High Incidence Of Insulin Resistance Research Articles

The Association between Tooth Loss and Insulin Resistance Mediated by Diet Quality and Systemic Immunoinflammatory Index

(1) Background: Both tooth loss and diabetes have high global prevalence, and both have a significant influence on patients’ general health and quality of life. Previous research has indicated a possible connection between tooth loss and diabetes, but it has been unclear whether tooth loss has an effect on the development of diabetes and how it affects it. We aim to investigate the relationship between insulin resistance (IR) and tooth loss and examine how the systemic immune-inflammation index (SII) level and diet quality mediate it. (2) Methods: The cross-sectional study data were obtained from the National Health and Nutrition Examination Survey (NHANES). After describing and comparing baseline data, we used regression models to evaluate the relationship between IR and tooth loss, diet quality and tooth loss and IR, SII and tooth loss and IR. Furthermore, we applied bootstrapping to test the mediation effect of diet quality and SII between tooth loss and IR. Diet quality is reflected by the HEI (Healthy Eating Index)-2015 score. (3) Results: The total number of subjects included was 8197, with 3861 individuals belonging to the IR group (HOMA-IR ≥ 2.5) and 4336 in the non-IR group (HOMA-IR < 2.5). In the model with all covariates adjusted, tooth loss in the fourth quartile was found to be positively correlated with an increase in HOMA-IR (OR = 1.301; 95% confidence interval (CI) = [1.102, 1.537]; p < 0.001) compared to the first quartile; tooth loss in the fourth quartile correlated with the HEI-2015 score compared to the first quantile (β = −0.121, 95% CI = [−4.839, −2.974], p < 0.001); and the highest number of tooth loss was found to have a significant effect on SII (β = 0.032; 95%CI = [1.777, 47.448]; p < 0.05). Compared to average diet quality, best diet quality acts as a safeguard against elevated HOMA-IR (OR = 0.776; 95% CI = [0.641, 0.939]; p < 0.01); inadequate diet quality is a risk factor (OR = 1.267; 95%CI = [1.138, 1.411]; p < 0.001) conversely. Meanwhile, it can be seen that compared with the first quantile of SII, the highest score is significantly correlated with the higher incidence of IR (OR = 1.363; 95%CI = [1.179, 1.575]; p < 0.001). Diet quality and SII played a partial mediating role in the relationship between HOMA-IR and tooth loss, and the mediating effect ratio for the total effect value was 4.731% and 4.576%, respectively. The mediating effect of SII and diet quality in the association of the relationship between HOMA-IR and tooth loss both was 0.003 (95%CI = [0.001, 0.004]). (4) Conclusions: Our study revealed the relationship between IR and tooth loss, and further explored the mediating role of SII and diet quality between the number of missing teeth and IR, emphasizing that improving diet quality and reducing SII can effectively prevent and treat IR and related diseases. It provides new theoretical support for the study of IR mechanisms and new ideas and approaches to deal with related diseases.

Association of Metabolic Dysfunction-Associated Steatotic Liver Disease/Non-alcoholic Fatty Liver Disease With Type 2 Diabetes Mellitus: A Case-Control Study in a Tertiary Care Hospital in Pakistan.

Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels, insulin resistance, and relative insulin deficiency. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the term used to describe fatty liver (steatosis) in individuals without a history of significant alcohol intake. MASLD is progressively known as the leading cause of chronic liver disease. Dietary factors, a significant risk factor for developing T2DM and cardiovascular disease, also contribute to MASLD development. The risk of developing MASLD increases with age, particularly in patients with diabetes mellitus. This risk is notably elevated among South Asians due to their higher incidence of insulin resistance and metabolic syndrome. Importantly, MASLD is acknowledged as a component of the metabolic syndrome, with insulin resistance playing a central role in its development. Objective To determine the association between MASLD and T2DM in patients presenting at a tertiary care hospital in Pakistan. Methodology This case-control study was conducted for one year in a tertiary care hospital in Gujranwala, Pakistan. A total of 380 patients were enrolled through convenient sampling and were analyzed according to two groups: those with diabetes (case) and those without diabetes (control). All participants were assessed for serum aspartate transaminase (AST) and alanine transaminase (ALT) levels and underwent abdominal ultrasound to determine hepatic fibrosis. A diagnosis of MASLD was made only in the presence of hepatic steatosis with AST and ALT values of more than 40 IU. The odds ratio (OR) was calculated, and stratified analysis was conducted according to gender, age, and BMI. A p-value of ≤0.05 was considered statistically significant. Results In our study, 55.53% of patients were male, while 44.47% were female. The average BMI (±SD) of the patients was 23.66±3.08 kg/m2. Among the cases group, the MASLD was noted in 91 (47.9%) patients, while among the controls group, the MASLD was noted in 64 (33.7%) patients with a statistically significant OR of 1.810 (1.19-2.74). Conclusion In conclusion, MASLD is significantly associated with T2DM, regardless of gender and BMI of patients. We recommend screening T2DM patients for the presence of MASLD at regular intervals to prevent hazardous consequences of MASLD in adult populations, particularly those with features of metabolic syndrome. Further larger-scale studies investigating the impact of T2DM on MASLD are required to reduce morbidity and decrease disease burden, especially in prevalent areas.

