Low-grade inflammation in persons with recently diagnosed type 2 diabetes: The role of abdominal adiposity and putative mediators.

AIMS: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities. MATERIALS AND METHODS: We measured waist circumference, clinical characteristics, and inflammatory markers i.e. tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP), in >9000 persons with recently diagnosed T2D. We applied multiple mediation analysis using structural equation modelling, with adjustment for age and sex. RESULTS: Waist circumference as a proxy for abdominal adiposity was positively associated with all inflammatory markers. Hence, a one-standard deviation (SD) increase in waist circumference (SD = 15 cm) was associated with a 22%, 35%, and 46% SD increase in TNF-α (SD = 1.5 pg/mL), IL-6 (SD = 4.4 pg/mL), and hsCRP (SD = 6.9 mg/L), respectively. The level of hyperinsulinaemia assessed by fasting C-peptide was quantitatively the most important mediator, accounting for 9%-25% of the association between abdominal adiposity and low-grade inflammation, followed by low physical activity (5%-7%) and high triglyceride levels (2%-6%). Although mediation of adiposity-induced inflammation by greater comorbidity and higher glycated haemoglobin levels reached statistical significance, their impact was minor (1%-2%). CONCLUSIONS: In persons with recently diagnosed T2D, there was a clear association between abdominal adiposity and low-grade inflammation. A considerable part (20%-40%) of this association was mediated by other factors, with hyperinsulinaemia as a potentially important driver of adiposity-induced inflammation in T2D.

Dietary and lifestyle indices for hyperinsulinemia and colorectal cancer risk: a case-control study.

BACKGROUND: The incidence of colorectal cancer (CRC) has increased in Iran, and determining the dietary patterns that can contribute to reducing or increasing the risk of CRC will help better control this disease. Therefore, in the current study, we assessed the association between the empirical lifestyle index for hyperinsulinemia (ELIH) and the empirical dietary index for hyperinsulinemia (EDIH) with the CRC odds. METHODS: The present case (n = 71)-control (n = 142) study was carried out in several CRC surgical units of hospitals in Tehran, Iran. A semi-quantitative food frequency questionnaire containing 168 items was used to assess participants' dietary intakes. The EDIH and ELIH scores were calculated by food groups and some variables such as body mass index and physical activity. Logistic regression models were applied to evaluate the association between the EDIH and ELIH scores with CRC odds. RESULTS: According to baseline features of the study participants, there were significant differences between the controls and cases in ELIH score, fiber intake, taking aspirin, and family history of CRC in first- and second-degree relatives. Also, we found that the odds of CRC increased significantly in the last tertile compared to the first tertile in EDIH and ELIH in the adjusted model (odds ratio (OR) = 3.12; 95% confidence interval (CI): 1.30-7.48 and OR = 4.72; 95% CI: 1.15-19.39, respectively). CONCLUSIONS: In conclusion, the result of this study indicated that CRC odds was significantly greater in subjects with higher EDIH and ELIH scores. Also, according to the results of this study, lifestyle and diet with insulinemic potential can influence the CRC risk.

The Rising Incidence of Hyperinsulinemic Hypoglycemia: Connection With Maternal Health.

OBJECTIVE: Due to a perceived rise in hyperinsulinemic hypoglycemia (HH) cases over time, notably during the COVID-19 pandemic, institutional experiences between 2013 and 2021 were reviewed to evaluate trends, characteristics, and outcomes in children with HH. METHODS: Charts of all children diagnosed with HH during the study period and evaluated by Pediatric Endocrinology were reviewed. HH was defined per Pediatric Endocrine Society guidelines. Regression analysis compared rates of change in HH cases and maternal risk factors over time. RESULTS: The incidence of HH began to rise in April 2016 and became significant in March 2017 (P < .001), with a more rapid rate of rise during the first year of the COVID-19 pandemic (P < .001). Seventy-four children with HH were identified over 9 years; 43% (n = 32) were diagnosed in 2020-2021. Maternal hypertensive disorders demonstrated longitudinal association with hyperinsulinism cases (P < .001). CONCLUSION: While HH diagnoses were on the rise for much of the 9-year study period, nearly half of all infants were diagnosed during the COVID-19 pandemic in 2020 to 21. The trends in HH diagnoses correlated with maternal hypertensive disorders. More studies exploring the roles of maternal health, hypertension, and stress and development of HH in offspring are needed.

