Higher Degree Of Insulin Resistance Research Articles

Clinical features and metabolic complications for non-alcoholic fatty liver disease (NAFLD) in youth with obesity.

Pediatric obesity has become in the last forty years the most common metabolic disease in children and adolescents affecting about 25% of the pediatric population in the western world. As obesity worsens, a whole-body insulin resistance (IR) occurs. This phenomenon is more pronounced during adolescence, when youth experience a high degree of insulin resistance due the production of growth hormone. As IR progresses, the blunted control of insulin on adipose tissue lipolysis causes an increased flux of fatty acids with FFA deposition in ectopic tissues and organs such as the liver, leading to the development of NAFLD. In this brief review, we will discuss the clinical implications of IR and NAFLD in the context of pediatric obesity. We will review the pathogenesis and the link between these two entities, the major pathophysiologic underpinnings, including the role of genetics and metagenomics, how these two entities lead to the development of type 2 diabetes, and which are the therapeutic options for NAFLD in youth.

Insulin resistance in women with recurrent miscarriage: a systematic review and meta-analysis

This review aimed to investigate the association of insulin resistance (IR) in women with recurrent pregnancy loss compared to women with normal pregnancy history. PubMed, EMBASE, the Web of Science and Google Scholar databases were accessed to collect published observational studies that compared IR of recurrent pregnancy loss women with healthy women until the 6th of October 2022. Outcomes assessed in this review and meta-analysis included fasting blood glucose, fasting plasma insulin, homeostasis model assessment for IR, glucose to insulin ratio. Mean differences, odds ratios with 95% confidence interval were pooled using the fixed or random effect models. Sensitivity analyses were performed to validate the robustness of the results. Review Manager version 5.4.1 and Stata version 8.0 were used. A total of nineteen studies involving 4453 individuals were included. Recurrent pregnancy loss patients presented significantly higher fasting blood glucose, fasting plasma insulin, homeostasis model assessment for IR, and lower glucose to insulin ratios. Additionally, recurrent pregnancy loss patients had higher rates of IR as defined by abnormal fasting plasma insulin, homeostasis model assessment for IR, and glucose to insulin ratio. Sensitivity analyses validated the robustness of the results. In the current review, we show that recurrent pregnancy loss is associated with a higher degree of IR and highlight the importance of screening and treatment of IR.

ODP214 INSULIN REQUIRING DIABETES MELLITUS(IRDM) and CAD

Abstract Background Several studies have shown a higher risk of coronary artery disease(CAD) in insulin-requiring T2 diabetes mellitus(IRDM) patients which could be linked with DNA methylation(proinflammatory cytokines),histone deacetylase activity(mitochondrial function-oxidant stress) and micro RNAs impacting insulin secretion and action, endothelial function and atherosclerotic process. [1,2,3,4,5]. Insulin therapy has been shown to be associated with atherosclerosis. [3]Clinical Study: A retrospective study of twenty T2 DM patients was done to observe the association of IRDM and CAD. There was equal sex distribution with mean age of 55 years in males and 50 years in females. Ten (50%)patients were insulin requiring(IRDM),having a mean insulin requirement of 0.57 units/kg in males and 0.98 units/kg in females. Seven(35%) patients had CAD;five(50%)of IRDM and two(20%)of non-insulin requiring patients. The mean insulin dose of IRDM patients with CAD was 0.74 units/kg in males and 1.3 units/kg in females and those without CAD was 0.30 units/kg in males and 0.73 units/kg in females. There was no significant difference in the prevalence of hypertension, dyslipidemia and nephropathy between the patients with or without CAD. All the three IRDM males with CAD had BMI less than 25 kg/m 2 where as both the IRDM females with CAD had BMI greater than 25 kg/m 2 . Both the IRDM females with CAD had CAD before institution of insulin therapy, though they ultimately required higher insulin dose denoting higher degree of insulin resistance(IR) and suggesting non-contribution of insulin therapy in the pathogenesis of CAD. Conclusion This study highlights a)higher incidence of CAD in IRDM patients, b)higher insulin requirement in CAD patients,c)higher insulin dose in females as compared to males and d)females(all obese)having CAD earlier than males,having CAD before insulin therapy but requiring higher dose than non-CAD females. These could be due to a) insulin deficiency and predominantly IR impacting IRDM[3];b)IR enhancing atherosclerosis((through proinflammatory cytokines, oxidant stress and procoagulant activity (not measured)promoting CAD[2,3,4,]);c)higher BMI[6] and associated greater IR[3] contributing to higher insulin dose in females, though,they required insulin much later;some studies have shown female gender having a protective effect on insulin initiation[5];d)the overlap of traditional CV risk factors viz. dyslipidemia,hypertension, nephropathy in IRDM and non-IRDM patients with or without CAD points towards the predominant contribution of proinflammatory cytokines viz CRP and procoagulants viz . PAI in the aetiopathogenesis of CAD[4]. Further studies on larger patient population are required to substantiate these observations.

