveness in inflammatory diseases, prostaglandin E2 production, liver complication, gastric injury, alcoholism, insulin-resistant endothelial dysfunction, aldose reductase enzyme, hyperlipidemia, estrogenic activity, and stroke. In addition, the bioavailability of kakkalide was also discussed in the present paper. Present work also revealed the significance of analytical techniques for the separation, isolation and identification of kakkalide in different biological and non-biological samples. CONCLUSION: Present paper signified the health-beneficial aspects of kakkalide in medicine.

A machine learning-based classification of adult-onset diabetes identifies patients at risk of liver-related complications.

Background & aims: Diabetes mellitus is a major risk factor for fatty liver disease development and progression. A novel machine learning method identified five clusters of patients with diabetes, with different characteristics and risk of diabetic complications using six clinical and biological variables. We evaluated whether this new classification could identify individuals with an increased risk of liver-related complications. Methods: We used a prospective cohort of patients with a diagnosis of type 1 or type 2 diabetes without evidence of advanced fibrosis at baseline recruited between 2000 and 2020. We assessed the risk of each diabetic cluster of developing liver-related complications (i.e. ascites, encephalopathy, variceal haemorrhage, hepatocellular carcinoma), using competing risk analyses. Results: We included 1,068 patients, of whom 162 (15.2%) were determined to be in the severe autoimmune diabetes subgroup, 266 (24.9%) had severe insulin-deficient diabetes, 95 (8.9%) had severe insulin-resistant diabetes (SIRD), 359 (33.6%) had mild obesity-related diabetes, and 186 (17.4%) were in the mild age-related diabetes subgroup. In multivariable analysis, patients in the SIRD cluster and those with excessive alcohol consumption at baseline had the highest risk for liver-related events. The SIRD cluster, excessive alcohol consumption, and hypertension were independently associated with clinically significant fibrosis, evaluated by liver biopsy or transient elastography. Using a simplified classification, patients assigned to the severe and mild insulin-resistant groups had a three- and twofold greater risk, respectively, of developing significant fibrosis compared with those in the insulin-deficient group. Conclusions: A novel clustering classification adequately stratifies the risk of liver-related events in a population with diabetes. Our results also underline the impact of the severity of insulin resistance and alcohol consumption as key prognostic risk factors for liver-related complications. Impact and implications: Diabetes represents a major risk factor for NAFLD development and progression. This study examined the ability of a novel machine-learning approach to identify at-risk diabetes subtypes for liver-related complications. Our results suggest that patients that had severe insulin resistance had the highest risk of liver-related outcomes and fibrosis progression. Moreover, excessive alcohol consumption at the diagnosis of diabetes was the strongest risk factor for developing liver-related events.

Polygenic scores of diabetes-related traits in subgroups of type 2 diabetes in India: a cohort study.

Background: A machine-learning approach identified five subgroups of diabetes in Europeans which included severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD) with partially distinct genetic aetiologies. We previously validated four of the non-autoimmune subgroups in people with young-onset type 2 diabetes (T2D) from the Indian WellGen study. Here, we aimed to apply European-derived centroids and genetic risk scores (GRSs) to the unselected (for age) WellGen to test their applicability and investigate the genetic aetiology of the Indian T2D subgroups. Methods: We applied European derived centroids and GRSs to T2D participants of Indian ancestry (WellGen, n = 2217, 821 genotyped) and compared them with normal glucose tolerant controls (Pune Maternal Nutrition Study, n = 461). Findings: SIDD was the predominant subgroup followed by MOD, whereas SIRD and MARD were less frequent. Weighted-GRS for T2D, obesity and lipid-related traits associated with T2D. We replicated some of the previous associations of GRS for T2D, insulin secretion, and BMI with SIDD and MOD. Unique to Indian subgroups was the association of GRS for (a) proinsulin with MOD and MARD, (b) liver-lipids with SIDD, SIRD and MOD, and (c) opposite effect of beta-cell GRS with SIDD and MARD, obesity GRS with MARD compared to Europeans. Genetic variants of fucosyltransferases were associated with T2D and MOD in Indians but not Europeans. Interpretation: The similarities emphasise the applicability of some of the European-derived GRSs to T2D and its subgroups in India while the differences highlight the need for large-scale studies to identify aetiologies in diverse ancestries. The data provide robust evidence for genetically distinct aetiologies for the T2D subgroups and at least partly mirror those seen in Europeans. Funding: Vetenskapsrådet, Diabetes Wellness, and Hjärt-Lungfonden (Sweden), DST (India), Wellcome Trust, Crafoord Foundation and Albert Påhlsson Foundation.