High insulinemic potential of diet and lifestyle is associated with increased risk of chronic kidney disease incident in adults.

BACKGROUND: The role of higher insulinemic effects of dietary pattern and lifestyle factors on the risk of chronic kidney disease (CKD) is not well-studied. In the current study, we aimed to investigate the relationship between the insulinemic potential of diet and lifestyle with the risk of CKD in adults. METHODS: A total of 6044 individuals without CKD, aged>18 years, were recruited from among participants of the Tehran Lipid and Glucose Study (third and fourth surveys) and followed a mean of 6.03 years(follow-up rate:94.95%). The dietary intake data were collected using a food frequency questionnaire. The insulinemic potential of diet and lifestyle was determined based on four empirical indices, including the empirical dietary index for hyperinsulinemia (EDIH), the empirical dietary index for insulin resistance (EDIR), the empirical lifestyle index for hyperinsulinemia (ELIH), and the empirical lifestyle index for insulin resistance (ELIR). RESULTS: Mean ± SD age of all study participants (54.3% women) was 37.8 ± 12.8 years. During the 6.03 years of follow-up (46,889.8 person-years), 1216(20.1%) new cases of CKD were identified. According to the multivariable-adjusted model, the risk of CKD incident is increased across quintiles of EDIR (OR = 1.29;95% CI: 1.06-1.57), ELIH (OR = 1.35; 95%CI: 1.10-1.67), and ELIR (OR = 1.24; 95%CI:1.02-1.51). However, no significant relationship was found between the EDIH score and the risk of CKD. CONCLUSION: Results of the current study showed that dietary pattern with a high EDIR score and a lifestyle with higher ELIH and ELIR scores may be related to increasing the risk of CKD incident. However, no significant association was observed between EDIH score and CKD incident.

Cancer and its predictors in Chinese adults with newly diagnosed diabetes and impaired glucose tolerance (IGT): a 30-year follow-up of the Da Qing IGT and Diabetes Study.

BACKGROUND: We aimed to explore if hyperglycaemia and hyperinsulinemia in the diabetes and prediabetes population were associated with increased risk of cancer occurence. METHODS: Overall, 1700 participants with different glycaemic statuses were screened from the 110,660 residents of Da-Qing, China, in 1985. They were followed up to 30 years to access cancer outcomes. RESULTS: Cancer was identified in 15.2% (259/1700) of the participants. The incidence of cancer in the normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes groups was 6.06, 6.77, and 7.18 per 1000 person-years, respectively (P = 0.02). In the Fine-Gray model with all cause death as competing risk, compared with the NGT controls, both IGT and diabetes groups demonstrated significantly higher risk of cancer (for the IGT group, adjusted hazard ratio (aHR) = 1.77, 95% CI 1.38-2.27, P < 0.0001; for the diabetes, aHR = 3.34, 95% CI 2.64-4.22, P < 0.0001). Among the IGT participants, progress to diabetes (aHR = 2.28, 95%CI 1.24-4.20, P = 0.008) and insulin-area under the curve at baseline (for 1 SD increase, aHR = 1.39, P = 0.02) were also associated with the risk of cancer after adjustment of covariables. CONCLUSIONS: Hyperglycaemia in patients with diabetes, hyperinsulinemia, and progression to diabetes in people with IGT is significantly associated with the long-term increased risk of cancer occurrence.

Dietary and lifestyle indices for hyperinsulinemia with the risk of obesity phenotypes: a prospective cohort study among Iranian adult population.