Effect of Magnesium Supplementation on Insulin Resistance in Polycystic Ovary Syndrome: A Randomized, Single-blind, Placebo-Controlled Trial Study

Background: It has been revealed that low serum magnesium (Mg) is often associated with insulin Resistance (IR), cardiovascular problems, diabetes mellitus, and hypertension. Patients with polycystic ovary syndrome (PCOS) are known to have a high incidence of insulin resistance. Objective: To assess the effects of magnesium supplementation on insulin resistance in polycystic ovary syndrome. Methods: This randomized controlled study was conducted in the Department of Reproductive Endocrinology and Infertility, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from January 2021 to December 2021. A total of 74 women diagnosed of infertility with PCOS were included in this study. Eligible women who gave their informed consent were allocated into either group A: (Magnesium oxide) or group B (placebo) on the basis of a computerized generated table system allocated into two groups 37 patients (group-A) and 37 patients (group -B). Group A received magnesium oxide & group B received a placebo for 12 weeks. After 12 weeks of treatment, both groups were advised to repeat biochemical assay for fasting glucose, fasting insulin, HOMA-IR, serum testosterone & serum lipid profile at the follow-up visit. Results: Magnesium supplementation for 12 weeks among women with PCOS had favorable effects on waist circumference (changes from baseline in the intervention group: -0.76±3.1 vs. -1.7±1.8 cm in the placebo group) and BMI (-2.13±0.98 vs. -0.32±0.52 kg/m2) compared with the placebo group. Magnesium oxide led to a significant reduction in HOMA-IR (-1.49±0.95 vs. 0.09± 0.29) compared with placebo. Serum triglycerides was significantly decreased (-36.7±53.5 vs. 0.1±17.9 mg/d) in the magnesium group than placebo. HDL level was significantly increased in the magnesium group (2.3±5.9 mg/dl), while HDL level was decreased in the placebo group (-1.7±2.7 mg/dl). Significant mean change of total testosterone in magnesium group (0.43±0.35 ng/dL) than placebo group (-0.01±0.05 ng/dL). However, total cholesterol and LDL were also decreased in the magnesium group than in the placebo group, but the difference was not statistically significant (p>0.05) compared between the two groups. Conclusion: The present study provides evidence showing that magnesium supplementation resulted in reduced WC, BMI, HOMA-IR, total cholesterol, triglyceride, LDL, and testosterone levels in women with PCOS. Also, magnesium supplementation might increase serum HDL levels. Though there was a significantly increased pregnancy rate of magnesium supplementation than in a placebo group.

Correlation of Serum Adiponectin Level with Insulin Resistance in Healthy Obese Individuals: A Case-control Study