100-OR: Association of Recent Myocardial Infarction with Insulin Resistance and Fatty Liver Disease in Type 2 Diabetes

Insulin resistance and nonalcoholic fatty liver disease (NAFLD) frequently associate with type 2 diabetes (T2D) and cardiovascular disease and worsen their prognosis. We hypothesized that people with recent myocardial infarction (MI) have lower left ventricular ejection fraction (EF) and higher degree of insulin resistance (IR) , hepatocellular lipid content (HCL) and risk of hepatic fibrosis than matched people without MI. Thus, participants of the “DIabetes and ST-Elevation MI (DISTEMI) Study” were examined 6-12 weeks after MI (MI+; n=53, 28% T2D) and compared to age-, sex-, BMI-matched people without MI (MI-; n=48, 31% T2D) . Insulin sensitivity was assessed during fasting (Homeostasis Model Assessment (HOMA) 2-IR) and hyperinsulinemic-euglycemic clamps (M-value) . EF, HCL and liver stiffness, associated with fibrosis stages, were quantified by 1H-magnetic resonance imaging, spectroscopy and elastography, respectively. MI+ had a lower EF (47±2 vs. 58±1 %, p<0.0001) and M-value (7.3±0.4 vs. 8.2±0.4 mg*kg-1*min-1, p<0.05) compared to MI-, which was mainly due to a difference between the T2D groups (EF: 39±6 vs. 52±2 %, p<0.001; M-value: 4.2±0.5 vs. 6.1±0.6 mg*kg-1*min-1, p<0.05) . HCL (3.4±0.8 vs. 5.8±0.9 %) and liver stiffness (2.2±0.1 vs. 2.3±0.1 kPa) were comparable between MI+ and MI-. HCL correlated negatively with M-value (r=-0.95, p<0.05) and positively with systolic blood pressure (r=0.91, p<0.05) in MI+ with T2D. In MI+ without T2D, HCL correlated positively with HOMA2-IR (r=0.58, p<0.01) and BMI (r=0.53, p<0.01) . In conclusion, recent myocardial infarction in people with type 2 diabetes associates with decreased ejection fraction and increased insulin resistance. The correlation between insulin resistance and liver fat content suggests that HCL can serve as a non-invasive cardiovascular marker and may identify persons with a worse outcome after myocardial infarction. Disclosure C.Möser: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. O.P.Zaharia: n/a. F.C.Michlotti: None. Y.Kupriyanova: None. V.Schrauwen-hinderling: None. P.Bobrov: None. V.Burkart: None. M.Kelm: Board Member; DGIM-Deutsche Geselleschaft für Innere Medizin, DGK-Deutsche Gesellschaft für Kardiologie, DSHF-Deutsche Stiftung für Herzforschung, ESC- European Society of Cardiology, Other Relationship; Abiomed , Bayer AG, diaplan, Kel Con GmbH, Research Support; Abiomed Europe GmbH, B.Braun, Edwards Lifesciences Corporation, European Union, IPP Med GmbH - Institut für Pharmakologie u. präventive Medizin GmbH, Mars Scientific Advisory Council (MSAC) , Medicure Inc., Microvision Medical. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. Funding Research Network SFB 1116 of the German Research Foundation

A New Oral Model to Assess Postprandial Lactate Production Rate.

