Insulin-glucose Ratio Research Articles

Effect of glucose-insulin-potassium on lactate levels at the end of surgery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a randomized controlled trial

IntroductionCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications.Methods and analysisThe modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization.Ethics and disseminationThe trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals.Trial registrationChiCTR2200057258. Registered on March 5, 2022.

7350 Association between thyroid function and insulin resistance indices in Korean adolescents: Findings from the 2014-2015 KNHANES

Abstract Disclosure: E. Mun: None. H. Lee: None. J. Choi: None. R. Lee: None. K. Kim: None. H. Kim: None. Purpose: Obesity and diabetes are rising concerns among adolescents. There are several studies regarding to the association between thyroid function and IR. However, there are limited studies focus on adolescents. Furthermore, there is a lack of studies evaluating various IR indices. We investigated the association between thyroid function and insulin resistance indices in adolescents with normal thyroid function. Methods: This cross-sectional study included 465 adolescents (aged 12-18, 255 boys, 210 girls) based on data from the Korea National Health and Nutritional Examination Survey2014-2015. Thyroid function was assessed using serum thyrotropin (TSH) and free thyroxine (fT4), while IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), glucose/insulin ratio (GIR), TyG (triglyceride-glucose index), and TG/HDL. Multiple linear regression analyzed the relationship between thyroid function and IR, stratified by sex. Nonlinearity was assessed through a restricted cubic spline model. Results: The mean TSH (uIU/mL) and fT4 (ng/dL) were 2.70 and 1.29, respectively. Boys had higher TSH (2.86 vs. 2.52, p = 0.013) and fT4 (1.33 vs. 1.24, p < 0.001) than girls, with significant gender differences. In girls, fT4 negatively correlated with HOMA-IR and positively with GIR. No significant relationship was found between thyroid function and IR in boys. When analyzed stratified by level of obesity, the association between IR and thyroid function was clear in the overweight/obese group in both sexes. Overweight and obese groups showed relationships between fT4 and HOMA-IR (β = 0.08, p = 0.04 in boys; β = -0.12, p < 0.01 in girls) and QUICKI (β = -4.14, p = 0.03 in boys; β = 6.60, p < 0.01 in girls). TSH correlated with TyG (β = 1.01, p = 0.04 in boys; β = 1.38, p = 0.01 in girls). In girls, fT4 was also related to TG/HDL (β = -0.06, p < 0.05) and GIR (β = 0.14, p < 0.01). Nonlinear analysis found no significant relationship between thyroid function and IR. Conclusion: The relationship between thyroid function and IR was more pronounced in the overweight and obese groups. Our study suggests that the correlation between thyroid function and insulin resistance in adolescents may vary based on gender and IR indices. Presentation: 6/1/2024

Disturbed glucose homeostasis and its increased allostatic load in response to individual, joint and fluctuating air pollutants exposure: Evidence from a longitudinal study in prediabetes

We investigated the effect of individual, joint and fluctuating exposure to air pollution (PM2.5, BC, NO3−, NH4+, OM, SO42−, PM10, NO2, SO2, O3) on glucose metabolisms among prediabetes, and simultaneously explored the modifying effect of lifestyle. We conducted a longitudinal study among prediabetes during 2018–2022. Exposure windows within 60-days moving averages and their variabilities were calculated. FBG, insulin, HOMA-IR, HOMA-B, triglyceride glucose index (TyG), glucose insulin ratio (GI) and allostatic load of glucose homeostasis system (AL-GHS) was included. Linear mixed-effects model and BKMR were adopted to investigate the individual and overall effects, respectively. We also explored the preventive role of lifestyle. Individual air pollutant was associated with increased FBG, insulin, HOMA-IR, HOMA-B, TyG, and decreased GI. People with FBG ≥6.1 mmol/L were more susceptible. Air pollutants mixture were only associated with increased HOMA-B, and constituents have the highest group-PIP. Air pollutants variation also exert harmful effect. We observed similar diabetic effect on AL-GHS. Finally, the diabetic effect of air pollutants disappeared if participants adopt a favorable lifestyle. Our findings highlighted the importance of comprehensively assessing multiple air pollutants and their variations, focusing on metabolic health status in the early prevention of T2D, and adopting healthy lifestyle to mitigate such harmful effect.