Introduction: Obesity, emerging as a worldwide health burden having potential risk for development of atherosclerosis, diabetes, coagulopathy, arthritis and metabolic syndrome. Obesity is classified in terms of various anthropometric modalities like Body Mass Index (BMI), Waist Circumference (WC) and Waist Hip Ratio (WHR) etc. Adipocyte secretes adiponectin that has an important role in energy homeostasis and lipid metabolism. Adiponectin level reduces in obesity and its deficiency results in higher incidence of insulin resistance. Adiponectin has insulin sensitising, antiatherogenic and anti inflammatory properties. Aim: To compare the level of serum adiponectin, fasting plasma insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in healthy obese individuals with healthy non obese controls and also to find out the correlation of serum adiponectin with fasting plasma insulin level and HOMA-IR in healthy obese cases. Materials and Methods: This case-control study was conducted in Department of Biochemistry, MKCG MCH, Berhampur, Odisha, India, during the period of October 2019 to October 2020 which included 86 subjects. Of which 43 were healthy obese individuals and 43 were age and sex matched healthy non obese volunteers, in the age group of 20-45 years were taken as controls. About 4 mL of whole blood was collected to measure fasting plasma glucose, fasting plasma insulin and serum adiponectin. Statistical Package for the Social Sciences (SPSS) version 16.0 was used to do the statistical analysis and for correlation Pearson correlation test was done. Results: In present study, maximum cases and controls were within the range of 20-35 years. Out of 43 cases, 25 were males and 18 were females and out of 43 controls, 27 were males and 16 were females. Insulin resistance and Fasting Plasma Glucose were significantly higher in healthy obese cases as compared to controls. Serum adiponectin in cases (2.35±0.77) was found to be significantly lower than controls (8.10±2.98). Present study found statistically significant negative correlation of serum adiponectin with fasting plasma insulin (r=-0.918, p<0.001) and HOMA-IR (r=-0.934, p<0.001). Conclusion: Negative correlation of adiponectin and positive correlation of insulin resistance in obesity suggest inflammation which may lead to development of metabolic syndrome. So adiponectin is a target for future research to reduce morbidity and mortality in relation to obesity.

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 asHOMA-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 forparametric 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 resistancewas 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 extremelylow 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 levels of DDIT4 and mTOR, and contributions of BMI, inflammation and insulin sensitivity in hyperlipidemia.

Evidence shows a high incidence of insulin resistance, inflammation and excess body mass index (BMI) in adults with hyperlipidemia. The present study aimed to determine the circulating levels of DNA damage inducible transcript 4 (DDIT4) and mTOR and assess the contributions of lipids, inflammatory markers, insulin sensitivity and BMI in hyperlipidemia. The study subjects were divided into a hyperlipidemia group and a normal control group (n=55 per group). Sex, age, blood pressure, waist circumference (WC), height, weight and BMI were recorded. Fasting venous blood samples were collected and an automatic biochemical analyzer was used to detect fasting blood glucose (FBG), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Quantitative ELISA kits were used to determine the levels of DDIT4, mTOR and inflammatory markers and calculate the homeostatic model assessment of insulin resistance (HOMA-IR). Compared with the normal control group, the hyperlipidemia group had significantly increased blood pressure, WC, weight, BMI, FBG, FINS, HOMA-IR, mTOR and inflammatory markers, but significantly reduced DDIT4. A concurrent correlation analysis showed that insulin resistance was positively correlated with blood pressure, BMI, lipid profiles (TG, TC, LDL-C), mTOR and inflammatory markers, but negatively correlated with HDL-C and DDIT4. Lipid profiles were positively correlated with BMI, mTOR and inflammatory markers, but negatively correlated with DDIT4. A factor analysis identified four domains in hyperlipidemia (inflammation-lipid 1 domain, 44.429%; overweight domain, 21.695%; insulin sensitivity domain, 11.782%; lipid 2 domain, 6.723%). In conclusion, people with hyperlipidemia have elevated mTOR and reduced DDIT4 and are accompanied by abnormal indicators such as insulin sensitivity, BMI and inflammatory factors. The identified domains may be applied to predict the outcomes of cardiovascular diseases and metabolic diseases in the future.

CORRELATION BETWEEN MAGNESIUM & INSULIN RESISTANCE IN POLYCYSTIC OVARY SYNDROME (PCOS)

PCOS is a hormonal disorder common among women of reproductive age. Patients with PCOS are known to have a high incidence of insulin resistance. Serum magnesium (Mg) is often associated with insulin resistance among patients with PCOS. This case - control study was conducted at SRM Medical College Hospital and Research Centre, Tamil Nadu, India. Total of 62 participants between the age group of 20- 40 years were recruited in the study, in which 31 were healthy controls and 31 were cases with PCOS. FBG, HbA1c, lipid profile, serum magnesium, serum insulin was estimated. Students ‘t’ test was done to compare the mean levels between groups. Low serum magnesium, higher levels of insulin and insulin resistance is seen in PCOS compare to non-PCOS group. The correlation of analysed biochemical parameters were done among PCOS group. Negative correlation of mg with insulin, FBS and HOMA-IR was observed. The evidence showing that low serum magnesium is associated with insulin resistance in PCOS individuals.

