High Insulin Resistance in Saudi Women with Unexplained Recurrent Pregnancy Loss: A Case-control Study.

Background: Unexplained recurrent pregnancy loss (RPL) accounts for >50% of the patients with RPL. Insulin resistance (IR) is a potential cause of unexplained RPL. Objectives: To evaluate the relationship between insulin resistance (IR) and unexplained RPL among Saudi women. Methods: This is a single-center, case-control study conducted at a tertiary hospital in the Eastern Province of Saudi Arabia. The study group comprised Saudi women with unexplained RPL, while the control group had Saudi women with at least one live birth and no RPL. Blood samples were taken to determine the fasting glucose (FG) and fasting insulin (FI) levels. Women with diabetes mellitus and polycystic ovarian syndrome were excluded. A homeostatic model assessment of insulin resistance index (HOMA-IR) value ≥3 was considered as IR. Results: The study and control groups comprised 43 and 56 women, respectively. Between the groups, there was a significant difference in the mean age (case: 37.9 ± 5.4 years; control: 32.2 ± 5.9 years; P < 0.0001) and the mean BMI (case: 31.5 ± 6.0; control: 26.1 ± 2.8; P < 0.0001). FG level was slightly higher in the control group (90.9 mg/dL vs 88.7 mg/dL; P = 0.068). FI level was significantly higher in the study group (16.33 µU/mL vs. 6.17 µU/mL; P < 0.0001). HOMA-IR of ≥3 was significantly more common in the study group (n = 22; 51.2%) than the control group (4; 7.1%) (P < 0.0001). After adjusting for age and BMI, IR ≥3 was found to be independently associated with unexplained RPL (aOR: 13.2; 95% CI: 3.77-46.36). Conclusions: This study showed that Saudi women with unexplained RPL had significantly higher levels of fasting insulin and insulin resistance than those without a history of RPL. Therefore, it is recommended to assess IR in women with RPL.

Evaluation of the effects of vitamin D deficiency and cigarette smoking on insulin resistance in type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

There are contradictory findings regarding the effects of vitamin D supplementation and cigarette smoking on glucose metabolism in individuals with type 2 diabetes mellitus (T2DM). Consequently, this meta-analysis focused on the association between vitamin D interventions and smoking cessation on glycemic control in T2DM patients. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cochrane Library, EMBASE and PubMed databases were used for a language-inclusive literature search until November 2022. The primary outcomes of this meta-analysis were changes in glycated hemoglobin (HbA1c) level, vitamin D concentration and body mass index (BMI) values. This meta-analysis included 14 randomized controlled trials (RCTs) with a total of 23,289 individuals with T2DM. Nine RCTs were related to vitamin D supplementation interventions, and 5 RCTs were related to smoking cessation interventions. The studies on vitamin D supplementation showed a substantial change in the intervention group, with a risk ratio (RR) of 0.72 (95% confidence interval (95% CI): 0.58, 0.88; p = 0.001) and an odds ratio (OR) of 0.52 (95% CI: 0.34, 0.78; p = 0.002); high heterogeneity was observed (I2 ≥ 95%). Similarly, the smoking cessation studies showed a substantial change in the intervention group, with a RR of 0.92 (95% CI: 0.86, 0.99; p = 0.04) and an OR of 0.86 (95% CI: 0.74, 0.99; p = 0.04); high heterogeneity was observed (I2 = 87%). In conclusion, both vitamin D supplementation and smoking cessation are associated with moderate BMI decline and an improvement of insulin sensitivity in people with T2DM.

Prevalence estimates of the insulin resistance and associated prevalence of heart failure among United Status adults.

BACKGROUND: The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. METHODS: The Nation Health and Nutrition Examination Survey (NHANES) (2009-2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. RESULTS: This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation (r = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02-1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1-3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). CONCLUSIONS: Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis.

Background & Aims: Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis. Methods: Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy. Results: Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] -9 µg/L efruxifermin vs. -3.4 µg/L placebo; p = 0.0130) and ELF score (-0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB -5.7 kPa efruxifermin vs. -1.1 kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients. Conclusions: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies. Lay summary: Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH. Clinical Trial Number: NCT03976401.