Pediatric obesity predisposes children and adolescents to early onset insulin resistance and dysglycemia. In the last 20 years this has led to a rise in the prevalence of prediabetes, diabetes and fatty liver in youngsters, due to the high degree of insulin resistance experienced by these patients and the consequent high availability of glucose. As glucose accesses the liver, it is partly metabolized through glycolysis, whose main product is pyruvate that is then converted into Acetyl CoA and lactate. Therefore, lactate production rate (LPR) represents the best proxy for the assessment of glycolysis. Since to date there are not methods to estimate postprandial LPR, here we proposed a novel oral glucose-lactate model to estimate LPR during an oral glucose tolerance test and tested it in 24 youth with and without obesity. The model is based on the oral glucose minimal model and assumes that LPR is a fraction (fr) of glucose disposal rate, proportional to glucose concentration and controlled by insulin action. The model well fitted the glucose and lactate data, and provided both precise parameter estimates (e.g., fr = 22.5 [12.6-54.1]%, median [IQR]), CV = 18 [13-25]%) and LPR time course. The proposed model is a valid tool to assess LPR, and thus glycolysis, during OGTT in nondiabetic subjects. The proposed methodology will allow to assess postprandial LPR in simple and cost-effective way.

RELATIONSHIPS BETWEEN OSTEOCALCIN LEVEL AND HORMONAL METABOLIC DISORDERS IN TYPE 2 DIABETIC MEN WITH VARIOUS DEGREES OF OBESITY (LITERATURE REVIEW AND OWN RESEARCH)

The bone hormone osteocalcin is formed by osteoblasts and is partially released into the bloodstream during bone resorption, being a biomarker of bone remodeling. Osteocalcin also plays an important role in the endocrine regulation of metabolic and energy processes in the body and in their coordination. Osteocalcin uses a feedback mechanism to regulate insulin secretion, insulin sensitivity of peripheral tissues, and adipokine levels. In general, the secretion of osteocalcin and insulin are important factors in the formation of hormonal-metabolic phenotype, body composition, determination of regional distribution and metabolic activity of both bone and adipose tissue.The aim of this study was to establish the relationship between osteocalcin concentration and hormonal changes in men with type 2 diabetes with and without obesity on the background of involutive changes. Results. 64 men with type 2 diabetes, older than 50 years, were divided into 2 groups by BMI: 1) non-obese, BMI <30 kg / m2 (n = 31); 2) -obese, BMI ≥ 30 kg / m2 (n = 33). Lower levels of insulin secretion (lower serum C-peptide and insulin levels) were observed in non-obese patients in the absence of a compensatory increase in proinsulin levels. It can be assumed that the increase in the concentration of osteocalcin in group 1 is compensatory, although it does not have a significant effect on blood glucose levels. However, it may have a protective effect on the severity of insulin resistance syndrome and related metabolic disorders. Lower levels of osteocalcin in the obese group were associated with a higher degree of insulin resistance and insulin secretion. There was no significant difference between the two groups in serum proinsulin levels, as well as in androgen supply, which was assessed by the levels of total testosterone, testosteronestradiol-binding globulin, and free testosterone index. Conclusion. Lower levels of osteocalcin may be a marker of an increased risk of adverse metabolic changes in obese patients with type 2 diabetes, followed by complications compared to non-overweight patients

Characteristics of gestational diabetes subtypes classified by oral glucose tolerance test values.

BackgroundIn clinical practice, gestational diabetes mellitus (GDM) is treated as a homogenous disease but emerging evidence suggests that the diagnosis of GDM possibly comprises different metabolic entities. In this study, we aimed to assess early pregnancy characteristics of gestational diabetes mellitus entities classified according to the presence of fasting and/or post‐load hyperglycaemia in the diagnostic oral glucose tolerance test performed at mid‐gestation.MethodsIn this prospective cohort study, 1087 pregnant women received a broad risk evaluation and laboratory examination at early gestation and were later classified as normal glucose tolerant (NGT), as having isolated fasting hyperglycaemia (GDM‐IFH), isolated post‐load hyperglycaemia (GDM‐IPH) or combined hyperglycaemia (GDM‐CH) according to oral glucose tolerance test results. Participants were followed up until delivery to assess data on pharmacotherapy and pregnancy outcomes.ResultsWomen affected by elevated fasting and post‐load glucose concentrations (GDM‐CH) showed adverse metabolic profiles already at beginning of pregnancy including a higher degree of insulin resistance as compared to women with normal glucose tolerance and those with isolated defects (especially GDM‐IPH). The GDM‐IPH subgroup had lower body mass index at early gestation and required glucose‐lowering medications less often (28.9%) as compared to GDM‐IFH (47.8%, P = .019) and GDM‐CH (54.5%, P = .005). No differences were observed in pregnancy outcome data.ConclusionsWomen with fasting hyperglycaemia, especially those with combined hyperglycaemia, showed an unfavourable metabolic phenotype already at early gestation. Therefore, categorization based on abnormal oral glucose tolerance test values provides a practicable basis for clinical risk stratification.