Interactions between nocturnal melatonin secretion, metabolism, and sleeping behavior in adolescents with obesity

Background/objectivesSleeping behavior and individual prospensity in sleep timing during a 24 h period, known as chronotypes, are underestimated factors, which may favor the development of obesity and metabolic diseases. Furthermore, melatonin is known to play an important role in circadian rhythm, but was also suggested to directly influence metabolism and bodyweight regulation. Since disturbed and shifted sleep rhythms have been observed in adolescents with obesity, this study aimed to investigate potential interactions between melatonin secretion, chronobiology, and metabolism. In addition, the influence of artificial light especially emitted by electronic devices on these parameters was of further interest.Subjects/methodsWe performed a cross-sectional study including 149 adolescents (mean age 14.7 ± 2.1 years) with obesity. Metabolic blood parameters (e.g., cholesterol, triglycerides, uric acid, and insulin) were obtained from patients and correlated with nocturnal melatonin secretion. Melatonin secretion was determined by measuring 6-sulfatoxymelatonin (MT6s), the major metabolite of melatonin in the first-morning urine, and normalized to urinary creatinine levels to account for the urinary concentration. Chronobiologic parameters were further assessed using the Munich ChronoType Questionnaire.ResultsSubjects with insulin resistance (n = 101) showed significantly lower nocturnal melatonin levels compared to those with unimpaired insulin secretion (p = 0.006). Furthermore, triglyceride (p = 0.012) and elevated uric acid levels (p = 0.029) showed significant associations with melatonin secretion. Patients with late chronotype showed a higher incidence of insulin resistance (p = 0.018). Moreover, late chronotype and social jetlag were associated with the time and duration of media consumption.ConclusionWe identified an association of impaired energy metabolism and lower nocturnal melatonin secretion in addition to late chronotype and increased social jetlag (misalignment of biological and social clocks) in adolescents with obesity. This might point towards a crucial role of chronotype and melatonin secretion as risk factors for the development of pediatric and adolescent obesity.

Dihydromyricetin Ameliorates Inflammation-Induced Insulin Resistance via Phospholipase C-CaMKK-AMPK Signal Pathway.

Patients with metabolic syndrome have a higher risk of type II diabetes and cardiovascular disease. The metabolic syndrome has become an urgent public health problem. Insulin resistance is the common pathophysiological basis of metabolic syndrome. The higher incidence of insulin resistance in obese groups is due to increased levels of inflammatory factors during obesity. Therefore, developing a therapeutic strategy for insulin resistance has great significance for the treatment of the metabolic syndrome. Dihydromyricetin, as a bioactive polyphenol, has been used for anti-inflammatory, antitumor, and improving insulin sensitivity. However, the target of DHM and molecular mechanism of DHM for preventing inflammation-induced insulin resistance is still unclear. In this study, we first confirmed the role of dihydromyricetin in inflammation-induced insulin resistance in vivo and in vitro. Then, we demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance by activating Ca2+-CaMKK-AMPK using signal pathway blockers, Ca2+ probes, and immunofluorescence. Finally, we clarified that dihydromyricetin activated Ca2+-CaMKK-AMPK signaling pathway by interacting with the phospholipase C (PLC), its target protein, using drug affinity responsive target stability (DARTS) assay. Our results not only demonstrated that dihydromyricetin resisted inflammation-induced insulin resistance via the PLC-CaMKK-AMPK signal pathway but also discovered that the target protein of dihydromyricetin is the PLC. Our results provided experimental data for the development of dihydromyricetin as a functional food and new therapeutic strategies for treating or preventing PLC.

The relationship between insulin resistance, bone mineral density, and fracture risk in postmenopausal women

Background/Aim. Skeletal muscles and bones are essential tissues that, in addition to supporting the body, are the primary site of postprandial glucose intake, which is significantly associated with insulin resistance. The aim of this study was to determine the effect of insulin resistance on bone mineral density (BMD) and fracture risk and re-evaluate the relationship between muscle properties and BMD and insulin resistance in postmenopausal women in Serbia. Methods. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated in postmenopausal women who were divided into two groups. The ?cut-off? value of insulin resistance for the group with ?Low HOMA-IR? was < 2, and for ?High HOMA-IR? > 2. Fat mass (FM), lean mass (LM), and BMD were measured on the hip and spine using a densitometer with dual-energy X-ray absorptiometry. Results. FM and LM had an evident impact on BMD. The decrease in LM and fat buildup was associated with a higher incidence of insulin resistance. A positive correlation was confirmed between HOMA-IR and BMD on the spine and hip, but there was no correlation between insulin resistance and fracture risk. Conclusion. LM and FM have significant effects on BMD. The association between LM, FM, BMD and the onset of insulin resistance in postmenopausal women is confirmed. However, women with higher insulin resistance levels and higher BMD do not have a lower fracture risk.