BACKGROUND: Previous studies have cited insulin-related disorders, including hyperinsulinemia, as one of the main causes of obesity risk and metabolic disorders. We aimed to investigate the association of the Empirical Dietary Index for Hyperinsulinemia (EDIH) and Empirical Lifestyle Index for Hyperinsulinemia (ELIH) with the risk of obesity phenotypes among Iranian adults. METHODS: Present study was conducted on 2705 subjects, including 1604 metabolically healthy normal weights (MHNW) and 1101 metabolically healthy obesity (MHO) individuals. Obesity phenotypes, including MHNW, MHO, metabolically unhealthy normal weights (MUNW), and metabolic unhealthy obesity (MUO), were determined using the criteria of the Joint International statement (JIS) for metabolic syndrome. Dietary intake data from the previous year was gathered using a food frequency questionnaire. Cox proportional hazard regression was used to estimate the hazard ratio and 95% confidence intervals (HRs and 95% CIs) of obesity phenotypes incident across tertiles of EDIH and ELIH scores. RESULTS: The mean ± SD of age and BMI of all participants were 33.5 ± 12.2 years and 24.3 ± 3.8 kg/m2, respectively. In the multivariable-adjusted model, a higher ELIH score was associated with a greater risk for incidence of MUO (HR: 3.47, 95%CI: 2.54-4.74; Ptrend = < 0.001) and MHO (HR: 3.61, 95%CI: 2.73-4.77; Ptrend = < 0.001). Also, a higher score of EDIH was related to an increased risk of MUO incidence (HR: 1.35, 95%CI: 1.02-1.79; P for trend = 0.046). However, there was no significant association between a higher score of EDIH and the risk of MHO. CONCLUSION: Our findings revealed that a high insulinemic potential of diet and lifestyle, determined by EDIH and ELIH indices, may be related to an increase in the simultaneous occurrence of obesity with metabolic disorders in Iranian adults.

Do variations in insulin sensitivity and insulin secretion in pregnancy predict differences in obstetric and neonatal outcomes?

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is generally defined based on glycaemia during an OGTT, but aetiologically includes women with defects in insulin secretion, insulin sensitivity or a combination of both. In this observational study, we aimed to determine if underlying pathophysiological defects evaluated as continuous variables predict the risk of important obstetric and neonatal outcomes better than the previously used dichotomised or categorical approaches. METHODS: Using data from blinded OGTTs at mean gestational week 28 from five Hyperglycemia and Adverse Pregnancy Outcome study centres, we estimated insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral disposition index [DI]) in 6337 untreated women (1090 [17.2%] with GDM as defined by the International Association of Diabetes and Pregnancy Study Groups). Rather than dichotomising these variables (i.e. GDM yes/no) or subtyping by insulin impairment, we related insulin secretion and sensitivity as continuous variables, along with other maternal characteristics, to obstetric and neonatal outcomes using multiple regression and receiver operating characteristic curve analysis. RESULTS: Stratifying by GDM subtype offered superior prediction to GDM yes/no only for neonatal hyperinsulinaemia and pregnancy-related hypertension. Including the DI and the Matsuda score significantly increased the area under the receiver operating characteristic curve (AUROC) and improved prediction for multiple outcomes (large for gestational age [AUROC 0.632], neonatal adiposity [AUROC 0.630], pregnancy-related hypertension [AUROC 0.669] and neonatal hyperinsulinaemia [AUROC 0.688]). Neonatal hypoglycaemia was poorly predicted by all models. Combining the DI and the Matsuda score with maternal characteristics substantially improved the predictive power of the model for large for gestational age, neonatal adiposity and pregnancy-related hypertension. CONCLUSION/INTERPRETATION: Continuous measurement of insulin secretion and insulin sensitivity combined with basic clinical variables appeared to be superior to GDM (yes/no) or subtyping by insulin secretion and/or sensitivity impairment in predicting obstetric and neonatal outcomes in a multi-ethnic cohort. Graphical abstract.

Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study.

