High Prevalence Of Insulin Resistance Research Articles

Association of severity of menstrual dysfunction with cardiometabolic risk markers among women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is associated with a wide range of unfavorable cardiometabolic risk factors, including obesity, hypertension, insulin resistance, impaired glucose metabolism, dyslipidemia, and metabolic syndrome. Compared with women with regular menstrual cycles, women with a history of irregular menstrual periods have an increased unfavorable cardiometabolic risk. Recently, the association between the severity of oligomenorrhea and hyperinsulinemia and insulin resistance has been demonstrated. However, evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is scarce. This work was a prospective cross-sectional study. A total of 154 women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. PCOS women with eumenorrheic (eumeno group), oligomenorrhea (oligo group), and amenorrhea (ameno group) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test, and homeostasis model assessment of insulin resistance. A trend toward an increase in unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of insulin resistance, prediabetes, dyslipidemia, and metabolic syndrome was observed in the ameno group (n = 57) as compared with the eumeno (n = 24) or oligo group (n = 73). A higher prevalence of insulin resistance (odds ratio [OR]: 3.02; 95% confidence interval [CI]: 1.03-8.81) and prediabetes (OR: 3.94; 95% CI: 1.01-15.40) was observed in the ameno group than in the eumeno group, and a higher proportion of dyslipidemia (OR: 2.44; 95% CI: 1.16-5.15) was observed in the ameno group than in the oligo group in the binary logistic regression analysis after adjusting for confounding factors. PCOS women with amenorrhea show a higher prevalence of insulin resistance, prediabetes, and dyslipidemia compared with those with oligomenorrhea or eumenorrhea. The severity of menstrual dysfunction could be used as a readily obtainable marker for the identification of PCOS women at greatest risk of cardiometabolic diseases.

Increased insulin resistance with reduced beta cell function in recovered COVID-19 Ghanaians

AimThis study compares levels of insulin resistance and beta-cell function and their relationship with liver enzymes in recovered COVID-19 participants and their uninfected counterparts in a cross-sectional study design in the Tamale metropolis of Ghana. MethodsBiochemical indices for liver function, lipid metabolism, inflammation and oxidative stress were assessed under fasting state in 110 recovered COVID-19 and 116 uninfected participants. The homeostatic model assessment of insulin resistance (HOMA-IR) and the triglyceride-glucose index (TyG) were employed for the assessment of insulin resistance. ResultsRecovered COVID-19 participants presented lower (P < 0.05) levels of fasting glucose, insulin, alkaline phosphatase, creatinine and beta-cell function but higher (P < 0.05) levels of alanine/aspartate transferase, total bilirubin, direct bilirubin, total cholesterol, high-density lipoprotein cholesterol and HOMA-IR than their uninfected counterparts. The mean levels of the remaining indices were comparable (P > 0.05) between the study groups. Prevalence of insulin resistance ranged from 61 % (71/116) to 81 % (89/110) for the uninfected and recovered COVID-19 participants respectively. Selected liver enzymes associated with HOMA-IR and TyG. ConclusionThe risk of developing type 2 diabetes mellitus appears higher in recovered COVID-19 participants than their uninfected counterparts despite the high prevalence of insulin resistance in both groups.

OR20-01 Machine Learning-based Steroid Metabolome Analysis In Women With Polycystic Ovary Syndrome Reveals Three Distinct Androgen Excess Subtypes With Different Metabolic Risk Profiles.