Insulin resistance and high molecular weight adiponectin in obese and non-obese patients with Polycystic Ovarian Syndrome (PCOS)

BackgroundPolycystic ovarian syndrome (PCOS) is the most common endocrinopathy among young women. Insulin resistance is a key feature in the pathogenesis of PCOS; also high molecular weight adiponectin is a marker of insulin resistance. The aim of this study was to evaluate the insulin resistance, metabolic and androgenic profiles and high molecular weight adiponectin in obese and non-obese PCOS patients.MethodsIn this cross-sectional study in outpatient endocrinology clinics of Shiraz University of Medical Sciences, 80 women aged 17–43 years old with PCOS were enrolled. Biochemical and hormonal assay was done on fasting blood sample on the third day of follicular phase.ResultsThe individuals had a mean age of 28.39 ± 6.56 years, mean weight of 65.41 ± 12.59 Kg, mean BMI of 25.5 ± 4.9, and mean waist circumference of 88.0 ± 13.1 cm. Of all individuals 20% had frank insulin resistance with HOMA-IR > 3.8. Although the obese PCOS patients had lower levels of high molecular weight adiponectin (P = 0.03) than the normal weight PCOS individuals, the level of insulin and insulin resistance was not different in them (P = 0.13, 0.13). Patients with classic PCOS phenotype significantly had higher levels of insulin resistance and free androgen index (P < 0.001, 0.001). We found a significant correlation between the insulin level and free androgen index (correlation coefficient: 0.266 and P = 0.018) after adjusting for BMI.ConclusionThis cross-sectional study showed a high incidence of insulin resistance in PCOS patients independent of obesity, and determined BMI related lower level of high molecular weight adiponectin in obese PCOS individuals. More detailed studies are warranted for evaluation of insulin resistance and its pathophysiologic role in PCOS.

Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.

BackgroundOur 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).MethodsThis 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.ResultsSerum 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).ConclusionsLow serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.

Unhealthy Alcohol Use is Associated with a Higher Prevalence of Dysglycemia in Persons Living with HIV

Chronic alcohol consumption is the most common and costly form of substance abuse in the United States and is highly prevalent in persons living with HIV (PLWH). Combination antiretroviral therapy (ART) has significantly increased longevity in PLWH and over 50% of PLWH in the U.S.A. are 50 years of age or older. Aging, unhealthy alcohol use and increased survival of PLWH on ART are complicated by metabolic dysregulation. The goal of the current study was to test the hypothesis that unhealthy alcohol use in PLWH increases the prevalence of dysglycemia following an oral glucose tolerance test (OGTT). Participants with a fasting blood glucose (FBG) of 94–125mg/dL (n=105) were recruited from a cohort of in‐care PLWH (≥ 18 years) enrolled in the ongoing translational study, New Orleans Alcohol Use in HIV (NOAH) and from the Greater New Orleans area. Alcohol use was determined by the Alcohol Use Disorders Identification Test (AUDIT). An AUDIT score ≥ 5 was defined as unhealthy alcohol use (n=47) versus an AUDIT score of &lt; 5 (n=52). Questionnaires (i.e. AUDIT and Timeline Followback) and Phosphatidylethanol (PEth) were used to further describe and confirm alcohol use. All participants underwent an OGTT, which included an assessment of plasma glucose 2 hours following consumption of a standard glucose solution (75g, Trutol). Circulating insulin, c‐peptide and adiponectin were measured. Anthropometric measurements included assessment of weight, Body Mass Index, and waist/hip ratio (WHR). Among participants with an impaired FBG, 44.8% exhibited unhealthy alcohol use. 2‐h plasma glucose values were positively correlated with AUDIT, PEth and 2‐h insulin levels and there was a moderate, but not statistically significant (p = 0.06) increase in 2‐h plasma glucose levels following OGTT in participants with unhealthy alcohol use. AUDIT was also positively correlated with Timeline Followback (grams of alcohol) and PEth values, supporting the use of AUDIT as a valid marker of alcohol use. WHR, which is indicative of abdominal obesity, and has been linked to a higher incidence of insulin resistance, was higher in participants with unhealthy alcohol use and was positively correlated with FBG. Based on the results from the OGTT, participants were divided into 3 categories, Normal (2‐h glucose &lt;140mg/dL), Prediabetic (140–199mg/dL) and Diabetic (≥200mg/dL). Of the participants with Normal plasma glucose, 37.3% exhibited unhealthy alcohol use. Among Prediabetics, 70.6% exhibited unhealthy alcohol use and in Diabetics, 80% exhibited unhealthy alcohol use. Unhealthy alcohol use (AUDIT ≥5) was associated with a 4.13 odds ratio (1.54, 11.08) of being Prediabetic or Diabetic. Overall, these data support our hypothesis that in PLWH with impaired fasting glucose, unhealthy alcohol use is associated with dysglycemia following an OGTT. These results suggest that directed interventions that focus on glucose regulation and alcohol use, including aerobic exercise, could have a profound impact on ameliorating the risk of developing metabolic comorbidities in this population of at‐risk PLWH.Support or Funding InformationNIH NIAAA UH2AA026198 to PEM

Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans.

African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain poorly defined. We previously demonstrated that sedentary lean AAW have lower peripheral insulin sensitivity, reduced maximal aerobic fitness (VO2max), and lower resting metabolic rate (RMR) than CW. We have also demonstrated that skeletal muscle mitochondrial respiration is lower in AAW and appears to play a role in these racial differences. The goal of this study was to assess mitochondrial pathways and dynamics to examine the potential mechanisms of lower insulin sensitivity, RMR, VO2max, and mitochondrial capacity in AAW. To achieve this goal, we assessed several mitochondrial pathways in skeletal muscle using gene array technology and semiquantitative protein analysis. We report alterations in mitochondrial pathways associated with inner membrane small molecule transport genes, fusion-fission, and autophagy in lean AAW. These differences were associated with lower insulin sensitivity, RMR, and VO2max. Together these data suggest that the metabolic racial disparity of insulin resistance, RMR, VO2max, and mitochondrial capacity may be mediated by perturbations in mitochondrial pathways associated with membrane transport, fission-fusion, and autophagy. The mechanisms contributing to these differences remain unknown.

Obesity-related thyroiditis in childhood: relationship with insulin resistance

Background Thyroid dysfunction is the most common hormonal abnormality in obesity. It should actually be considered as an adaptation response to fat excess. However, little has been reported on the morphology of the thyroid gland, and no data regarding the relationship between thyroid gland changes and metabolic parameters are available in obese adolescents. Objective The study aimed to evaluate the frequency of non-autoimmune thyroiditis in obese adolescents and compare the metabolic status of patients with or without thyroiditis. Methods A total of 218 obese children and 49 age-matched control healthy children were included. Thyroid ultrasonography (USG) was performed in all participants, as well as thyroid hormone levels, thyroid antibodies (Abs), lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (HsCRP) were determined. Obese children were divided into three groups according to the presence of thyroid autoantibodies and USG findings of thyroiditis (Group-1: Abs [-], normal thyroid morphology/Group-2: Abs [+], abnormal thyroid morphology/Group-3: Abs [-], abnormal thyroid morphology). The relationship between body mass index, metabolic parameters and thyroid gland status was analyzed. Results Seventy-two of 218 obese patients (33%) had non-autoimmune thyroiditis (Group-3). The rate of insulin resistance was significantly higher in Group-3 than in Group-1 (p = 0.024). Similarly, the frequency of metabolic syndrome (MS) was higher in Group-3 (44.3%) than in Group-1 (27.1%) (p = 0.014). Conclusions Obese adolescents with non-autoimmune thyroiditis had a higher incidence of insulin resistance. This finding supported the hypothesis that insulin resistance may have an effect on thyroid morphology. Further randomized trials investigating this relationship are required.