The Metabolic Switch of Physical Activity in Non-Obese Insulin Resistant Individuals.

Healthy non-obese insulin resistant (IR) individuals are at higher risk of metabolic syndrome. The metabolic signature of the increased risk was previously determined. Physical activity can lower the risk of insulin resistance, but the underlying metabolic pathways remain to be determined. In this study, the common and unique metabolic signatures of insulin sensitive (IS) and IR individuals in active and sedentary individuals were determined. Data from 305 young, aged 20-30, non-obese participants from Qatar biobank, were analyzed. The homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires were utilized to classify participants into four groups: Active Insulin Sensitive (ISA, n = 30), Active Insulin Resistant (IRA, n = 20), Sedentary Insulin Sensitive (ISS, n = 21) and Sedentary Insulin Resistant (SIR, n = 23). Differences in the levels of 1000 metabolites between insulin sensitive and insulin resistant individuals in both active and sedentary groups were compared using orthogonal partial least square discriminate analysis (OPLS-DA) and linear models. The study indicated significant differences in fatty acids between individuals with insulin sensitivity and insulin resistance who engaged in physical activity, including monohydroxy, dicarboxylate, medium and long chain, mono and polyunsaturated fatty acids. On the other hand, the sedentary group showed changes in carbohydrates, specifically glucose and pyruvate. Both groups exhibited alterations in 1-carboxyethylphenylalanine. The study revealed different metabolic signature in insulin resistant individuals depending on their physical activity status. Specifically, the active group showed changes in lipid metabolism, while the sedentary group showed alterations in glucose metabolism. These metabolic discrepancies demonstrate the beneficial impact of moderate physical activity on high risk insulin resistant healthy non-obese individuals by flipping their metabolic pathways from glucose based to fat based, ultimately leading to improved health outcomes. The results of this study carry significant implications for the prevention and treatment of metabolic syndrome in non-obese individuals.

Associations of healthful and unhealthful plant-based diets with plasma markers of cardiometabolic risk.

PURPOSE: Plant-based diets, particularly when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes and cardiovascular disease. However, the impact of plant-based diets that distinguish between healthy and unhealthy plant foods on cardiometabolic biomarkers remains unclear. METHODS: Dietary information was collected by two 24-h recalls among 34,785 adults from a nationwide cross-sectional study. Plasma levels of insulin, C-peptide, glucose, C-reactive protein (CRP), white blood cell (WBC) count, triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) were measured. Linear regression was used to evaluate the percentage difference in plasma marker concentrations by three plant-based diet indices, namely the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI). RESULTS: Greater hPDI-adherence scores (comparing extreme quartiles) were associated with lower levels of insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), TG/HDL-C ratio, CRP, WBC count, and TG, and higher levels of HDL-C, with the percentage differences of - 14.55, - 15.72, - 11.57, - 14.95, - 5.26, - 7.10, and 5.01, respectively (all Ptrend ≤ 0.001). Conversely, uPDI was associated with higher levels of insulin, C-peptide, HOMA-IR, TG/HDL-C ratio, CRP, WBC count, and TG, but lower HDL-C, with the percentage differences of 13.71, 14.00, 14.10, 10.43, 3.32, 8.00, and - 4.98 (all Ptrend ≤ 0.001), respectively. Overall PDI was only associated with lower levels of CRP and WBC count (all Ptrend ≤ 0.001). CONCLUSION: Our findings suggest that hPDI may have positive, whereas uPDI may have negative impacts on multiple cardiometabolic risk markers, and underscore the need to consider the quality of plant foods in future PDI studies.

HM-chromanone from Portulaca oleracea L. inhibits protein tyrosine phosphatase 1B and mitigates glucose production in insulin-resistant HepG2 cells.

This study aimed to identify the effect of (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (HM-chromanone), isolated from Portulaca oleracea L., on tyrosine phosphatase 1B (PTP1B) and glucose production in insulin-resistant HepG2 cells. The results revealed that HM-chromanone significantly decreases PTP1B expression and glucose production in insulin-resistant HepG2 cells. Furthermore, a molecular docking stimulation showed HM-chromanone inhibits PTP1B by binding to its active site. Additionally, HM-chromanone was found to significantly modulate insulin receptor substrate-1 (IRS1) by decreasing phosphorylated serine 307 and increasing phosphorylated tyrosine 612 and activating phosphatidylinositol 3-kinase (PI3K) in insulin-resistant HepG2 cells. Furthermore, HM-chromanone augmented the phosphorylation of Akt and forkhead box protein O1 in insulin-resistant HepG2 cells in a dose-dependent manner at the concentrations of 15-60 µM. Additionally, it significantly reduced the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, which are main enzymes included in hepatic gluconeogenesis. Consequently, HM-chromanone was confirmed to significantly decrease glucose production and increase glucose uptake in insulin-resistant HepG2 cells.