Abstract Disclosure: T.P. Rocha: None. E. Melson: None. R.J. Veen: None. L. Abdi: None. T. McDonnell: None. V. Tandl: None. J. Hawley: None. L. Wittemans: None. A. Anthony: None. L. Gilligan: None. F. Shaheen: None. P. Kempegowda: None. C.D. Gillett: None. L. Cussen: None. C. Missbrenner: None. F. Lajeunesse-Trempe: None. H. Gleeson: None. A. Rees: None. L. Robinson: None. C. Jayasenna: None. H.S. Randeva: None. H.S. Randeva: None. G.K. Dimitriadis: None. L.G. Gomes: None. A. Sitch: None. E. Vradi: Employee; Self; Bayer Schering Pharma. A.E. Taylor: None. M.W. O'Reilly: None. B.M. Obermayer-Pietsch: None. M. Biehl: None. W. Arlt: None. Introduction: Polycystic ovary syndrome affects 10% of women and is associated with an increased risk of type 2 diabetes, hypertension, and fatty liver disease. Androgen excess, a defining feature of PCOS, has been implicated as a driver of metabolic risk. Adrenal-derived 11-oxygenated androgens are a component of PCOS-related androgen excess and are preferentially activated in adipose tissue. Here, we aimed to identify PCOS sub-types with distinct steroid metabolomes and compare their cardiometabolic risk parameters. Methods: We prospectively recruited 488 treatment-naïve women with PCOS fulfilling diagnostic Rotterdam criteria [median age 28 (IQR 24-32) years; BMI 27.5 (22.4-34.6) kg/m2] at eight centres in the UK &amp; Ireland (n=208), Austria (n=242), and Brazil (n=38). Participants underwent a standardised assessment, including insulin sensitivity at baseline (HOMA-IR) and across a 2-h oGTT (Matsuda ISI). We used tandem mass spectrometry to measure 11 androgenic serum steroids, including classic and 11-oxygenated androgens. Results were analysed by unsupervised k-means clustering, followed by a comparison of clinical and metabolic phenotype parameters. Results: Machine learning analysis identified three distinct androgen metabolomes: a cluster with mainly gonadal-derived androgen excess (GAE; testosterone, dihydrotestosterone; 21.5% of women), a cluster with mainly adrenal-derived androgen excess (AAE; 11-oxygenated androgens; 21.7%), and a cluster with comparably mild androgen excess (MAE; 56.8%). Age and BMI were similar between groups. Compared to GAE and MAE, the AAE cluster had the highest rates of hirsutism (76.4% vs 67.6% vs 59.9%) and female pattern hair loss (32.1% vs 14.3% vs 21.7%). The AAE cluster had significantly increased insulin resistance as indicated by higher fasting insulin,120min insulin and HOMA-IR, and lower ISI than GAE and MAE clusters (all p&amp;lt;0.01). The AAE cluster had a 2-3fold higher prevalence of impaired glucose tolerance and newly diagnosed type 2 diabetes. Conclusion: Unsupervised cluster analysis revealed three distinct androgen excess subtypes in PCOS. Women within the adrenal androgen excess cluster had a significantly higher prevalence of insulin resistance, impaired glucose tolerance and type 2 diabetes. These results implicate 11-oxygenated androgens as drivers of metabolic risk in PCOS and provide proof-of-principle for an androgen-based stratification tool to guide preventative and therapeutic strategies in PCOS. Presentation Date: Saturday, June 17, 2023

P-648 Association of severity of menstrual dysfunction with cardiometabolic risk markers in polycystic ovary syndrome

Abstract Study question Is the severity of menstrual dysfunction related to cardiometabolic risk markers in women with polycystic ovary syndrome (PCOS)? Summary answer PCOS women with amenorrhea, compared to those with oligomenorrhea or eumenorrhea, show a higher prevalence of insulin resistance (IR), prediabetes and hypertriglyceridemia. What is known already PCOS is associated robustly with a wide range of unfavorable cardiometabolic risk markers, including obesity, glucolipid metabolism disorders and metabolic syndrome. Many epidemiological studies have found compared to the women with regular menstrual cycles, women with a history of irregular menstruation increased the risks of metabolic syndrome and coronary heart disease. Recently, the association between the severity of menstrual cyclicity and hyperinsulinemia and IR has been demonstrated, suggesting menstrual history could be a simple but clinically important marker of metabolic dysfunction risk. But evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is very limited. Study design, size, duration In this prospective cross-sectional study, one hundred and fifty-four women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. The association of menstrual cycle regularity with cardiometabolic risk markers including obesity, hypertension, glycemic abnormalities, dyslipidemia and metabolic syndrome was systematically analyzed. Participants/materials, setting, methods In a university-affiliated hospital, PCOS participants with eumenorrheic (Eumeno, n = 24), oligomenorrhea (Oligo, n = 73) and amenorrhea (Ameno, n = 57) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test (OGTT) and homeostasis model assessment of IR. Main results and the role of chance Adjusting for age, BMI and waist circumference, a trend toward an increase of unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of IR, prediabetes, hypertriglyceridemia and prevalence of metabolic syndrome was observed in Ameno group than in other menstrual categories. A significantly higher prevalence of IR, prediabetes and hypertriglyceridemia was demonstrated in Ameno group compared to the Eumeno or Oligo group. In logistic regression, adjusting for age, BMI, and waist circumference, Ameno women were more likely to have: IR than Eumeno women (odds ratio [OR]: 2.90; 95% CI: 1.01 to 8.31); prediabetes than Eumeno women (OR: 4.06; 95% CI: 1.05 to 15.77) and hypertriglyceridemia than Oligo women (OR: 4.43; 95% CI: 1.74 to 11.26). Moreover, the prevalence of IR, prediabetes and hypertriglyceridemia was still significantly higher in Ameno group than that in the Oligo or Eumeno group when further adjusted for free androgen index in the logistic regression. The proportion of Type 2 Diabetes, high total cholesterol, high low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) cholesterol was similar across the three groups. Limitations, reasons for caution Our study was limited by its cross-sectional nature, and another limitation was the cycle regularity question relied on the participant’s interpretation of irregular, although we have acquired the detailed menstrual cycle history and further reviewed at consultation, yet some exposure misclassification might also be present. Wider implications of the findings Our study used menstrual cycle as a readily obtainable marker for identification of PCOS women at greatest risk of IR, prediabetes and hypertriglyceridemia, which would emphasize the importance of menstrual cycle regularity and help refine the current recommendations concerning the screening of PCOS subjects for cardiometabolic diesases. Trial registration number 20210728