Influence of metabolic syndrome on female fertility and in vitro fertilization outcomes in PCOS women

With a high incidence of insulin resistance, central obesity and dyslipidemia, women with polycystic ovary syndrome are susceptible to metabolic syndrome (MetS). Our objective was to explore whether metabolic syndrome had an effect on overall female fertility and invitro fertilization outcomes in infertile women with polycystic ovary syndrome. This was a secondary analysis of a multicenter randomized trial in 1508 women with polycystic ovary syndrome, which was originally designed to compare the live birth rate after fresh-embryo transfer vs frozen embryo transfer (Frefro-PCOS). At baseline, metabolic parameters, including body mass index, waist and hip circumference, blood pressure, lipid profile, fasting, and 2 hour glucose and insulin levels after a 75 g oral glucose tolerance test were measured. All subjects were divided into a metabolic syndrome group (metabolic syndrome) and absence of metabolic syndrome group (nonmetabolic syndrome) according to diagnostic criteria. Descriptive statistics and logistic regression models tested the association between metabolic syndrome and overall fertility and invitro fertilization cycle stimulation characteristics and clinical outcomes. Metabolic syndrome was identified in 410 of 1508 infertile women with polycystic ovary syndrome (27.2%). Patients with metabolic syndrome had longer infertility duration (4.0 ± 2.2 vs 3.7 ± 2.2, P= .004) compared with those without metabolic syndrome. During ovarian stimulation, those with metabolic syndrome required significantly higher and longer doses of gonadotropin and had lower peak estradiol level, fewer retrieved oocytes, available embryos, a lower oocyte utilization rate, and ovarian hyperstimulation syndrome than those with nonmetabolic syndrome. The cumulative live birth rate did not show a significant between-group difference (57.8% vs 62.2%, P= .119). Multivariate logistic regression analysis adjusted for age, duration of infertility, body mass index, thyroid-stimulating hormone, metabolic syndrome group, homeostatic model assessment of insulin resistance, metformin utilization, number of available embryos, and embryos transferred showed that the number of embryos transferred and the number of available embryos were positively but metabolic syndrome negatively associated with the cumulative live birth rate (odds ratio, 2.18, 1.10, and 0.70, respectively, P < .05). Women with polycystic ovary syndrome with metabolic syndrome have a negative impact from female fecundity, and this suggests an adverse effect on invitro fertilization cycle stimulation characteristics and clinical outcomes.

The association between serum zinc levels and insulin resistance among polycystic ovary syndrome patients in Duhok City, Kurdistan Region, Iraq

Background: Polycystic ovary syndrome (PCOS) is a relatively common endocrine and metabolic problem. Patients with PCOS are known to have a higher incidence of insulin resistance. The homeostasis model assessment (HOMA) is an indirect, rapid, accurate, and cost-effective method of assessing insulin resistance based on patient's fasting plasma insulin and glucose concentrations. Several studies have reported a significant correlation between HOMA and the traditional hyperinsulinemic-euglycemic clamp method. Zinc deficiency promotes insulin resistance, and that zinc supplementation can prevent or, at least, alleviate insulin resistance in selected patient populations. Objective: The current study primarily aims at defining the association between insulin resistance and zinc deficiency among both PCOS and selected controls. It also looks at certain risk factors associated with obesity among the study population in Duhok City, Kurdistan Region, Iraq. Materials and Methods: The current case–control study was performed at Azadi Teaching Hospital/Gynecological Outpatient Clinic in Duhok City/Kurdistan Region/Iraq. The study included 80 women (40 cases with PCOS and 40 controls of healthy women). Results: There was no age difference between both groups (Mean = 26.77 years, standard deviation [SD] = 6.42 years for PCOS cases versus mean and SD of 27.57 years and 6.45 years, respectively; P= 0.48). Likewise, there was no difference in the serum zinc levels between cases and controls. However, patients with PCOS had significantly higher Body mass index and HOMA scores compared to the controls (P = 0.005 and 0.007, respectively). Conclusion: Higher serum zinc levels are independently associated with lower HOMA. Patients with PCOS had significantly higher insulin resistance when compared to the controls of similar age and zinc level.

The clinical significance of insulin resistance in non-diabetic patients with early forms of non-alcoholic fatty liver disease.