5-HEPE reduces obesity and insulin resistance by promoting adipose tissue browning through GPR119/AMPK/PGC1α activation.

AIMS: Activating thermogenic program in brown adipocytes serves as a potential therapeutic target for increasing energy expenditure during the treatment of metabolic diseases. 5(S)-hydroxy-eicosapentaenoic acid (5-HEPE), an omega-3 unsaturated fatty acid metabolite, has been shown to enhance insulin secretion in vitro. However, its role in modulating obesity-related diseases remains largely unclear. MAIN METHODS: To investigate this further, mice were fed with a high-fat diet for 12 weeks and then injected intraperitoneally every other day with 5-HEPE for 4 additional weeks. KEY FINDINGS: In vivo, our results demonstrated that 5-HEPE alleviated the HFD-induced obesity and insulin resistance, leading to a significant decrease in subcutaneous fat and epididymal fat index and an increase in brown fat index. Compared to the HFD group, the 5-HEPE group mice had lower ITT and GTT AUC and lower HOMA-IR. Moreover, 5HEPE effectively increased energy expenditure of mice. 5-HEPE also significantly promoted brown adipose tissue (BAT) activation and browning in white adipose tissue (WAT) by up-regulating genes and proteins expression of UCP1, Prdm16, Cidea, and PGC1α. In vitro, we found 5-HEPE significantly promoted 3T3-L1 browning. Mechanistically, 5-HEPE acts by activating the GPR119/AMPK/PGC1α pathway. In conclusion, this study emphasizes a critical role of 5-HEPE in improving body energy metabolism and adipose tissue browning in HFD-fed mice. SIGNIFICANCE: Our results suggest that 5-HEPE intervention may be an effective target for preventing obesity-related metabolic diseases.

Women With Polycystic Ovary Syndrome: A Review of Susceptibility to Type 2 Diabetes.

The polycystic ovarian syndrome affects many women today. Previous research has demonstrated a direct link between it and serious ailments such as type 2 diabetes, heart disease, and infertility. Originally thought to be a reproductive disorder, polycystic ovarian syndrome (PCOS) is now understood to be a metabolic and psychological disorder. Women of reproductive age suffering from PCOS undergo hormonal imbalances in which progesterone, insulin, and testosterone are produced in excess. PCOS exhibits a variety of characteristics as well as a heterogeneity of symptoms, including acne, hirsutism, androgenic alopecia, irregular menstruation, infertility, obesity, and mood disorders like despair and anxiety. Chronic anovulation, hyperandrogenism, type 2 diabetes, dyslipidemia, and an elevated threat of coronary artery disease are some of its defining characteristics. PCOS develops due to interacting genetic and environmental factors. From a gynaecological curiosity, it grew into a multisystem endocrinopathy. It is fascinating to learn how hormonal issues result in gynaecological problems. Insulin resistance, compensatory hyperinsulinism, and an increase in ovarian androgenic hyperresponsiveness to circulating insulin are all directly related to hyperandrogenism and anovulation. Independent of weight, insulin resistance is more common with PCOS and plays a crucial role in the syndrome's metabolic and reproductive complications. Anovulation, polycystic ovaries, and elevated luteinizing hormones, which increase circulating androgen, are all caused by a reduction in follicle-stimulating hormone. High androgen levels cause hyperinsulinemia, which leads cells to become insulin resistant and makes PCOS patients more likely to develop diabetes mellitus. Later research established that women with polycystic ovarian shape and persistent anovulation are the only ones susceptible to insulin resistance. Insulin resistance is thus a distinct characteristic of the condition. The purpose of this review paper is to investigate how PCOS ultimately results in type 2 diabetes mellitus.