Correlation Between Insulin Resistance and Psoriatic Arthritis Disease Activity: A Cross-Sectional Study.

OBJECTIVES: Most psoriatic arthritis (PsA) research and studies focus solely on the skin and joint manifestations, but there is also an increased risk of metabolic disorders, including insulin resistance (IR). This study aims to discover the relationship between IR and disease activity (DA) in PsA and its phenotype. MATERIALS AND METHODS: Patients with PsA classified using the CASPAR criteria with the disease activity was measured using the DAPSA score, and IR was identified as an elevated HOMA-IR of >2.5. The disease phenotype was determined with Moll and Wright's classification of the PsA subtype. The Pearson correlation test examined the relationship between DA and IR. The descriptive analysis was conducted to determine the relationship between the DAPSA score and HOMA-IR value in each PsA phenotype. All tests were two-tailed, analysed with GraphPad Prism 9, and a P-value of less than .05 was considered statistically significant. RESULTS: From thirty-one patients, there was a strong and positive relationship between DA and IR (r = .768, P = .000). We also observed variations in DAPSA score and HOMA-IR value across different phenotypes, with symmetrical polyarthritis exhibiting the highest DAPSA score (21.55 ± 3.50) and HOMA-IR value (2.913 ± .5392) despite asymmetrical oligoarthritis that being the most frequent phenotype. CONCLUSION: Our study revealed a significant association between disease activity and insulin resistance in PsA patients, with the symmetrical polyarthritis phenotype demonstrating the highest levels of DAPSA score and IR value. This finding allowed rheumatologists to behold this manifestation and could improve PsA patients' long-term outlook.

Influence of Subclinical Hypothyroidism on Women With Polycystic Ovary Syndrome: A Literature Review.

Subclinical hypothyroidism (SCH) is a commonly encountered condition in women with polycystic ovary syndrome (PCOS). Nevertheless, it is unclear whether SCH has any potential impact on the metabolic and reproductive profiles of women with PCOS. Hence, this literature review explores and establishes the link between these two conditions. In women with PCOS, SCH was found to aggravate insulin resistance and dyslipidemia. It was also linked to hormonal imbalances leading to higher infertility rates among the PCOS-SCH group. Therefore, women with PCOS must be screened for thyroid function frequently and managed accordingly.

A Cardiac Amino-Terminal GRK2 Peptide Inhibits Maladaptive Adipocyte Hypertrophy and Insulin Resistance During Diet-Induced Obesity.

Heart disease remains the leading cause of death, and mortality rates positively correlate with the presence of obesity and diabetes. Despite the correlation between cardiac and metabolic dysregulation, the mechanistic pathway(s) of interorgan crosstalk still remain undefined. This study reveals that cardiac-restricted expression of an amino-terminal peptide of GRK2 (ßARKnt) preserves systemic and cardiac insulin responsiveness, and protects against adipocyte maladaptive hypertrophy in a diet-induced obesity model. These data suggest a cardiac-driven mechanism to ameliorate maladaptive cardiac remodeling and improve systemic metabolic homeostasis that may lead to new treatment modalities for cardioprotection in obesity and obesity-related metabolic syndromes.

Triglyceride-Glucose Index Correlate With Telomere Length in Healthy Adults From the National Health and Nutrition Examination Survey.