Insulin resistance, does it exist? The current state of knowledge

Insulin resistance is a growing concern worldwide, affecting millions of people and increasing the risk of various metabolic disorders, including type 2 diabetes, cardiovascular diseases, and fatty liver disease. This paper aims to display the symptoms of insulin resistance and the importance of early detection through various diagnostic tests such as fasting insulin levels, oral glucose tolerance tests, and HOMA-IR scores. Despite the high prevalence of insulin resistance, there is currently no known cure for this condition as it is not a disease in itself. However, lifestyle modifications, including exercise and dietary changes, can effectively manage and prevent the progression of insulin resistance and its associated complications. This study emphasizes the importance of raising awareness about insulin resistance and its adverse effects on individuals' health and the healthcare system's burden. Early detection and management of insulin resistance can significantly reduce the risk of developing metabolic disorders and prevent serious health complications.

Insulin resistance metabolomic profile in non-diabetic women with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have a higher prevalence of insulin resistance (IR) and metabolic syndrome (MetS) than controls. To evaluate IR in non-diabetic women with SLE by means of biomarkers using high-throughput metabolomic techniques. Cross-sectional study in patients with SLE. A metabolomic approach was employed using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry. MetS was evaluated according to NCEP-ATP III criteria. Seventy patients with SLE were included, out of whom 45 (64.2%) and 27 (38.5%) had IR and MetS, respectively. Patients with IR had a higher body mass index and hypertension more often than those without IR. Chronic damage and disease activity were not related to IR. A Quantose-IR score ≥ 63 was more common in patients with MetS (81.5 vs. 53.5%; p = 0.02). Quantose-IR score was also correlated with the number of criteria for MetS (r: 0.35; p = 0.003). In non-diabetic women with SLE, the prevalence of IR based on Quantose-IR score was 64.2%.

Insulin Resistance and Hypertension among Type 2 Diabetes Subjects in a Tertiary Institution in South East Nigeria

Background: Type 2 diabetes mellitus (T2DM) is frequently associated with hypertension (HTN), adding significantly to its overall morbidity and mortality. Aim: This study aimed to investigate the relationship between insulin resistance (IR) and blood pressure and other factors associated with both conditions. Patients, Materials and Methods: A case–control study of 180 subjects consisting of 60 with T2DM and HTN, 60 with T2DM and normal blood pressure, and 60 without T2DM or HTN (control). Sociodemographic, anthropometric, and clinical parameters were obtained from each subject and control. IR was derived from homeostasis model assessment (HOMA)-IR index calculated from fasting blood glucose and insulin. Results: The mean age of subjects with T2DM and HTN was 49.58 ± 10.50 years, that of subjects with T2DM and normotension was 48.50 ± 10.44 years, while that of controls was 48.85 ± 10.15 years. IR (HOMA-IR ≥2) was found in 96.7% of subjects with T2DM and HTN, 88.3% of those with T2DM and normotension, and 1.7% of subjects with neither of both conditions. Central obesity (Waist circumference “WC”), overweight, and obesity (BMI) significantly related to IR in subjects with T2DM and HTN (p = 0.020, 0.021 and 0.016 respectively) while only WC and obesity (BMI) significantly related to IR in subjects with T2DM and normotension (p = 0.001 and 0.036 respectively). Conclusions: There is a high prevalence of IR in T2DM subjects which is heightened by the presence of HTN.

Clinical and metabolic characteristics of males with early-onset androgenetic alopecia.