Association between Thyroid Function and Insulin Resistance Indices in Korean Adolescents: Findings from the 2014-2015 Korea National Health and Nutrition Examination Survey.

This study investigated the sex-specific association between thyroid function and various insulin resistance (IR) indices, including noninsulin-based IR indices, in euthyroid adolescents. A total of 465 adolescents (aged 12-18 years; 255 boys and 210 girls) based on data from the 2014-2015 Korea National Health and Nutrition Examination Survey were included. Serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (fT4) were used to assess thyroid function, whereas the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), glucose/insulin ratio (GIR), triglyceride-glucose (TyG) index, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to assess IR. The relationship between thyroid function and IR was analyzed using multiple linear regressions stratified by sex, considering obesity status. The relationship between thyroid function and IR varied depending on sex and was more pronounced in the overweight/obesity subgroup for both boys and girls. In overweight and obese boys and girls, fT4 was significantly associated with HOMA-IR and QUICKI with conflicting association directions. TSH was also positively associated with the TyG index in both sexes. The findings suggest that the relationship between thyroid function and IR in adolescents might vary depending on sex, and the degree of association was significant in obese adolescents.

Comparisons of Insulin Resistance- and Steatosis-Based Scores in Monitoring Metabolic Associated Fatty Liver Disease Treatment Response

Background: Quantitative measurements of liver fat contents (LFCs) by magnetic resonance imaging derived-proton density fat fraction (MRI-PDFF) are accurate but limited by availability, convenience, and expense in the surveillance of metabolic associated fatty liver (MAFLD). Insulin resistance (IR) and steatosis-associated serum indices are useful in screening for MAFLD, but their value in monitoring MAFLD with or without chronic hepatitis B virus (CHB) infection remains unclear and we aimed to evaluate these scores in predicting changes in LFC. Methods: We conducted a prospective study between January 2015 and December 2021 with 620 consecutive participants with MAFLD (212 participants with CHB) who received a 24-week lifestyle intervention. The homeostasis model assessment of IR (HOMA-IR), HOMA2 index, glucose-insulin ratio, quantitative insulin sensitivity check index, fasting insulin resistance index, fatty liver index (FLI), hepatic steatosis index (HSI), liver fat score (LFS), visceral adiposity index, and triglycerides * glucose were calculated. Results: When using endpoints such as LFS improvements of ≥5% or 10% or escalations of ≥5%, LFS had the highest area under the curve (AUC) values at all endpoints for MAFLD alone (0.756, 95% CI: 0.707–0.805; 0.761, 95% CI: 0.705–0.818; 0.807, 95% CI: 0.713–0.901, all p < 0.05, respectively). With CHB, the FLI (AUC = 0.750) and HIS (AUC = 0.770) exhibited the highest AUCs between the former two outcomes, respectively, but no score could predict LFC escalation of ≥5%. Conclusion: Among IR and steatosis scores, changes in LFC through lifestyle interventions can be captured with LFS possessing moderate precision but not in those with CHB.

RF10 | PMON215 Greater changes in metabolic hormones are associated with a smaller decrease in pulsatile LH secretion in response to short term moderate energy restriction in healthy, young women