Aim: The present investigation was designed to test the association between leukocyte telomere length (LTL) and two simple markers of insulin resistance, that is, homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride-glucose (TyG) index in U.S. adults without metabolic diseases. Methods: A total of 6489 U.S. adults without diabetes from NHANES 1999-2002 were analyzed. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. HOMA-Index was calculated as fasting plasma glucose (mmol/L) × fasting serum insulin (mU/mL)/22.5. LTL was obtained using the quantitative polymerase chain reaction method. Multivariate linear regression analysis was assessed to evaluate the association of TyG index HOMA-IR with LTL. We further conducted a generalized additive model (GAM) and a fitted smoothing curve with penalized spline method. Results: It was found that the mean LTL was 5796.1 bp in the measured healthy adults. Overall, TyG index was significantly associated with LTL, while HOMA-IR was not. Compared with participants in tertile 1 of the TyG index, the ß (95% CI) for those in the second (8.27 to 8.77) and third (≥ 8.77) were -4.31 (95% CI: -48.12~39.49) and -95.98 (95% CI: -145.08~-46.89), respectively. Subjects with TyG index ≥ 8.77 had statistically significant shorter LTL (ß = -93.33, 95%CI: -134.33~-52.32), compared with TyG index < 8.77. We further explored a dose-response relation between TyG index by a decile approach [≤ 7.81 (reference), 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, 8.52-8.68, 8.68-8.83, 8.83-9.03, 9.03-9.33, and >9.33] and LTL. Five subgroups (TyG index 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, and 8.52-8.68) did not show significant effect on LTL; while there was a significantly shorter LTL for participants with the TyG index > 8.68, supporting a threshold effect of TyG index on LTL. Conclusions: The results suggested that higher TyG index (> 8.68) was closely related to shorter LTL and the TyG index was better associated with LTL than HOMA-IR.

Association of Cardiometabolic Disease With Cancer in the Community.

Background: Obesity and cardiometabolic dysfunction have been associated with cancer risk and severity. Underlying mechanisms remain unclear. Objectives: The aim of this study was to examine associations of obesity and related cardiometabolic traits with incident cancer. Methods: FHS (Framingham Heart Study) and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants without prevalent cancer were studied, examining associations of obesity, body mass index (BMI), waist circumference, visceral adipose tissue (VAT) and subcutaneous adipose tissue depots, and C-reactive protein (CRP) with future cancer in Cox models. Results: Among 20,667 participants (mean age 50 years, 53% women), 2,619 cancer events were observed over a median follow-up duration of 15 years. Obesity was associated with increased risk for future gastrointestinal (HR: 1.30; 95% CI: 1.05-1.60), gynecologic (HR: 1.62; 95% CI: 1.08-2.45), and breast (HR: 1.32; 95% CI: 1.05-1.66) cancer and lower risk for lung cancer (HR: 0.62; 95% CI: 0.44-0.87). Similarly, waist circumference was associated with increased risk for overall, gastrointestinal, and gynecologic but not lung cancer. VAT but not subcutaneous adipose tissue was associated with risk for overall cancer (HR: 1.22; 95% CI: 1.05-1.43), lung cancer (HR: 1.92; 95% CI: 1.01-3.66), and melanoma (HR: 1.56; 95% CI: 1.02-2.38) independent of BMI. Last, higher CRP levels were associated with higher risk for overall, colorectal, and lung cancer (P < 0.05 for all). Conclusions: Obesity and abdominal adiposity are associated with future risk for specific cancers (eg, gastrointestinal, gynecologic). Although obesity was associated with lower risk for lung cancer, greater VAT and CRP were associated with higher lung cancer risk after adjusting for BMI.

Association between Relative Handgrip Strength and Insulin Resistance in Korean Elderly Men without Diabetes: Findings of the 2015 Korea National Health Nutrition Examination Survey.

BACKGROUND: Evidence regarding the association between handgrip strength (HGS) and insulin resistance in a non-diabetic population is scarce. This study aimed to investigate the association between relative HGS and insulin resistance in older men without diabetes, using a representative sample of the Korean male population. METHODS: The study population comprised 206 participants aged 65-80 years, selected from the 2015 Korea National Health and Nutrition Examination Survey. Insulin resistance was defined as the upper tertile of the homeostatic model assessment of insulin resistance (HOMA-IR). Odds ratios and 95% confidence intervals for insulin resistance were assessed using multiple logistic regression analyses after adjusting for confounding variables. RESULTS: The prevalence of insulin resistance decreased with increasing relative HGS. The prevalence in the T1, T2, and T3 groups was 46.0%, 32.2%, and 26.4%, respectively. Compared with the individuals in the highest tertile of relative HGS, the odds ratio (95% confidence interval) for insulin resistance in individuals in the lowest quartile was 2.82 (1.10-7.21) after adjusting for age, smoking, alcohol consumption, aerobic exercise, resistance exercise, systolic blood pressure, total cholesterol, residential area, household income, and education level. CONCLUSION: Lower relative HGS was inversely associated with an increased risk of insulin resistance in older Korean men without diabetes. In clinical practice, relative HGS, which is a simple and inexpensive tool, could be a useful measure for identifying older men with insulin resistance. Moreover, these findings suggest that muscle strengthening exercises should be considered to reduce insulin resistance and increase insulin sensitivity.