Background Men with early-onset androgenetic alopecia (AGA) often have an abnormal hormonal milieu. Objective To ascertain the clinico-phenotypic characteristics and the prevalence of hormonal and metabolic changes in men with early-onset AGA. Methods Consecutive male patients less than 30 years of age with a Norwood-Hamilton grade ≥3 AGA were recruited in this comparative cross-sectional study. After endocrine evaluation they were classified into two groups, that is, Group A consisting of subjects with an altered hormonal profile and Group B with normal hormonal profiles. The groups were assessed for differences in disease phenotype and severity (Norwood-Hamilton grade), insulin resistance and parameters of metabolic syndrome (ATP III guidelines). Results Altered hormonal profiles were seen in 34 of the 100 subjects with AGA, while insulin resistance and metabolic syndrome were noted in 44 and 26 respectively. Altered hormonal profiles were significantly associated with insulin resistance and severe alopecia (grade 4 and above Hamilton-Norwood Scale). Insulin resistant Group A patients had a significantly higher prevalence of severe alopecia (>grade 4) (P = 0.0036). The prevalence of metabolic syndrome was similar in both groups. Limitation The cross sectional study design was a drawback of this study. Further, a control arm without AGA was not included and the sample size of 100 was selected arbitrarily. Conclusion An altered hormonal profile and insulin resistance was noted in a third of the males with early-onset AGA. Subjects with altered hormonal profiles had a higher prevalence of insulin resistance and were likely to have severe grades of AGA.

Evaluation of socio-demographic and clinical characteristics of PCOS patients attending a tertiary care institute in Colombo

Background and objectivesPolycystic ovary syndrome (PCOS) is a common endocrine disorder with heterogeneous aetiology. It is characterized by irregular menses and or oligo/anovulation, hyper-androgenism, and polycystic ovaries. The prevalence and diagnosis of PCOS changes depending on which clinical criteria are utilized to confirm the diagnosis. The prevalence can be high as 8–13% when the Rotterdam criteria are used. However, there is significant inter-individual variation in presentation. We have studied the socio-demographic and clinical characteristics of PCOS patients attending the Endocrinology clinic in a tertiary care institute in Sri Lanka.MethodsA descriptive cross sectional study was conducted from September 2019 to September 2020 at the Endocrinology Unit of the National Hospital of Sri Lanka. All the patients who met the inclusion and exclusion criteria and who has a diagnosis of PCOS made according to Rotterdam criteria were recruited in to the study. After obtaining informed written consent, the data was collected using an interviewer administered questionnaire. HOMA-IR was calculated using the fasting insulin and blood glucose level.ResultsThe study enrolled sixty females. The mean age was 26.7 years (range 18–44). The mean weight was 64.8 (SD = 11.9) kg and BMI was 27.1 (SD = 4.8) kg/m−2. According to Asian BMI cut-offs, 1 (1.7%) patient was underweight and 13 (21.7%) had normal weight. Forty six (76.7%) had their weight in the overweight or obese category. Fifty four (90.0%) patients had clinical or biochemical evidence of hyperandrogenism while 24 (40%) had polycystic ovaries on trans-abdominal ultrasound scan and 50 (83.3%) had irregular menstrual cycles. According to the body fat percentage assessed by the whole body DEXA scan 4.1% normal body fat, while 50.0% and 45.8% had overweight and obesity respectively. HOMA-IR detected 61.1% to have high insulin resistance. Out of the patients who had USS of the abdomen 27.5% had co-existent non-alcoholic fatty liver. Fifty four percent of the patients had sub/infertility.ConclusionsThe majority of the population were overweight or obese and had higher prevalence of insulin resistance and non-alcoholic fatty liver. Out of the clinical characteristics used to make the diagnosis of PCOS, the presence of clinical or biochemical evidence of hyperandrogenism and irregular menstrual cycles are more common than the detection of polycystic ovaries on trans-vaginal USS. The higher prevalence of overweight, obesity, insulin resistance and NAFLD associated with PCOS makes the diagnosis and management of the disease crucial to prevent long term consequences of the disease.

Triglyceride-glucose index is associated with poor sleep quality in apparently healthy subjects: A cross-sectional study.

We aimed to evaluate the association between the triglyceride glucose index (TyG index) and sleep quality and to establish a cut-off value for the TyG index based on the prevalence of subjects with insulin resistance (IR). This cross-sectional study involved Brazilian health professionals (20-59 years). A total of 138 subjects answered the Pittsburgh Sleep Quality questionnaire to evaluate sleep quality. They were categorized into two groups: good sleep quality (global score ≤ 5 points) and poor sleep quality (global score ≥ 6 points). Also, we classified the subjects as having a high (>8.08 or >4.38) or low TyG index (≤ 8.08 or ≤4.38). The majority of the subjects (70%) with high TyG index values (>8.08 or >4.38) reported poor sleep quality (p ≤ 0.001). Those with poor sleep quality had a 1.44-fold higher prevalence of IR (TyG index >8.08 or >4.38) compared to those with good sleep quality, regardless of sex, total cholesterol, LDL/HDL ratio, insulin, complement C3, CRP, and adiponectin (p ≤ 0.001). Our data showed a positive and significant association between the TyG index and poor sleep quality. Thus, these findings support the association between poor sleep quality and IR.