Hepatic Steatosis and Fibrosis in Type 2 Diabetes: A Risk-Based Approach to Targeted Screening.

Non-alcoholic fatty liver disease (NAFLD) is common in people with type 2 diabetes mellitus (T2DM). We aimed to explore predictive factors of NAFLD in T2DM and identify high risk subgroups. This was a cross-sectional study including 100 individuals with T2DM and 100 without diabetes matched for age, sex, and body mass index (BMI). Hepatic steatosis grades (calculated by controlled attenuation parameters-CAP score-3), and liver fibrosis stages (F0-F4) were determined using transient elastography. The frequency of NAFLD was comparable between the two study groups. However, CAP scores were significantly higher in individuals with diabetes (294.90 ± 53.12 vs. 269.78 ± 45.05 dB/m; P < 0.001). Fifty percent of individuals with diabetes had severe steatosis (S3), while this figure was 31.6% in those without diabetes (P < 0.05). Significant fibrosis (F2-F4) was more frequent in individuals with T2DM (13% vs. 4.1%, P = 0.02). Individuals with T2DM and advanced fibrosis had significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and CAP score compared to those without fibrosis (P < 0.05). In the regression analysis, a model including BMI, WHR, AST and female gender explained 50% of the variation in CAP score in patients with diabetes (all P < 0.05, adjusted R2 : 0.508). CAP scores were also the major determinant of liver fibrosis in this group (OR: 1.04; CI: 1.017-1.063; P = 0.001). Individuals with diabetes are more likely to have severe fibrosis. Obesity (especially central obesity), the female gender, elevated liver enzymes, and higher degree of insulin resistance are associated with more advanced liver disease in individuals with T2DM.

Association between maternal triglycerides and disturbed glucose metabolism in pregnancy

AimsDyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy.MethodsSixty-seven pregnant women received a detailed metabolic characterization at 12+0–22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0–27+6 weeks of gestation.ResultsElevated triglycerides in early gestation were associated with insulin resistance and β-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03–1.34, p=0.022 for an increase of 10 mg/dl).ConclusionsHypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and β-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.

Telomere biology and metabolic disorders: the role of insulin resistance and type 2 diabetes

BACKGROUND: Insulin resistance accelerates the aging process, but its speed depends on the individual characteristics of the metabolism. One of the reasons for the different aging rates in individuals with insulin resistance is the initially different “genetic protection” of cells, which many scientists associate with replicative cellular aging.AIMS: to study the relationship between the state of carbohydrate metabolism and markers of replicative cell aging in individuals with different sensitivity to insulin.MATERIALS AND METHODS: The observation study included 305 patients. The parameters of glucose metabolism and telomere biology were studied.RESULTS: The mean age of the patients was 51.5±13.3 years. Patients were divided into three groups depending on presence of insulin resistance: healthy, with insulin resistance and with type 2 diabetes. The mean age of healthy patients was 48.82±13.87 years, in insulin resistance group — 53.04±12.8, in 2 diabetes mellitus — 58.4±7.90. The median telomere length was 9.76. The median telomerase activity was 0.48. Both telomere length and telomerase activity progressively decrease as insulin resistance increases. In patients with diabetes, short telomere lengths and low telomerase activity predominated. The insulin resistance index has the greatest impact on the risk of detecting “short” telomeres. In patients with insulin resistance, an increase in glycated hemoglobin increases the likelihood of detecting short telomeres by 2.4 times, and in diabetes mellitus by 4.26 times, an increase in fasting plasma glucose by 90%, and an increase in HOMA-IR by 35%. An increase in insulin resistance increases the risk of detecting «low» telomerase activity by 53% and the risk of detecting «very low» telomerase activity by 92%. A decrease in synsulin resistance increases the chance of increasing telomerase activity to «very high» by 51%.CONCLUSION: Shorter telomeres are associated with more pronounced disorders of carbohydrate metabolism and a higher degree of insulin resistance. Further studies of metabolic status are necessary to personalize their lifestyle and treatment goals.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. Compared with women in the normal glucose tolerance group (n=651), women in the GDM-R group (n=143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n=37) and GDM-B (n=56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