Abstract Background Energy restriction may result in hypothalamic amenorrhea by inhibiting GnRH secretion and downstream pulsatile LH secretion. Energy restriction also leads to adaptive changes in metabolic hormones. We sought to determine whether metabolic changes in response to energy restriction predict or mitigate inhibition of GnRH secretion. Methods Nineteen healthy women, (mean age ± SD; 23.36 ± 2.08 yrs) with regular ovulatory cycles and no evidence of energy restriction or excessive exercise, underwent two 5-day dietary interventions with identical exercise in the early follicular phase of two menstrual cycles. A neutral energy availability (NEA; 45 kCal/kg*LBM/d) was followed by a deficient energy availability (DEA; 20 kCal/kg*LBM/d) diet. On day five of each intervention, body composition was analyzed (BodPod®), and blood was sampled between 0800 —1600 hours for LH, TSH and GH, every 10 min, cortisol every 30 min, T3, reverse T3 (rT3) and T4 every 60 min, free T3 (FT3), free T4 (FT4) and TBG at 0800 h and 1600 h. We correlated means of pulsatile LH pulse frequency (LHPF) with integrated metabolic hormone changes across the day in the subset of women with reduced or unchanged LHPF after DEA (n=10) using linear regression. Results In ∼50% of healthy young women, LHPF decreased or was unchanged in response to short-term moderate energy deprivation. BMI and bodyweight declined after DEA in both groups while % fat mass was unchanged. TSH, T3, leptin, insulin declined, and T4 increased from NEA to DEA while glucose, cortisol and GH were unchanged. In subjects with reduced/unchanged LHPF, % delta T3 correlated inversely with delta LHPF (r=-0.727, p=0.017). Similarly, non-fasting delta TSH correlated inversely with % delta LHPF (r=-0.643, p=0.045), and % delta AUC TSH (r=-0.642, p=0.045) correlated inversely with DEA LHPF. Percent delta insulin (r= -0.722, p=0.018) and % delta insulin AUC (r= – 0.688, p=0.028) correlated inversely with delta LHPF. Percent delta insulin-glucose ratio (r=-0.772, p=0.009) and % change in AUC insulin-glucose ratio (r=-0.759, p=0.011) also correlated inversely with delta LHPF. This inverse relationship was preserved when insulin was normalized for caloric intake (n-insulin) was correlated with % delta LHPF (r=-0.722, p=0.018) and % delta AUC n-insulin correlated with delta LHPF (r= -0.631 and p= 0.050). Delta AUC leptin (r=-0.684, p=0.029) and % delta AUC leptin (r=-0.670, p=0.034) also correlated inversely with delta LHPF. Mean cortisol at NEA correlated inversely with LHPF during DEA (r=-0.816, p=0.007), implying that higher baseline cortisol levels may predict a greater relative fall in LHPF. Cortisol AUC in DEA also correlated inversely with LHPF in DEA (r=-0.722, p=0.028). Conclusion Our data suggest that greater changes in metabolic hormones may protect against the inhibitory effect of moderate energy deprivation on GnRH secretion in healthy young women with normal reproductive function. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Anti-Diabetic and Antioxidant Effects of Methanolic Flower Head Extract of Tagetes Patula in Streptozotocin and Dexamethasone Induced Diabetic Rats

&#x0D; Diabetes is a chronic metabolic disorder characterized by a high blood glucose concentration, i.e., hyperglycemia or caused by insulin deficiency, often combined with insulin resistance. In the Present study, the antidiabetic and antioxidant activity of the methanolic extract of Tagetes patula flower heads was screened out in rodent models. The pharmacological evaluation was carried out using 200 and 400 mg/kg, b.w. The in-vivo antidiabetic activity was performed in streptozotocin, dexamethasone- induced diabetic models and oral glucose tolerance test. Metformin hydrochloride was used as a standard. The parameters like blood glucose levels, insulin levels, homeostasis assessment of insulin resistance, insulin sensitivity, and fasting glucose-insulin ratio were estimated in these models. The in-vitro antioxidant activity of methanolic extract of Tagetes patula was performed by using hydroxyl radical scavenging assay and Ascorbic acid was used as a standard. The preliminary phytochemical screening of Tagetes patula revealed the presence of phytoconstituents like alkaloids, flavonoids, saponins, steroids, phenols, carbohydrates, triterpenoids, and tannins. The extract showed a significant decrease in the elevated blood glucose levels in streptozotocin, dexamethasone-induced diabetic models, and also in the oral glucose tolerance test. The extract prevented insulin resistance and significantly increased insulin sensitivity in the dexamethasone-induced model. The various phytochemical constituents like alkaloids, flavonoids, saponins, steroids, and phenols might be responsible for lowering the blood glucose levels in the animal models mentioned above. The extract showed significant scavenging activity against hydroxyl free radicals. From the above outcomes, it is flawless that the methanolic extract of Tagetes patula has antidiabetic and antioxidant activities.&#x0D;