Metabolic effect of orchidectomy on C57BL6/J mice exposed to intermittent hypoxia

IntroductionSleep apnea (SA) is characterized by obstructions of the airways or cessation of breathing during sleep leading to intermittent hypoxia (IH). IH is a source of oxidative stress and inflammation altering the functions of pancreas, liver, muscles and adipose tissue. As a consequence, sleep apnea patients have a high prevalence of insulin resistance and glucose intolerance which can lead to type 2 diabetes. In mice, exposures to IH induce adipose tissue inflammation, liver injury and worsen the pancreatic β‐cell injury in a model of diabetes. While these effects are associated with insulin resistance, glucose tolerance is improved, notably via an enhanced glucose uptake by skeletal muscles. In men, sleep apnea and diabetes are also characterized by low testosterone levels. Interestingly, testosterone levels are positively corelated with insulin sensitivity in human, and low testosterone levels can be associated with inflammation, oxidative stress and insulin resistance. Therefore, we tested the hypothesis that testosterone modulates the metabolic alterations induced by IH in male mice.MethodWe used intact (Sham) or orchidectomized (ORX) C57BL/6J male mice exposed for 14 days to IH (12h / day, 10 cycles / h, 6% nadir oxygen) or normoxia (Nx). The animals were weighed, and we assessed body composition in terms of lean and fat mass, as well as fluid content by using a small animal MRI scanner before the surgery, before IH or Nx exposures and at the end of the protocol. The day after the last IH session, mice were fasted for 6h, we measured fasting glycaemia and insulinemia then we performed a glucose tolerance test.ResultsIn Sham mice, IH decreased bodyweight and fat mass. This was associated with a decrease of fasting glycaemia, insulinemia and HOMA‐IR (index of insulin resistance), and improved glucose sensitivity. ORX decreased bodyweight and lean tissue mass, associated with lower fasting glycemia, insulinemia, HOMA‐IR and improved whole body glucose sensitivity. ORX mice exposed to IH had a decrease of both fat and lean tissue mass leading to further reduction of body weight. However, there was no additive effects of ORX and ORX IH for fasting glycaemia, insulinemia, HOMA‐IR and glucose sensitivity.ConclusionIH and ORX respectively reduce fat and lean tissue mass, and these effects are additive when both stimuli are applied simultaneously. Contrastingly, there are no additive effects of IH and ORX on the metabolic parameters reported here.

Hyperglucagonemia in Pediatric Adiposity Associates With Cardiometabolic Risk Factors but Not Hyperglycemia.

ContextIn adults, hyperglucagonemia is associated with type 2 diabetes, impaired glucose tolerance, and obesity. The role of glucagon in pediatric overweight/obesity remains unclear.ObjectiveWe examined whether fasting concentrations of glucagon are elevated in youth with overweight/obesity and whether this associates with cardiometabolic risk profiles.MethodsAnalyses were based on the cross-sectional HOLBAEK study, including children and adolescents 6 to 19 years of age, with overweight/obesity from an obesity clinic group (n = 2154) and with normal weight from a population-based group (n = 1858). Fasting concentrations of plasma glucagon and cardiometabolic risk outcomes were assessed, and multiple linear and logistic regressions models were performed.ResultsThe obesity clinic group had higher glucagon concentrations than the population-based group (P < 0.001). Glucagon positively associated with body mass index (BMI) standard deviation score (SDS), waist, body fat %, liver fat %, alanine transaminase (ALT), high-sensitivity C-reactive protein, homeostasis model assessment of insulin resistance, insulin, C-peptide, LDL-C, triglycerides, SDS of diastolic and systolic blood pressure, and was inversely associated with fasting glucose. The inverse relationship between glucagon and glucose was attenuated in individuals with high BMI SDS and high fasting insulin. Glucagon was associated with a higher prevalence of insulin resistance, increased ALT, dyslipidemia, and hypertension, but not with hyperglycemia. Glucagon was positively associated with fasting total glucagon-like peptide-1.ConclusionCompared with normal weight peers, children and adolescents with overweight/obesity had elevated concentrations of fasting glucagon, which corresponded to worsened cardiometabolic risk outcomes, except for hyperglycemia. This suggests hyperglucagonemia in youth may precede impairments in glucose regulation.