To assess the presence of insulin resistance (IR) in non-diabetic patients with early forms of non-alcoholic fatty liver disease (NAFLD) - liver steatosis (LS) and steatohepatitis (SH) of mild activity and the influence of IR on the clinical course of these diseases. 134 patients with NAFLD were examined: 54 with LS and 80 with SH. The control group consisted of 37 healthy donors. Anthropometric parameters (body mass index (BMI), waist circumference (WC)), clinical and biochemical blood indices, including the blood level of cytokeratin-18 fragments (CK-18), TNF-α and IL-6 cytokines, insulin were evaluated. The HOMA index and the fibrosis index (NAFLD FS) were calculated. Patients were divided into groups: I - with the absence of IR (HOMA-index &lt;2.7), II - with the presence of IR (HOMA-index&gt; 2.7). Indicators of hepatic injury, inflammation, cholestasis, fibrosis and atherogenic dyslipidemia are higher in patients with LS of group II (with IR) than in group I patients (without IR). BMI, WC, γ-glutamil transpeptidase, CK-18 and fibrosis index are significantly higher in group II patients with SH compared with group I, there is no significant difference in the level of cytolysis, inflammation and dyslipidemia indices. A high incidence of IR in non-diabetic patients with LS (37.0%) and SH (55.0%) was found and the effect of IR on the clinical course of these diseases was revealed. Insulin resistance in non-diabetic patients with NAFLD was detected in SH (55.0%) with higher frequency than in LS (37.0%). In LS, IR is associated with impaired hepatic cell damage, intrahepatic cholestasis, atherogenic dyslipidemia and fibrosis. In SH, IR is combined with reliable growth in indicators of hepatocyte apoptosis, cytokine proinflammatory status and fibrosis. IR determines the progressing course of NAFLD, promoting the transformation of steatosis into steatohepatitis and steatohepatitis into fibrosis and liver cirrhosis.

Acanthosis nigricans: A screening test for insulin resistance - An important risk factor for diabetes mellitus type-2.

Background:Acanthosis nigricans (AN) is one of the signs suggestive of high insulin resistance (IR). IR is one of the mechanisms involved in pathogenesis of diabetes mellitus type-2 (DM Type-2). Thus, early detection of IR in children may allow us time to intervene well before the development of DM Type-2. In this study, 62% of children having AN had high IR. In children having both, AN and high body mass index (BMI), the incidence of IR was about 80%. This suggests that these easily detectable parameters alone can be useful in screening children at high risk of developing DM Type-2 in future. These simple criteria thus hold promise for use in high throughput screening programs for diabetes.Context:A pilot study conducted by the authors showed that children with AN have a high incidence of IR. The detection of IR in children may allow us time to intervene well before the development of DM Type-2. Detection of DM Type-2 by hyperglycemia may be too late to prevent the onset of microvascular changes.Aims:This study aims to determine whether easily observable presence of AN can be used to screen for increased IR in children, and thereby to detect this important risk factor for DM Type-2.Settings and Design:Cross-sectional, observational study. Two schools, one with children belonging to average economic background and the other, a residential school with children of affluent parents. Selection of children was done randomly.Subjects and Methods:The study was conducted among 507 children in the age group of 10–18 years. Physical examination for the detection of AN, height and weight measurements, waist circumference, fasting plasma glucose, fasting plasma insulin, and lipid profile was done. Homeostatic model assessment of insulin resistance was calculated.Statistical Analysis Used:Data analysis was performed using descriptive statistics and inferential statistical methods. The association between categorical variables was done by Chi-square test.Results:The presence of AN positively correlated with high IR, and when combined with increased BMI, the incidence rate of IR is 80%.Conclusions:AN can be used as a screening method to identify children at risk of DM Type-2-since those who have high IR have a high possibility of having DM Type-2 in future. Hence, early screening and simple, but effective interventional strategies can be instituted at this age, which may prevent or delay diabetes in the long run.

Incidence of insulin resistance and diabetes in patients with portosystemic shunts without liver dysfunction.

ObjectiveTo investigate the incidence of insulin resistance (IR) and diabetes in patients with chronic hepatic schistosomiasis japonica (HSJ) and portosystemic shunts (PSS).MethodsPre- and post-contrasted computed tomography images obtained from patients with HSJ and control subjects were reviewed by two radiologists who identified and graded any shunting vessels. Anthropometric measurements, hepatic enzymes, lipid profile, blood levels of albumin, glucose, insulin and homeostasis model assessment (HOMA-2) index of all participants were also assessed.ResultsFifty-two patients with HSJ and 30 control subjects were involved in the study. The coronary, short gastric and perisplenic veins were the most common shunting vessels. There were no significant differences between patients and controls in terms of body mass index or liver function. The degree of shunting vessels, blood glucose, oral glucose tolerance test120/0, insulin, HOMA-2 index, glycosylated haemoglobin, cholesterol, high- and low-density lipoprotein, and C-reactive protein were significantly higher in the patients with IR. A positive correlation was found between the degree of the shunting vessels and the HOMA-2 index.ConclusionsPatients with chronic HSJ and PSS without liver dysfunction had a high incidence of IR and diabetes. The study showed that PSS and IR are related and therefore patients with PSS should be screened for IR and vice versa.