Glucose Insulin Ratio in Hyper Insulinemic Women with Polycystic Ovarian Syndrome

Background: Women with polycystic ovarian syndrome (PCOS) have insulin resistance and hyperinsulinemia that may play a key role in the pathogenesis of PCOS. Objectives: To determine and compare glucose-insulin ratio in hyper-insulinemic women with the polycystic ovarian syndrome and healthy controls. Materials &amp; Methods: A cross-sectional comparative study was conducted at Lahore General Hospital. A total of 80 women 24-35 years of age were recruited from Lahore General Hospital. 50 women had PCOS, and 30 were healthy controls. PCOS was diagnosed by using the Rotterdam criteria. Height, weight, and waist circumference were measured. Glucose and insulin were estimated by the glucose oxidase method and ELISA, respectively. HOMA-IR was calculated to determine insulin resistance (IR). HOMA- β was calculated to assess the β-cell function. Fasting glucose and insulin ratio were also calculated. Results: Mean age of the women with PCOS and healthy controls was 29.89±3.54 and 28.60±1.12 years, respectively (p&gt;0.54). BMI and waist circumference of women with PCOS were higher compared to healthy controls (p&gt;0.45). Fasting glucose, fasting insulin, HOMA- β, and IR were significantly higher in women with PCOS compared to healthy controls (p&lt;0.001). Conclusion: In addition to HOMA IR, the glucose-insulin ratio may be considered to assess hyperinsulinemia in women with polycystic ovary syndrome.

Ambient air pollution during pregnancy and cardiometabolic biomarkers in cord blood

Background/Objectives:Prenatal air pollution exposure has been associated with adverse childhood cardiometabolic outcomes. It is unknown whether evidence of metabolic disruption associated with air pollution is identifiable at birth. We examined exposure to prenatal ambient air pollution and cord blood cardiometabolic biomarkers among 812 mother-infant pairs in the Healthy Start study.Methods:Using inverse-distance-weighted interpolation of ambient concentrations obtained from stationary monitors, we estimated daily particulate matter ≤2.5 micrometers (PM2.5) and ozone (O3) concentrations at participant residences. Daily estimates were averaged by trimester, full-pregnancy, and the 7 and 30 days prior to delivery. Associations of air pollution with the following cord blood biomarkers were estimated via multivariable linear regression: glucose, insulin, glucose/insulin ratio (GIR), leptin, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, free fatty acids, and triglycerides.Results:In this Denver-based cohort, PM2.5 concentrations were lower than in many US urban areas, but O3 concentrations regularly exceeded federal air quality standards. Higher O3 concentrations during pregnancy were consistently associated with higher insulin and lower GIR in cord blood. For example, an interquartile range increase in full pregnancy O3 (6.3 parts per billion [ppb]) was associated with 0.13 log-µIU/ml (95% confidence interval [CI] = 0.04, 0.22) higher cord blood insulin, after adjusting for PM2.5 and other confounders. We found positive, but generally nonsignificant, associations between PM2.5 and leptin and isolated associations between pollutants during certain exposure periods and lipids.Conclusions:In this cohort with moderately high O3 exposure, prenatal concentrations of O3 were positively associated with cord blood insulin. Future studies should examine the implications for offspring long-term health.

Lipid accumulation product (LAP) as a potential index to predict risk of insulin resistance in young, non-obese Asian Indian males from Southern India: observations from hyperinsulinemic-euglycemic clamp studies

IntroductionWe aimed to compare the predictive accuracy of surrogate indices namely the lipid accumulation product (LAP) index, homeostatic model of assessment of insulin resistance (HOMA-IR), fasting glucose-insulin ratio (FG-IR) and...