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study.

Background: Diabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease. Methods: In this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained. Results: Participants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial ß-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1). Conclusion: In this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

Comparison of Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and the Level of Cortisol Between Preterm and Term Newborns.

Introduction According to the thrifty (Barker's) phenotype hypothesis, poor nutrition in fetal and early infancy plays a role in the development and function of the beta cells of the islets of Langerhans, which leads to the development of type 2 diabetes mellitus. Insulin resistance is due to decreased suppressive effect of insulin on hepatic glucose production. Thus, elevated insulin levels during perinatal life may predispose the infant to the development of diabetes mellitus in future life. Intrauterine undernutrition plays an important role in causing adult insulin resistance and diabetes but the exact cause is still unknown. Preterm infants born small for gestational age (SGA) show lower adrenocortical response to stimulation due to an immature hypothalamic-pituitary axis. Methods The cross-sectional study conducted at Rajendra Institute of Medical Sciences, Ranchi from June 2020 to November 2021 included 216 newborns enrolled as per the inclusion and exclusion criteria. Maternal and neonatal details were collected at birth and recorded. Cord blood samples for measurement of serum insulin, glucose, and cortisol were collected from 84 preterm and 132 term neonates. Using this information, homeostasis model assessment-insulin resistance (HOMA-IR) was calculated using a mathematical formula. Insulin resistance was defined as HOMA-IR > 2.5. Based on birth weight and gestational age, they were further categorized into SGA, appropriate for gestational age (AGA), and large for gestational age (LGA). The parametric data were presented as means ± standard deviation (SD), and nonparametric data as medians (first quartile and third quartile). The Student's (independent samples) t-test and Mann-Whitney U test were used to compare mean differences between the two groups for parametric and nonparametric data, respectively. The Spearman correlation coefficient was used to determine the significant association between variables. Results Umbilical cord plasma glucose and serum insulin were high in preterm in comparison to term newborns. Serum cortisol levels were high in term than in preterm newborns. HOMA-IR showed a very strong positive correlation with serum insulin and a moderate positive correlation with serum glucose. HOMA-IR showed a strong negative correlation with gestational age and a moderate negative correlation with birth weight. Insulin resistance was seen in 34 preterm newborns and two term newborns. Insulin resistance was seen in 29.8% (n = 25) of SGA preterm babies, 7.1% (n = 6) of AGA preterm babies, and 1.5% (n = 2) of AGA term newborns. A total of 55.6% of newborns were below normal weight (48.1% had low birth weight, 4.6% had very low birth weight, and 2.8% had extremely low birth weight). Conclusion Our study suggests that preterm newborns are more insulin resistant at birth than term newborns. SGA preterm babies are having a higher incidence of insulin resistance compared to AGA preterm babies. It is clear that high insulin level is needed to overcome high insulin resistance in the very early gestational period. Serum cortisol increases as gestational age and birth weight increase. Thus, serum cortisol helps in the maturation of the fetus and neonatal adaptation at birth.

Circulating chemerin levels in women with polycystic ovary syndrome: a meta-analysis.

OBJECTIVE: The present meta-analysis was conducted to investigate the association between circulating chemerin levels and polycystic ovary syndrome (PCOS) in women. METHODS: Relevant studies published up to May 2020 were searched from PubMed, Ovid, the Cochrane Library, and Clinical Trial Database. A random effects model was used to measure the strength of association between PCOS and chemerin by using the standardized mean difference (SMD) and 95% confidence interval (CI). All data were analyzed using Stata 12.0 (version 12; Stata-Corp, College Station, TX). RESULTS: The final meta-analysis included eight studies with 15 results including a total of 897 participants (524 patients with PCOS and 373 controls). The circulating chemerin levels were higher in patients with PCOS (random effects SMD = 1.07; 95% CI: 0.55-1.59; p < .001) than in controls. However, considerable heterogeneity across studies was not eliminated in subgroup analyses. The meta-regression analysis further suggested that region is the main source of heterogeneity (p = .001). CONCLUSIONS: Our meta-analysis indicated that women with PCOS have significantly higher circulating chemerin levels than in healthy women, indicating that chemerin may be involved in the pathogenesis of PCOS.