INTRODUCTION: Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents. OBJECTIVES: To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents. METHODS: 81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses. RESULTS: Two groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3-4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1-2). (2) Metabolites associated with obesity status: obese adolescents (groups 2-4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1). CONCLUSIONS: Obesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

Association of the insulinemic potential of diet and lifestyle with risk of diabetes incident in Tehranian adults: a population based cohort study.

BACKGROUND: We aimed to assess the associations between insulinemic potential of diet and lifestyle and the risk of diabetes incident, using four empirical indices including the empirical dietary index for hyperinsulinemia (EDIH), the empirical dietary index for insulin resistance (EDIR), empirical lifestyle index for hyperinsulinemia (ELIH), and empirical lifestyle index for insulin resistance (ELIR). METHODS: A total of 3734 individuals, aged ≥ 20 years old, who were free of diabetes at baseline (2008-2011), were followed for 6.2 years (2015-2018) to ascertain incident diabetes. The food frequency questionnaire was used to collect dietary intakes at baseline. Odds ratio (OR) of diabetes were calculated across quartiles of EDIH, EDIR, ELIH, and ELIR using logistic regression, which controlled for confounding factors. RESULTS: The mean ± SD age and BMI of individuals (45.1 % male) were 40.9 ± 12.0 years and 27.1 ± 4.1 kg/m2, respectively. At the end of follow-up, 253 (6.8 %) diabetes cases were identified. In the multivariable-adjusted model, individuals in the highest quartile of EDIR (1.58;95 %CI:1.03-2.44, P for trend = 0.025), ELIH (1.89;95 %CI:1.20-2.97, P for trend = 0.004), and ELIR (1.74; 95 %CI:1.11-2.72, P for trend = 0.031) had increased the risk of diabetes. However, no significant associations were found between the score of EDIH and diabetes incident. CONCLUSIONS: Higher adherence to EDIR, ELIH, and ELIR scores were associated with increased risk of diabetes, while no significant association was found between EDIH score and diabetes incident.

Hyperinsulinemia during pregnancy across varying degrees of glucose tolerance: An examination of the Kraft database.

AIM: Hyperinsulinemia is a known underlying driver of metabolic disease; however, its role in pregnancy complications is less understood due to insulin measurement not being a part of standard clinical assessments. This study aimed to characterize hyperinsulinemia in pregnancy by gestational diabetes (GD) status using Kraft methodology. METHODS: We analyzed historical data from 926 pregnant women who underwent a 100-g oral glucose tolerance test (OGTT), which included insulin measurement. Subjects were grouped by GD diagnosis status ("Normal", "Borderline", "GD") and insulin responses over 3 h were compared between groups. RESULTS: "GD" was diagnosed in 20.3% of the subjects and 13.8% were grouped as "Borderline." The prevalence of hyperinsulinemia using the Kraft algorithm was 33.1% for Kraft IIB and 42.0% for Kraft III. Compared to normal glucose-tolerant mothers, individuals from the "Borderline" group had an exacerbated insulin response, although not to the same magnitude as those with "GD." CONCLUSIONS: Dynamic OGTT insulin measurement during pregnancy may provide a meaningful assessment of metabolic risk among women who would otherwise not be diagnosed with GD.

Lipoprotein(a) and Hyperinsulinemia in Healthy Normal-weight, Prepubertal Mexican Children.