Ambient air pollution exposure during pregnancy and cardio-metabolic markers in cord blood: The Healthy Start study

BACKGROUND AND AIM: Prenatal air pollution exposure has been associated with adverse cardiometabolic outcomes in childhood. It is unknown whether evidence of metabolic disruption associated with air pollution may be identified at birth. We estimated associations between maternal residential exposure to air pollution during pregnancy and metabolic and lipid biomarkers in cord blood collected at delivery. METHODS: This study included 812 mother-infant pairs enrolled in the prospective, Colorado-based Healthy Start study (2009-2014). Using inverse-distance-weighted interpolation of data obtained from stationary monitors, we estimated daily particulate matter ≤2.5 micrometers (PM2.5) and ozone (O3) concentrations at participant residences. Daily estimates were averaged by trimester, full pregnancy, and the 7- and 30- days prior to delivery. Outcomes were cord blood concentrations of glucose, insulin, leptin, total and high-density lipoprotein cholesterol, free fatty acids, and triglycerides. Glucose-insulin ratio was calculated as an indirect measure of insulin sensitivity. We used multiple linear regression to estimate associations between PM2.5 and O3 and cord blood metabolic and lipid biomarkers. Covariates included maternal, infant, and meteorological characteristics. RESULTS:Higher O3 exposure, during both recent and longer-term exposure periods during pregnancy, was consistently associated with higher insulin and lower glucose-insulin ratio in cord blood. For example, an interquartile range increase in full pregnancy O3 (6.3 ppb) was associated with a 0.12 log-µIU/ml (95% confidence interval: 0.03, 0.21) increase in cord blood insulin, after adjusting for covariates. There was limited evidence supporting positive associations between PM2.5 and leptin and O3 and total cholesterol. There were inverse associations between PM2.5 and triglycerides, during certain periods of pregnancy. CONCLUSIONS:Prenatal air pollution exposure was associated with cardiometabolic biomarkers in cord blood, most notably for O3 and insulin. Future studies should examine whether these changes persist into childhood and their implications on offspring health. KEYWORDS: prenatal exposure, air pollution, lipids, metabolism, neonate

Effect of dietary fat intake and genetic risk on glucose and insulin-related traits in Brazilian young adults

PurposeThe development of metabolic diseases such as type 2 diabetes (T2D) is closely linked to a complex interplay between genetic and dietary factors. The prevalence of abdominal obesity, hyperinsulinemia, dyslipidaemia, and high blood pressure among Brazilian adolescents is increasing and hence, early lifestyle interventions targeting these factors might be an effective strategy to prevent or slow the progression of T2D.MethodsWe aimed to assess the interaction between dietary and genetic factors on metabolic disease-related traits in 200 healthy Brazilian young adults. Dietary intake was assessed using 3-day food records. Ten metabolic disease-related single nucleotide polymorphisms (SNPs) were used to construct a metabolic-genetic risk score (metabolic-GRS).ResultsWe found significant interactions between the metabolic-GRS and total fat intake on fasting insulin level (Pinteraction = 0.017), insulin-glucose ratio (Pinteraction = 0.010) and HOMA-B (Pinteraction = 0.002), respectively, in addition to a borderline GRS-fat intake interaction on HOMA-IR (Pinteraction = 0.051). Within the high-fat intake category [37.98 ± 3.39% of total energy intake (TEI)], individuals with ≥ 5 risk alleles had increased fasting insulin level (P = 0.021), insulin-glucose ratio (P = 0.010), HOMA-B (P = 0.001) and HOMA-IR (P = 0.053) than those with < 5 risk alleles.ConclusionOur study has demonstrated a novel GRS-fat intake interaction in young Brazilian adults, where individuals with higher genetic risk and fat intake had increased glucose and insulin-related traits than those with lower genetic risk. Large intervention and follow-up studies with an objective assessment of dietary factors are needed to confirm our findings.