Vitamin D Deficiency Is Inversely Associated with Homeostatic Model Assessment of Insulin Resistance.

The study was conducted to comprehensively assess the association of the concentration of vitamin D in the blood and insulin resistance in non-diabetic subjects. The objective was to pool the results from all observational studies from the beginning of 1980 to August 2021. PubMed, Medline and Embase were systematically searched for the observational studies. Filters were used for more focused results. A total of 2248 articles were found after raw search which were narrowed down to 32 articles by the systematic selection of related articles. Homeostatic Model Assessment of Insulin Resistance (HOMAIR) was used as the measure of insulin resistance and correlation coefficient was used as a measure of the relationship between vitamin D levels and the insulin resistance. Risk of bias tables and summary plots were built using Revman software version 5.3 while Comprehensive meta-analysis version 3 was used for the construction of forest plot. The results showed an inverse association between the status of vitamin D and insulin resistance (r = -0.217; 95% CI = -0.161 to -0.272; p = 0.000). A supplement of vitamin D can help reduce the risk of insulin resistance; however further studies, like randomized controlled trials are needed to confirm the results.

A Rare Case of Subcutaneous Insulin Resistance Presumed to be due to Paraneoplastic Process in Pancreatic Adenocarcinoma.

OBJECTIVE: We describe a rare case of profound subcutaneous insulin resistance (SIR) presumed due to a paraneoplastic process caused by pancreatic adenocarcinoma that improved with intravenous insulin and tumor resection. METHODS: An 80-year-old man with previously well-controlled type 2 diabetes mellitus had worsening glycemic control (hemoglobin A1C increase of 6.5% to 8.6% over 4 months) following a recent diagnosis of pancreatic adenocarcinoma. His blood glucose was uncontrolled at 600 mg/dL despite rapid up-titration of a subcutaneous basal-bolus insulin regimen totaling 1000 units/d. Extensive evaluation of insulin resistance including insulin antibodies and anti-insulin receptor antibodies was negative. Due to clinical deterioration, the patient underwent pancreaticoduodenectomy before the completion of neoadjuvant chemotherapy. The patient received intravenous insulin before surgery, which resulted in rapid improvement in glycemic control. The patient's blood glucose normalized, and he was maintained on metformin monotherapy following pancreaticoduodenectomy. RESULTS: This patient had evidence of SIR in the setting of pancreatic adenocarcinoma. SIR was likely a paraneoplastic process as glycemic control improved after tumor resection. Interestingly, the patient did not have hyperinsulinemia but rather evidence of ß-cell dysfunction, which highlights the possibility of exogenous insulin resistance. CONCLUSION: Paraneoplastic processes due to pancreatic adenocarcinoma can cause SIR, marked by profound hyperglycemia and deteriorating functional status. It is, therefore important to recognize this rare syndrome and appropriately escalate to a higher level of care and consider proceeding with tumor resection.

The impact of oral carbohydrate-rich supplement taken two hours before caesarean delivery on maternal and neonatal perioperative outcomes -- a randomized clinical trial.

BACKGROUND: To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes. METHODS: Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants' blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women's perioperative symptoms and signs were recorded. RESULTS: Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (ß = - 3.50, 95% CI - 5.45 to - 1.56), as well as postoperative HOMA-IR index (ß = - 0.74, 95% CI - 1.15 to - 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (ß = 0.40, CI 0.17 to 0.62). CONCLUSION: Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women's preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033163 . Data of Registration: 2020-5-22.

Salivary resistin level and its association with insulin resistance in obese individuals.