The Relationship Between Polycystic Ovarian Syndrome, Periodontal Disease, and Osteoporosis.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder to affect women in their reproductive years. There has been growing concern that women with PCOS may suffer from long-term metabolic consequences due to the high degree of insulin resistance that is often present in PCOS. However, few longitudinal studies exist in this area and there is a paucity of data on whether women with PCOS are at risk of other chronic diseases as they age. Specifically, current evidence suggests that reproductive-age women with PCOS may be at increased risk for both osteoporosis and periodontal disease (PD)-both these chronic diseases can have serious implications for health and quality of life. However, few studies have addressed how risk factors for osteoporosis and PD may be altered by aging in PCOS. The PCOS phenotype of women beyond reproductive years is poorly understood, and it is not known whether the metabolic profile of older women with PCOS results in an increased risk of osteoporosis and PD. The objective of this review is to discuss the relationships between PCOS, osteoporosis, and PD, and how these relationships could be impacted during aging. The long-term goal of this review is to provide direction for future research that is needed to more clearly elucidate these relationships and eventually provide a basis for evidence-based health recommendations.

Explore the Characteristics of Age, BMI and Blood Composition of Breast Cancer Patients Based on Multivariate Statistical Analysis

In this paper, through a series of analysis and testing of breast cancer detection data, the statistical rules of multiple objects and multiple indicators are analyzed in the case of their correlation. First of all, univariate diagnosis and multivariate diagnosis were performed on the data. Among them, when studying the correlation between variables, it was found that HOMA had a clear linear positive correlation with insulin content in blood. It is worth noting that some patients with breast cancer show a high degree of insulin resistance and blood insulin content, which is a feature not found in samples without breast cancer. Then, through single factor analysis of variance, we believe that there were significant differences in blood test conditions, ages, and BMI indicators of samples of different health conditions. Next, the principal component analysis was used to reduce the dimension of the data. In this study, the differences in age, BMI, and blood component content between the two groups with different health conditions can be summarized by these two independent factors. Among them, the absolute value of the MCP-1 (monocyte chemoattractant protein 1) coefficient in the main component 1 is large, reflecting the characteristics of the blood component of the sample; the load values of glucose and leptin in the main component 2 are large, reflecting similar results. Then, assuming the use of m = 3 factor model and the use of maximum likelihood method and principal component method, the original data and factor rotation data are re-analyzed, so that the variables are reduced to 3 factors for analysis. Among them, the maximum likelihood method is used to estimate the factor rotation data. The first factor reflects the insulin resistance factor attributed to insulin and HOMA indicators, and the second factor reflects the body fat and thin factor attributed to BMI and leptin. The third factor reflects the glucose content in the blood. Finally, by setting different misjudgment costs for discriminant analysis, the obtained APER is 0.1638 and EAER is 0.1872. Among them, the probability of discriminating patients with breast cancer from not having breast cancer is 0.09375, which is a low rate of misjudgment and also means the model established in this paper is efficient.

Phenotype and genotype of polycystic ovary syndrome in Asia: Ethnic differences.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, and ethnic diversity has been reported in its manifestation. This review addressed phenotype and genetic studies in Asian women with PCOS. Generally, East Asians are less hirsute, and the hirsutism score cutoff is lower than the Caucasian counterpart. It is not clear whether there are any significant differences in the prevalence or severity of irregular menstruation (IM) or characteristics of polycystic ovary (PCO) across ethnicities. Interestingly, the IM/PCO subgroup is a relatively common phenotype in East Asian patients but not in Caucasian patients. The prevalence of insulin resistance in PCOS patients varies depending on the index used and the cutoff, but women with PCOS showed a higher degree of insulin resistance than those of controls across ethnicities. Lower body mass index (BMI) and lower prevalence of metabolic syndrome were reported in East Asian patients, but despite lower BMI, a comparative study reported that Asian women with PCOS were more likely to have diabetes compared with Caucasian patients, suggesting they also have metabolic complications. Unlike East Asian patients, South Asian patients showed an increased degree of hirsutism, early onset of symptoms, and severe insulin resistance and metabolic risks compared with Caucasians. Genetic components play important roles in the pathogenesis of PCOS, and genome-wide association studies of PCOS suggest that similar genetic risk factors exist between Asian and Caucasian patients. Continuous comparative studies are needed to standardize the diagnosis and management of PCOS across different ethnicities.