The consumption of micronutrients in relation to calorie intake and risk of insulin resistance

Background and aimsAdequate dietary intakes of essential micronutrients are critical to prevent insulin resistance (IR)-related diseases. Even though the excess calorie intake linked with obesity is also associated with such diseases, no previous studies evaluated the importance of meeting the Dietary Reference Intake (DRI) of micronutrients in relation to calorie intake in those at risk for developing IR. Methods and resultsWe evaluated the relationship between the ability or failure to meet the DRI of micronutrients in relation to daily calorie intake in 463 childbearing-age women with a higher prevalence of IR. 56–65% women met the DRIs for vitamin B12, vitamin C, thiamine, and riboflavin while only 0%–49% met the DRIs for folate, pyridoxine, niacin, pantothenic acid, total carotene, vitamins A, D and E by consuming an acceptable number of calories. Women who met the DRIs of folate and vitamin C within acceptable daily calorie intakes were 59% and 66% less likely to have higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) compared to women who did not. ConclusionsUnderstanding the mechanisms that explain our findings will be of value to address IR-associated with exposure to high calorie/low-micronutrient dense diets consumed by childbearing-age women. Since there is a global recognition that IR has been increasing in adults and children, similar studies of this nature in pregnant women at risk for IR will provide much needed data to assess the burden of such adverse dietary habits in the offspring. Our study approach may form the foundation for such studies.

The mitochondrial profile in women with polycystic ovary syndrome: impact of exercise.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting pre-menopausal women and involves metabolic dysregulation. Despite the high prevalence of insulin resistance, the existence of mitochondrial dysregulation and its role in the pathogenesis of PCOS is not clear. Exercise is recommended as the first-line therapy for women with PCOS. In particular, high-intensity interval training (HIIT) is known to improve metabolic health and enhance mitochondrial characteristics. In this narrative review, the existing knowledge of mitochondrial characteristics in skeletal muscle and adipose tissue of women with PCOS and the effect of exercise interventions in ameliorating metabolic and mitochondrial health in these women are discussed. Even though the evidence on mitochondrial dysfunction in PCOS is limited, some studies point to aberrant mitochondrial functions mostly in skeletal muscle, while there is very little research in adipose tissue. Although most exercise intervention studies in PCOS report improvements in metabolic health, they show diverse and inconclusive findings in relation to mitochondrial characteristics. A limitation of the current study is the lack of comprehensive mitochondrial analyses and the diversity in exercise modalities, with only one study investigating the impact of HIIT alone. Therefore, further comprehensive large-scale exercise intervention studies are required to understand the association between metabolic dysfunction and aberrant mitochondrial profile, and the molecular mechanisms underlying the exercise-induced metabolic adaptations in women with PCOS.

Insulin Levels, BMI in Youth May Be Linked to Psychosis, Depression Risk in Adulthood

Back to table of contents Previous article Next article Clinical & ResearchFull AccessInsulin Levels, BMI in Youth May Be Linked to Psychosis, Depression Risk in AdulthoodTerri D'ArrigoTerri D'ArrigoSearch for more papers by this authorPublished Online:25 Mar 2021https://doi.org/10.1176/appi.pn.2021.3.3AbstractEarly signs of cardiometabolic dysfunction may be detectable before the onset of psychiatric disorders.iStock/Anetta_RDisrupted insulin sensitivity in childhood and adolescence may be a shared risk factor for cardiometabolic disorders and psychosis in adulthood, a study in JAMA Psychiatry has found. The study also found that a major increase in BMI around puberty may indicate a greater risk for adult depression.“Our findings may begin to challenge the received wisdom that the physical comorbidity associated with depression and psychosis is secondary to the mental disorder,” lead author Benjamin I. Perry, M.B.B.S., M.Sc., told Psychiatric News. Perry is a National Institute for Health Research (NIHR) doctoral research fellow in the Department of Psychiatry at the University of Cambridge in England. “Our results suggest the possibility that early subtle signs of cardiometabolic dysfunction may be detectable before the onset of the psychiatric disorders.”Perry and colleagues examined data from people aged 1 to 24 years in the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective study of approximately 15,000 British people. They obtained data on fasting insulin levels for 5,790 people measured at ages 9, 15, 18, and 24 years and BMI for 10,463 people measured at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years.“Previous research has mostly included single-point measures of cardiometabolic markers, yet repeat measures of these markers provide much greater resolution into potential underlying biological pathways,” Perry said.At puberty, children may be more susceptible to traumatic events such as bullying that may increase their risk of weight gain and depression, says Benjamin I. Perry, M.B.B.S., M.Sc.University of CambridgeStudy participants with persistently high fasting insulin levels from age 9 onward—roughly 3% of the study sample—had roughly five times the odds of being classified as having a mental state that put them at risk of psychosis and more than three times the odds of having a psychotic disorder at age 24. There was no evidence that fasting insulin levels were associated with depression.“It is already known from meta-analytic studies that people with first-episode psychosis, who are generally relatively young and without prior prolonged use of antipsychotic medications, have a higher prevalence of insulin resistance than matched controls,” Perry explained. “Our results therefore suggest that early signs of impairment to glucose-insulin homeostasis may in fact be detectable long before the first episode of psychosis, at least in some individuals.”There was no evidence that BMI was associated with an increased risk of psychosis. However, people who experienced a major increase in BMI starting at puberty onset had roughly 4.5 times the odds of having a depressive episode at age 24, a result that persisted even after the researchers adjusted for childhood behavioral and emotional problems. This suggests that the increased risk of adult depression may stem from the physical or physiological changes of a sudden increase in BMI at puberty, rather than any preexisting childhood depression that may have led to weight gain as the participants entered adolescence.The complexity of risk factors and how they combine over the life span points to the need for a large, conception-to-death cohort study, says William W. Eaton, Ph.D.Johns Hopkins Bloomberg School of Public HealthYet there may be more to it than that, said Perry. “The environment may also play an important part. Children at that age may be susceptible to traumatic life events, for example bullying, which may increase the risk of weight gain and longer-term depression.”William W. Eaton, Ph.D., a professor in the Department of Mental Health at Johns Hopkins Bloomberg School of Public Health in Baltimore, noted the usefulness of drawing data from the ALSPAC cohort.“The important thing is that [the researchers] focused on a range of ages early in the lifespan and used data from what is the most important cohort study on the planet, in many ways, because it starts with conception and continues for decades,” said Eaton, who was not involved in the research.“The complexity of risk factors and the way they combine over the life span point strongly to the need for a national conception-to-death cohort study that includes medical and psychiatric illness, one that is on the scale of 100,000 people over 100 years.”The study was supported in part by NIHR, the Wellcome Trust, and the Medical Research Council. ■“Longitudinal Trends in Childhood Insulin Levels and Body Mass Index and Associations With Risks of Psychosis and Depression in Young Adults” is posted here. 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Association of Insulin Resistance and β-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients.