The escalating global burden of type 2 diabetes mellitus necessitates the implementation of strategies that are both more reliable and faster in order to improve the early identification of insulin resistance (IR) in high-risk groups, including overweight and obese individuals. The use of salivary biomarkers offers a promising alternative to serum collection because it is safer, more comfortable, and less painful to obtain saliva samples. As obesity is the foremost contributory factor in IR development, the adipocytokines such as leptin, adiponectin, resistin, and visfatin secreted from the adipose tissue have been studied as potential reliable biomarkers for IR. Measurement of salivary adipokines as predictors for IR has attracted widespread attention because of the strong correlation between their blood and salivary concentrations. One of the adipokines that is closely related to IR is resistin. However, there are conflicting findings on resistin's potential role as an etiological link between obesity and IR and the reliability of measuring salivary resistin as a biomarker for IR. Hence this study reviewed the available evidence on the potential use of salivary resistin as a biomarker for IR in order to attempt to gain a better understanding of the role of resistin in the development of IR in obese individuals.

Comprehensive lipidomics reveals phenotypic differences in hepatic lipid turnover in ALD and NAFLD during alcohol intoxication.

BACKGROUND & AIMS: In experimental models, alcohol induces acute changes in lipid metabolism that cause hepatocyte lipoapoptosis and inflammation. Here we study human hepatic lipid turnover during controlled alcohol intoxication. METHODS: We studied 39 participants with 3 distinct hepatic phenotypes: alcohol-related liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and healthy controls. Alcohol was administrated via nasogastric tube over 30 min. Hepatic and systemic venous blood was sampled simultaneously at 3 time points: baseline, 60, and 180 min after alcohol intervention. Liver biopsies were sampled 240 min after alcohol intervention. We used ultra-high performance liquid chromatography mass spectrometry to measure levels of more than 250 lipid species from the blood and liver samples. RESULTS: After alcohol intervention, the levels of blood free fatty acid (FFA) and lysophosphatidylcholine (LPC) decreased, while triglyceride (TG) increased. FFA was the only lipid class to decrease in NAFLD after alcohol intervention, whereas LPC and FFA decreased and TG increased after intervention in ALD and healthy controls. Fatty acid chain uptake preference in FFAs and LPCs were oleic acid, linoleic acid, arachidonic acid, and docosahexaenoic acid. Hepatic venous blood FFA and LPC levels were lower when compared with systemic venous blood levels throughout the intervention. After alcohol intoxication, liver lipidome in ALD was similar to that in NAFLD. CONCLUSIONS: Alcohol intoxication induces rapid changes in circulating lipids including hepatic turnaround from FFA and LPC, potentially leading to lipoapoptosis and steatohepatitis. TG clearance was suppressed in NAFLD, possibly explaining why alcohol and NAFLD are synergistic risk factors for disease progression. These effects may be central to the pathogenesis of ALD. CLINICAL TRIALS REGISTRATION: The study is registered at Clinicaltrials.gov (NCT03018990). LAY SUMMARY: We report that alcohol induces hepatic extraction of free unsaturated fatty acids and lysophosphatidylcholines, hepatotoxic lipids which have not been previously associated with alcohol-induced liver injury. We also found that individuals with non-alcoholic fatty liver disease have reduced lipid turnover during alcohol intoxication when compared with people with alcohol-related fatty liver disease. This may explain why alcohol is particularly more harmful in people with non-alcoholic fatty liver and why elevated BMI and alcohol have a synergistic effect on the risk of liver-related death.

Screening of Family Members of Nonalcoholic Fatty Liver Disease Patients can Detect Undiagnosed Nonalcoholic Fatty Liver Disease Among Them: Is There a Genetic Link?