Effects of dietary wild bitter melon (Momordica charantia var. abbreviate Ser.) extract on glucose and lipid metabolism in HFD/STZ-induced type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Plant-based extracts to interfere with the onset of diabetes may be a promising approach towards type 2 diabetes mellitus (T2DM). Bitter gourd (Momordica charantia L.) is popularly consumed as an edible and medicinal resource with hypoglycemic effect in China. Wild bitter gourd (Momordica Charantia var. abbreviata Ser.) is a variant of bitter gourd, but there are relatively few studies on it. AIM OF THE STUDY: The purpose of the experiment is to first screen out the most effective extraction part of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. through the hypoglycemic activity experiment in vitro, and by using a high-fat and high-sugar diet with STZ-induced diabetic rat model in vivo to explore the possible mechanism of action against diabetes. MATERIALS AND METHODS: This study first performed α-glucosidase, PTP1B and lipase activities inhibition experiments on the alcohol and water extracts of Momordica charantia L. and Momordica Charantia var. abbreviata Ser. Sprague Dawley rats were either given normal feed or a high sugar and fat diet for four weeks, followed STZ (25 mg/kg, via i. p.) was given. Rats with fasting blood glucose ≥11.1 mmol/l after one week were deemed to be diabetic, treatments were administered for four weeks, and then blood samples were used to evaluate hematological and biochemical indicators, and liver was removed for post-analysis. The expression levels of p-AMPK, AMPK, p-PI3K, PI3K, p-AKT, AKT, p-GSK3ß, GSK3ß, p-IRS-1, IRS-1, GLUT2 were determined by Western blot. At the same time, the chemical components was identified by liquid-mass spectrometry. RESULTS: Data showed that the ethanol extract of wild bitter gourd (WBGE) had the best ability to regulate glucose and lipid metabolism in vitro. Therefore, we further investigated the antidiabetic effects of oral consumption of WBGE on high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM in SD rats. WBGE effectively reduced blood glucose and lipid levels, alleviated glucose intolerance and insulin resistant. Moreover, WBGE consumption could also inhibited oxidant responses and inflammatory damage. Mechanism studies have shown that WBGE may act by regulating AMPK/PI3K signaling pathway. On the other hand, the content of total phenol, total flavonoids, total saponins and total polysaccharide were measured by UV, 27 compounds were identified by LC-MS. CONCLUSIONS: These studies explored the role and mechanism of WBGE in regulating glucose and lipid metabolism, and may support the utilization and further investigation of wild bitter gourd as a dietary intervention strategy to prevent diabetes and related metabolic abnormalities.

Impact of anthocyanin component and metabolite of Saskatoon berry on gut microbiome and relationship with fecal short chain fatty acids in diet-induced insulin resistant mice.

Previous studies demonstrated that oral administration of Saskatoon berry powder (SBp) reduced fasting plasma glucose (FPG), insulin resistance, lipids, and inflammatory markers in diet-induced insulin resistant rodents. Mechanism for the beneficial effects of SB remains unclear. The present study examined the effects of high fat-high sucrose (HFHS) diet supplemented with or without 5% SBp, cyanidin-3-glucoside (C3G, an anthocyanin rich in SBp) at a dosage of C3G in 5% SBp, or equimolar concentration of protocatechuic acid (PCA, a relatively stable metabolite of C3G) for 11 weeks on FPG, cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), circulatory inflammatory markers, fecal microbiota, and short chain fatty acids in mice. HFHS diet significantly enhanced FPG, insulin, HOMA-IR, lipids and inflammatory markers, but reduced the abundance of fecal Bacteroidetes, Muribaculaceae and propionate compared to low fat diet. Supplementation of SBp, C3G or PCA significantly attenuated HFHS diet induced metabolic and inflammatory markers, and increased the abundances of fecal Muribaculaceae and propionate compared to HFHS diet alone. The abundances of fecal Muribaculaceae negatively correlated with FPG, lipids, HOMA-IR and inflammatory markers in the mice. The abundances of fecal propionate positively correlated with fecal Muribaculaceae and negatively correlated with the metabolic and inflammatory markers. The findings suggest that C3G in SBp and PCA contribute to the metabolic and anti-inflammatory effect of SBp in mice. The increases in fecal Muribaculaceae and propionate may play important regulatory roles in the anti-diabetic and anti-inflammatory benefits of SBp, C3G, and PCA in mice.

The role of obstetrician-gynecologists and reproductive endocrinologists in the blood glucose management of polycystic ovary syndrome.