Correlation between Insulin Resistance and LVEF in non Diabetic Chronic Heart Failure Patients admitted in a Tertiary Care Hospital

Background: Insulin resistance is a well-established composite index of systemic inflammatory and metabolic disorders. A wide variety of methods like, HOMA-IR (Homeostatic model assessment insulin resistance), FGIR (Fasting glucose insulin ratio), ISI-Composite (an index of whole body insulin sensitivity), QUICKI (quantitative insulin sensitivity check index) etc are available for assessing IR. Objective: To find out the correlation between insulin resistance and LVEF in non diabetic chronic heart failure patients. Methodology: This cross sectional study was carried out in the Department of Cardiology in Bangabandhu Sheikh Mujib Medical University, Shahbagh, Dhaka from February, 2019 to June, 2020. Patients admitted with chronic heart failure with reduced ejection fraction were included in this study. Patients with diabetic, prediabetic and patient who did not give written informed consent were excluded in this study. Results: LVEF 25-29% was 16 patients out of which 10(66.7%) had significant insulin resistance. LVEF 30- 34% was found in 28 patients, among them 16(41.0%) had no insulin resistance. LVEF 35-39% was found in 19 patients out of which 18(46.2%) had no insulin resistance. The difference was statistically significant (p&lt;0.05). A negative correlation (r=-0.340; p=0.006) was found between insulin resistance and LVEF. Conclusion: Majority non diabetic chronic heart failure patients had no insulin resistance. Significant negative correlation was found between insulin resistance and LVEF.&#x0D; University Heart Journal Vol. 17, No. 2, Jul 2021; 99-102

Surrogate markers and predictors of insulin resistance in Nigeria patients with Type 2 diabetes mellitus

Background: This study set out to identify and compare surrogate markers of insulin resistance (IR) in males and females and compare the prevalence of IR using different surrogate markers. Methods: The study was an analytical cross-sectional hospital-based study among Nigerians with Type 2 diabetes mellitus (T2DM). A total of 234 (131 T2DM and 103 healthy) persons were invited to participate in the study. One hundred and ninety-nine persons completed the study. The following anthropometric measurements were taken (height [m], weight [kg], waist circumference [cm], and hip circumference [cm]). IR score (IRS) was derived using these six measurements: fasting basal insulin, fasting C-peptide, glucose-insulin ratio, quantitative insulin sensitivity check index, homeostasis model assessment (HOMA-IR), HOMA-c-peptide. Results: Using an IRS of &gt;11 as criteria for IR, 52 (41.6%) of T2DM, and 21 (28.4%) of the control group were found to have IR. Forty-five percent of the DM females and 36.4% of DM males had IR, respectively, whereas 31.8% of the control females and 23.3% of control males had IR, respectively. Visceral Adiposity Index (VAI) had the best predictive value with the highest area under the receiver operating characteristic curve (0.648). Conclusion: The prevalence of IR is nonsignificantly higher in females than males. VAI is the best surrogate marker to predict the presence of IR among the male study participants, while waist circumference is the best surrogate marker to predict the presence of IR among the female study participants.

Effect of Vitamin D Supplementation on Ovulation among Women with PCO

Abstract Background: Polycystic Ovarian Syndrome (PCOS) is prevalent worldwide among female endocrine disorder, affect-ing nearly 5% to 12% of child bearing age women. PCOS is considered as the most common cause of an ovulatory infertility and it has clinical symptoms include an ovulation with or without oligo-ovulation, infertility, menstrual irregularity, polycystic ovaries and hyperandrogenism. Aim of Study: This study aim was to explore and compare the effects of Vitamin D supplementation vs. placebo on ovulation in women with PCOS. Patients and Methods: 400 women with PCOSwere in-cluded in this randomized controlled trial. Patients were randomly allocated into 2 groups as follows: Vitamin D group (n=200) and control group (n=200). Follow-up was done after three months by measuring change vitamin D level, change in insulin resistance as measured by fasting glucose and fasting insulin ratio, change in testosterone level, and change in free androgen index. Results: 200 of them allocated to control group. Among 200 women in vitamin D group, 160 women had vitamin D deficiency and the other 40 had normal vitamin D level. FBS, fasting insulin and HOMA-IR were statistically significantly higher in the vitamin D deficient subgroup and the control group compared to the normal vitamin D subgroups; 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 and hormonal profile. There were statistically significant differences between groups as regards FBS, fasting insulin, HOMA-IR, FAI, Testosterone, TC and LDL-C. Conclusion: We concluded that vitamin D seems to be a contributing etiopathogenic factor in anovulatory, metabolic and hormonal aberrations in women with PCOS that might have a potential adjuvant role to standard induction of ovulation regimen.