Integrative Chinese herbal medicine therapy reduced the risk of type 2 diabetes mellitus in patients with polycystic ovary syndrome: A nationwide matched cohort study

Ethnopharmacological relevancePolycystic ovary syndrome (PCOS) is a common condition that affects 5%–10% of women of reproductive age worldwide. Patients with PCOS have a high degree of insulin resistance and are at an increased risk of developing type 2 diabetes mellitus (T2DM). The currently available therapeutic approaches for PCOS mainly focus on symptomatic treatment. Aim of the studyThis study aimed to determine whether Chinese herbal medicine (CMH)-based interventions could reduce the risk of T2DM in PCOS patients. Materials and methodsThis retrospective study randomly selected 1 million enrollees from the National Health Insurance Database and identified 3797 patients who were newly diagnosed with PCOS in 1997–2010. After 1:1 frequency-matched by age, diagnosis of PCOS year and index days, we selected 342 eligible patients in each group. ResultsThe incidence of T2DM in the CHM group was significantly lower than that in the non-CHM group (hazard ratio = 0.31; 95% confidence interval, 0.15–0.64; p = 0.0014) after a mean follow-up period of 5.2 years (4.20 years for the comparison cohort). Five herbal formulas and two single herbs showed protective effects, and Paeonia lactiflora was a common ingredient in the five formulas. ConclusionsThus, CHM may help prevent T2DM-related complications in patients with PCOS. Further clinical and pharmacological analysis based on these findings is expected in the future.

Natural course of fatty liver in 36,195 South Korean adults

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, and yet the natural course remains unclear. Study population included 36,195 individuals who participated in a health-screening program and diagnosed with fatty liver by abdominal ultrasound. Participants were provided written information regarding fatty liver and advised to make lifestyle changes. Ultrasound was repeated after at least 6 months. After a mean follow up of 4.9 years (±3.4), 19.6% resolved their fatty liver. Individuals who resolved were more likely female (22.9% vs. 12.3%), thinner (body mass index [BMI], 25.2 ± 2.7 vs. 26 ± 2.7), and with lower HOMA-IR (1.4 vs. 1.7) (P .70.001). Decrease in BMI predicted resolution of fatty liver with 42% of those in the top quartile of BMI decline resolving compared with 5.7% in the lowest quartile (odds ratio [OR] (95% confidence interval [CI]) 15.65 (14.13–17.34), P < 0.001)). Baseline HOMA-IR also predicted resolution with those in the top quartile (most insulin resistant) being least likely to resolve (12%) vs. those in the lowest quartile (25%) (OR 0.36 [0.31–0.42], P < 0.001). Fatty liver disease is persistent. Individuals with higher degree of insulin resistance are also the most likely to have persistent steatosis at follow up.

Role of Vitamin D Supplementation Therapy on Ovulation and Insulin Resistance in Women with PCOS: A Randomized Controlled Trial