Background: This study aimed to compare the differences between reproductive endocrinologists (Repro-Endo) and obstetricians-gynecologists (Ob-Gyn; non-reproductive medicine specialty) in diagnosing, evaluating, and treating PCOS women with insulin resistance (IR).Methods: Repro-Endo and Ob-Gyn in China participated in this survey, and their responses were analyzed using χ2 tests, Fisher exact tests, and multivariable logistic regression analysis.Results: The study analyzed 2412 survey responses (92.3% OB-Gyn; 98.5% women). Physician's age, hospital grade, specialty, and the number of PCOS patients who visit the physicians, revealed that Repro-Endo participants were more likely to suggest an oral glucose tolerance test (OR, 1.727; 95% CI, 1.272-2.345) as their first choice than Ob-Gyn participants. The most common treatments for patients with PCOS were lifestyle modification (>95%) and metformin use (>80%). More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn (46.5% vs. 23.5%), and more OB-Gyn participants reported being unclear about the appropriate dosage of metformin for patients with obesity and PCOS (12.5% vs. 1.6%).Conclusion: This survey identified knowledge gaps in metabolic screening for patients with IR and PCOS. Similarly, it highlights the need to improve IR management education for physicians caring for PCOS women.

Comparing the Metabolic Profiles Associated with Fitness Status between Insulin-Sensitive and Insulin-Resistant Non-Obese Individuals.

(1) Background: Young non-obese insulin-resistant (IR) individuals could be at risk of developing metabolic diseases including type 2 diabetes mellitus. The protective effect of physical activity in this apparently healthy group is expected but not well characterized. In this study, clinically relevant metabolic profiles were determined and compared among active and sedentary insulin-sensitive (IS) and IR young non-obese individuals. (2) Methods: Data obtained from Qatar Biobank for 2110 young (20-30 years old) non-obese (BMI ≤ 30) healthy participants were divided into four groups, insulin-sensitive active (ISA, 30.7%), insulin-sensitive sedentary (ISS, 21.4%), insulin-resistant active (IRA, 20%), and insulin-resistant sedentary (IRS, 23.3%), using the homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires. The effect of physical activity on 66 clinically relevant biochemical tests was compared among the four groups using linear models. (3) Results: Overall, non-obese IR participants had significantly (p ≤ 0.001) worse vital signs, blood sugar profiles, inflammatory markers, liver function, lipid profiles, and vitamin D levels than their IS counterparts. Physical activity was positively associated with left handgrip (p ≤ 0.01) and levels of creatine kinase (p ≤ 0.001) and creatine kinase-2 (p ≤ 0.001) in both IS and IR subjects. Furthermore, physical activity was positively associated with levels of creatinine (p ≤ 0.01) and total vitamin D (p = 0.006) in the IR group and AST (p = 0.001), folate (p = 0.001), and hematocrit (p = 0.007) in the IS group. Conversely, physical inactivity was negatively associated with the white blood cell count (p = 0.001) and an absolute number of lymphocytes (p = 0.003) in the IR subjects and with triglycerides (p = 0.005) and GGT-2 (p ≤ 0.001) in the IS counterparts. (4) Conclusions: An independent effect of moderate physical activity was observed in non-obese apparently healthy individuals a with different HOMA-IR index. The effect was marked by an improved health profile including higher vitamin D and lower inflammatory markers in IRA compared to IRS, and a higher oxygen carrying capacity and lipid profile in ISA compared to the ISS counterparts.

Six HIT Sessions Improve Cardiorespiratory Fitness and Metabolic Flexibility in Insulin Resistant and Insulin Sensitive Adolescents with Obesity.

To evaluate the effect of high-intensity interval training (HIT) on the cardiorespiratory performance and substrate oxidation pattern in insulin-resistant and insulin-sensitive obese adolescents. METHODS: We recruited 25 obese adolescents in three schools, and trained them in six HIT sessions, comprising of six series at 100% and recovery at 50% peak velocity (Vpeak). For the evaluation, the participants were divided into two groups: insulin-resistant (IR, n = 12; HOMA index ≥3.16) and insulin-sensitive (IS, n = 13). All participants underwent cardiopulmonary and indirect calorimetry testing. We compared the effects of HIT before and after the intervention among the two groups. The data were analyzed using Student's t and Mann-Whitney (intergroup comparisons) and Student's t and Wilcoxon (pre- and post-training comparisons) tests; and Cohen's d (influence of HIT). RESULTS: There was a significant post-training increase in Vpeak, oxygen consumption (VO2), velocity (V), and heart rate (HR) at the exertion intensity at the first ventilatory anaerobic threshold (VAT1) in both groups (p < 0.05; d < 0.02). The exercise promoted changes in substrate oxidation rates of the groups, with an increase in carbohydrate oxidation (CHOox) for both IR (p = 0.064) and IS (p = 0.034). CONCLUSION: Six HIT sessions improved cardiorespiratory performance in both groups and increased CHOox in insulin-sensitive obese adolescents, suggesting its utility for increasing physical fitness and controlling glycemia in these population groups.