Revisiting the pathogenic role of insulin resistance in Duchenne muscular dystrophy cardiomyopathy subphenotypes.

Duchenne muscular dystrophy (DMD) is known to impact the subepicardial layer of the myocardium through chronic inflammation. Recent animal studies have shown predominant subendocardial involvement in rats with DMD. The primary outcome parameter was to determine by cardiovascular MRI (CMR) if two differential patterns of myocardial involvements exist in DMD; the secondary outcome parameters were to correlate the observed pattern with metabolic markers such as insulin resistance measures. Forty patients with DMD were screened using CMR to determine which of them had predominantly subendocardial dysfunction (SENDO group), or subepicardial/midmyocardial involvement (SEPMI group). Patients were subjected to body mass index measurement, serum creatinine kinase, serum lactate dehydrogenase enzyme, fasting glucose-insulin ratio (FGIR), full lipid profile, left ventricular ejection fraction (LVEF), left ventricle E/E´ ratio (the ratio of early mitral inflow velocity to average early diastolic velocities of the basal septum and mitral annulus) for left ventricle diastolic function, and myocardial layer strain discriminating echocardiography (MLSD-STE). Results: 26 patients displayed SENDO while 34 displayed SEPMI. SENDO group displayed overt insulin resistance; (FGIR (SENDO: 7 ± 1 vs. SEPMI: 5 ± 1, P < 0.001). FGIR was negatively correlated with Subendocardial Global Longitudinal Strain (ENDO-LS) with r = -0.75. DMD does not seem to influence the heart uniformly; DMD cardiomyopathy probably has two separate phenotypes with different mechanisms. Insulin resistance might be implicated in its pathogenesis and its reversal may help to slow disease progression.

Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. Pilot, randomized study analyzed according to intention-to-treat analysis. Pediatric cardiac ICU. Infants (≤ 6 mo) undergoing cardiopulmonary bypass. Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

A study on carotid artery intima-media thickness and metabolic risk factors in overweight and obese Indian children.

Carotid intima-media thickness (CIMT) serves as an early marker of atherosclerosis. Data on obesity-related risk factors and their association with carotid intima-media thickness among overweight and obese children are lacking. To compare CIMT of overweight and obese children with CIMT of normal BMI children. To compare various anthropometric and metabolic risk factors associated with increased CIMT among overweight and obese children. A descriptive study in a paediatric department of a tertiary care hospital including 50 age-matched normal BMI children and 50 overweight and obese children. Anthropometric data, blood pressure, CIMT (by B-mode ultrasonography), fasting blood sugar, fasting Insulin, fasting lipid profile, TSH, and FT4 were collected. HOMA-IR and fasting glucose-insulin ratio (FGIR) were calculated for insulin resistance. Cutoff for high CIMT was derived using ROC curve analysis. Overweight and obese children had higher mean CIMT than normal BMI children (0.5 ± 0.1mm vs 0.34 ± 0.05mm, respectively, P < 0.001). ROC analysis revealed 0.45mm as the cutoff for high CIMT. Among overweight and obese children, 31 children (62%) had high CIMT. Among metabolic risk factors for increased CIMT, only FGIR was observed to be significant. Compared to overweight and obese children with normal CIMT, those with higher CIMT had low FGIR value (5.2 ± 2.2mm vs 6.9 ± 2.6mm, respectively, P < 0.05). Overweight and obese children had significantly higher CIMT than controls. Even among overweight and obese children, those with increased CIMT had low FGIR (implying insulin resistance) compared to those with normal CIMT.