BackgroundThe interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, β-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism.MethodsA total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn, ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell dysfunction (HOMA-%β) were applied to elucidate the nexus between β-C-terminal telopeptide (β-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). β-CTX, OC and P1NP were detected by chemiluminescence.ResultsHOMA-IR was negatively associated with β-CTX, P1NP and OC (regression coefficient (β) -0.044 (-0.053, -0.035), Q4vsQ1; β -7.340 (-9.130, -5.550), Q4vsQ1 and β -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend <0.001). HOMA-%β was positively associated with β-CTX, P1NP and OC (β 0.022 (0.014, 0.031), Q4vsQ1; β 6.951 (5.300, 8.602), Q4vsQ1 and β 1.361 (0.921, 1.800), Q4vsQ1, respectively, all P for trend <0.001).ConclusionsOur results support that lower bone turnover biomarker (β-CTX, P1NP and OC) levels were associated with a combination of higher prevalence of insulin resistance and worse β-cell function among dysglycemia patients. It is feasible to detect bone turnover in diabetes or hyperglycemia patients to predict the risk of osteoporosis and fracture, relieve patients’ pain and reduce the expenses of long-term cure.

High Prevalence of Insulin Resistance in Asymptomatic Patients with Acute Intermittent Porphyria and Liver-Targeted Insulin as a Novel Therapeutic Approach.

Acute porphyria attacks are associated with the strong up-regulation of hepatic heme synthesis and over-production of neurotoxic heme precursors. First-line therapy is based on carbohydrate loading. However, altered glucose homeostasis could affect its efficacy. Our first aim was to investigate the prevalence of insulin resistance (IR) in an observational case-control study including 44 Spanish patients with acute intermittent porphyria (AIP) and 55 age-, gender- and BMI-matched control volunteers. Eight patients (18.2%) and one control (2.3%, p = 0.01) showed a high HOMA-IR index (cut-off ≥ 3.4). Patients with IR and hyperinsulinemia showed clinically stable disease. Thus, the second aim was to evaluate the effect of the co-administration of glucose and a fast-acting or new liver-targeted insulin (the fusion protein of insulin and apolipoprotein A-I, Ins-ApoAI) in AIP mice. The combination of glucose and the Ins-ApoAI promoted partial but sustained protection against hepatic heme synthesis up-regulation compared with glucose alone or co-injected with fast-acting insulin. In a prevention study, Ins-ApoAI improved symptoms associated with a phenobarbital-induced attack but maintained high porphyrin precursor excretion, probably due to the induction of hepatic mitochondrial biogenesis mediated by apolipoprotein A-I. In conclusion, a high prevalence of IR and hyperinsulinemia was observed in patients with AIP. The experimental data provide proof-of-concept for liver-targeted insulin as a way of enhancing glucose therapy for AIP.

Sex Differences in Insulin Sensitivity are Related to Muscle Tissue Acylcarnitine But Not Subcellular Lipid Distribution.