Introduction: Polycystic ovarian syndrome (PCOS) is the most prevalent worldwide female endocrine disorder, affecting nearly 5%-12% of reproductive-aged women. PCOS is the most common cause of anovulatory infertility and its foremost clinical symptoms include anovulation or oligo-ovulation, infertility, menstrual irregularity, polycystic ovaries and hyperandrogenism. PCOS is also common among infertile Arabian female population and it is associated with significant elevations in markers of metabolic syndrome, insulin resistance and cardiovascular risks. Unfortunately, PCOS is not a simple pathophysiologic process for which one treatment is sufficient to control all manifestations. Therefore, when choosing a treatment regimen, it should target specific manifestations and individualized patient goals.Aim of the Work: The aim of this study is to assess the safety and the efficacy of vitamin D supplementation therapy on ovulation and metabolic changes in women with PCOS.Study design: Prospective randomized controlled clinical trial.Patients and Methods: The current study was conducted in the infertility clinics of Ain Shams University Maternity Hospital in the period between May 2015 and May 2017. It included 300 women diagnosed with polycystic ovary syndrome attending the infertility clinics of Ain Shams University Maternity Hospital.Results: Being a classification criterion, 25OHD level was significantly lower in the vitamin D deficient subgroup compared to the normal vitamin D subgroup; whereas no significant differences were found between the vitamin D deficient group and the control group. In the same context, 25OHD level was statistically significantly lower in the control group compared to the normal vitamin D subgroup. Vitamin D deficient PCOS women tended to have higher degree of insulin resistance. Fasting glucose was statistically significantly higher in the vitamin D deficient subgroup compared to the normal vitamin D subgroup and the control group; and higher in the control group compared to the normal vitamin D subgroup. Fasting insulin level was statistically significantly higher in the vitamin D deficient subgroup and the control group compared to the normal vitamin D subgroup; whereas no statistically significant differences were found between the former two groups. HOMA2-IR was statistically significantly higher in the vitamin D deficient subgroup and the control group compared to the normal vitamin D subgroup; whereas no statistically significant differences were found between the vitamin D deficient subgroup and the control group. No statistically significant differences were found between the three groups in the various components of the lipid profile.Conclusion: Results of the thesis showed that cumulative ovulation rate was significantly higher in the vitamin D deficient subgroup following vitamin D supplementation compared to the normal vitamin D subgroup and the control group with a rate ratio of 1.27 and 1.22, respectively. Number needed to treat was calculated to be 5.34 and 6.38 compared to normal vitamin D subgroup and control group respectively, i.e. 6.38 women are needed to be supplemented with vitamin D for one of them to benefit compared to control women. No significant differences were found between the three subgroups regarding the median ovulating dose of clomiphene citrate. Also, no significant differences in the cumulative clinical pregnancy rate between the ovulatory women of the three subgroups.

Association of Insulin Resistance with Bone Strength and Bone Turnover in Menopausal Chinese-Singaporean Women without Diabetes.

Insulin resistance (IR) is accompanied by increased areal or volumetric bone mineral density (aBMD or vBMD), but also higher fracture risk. Meanwhile, imbalances in bone health biomarkers affect insulin production. This study investigates the effect of IR on proximal femur and lumbar spine BMD, femoral neck bending, compressive and impact strength indices (Composite Strength Indices) and circulating levels of parathyroid hormone (PTH), C-telopeptide of Type I collagen (CTx-1) and 25(OH) Vitamin D3, in a cohort of 97 healthy, non-obese, menopausal Chinese-Singaporean women. Lumbar spine aBMD was inversely associated with IR and dependent on lean body mass (LBM) and age. No such associations were found for vBMD of the third lumbar vertebra, aBMD and vBMD of the proximal femur, or circulating levels of PTH, CTx-1 and 25(OH) Vitamin D3. Composite Strength Indices were inversely associated with IR and independent of LBM, but after adjusting for fat mass and age, this association remained valid only for the impact strength index. Composite Strength Indices were significantly lower in participants with a high degree of IR. Our findings on IR and Composite Strength Indices relationships were in agreement with previous studies on different cohorts, but those on IR and BMD associations were not.

Hunk, a Serine/Threonine Protein Kinase, Regulates Insulin Secretion from Pancreatic Islets