Nutritional Biomarkers and Factors Correlated with Poor Sleep Status among Young Females: A Case-Control Study.

Poor sleep status is associated with several health problems. Nutritional biomarkers and factors related to poor sleep are understudied. This study aimed to identify nutrition biomarkers and factors related to sleep status in healthy young Saudi females. The study included 92 normal-weight and obese Saudi females aged 19−25. Fasting blood glucose, insulin, and lipid profiles were measured. Insulin resistance was calculated on the basis of the homeostasis model assessment of insulin resistance (HOMA-IR) method. Anthropometric, stress, physical activity, and dietary data were collected. Data on the polyphenol content in foods were retrieved from the Phenol-Explorer database. The sleep status was assessed using the Pittsburgh sleep quality index (PSQI). Associations between variables were assessed using the multiple logistic regression model. Around 76% of the participants had poor sleep status (PSQI > 5). Multiple logistic regression reported high polyphenol intake as a protective factor against poor sleep (OR 0.24; 95% CI 0.07−0.83; p = 0.03) and HOMA-IR as an independent risk for poor sleep (OR 4.97; 95% CI 1.11−22.31; p = 0.04). Other nutritional biomarkers and factors, such as BMI, lipid profile, and vitamins, revealed a trend but were not significant. In conclusion, poor sleep status is associated with insulin resistance and low polyphenol intake among women of reproductive age.

Effects of Hydroxy-Alpha-Sanshool on Intestinal Metabolism in Insulin-Resistant Mice.

To explore the hydroxy-alpha-sanshool (HAS) effects on the intestinal metabolites of insulin-resistant mice, the blank group (BG), model group (MG), and HAS dose group (DG) were designed. The insulin resistance (IR) model was induced through streptozotocin (STZ) combined with a high-fat and high-sugar diet. Based on the availability of the model, the HAS dose was given by gavage for 28 days. The determination of cecum and key serum indexes was made, including the contents of insulin (INS), triglycerides (TG), total cholesterol (TC), glycosylated serum protein (GSP), and glycosylated hemoglobin (GHb). The changes in gut microbiota and metabolites in cecal contents were detected by 16S rRNA gene amplicon sequencing and UPLC/HRMS technology, respectively. The results that the levels of GSP, GHb, TG, and TC were significantly increased; this was not the case for INS; or for the changes in the gut microbiota and metabolites in MG. However, the intervention of HAS effectively reversed these changes, for instance, it decreased levels of GSP, GHb, TG, TC, and alterations of metabolite composition for linoleic acid and tyrosine metabolism and recovered trends of declining species diversity and richness of the gut microbiota in MG. It was indicated that HAS alleviated IR by regulating the gut microbiota and metabolites and affecting lipid and amino acid metabolism pathways.

α-Linolenic acid rich-chia seed modulates visceral adipose tissue collagen deposition, lipolytic enzymes expression, insulin signaling and GLUT-4 levels in a diet-induced adiposity rodent model.

Given obesity and its associated metabolic disorders have reached epidemic proportions, the study of therapeutic strategies targeting white adipose tissue (WAT) are of main research interest. We previously shown that α-linolenic acid-rich chia seed was able to ameliorate a wide range of metabolic disorders including body fat accretion in sucrose-rich diet (SRD)-fed rats, an experimental model of visceral adiposity and insulin resistance. However, the mechanisms involved are not fully clarified. The aim of this study was to evaluate the effect of chia seed administration upon WAT remodeling and key enzymes that controls lipolysis, insulin signaling (tAKT, pAKT), and GLUT-4 levels in different visceral fat pad depots (epididymal -eWAT- and retroperitoneal -rWAT- adipose tissues) of SRD-fed rats. Results showed that chia seed reduces adipocytes hypertrophy, the increased lipid content and collagen deposition in both WAT. These changes were accompanied by a significant reduction of HSL and ATGL protein levels in eWAT and HSL protein levels in rWAT. Moreover, chia seed restored the altered expression pattern of the pAKT observed in SRD-fed rats, and modulated GLUT-4 levels. Chia seed could be a dietary intervention of great relevance with potential beneficial effects in the management of body fat excess and WAT function.