Sex differences in insulin sensitivity are present throughout the life-span, with men having a higher prevalence of insulin resistance and diabetes compared with women. Differences in lean mass, fat mass, and fat distribution-particularly ectopic fat-have all been postulated to contribute to the sexual dimorphism in diabetes risk. Emerging data suggest ectopic lipid composition and subcellular localization are most relevant; however, it is not known whether they explain sex differences in obesity-induced insulin resistance. To address this gap, this study evaluated insulin sensitivity and subcellular localization of intramuscular triacylglycerol, diacylglycerol, and sphingolipids as well as muscle acylcarnitines and serum lipidomics in people with obesity. Insulin sensitivity was significantly lower in men (P < 0.05); however, no sex differences were found in localization of intramuscular triacylglycerol, diacylglycerol, or sphingolipids in skeletal muscle. In contrast, men had higher total muscle acylcarnitine (P < 0.05) and long-chain muscle acylcarnitine (P < 0.05), which were related to lower insulin sensitivity (r = -0.42, P < 0.05). Men also displayed higher serum ceramide (P = 0.05) and lysophosphatidylcholine (P < 0.01). These data reveal novel sex-specific associations between lipid species involved in the coupling of mitochondrial fatty acid transport, β-oxidation, and tricarboxylic acid cycle flux that may provide therapeutic targets to improve insulin sensitivity.

Menstrual dysfunction in polycystic ovary syndrome: association with dynamic state insulin resistance rather than hyperandrogenism

To examine the relation of menstrual cyclicity abnormalities to hyperandrogenism (HA) and dynamic state insulin resistance (IR) in oligo-ovulatory women with polycystic ovary syndrome (PCOS). Prospective cross-sectional study. Tertiary-care academic center. Fifty-seven women with PCOS (1990 National Institutes of Health criteria) and 57 healthy control women matched by body mass index (BMI). Short insulin tolerance test (ITT). Menstrual cyclicity, sex hormone-binding globulin (SHBG), measures of HA (i.e., modified Ferriman-Gallwey score, total and free testosterone, dehydroepiandrosterone sulfate), and the rate constant for plasma glucose disappearance (kITT) derived from the short ITT. Adjusting for age, BMI, and ethnicity, the mean androgen measures were higher and SHBG trended lower, kITT was lower, and the prevalence of IR was higher in PCOS than in controls, independent of menstrual cyclicity. The optimal cutoff point for IR was set at kITT value of 3.57%/minute or lower. Overall, 79% of the women with PCOS had IR. To control further for the effect of ethnicity, a subgroup of 46 non-Hispanic white PCOS participants were studied; those who exhibited amenorrhea (n = 15) or oligomenorrhea (n = 19) had or tended toward having a lower kITT and a higher prevalence of IR than the women with PCOS and oligo-ovulatory eumenorrhea (n = 12). The kITT trended lower and the prevalence of IR trended higher in women with PCOS and amenorrhea than those with oligomenorrhea. The measures of SHBG and HA were similar across the three menstrual groups. Oligo-ovulatory women with PCOS and overt oligo/amenorrhea have greater degrees of IR but not HA when compared with oligo-ovulatory eumenorrheic women with PCOS, suggesting that IR and hyperinsulinemia but not HA play a role in determining the degree of menstrual dysfunction, which can be used as a clinical marker for the degree of IR in oligo-ovulatory PCOS.

Prevalence of Insulin Resistance in Urban Indian School Children Who Are Overweight/Obese: A Cross-Sectional Study.

Background: Limited data are available for insulin resistance (IR) in over-weight/obese children from the Indian subcontinent. Identifying predictors of IR in this population is important, as they may be used as a screening tool for future metabolic complications.Materials and Methods: This school-based cross-sectional study was conducted in an Eastern Indian city. Anthropometry and blood pressure measurements were carried out as per the published guidelines. Venous blood samples were taken in a fasting state to measure plasma glucose, insulin, and lipid profile. IR was measured quantitatively by a homeostatic model of assessment (HOMA-IR).Results: A total of 545 (28.2%) children who were overweight or obese were included. The male:female ratio was 1:1.27. The overall prevalence of metabolic syndrome (MS) in these children was 21.8%. Around 32.3% of children had HOMA-IR of ≥2.5, and 22.2% had HOMA-IR of ≥3.16. The mean HOMA-IR in children with MS was 5.46 compared to 2.18 in those without MS. An increased risk of IR with low HDL, high triglyceride, increased waist circumference, and increased BP (both systolic and diastolic) was found. This means that insulin resistance was more common in children who were overweight or obesity and had underlying MS.Conclusions: The present school-based study found a high prevalence of insulin resistance among children who were overweight or obese. This could predict an increased risk of future adverse cardio-vascular events in the studied children. The findings of this study would help in planning and implementing primary prevention programs targeting weight management and lifestyle change in schoolchildren.