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder caused by the failure of the pancreatic β‐cells to secrete sufficient insulin to maintain glucose homeostasis. Genetic factors make a strong contribution to the development of the T2DM. Therefore, identifying and characterizing novel genetic factors that play an important role in β‐cell function is critical to understand the heritability of T2DM. We have recently identified the Hunk (Hormonally Up‐Regulated Neu‐Associated Kinase) gene as a novel regulator of insulin secretion from a mouse genetic screen. Genetic variation near the HUNK gene is associated with T2DM in humans. However, no study has yet been reported on the role of Hunk in pancreatic β‐cells.We studied the role of Hunk in two model systems; in islets isolated from whole‐body Hunk knockout mice (HunkKO), and in INS1 cells, a rat insulinoma β‐cell line. We observed that compared to wild type (WT) mice, insulin secretion in response to several different secretagogues was elevated in islets from HunkKO mice. This difference in the secretory response between WT and HunkKO islets was larger if the mice were maintained on a western‐style high‐fat/high‐sucrose (HF/HS) diet, suggesting that Hunk may be required for the diet to exert a suppressive effect on β‐cell function.In contrast to our observations with WT versus HunkKO islets, we observed a very different result in INS1 β‐cells. We transiently overexpressed control Hunk (Hunkcontrol), a catalytically inactive mutant of Hunk that contains a point mutation in the kinase domain (HunkCi), or GFP in INS1 β‐cells; 48 hr later we measured insulin secretion in response to different segretagogues in all three groups of cells. Compared to GFP, cells expressing Hunkcontrol, but not HunkCi, secreted more insulin in response to glucose alone, or a combination of glucose plus fatty acid. This result suggests that the augmented secretory response by Hunkcontrol required Hunk's catalytic activity.Hunk is known to regulate cellular proliferation in other tissues; e.g., breast cancer. We asked if Hunk controls cellular proliferation in pancreatic islets. β‐cells in adult islets can be induced to proliferate in response to metabolic stress, such as high fat diet. We measured the level of expression for several key cell cycle regulatory genes in islets isolated from WT and HunkKO mice that were maintained on the HF/HS diet for 4 months. In addition, we used the insulin receptor antagonist, S961, to induce a very high degree of insulin resistance that has previously been shown to result in significant β‐cell proliferation. Following one week of S961 infusion, islets were isolated and the expression levels of the cell cycle transcripts were measured. Compared to WT mice, cell cycle expression was not altered in the HunkKO islets when mice maintained on either the HF/HS diet, or when treated with S961. These results suggest that Hunk does not regulate β‐cell proliferation in response to metabolic stress.ConclusionWe identified Hunk, a Serine/Threonine protein kinase as a novel regulator of insulin secretion from beta cells. We find that for this particular gene, overexpression in a cell line does not yield a result predicted from a knockout in the mouse.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Study of Visceral and Subcutaneous Abdominal Fat Thickness and Its Correlation with Cardiometabolic Risk Factors and Hormonal Parameters in Polycystic Ovary Syndrome.

Aim of the Study:This study aimed to compare the different adiposity parameters, namely visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) between patients with polycystic ovary syndrome (PCOS) and controls. In addition, it aimed to correlate these adiposity indices with hormonal parameters as well as cardiovascular (CV) risk factors in patients with PCOS.Materials and Methods:Newly diagnosed PCOS patients of reproductive age group according to Rotterdam criteria were included. Age- and body mass index (BMI)-matched healthy females with normal menstrual cycles were taken as controls. All the study participants underwent detailed clinical, biochemical, and hormonal evaluation. Transabdominal ultrasound (US) was performed for detailed ovary imaging and assessment of adiposity (SAT and VAT) parameters.Results:A total of 58 PCOS patients and 40 age- and BMI-matched controls were included. PCOS patients had significantly higher levels of androgens (P < 0.001), elevated highly sensitive C-reactive protein (P = 0.007), and higher degree of insulin resistance (P < 0.001) than controls. PCOS patients had a mean SAT of 2.37 ± 0.7 cm and mean VAT of 8.65 ± 1.78 cm. These parameters were significantly higher than controls who had a mean SAT of 2.01 ± 0.7 cm (P = 0.014) and mean VAT of 7.4 ± 1.89 cm (P = 0.003), despite both groups having similar BMI. Among PCOS cohort, VAT correlated positively with total testosterone (r = 0.295, P = 0.025) and negatively with dehydroepiandrosterone sulfate (r = −0.210, P = 0.114). However, no significant correlation was observed between SAT and androgens in PCOS group.Conclusion:PCOS patients, whether obese or nonobese, had elevated visceral adiposity than controls. VAT correlated positively with adverse CV risk factors and testosterone in PCOS patients. Hence, a simple and inexpensive ultrasonography screening of visceral fat may identify women who have adverse metabolic profile and enhanced CV risk.