Impact of 3-year changes in fasting insulin and insulin resistance indices on incident hypertension: Tehran lipid and glucose study

BackgroundTo examine the association between changes in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin-glucose ratio (IGR) levels, over approximately 3 years with incident hypertension.MethodsA total of 2814 Iranian participants (1123 men) without hypertension and known diabetes at baseline and the first examination were followed for a median of 6.32 years. The associations between quartiles of changes in fasting insulin and IR indices with incident hypertension were assessed using multivariate Cox proportional hazard regression analyses with first quartile as reference. The models were adjusted for baseline values of insulin or each IR index, and age, sex, smoking, physical activity, educational levels, marital status, history of cardiovascular diseases, baseline levels of systolic and diastolic blood pressures, estimated glomerular filtration rate, triglycerides, total cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose (only for insulin change) and both body mass index (BMI) per se, and its change. Akaike’s information criteria (AIC) was applied as indicator for goodness of fit of each predictive model. The discrimination ability of models was calculated using the Harrell’s C statistic.ResultsDuring the study, 594 incident cases of hypertension (253 men) were identified. The 4th quartile of changes in insulin, HOMA-IR, and IGR showed hazard ratios (95% confidence interval) of 1.31 (1.01–1.69), 1.18 (0.92–1.52), and 1.53 (1.18–1.98) for hypertension, respectively, in fully-adjusted models. Changes in fasting insulin levels and IR indices showed significant increasing trends for incident hypertension, moving from 1st to 4th quartiles (all P-values < 0.05). Focusing on model fitness, no superiority was found between changes in fasting insulin, HOMA-IR, and IGR to predict incident hypertension. The discriminatory powers of changes in fasting insulin and IR indices as assessed by C index were similar (i.e. about 80%).ConclusionChanges in fasting insulin and IR indices were significantly associated with developing hypertension among normotensive population even after considering BMI changes.

18 Improving the Safety of Insulin Treatment for Hyperkalemia

This study’s objective was to determine key clinical predictors of hypoglycemia following insulin therapy for the emergent management of hyperkalemia and derive a safe insulin treatment strategy. We performed a retrospective observational study across 4 hospitals that was inclusive of consecutive ED and hospitalized adults that received insulin for the management of hyperkalemia over a 12-month period. We excluded patients treated in the setting of cardiac arrest. The primary outcome was hypoglycemia (glucose < 70 mg/dL) following treatment. We performed multivariate logistic regression to determine clinical predictors of hypoglycemia. We then tested the pre-treatment glucose-insulin ratio (glucose divided by planned weight-based insulin dose) and tested its ability to alert clinicians to the risk of treatment related hypoglycemia. The study included 1,307 patients, of whom 507 were in the ED and 800 were inpatient. The mean pre-treatment K was 6.1 (SD 0.76). Hypoglycemic events occurred 238 times (18.4%). Patients in the ED had the highest rate of hypoglycemic events (23.3%) compared to hospitalized patients (15.3%, p<0.001). Patient’s with a pre-treatment glucose < 100 mg/dl had 31.0% the rate of hypoglycemia compared to those with higher glucose levels (13.7%, p<0.001). Adjusting for multiple clinical covariates, male sex (OR 1.4, 95% CI 1.1 - 2.0), insulin dosing > 0.1 units/kg (OR 1.5, 95% CI 1.1 - 2.1), and pre-treatment glucose < 100 mg/dl (OR 2.4, 95% CI 1.8 - 3.2) were significant predictors of hypoglycemia. The median glucose-insulin ratio was 1310 [IQR 915, 2025]. A ratio < 1310 identified 71.9% of hypoglycemic events (OR 3.0, 95% CI 2.2 - 4.1). Male sex, insulin dose, and pre-treatment glucose are predictors of hypoglycemia in the treatment of hyperkalemia. Attention to the simple ratio of the pre-treatment glucose to weight-based insulin dose identifies most patients at risk of hypoglycemia and can alert clinicians to adjust glucose and insulin administration proactively.