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) has multifactorial origin. Genetic and environmental factors lead to the biology of this complex disorder. In this study, we screened parents of cases with NAFLD and compared them with parents of cases without NAFLD to see its familial aggregation and the role of patatin-like phospholipase domain containing 3 (PNPLA3). METHOD: It was a cross-sectional study. Parents of probands with NAFLD and without NAFLD were screened with abdominal sonography, anthropometry, blood tests, transient elastography, and PNPLA3 polymorphism. RESULTS: We had enrolled 303 individuals: 51 probands with NAFLD, 50 probands without NAFLD, and their 202 parents. Parents of the NAFLD group had significantly higher metabolic risk factors as compared with parents of the non-NAFLD group. They had a significantly higher rate of fatty liver (P = 0.0001), mean serum aspartate aminotransferase levels (P = 0.011), mean serum alanine aminotransferase levels (P = 0.001),raised fasting and postprandial blood sugar levels, lower mean platelets (P = 0.033) and serum albumin levels (P = 0.005), and higher mean liver stiffness (P = 0.001) on transient elastography.Frequency of PNPLA3 polymorphism within NAFLD group was higher compared to the non-NAFLD group (mutant GG-13.3 vs 3.3%). Similarly, parents of NAFLD group had mutant GG in 15 % versus 5% in parents of non-NAFLD group, (P = 0.105, odds ratio 6), though it was not statistically significant but may be relevant. In this study, offsprings of parents with nonalcoholic steatohepatitis were likely to have GG homozygous allele. A NAFLD16 score based on parent's parameters was calculated to predict the probability of NAFLD occurrence in an overweight obese individual. CONCLUSION: Screening of parents of individuals with NAFLD will help in the identification of undiagnosed NAFLD cases and other metabolic risk factors among them as there is a familial aggregation of NAFLD. One can predict the occurrence of NAFLD in the next generation using the NAFLD16 score.

The Effect of Traditional Aerobic Exercise and Sprint Interval Training on Insulin Resistance in Men With Prediabetes: A Randomised Controlled Trial.

Introduction Prediabetes is an intermediate stage with hyperglycaemia below the threshold of diabetes mellitus. Insulin resistance is a significant factor in its pathogenesis. Lifestyle modifications are suggested and found to be more beneficial in this stage. Moderate-intensity exercise for 30 to 45 minutes a day is routinely recommended but has low compliance, and lack of time is a significant deterrent. Sprint interval training (SIT) is an alternate exercise regimen with higher intensity and less time requirement. The present study compares the effect of a three-month intervention of traditional aerobic exercise and sprint interval training on insulin resistance in prediabetic men. Methods The study subjects were males aged 25 to 40 years with prediabetes as per the American Diabetes Association criteria of fasting and two-hour plasma glucose levels. The study is a parallel-group randomised trial with one arm (AE group) involved in the traditional aerobic exercise (brisk walking) for 30 minutes, five days a week. The other arm was the sprint interval training (SIT) group performing an 'all-out' run effort for one minute followed by a recovery rest period of one and a half minutes, completing one cycle of two and half minutes. Four such cycles were completed in each session. Thus, the exercise sessions were just 10 minutes daily, three days a week. The duration of the intervention was three months. One hundred and sixty participants were recruited after screening and randomly assigned in a 1:1 ratio to the two groups. The primary outcome measure was insulin resistance estimated by homeostasis model assessment -estimated insulin resistance (HOMA-IR). The secondary outcome measures were fasting plasma glucose and serum insulin, glycated haemoglobin, body mass index and waist-hip ratio. Results The mean age of the AE group was 30.7 ± 3.3 years, and the SIT group was 31 ± 3.4 years. Seventy-two men from the AE group and 74 from the SIT group completed the study. After the three-month AE and SIT exercise, the per-protocol analysis reflected a significant reduction in insulin resistance, i.e., HOMA-IR (3.6 ± 1.1 to 3 ± 1.2, p<0.0001) after traditional aerobic exercise. Similarly, the HOMA-IR was significantly reduced after sprint interval training (3.3 ± 1.2 to 2.5 ± 1, p<0.0001). The intention-to-treat analysis also found that the reductions in HOMA-IR after both exercise protocols were statistically significant. The change in insulin resistance compared for the SIT vs AE group was not statistically significant. Secondary outcome measures HbA1c, fasting glucose, fasting insulin, BMI, and waist-hip ratio showed significant improvement with AE and SIT.  Conclusions The sprint interval training similarly improved insulin resistance and other parameters compared to the traditional exercise group. SIT can be a time-efficient exercise protocol suggested as a part of lifestyle modification for men with prediabetes.