Background. Given the numerous gaps in our knowledge about the biological interactions of lipoprotein(a) [Lp(a)], we determined whether Lp(a) was associated with hyperinsulinemia in healthy normal-weight, prepubertal children.Methods. A total of 131 healthy normal-weight Mexican children aged 6 to 9 years at Tanner stage 1 who were born appropriate for gestational age were enrolled in a case-control study. Children with hyperinsulinemia were allocated into the case group (n = 32), and children with normal insulin levels were allocated into the control group (n = 99). Birth weight, age, and body mass index were matching criteria. Multivariate logistic regression analysis was used to compute the odds ratio (OR) between Lp(a) and both hyperinsulinemia and insulin resistance. Furthermore, a multivariate linear regression analysis was performed to evaluate the association between Lp(a) and both insulin levels and HOMA-IR. Both models were adjusted by sex, age, birth weight, and body mass index.Results. The median (25-75 percentile) serum levels of Lp(a) [20.0 (13.7-29.6) versus 14.6 (10.6-26.7) mg/dL, p = .003] and insulin [24.5 (6.0-30) versus 7.9 (4.3-9.0) µU/L, p < .0005] were higher in the case group than in the control group. The logistic regression analysis showed that Lp(a) was associated with hyperinsulinemia (OR 5.86; 95%CI 2.5-13.6, p < .0005) and insulin resistance (OR 2.01; 95%CI 1.1-9.9, p = .004). In addition, the linear regression analysis showed a significant association between serum Lp(a) and insulin levels (ß 11.1; 95%CI 1.8-10.9, p < .0001) and the HOMA-IR index (ß 2.606; 95%CI 2.3-2.9, p < .0005).Conclusion. Lp(a) was associated with hyperinsulinemia and insulin resistance in healthy normal-weight, prepubertal children.

Risk Assessment and Determination of Factors That Cause the Development of Hyperinsulinemia in School-Age Adolescents.

Background and Objectives: Hyperinsulinemia and insulin resistance are not synonymous; if the risk of developing insulin resistance in adolescents is monitored, they do not necessarily have hyperinsulinemia. It is considered a condition of pre-diabetes and represents a condition of increased risk of developing DM (diabetes mellitus); it can exist for many years without people having the appropriate symptoms. This study aims to determine the risk of developing hyperinsulinemia at an early age in adolescents by examining which factors are crucial for its occurrence. Materials and Methods: The cross-sectional study lasting from 2019 to 2021 (2 years) was realized at the school children's department in the Valjevo Health Center, which included a total of 822 respondents (392 male and 430 female) children and adolescents aged 12 to 17. All respondents underwent a regular, systematic examination scheduled for school children. BMI is a criterion according to which respondents are divided into three groups. Results: After summary analyzes of OGTT test respondents and calculated values of HOMA-IR (homeostatic model assessment for insulin resistance), the study showed that a large percentage of respondents, a total of 12.7%, are at risk for hyperinsulinemia. The research described in this paper aimed to use the most popular AI (artificial intelligence) model, ANN (artificial neural network), to show that 13.1% of adolescents are at risk, i.e., the risk is higher by 0.4%, which was shown by statistical tests as a significant difference. Conclusions: It is estimated that a model using three different ANN architectures, based on Taguchi's orthogonal vector plans, gives more precise and accurate results with much less error. In addition to monitoring changes in each individual's risk, the risk assessment of the entire monitored group is updated without having to analyze all data.

Glycemic Status, Insulin Resistance, and Risk of Pancreatic Cancer Mortality in Individuals With and Without Diabetes.

INTRODUCTION: The impact of glycemic status and insulin resistance on the risk of pancreatic cancer in the nondiabetic population remains uncertain. We aimed to examine the association of glycemic status and insulin resistance with pancreatic cancer mortality in individuals with and without diabetes. METHODS: This is a cohort study of 572,021 Korean adults without cancer at baseline, who participated in repeat screening examinations which included fasting blood glucose, hemoglobin A1c, and insulin, and were followed for a median of 8.4 years (interquartile range, 5.3 -13.2 years). Vital status and pancreatic cancer mortality were ascertained through linkage to national death records. RESULTS: During 5,211,294 person-years of follow-up, 260 deaths from pancreatic cancer were identified, with a mortality rate of 5.0 per 10 person-years. In the overall population, the risk of pancreatic cancer mortality increased with increasing levels of glucose and hemoglobin A1c in a dose-response manner, and this association was observed even in individuals without diabetes. In nondiabetic individuals without previously diagnosed or screen-detected diabetes, insulin resistance and hyperinsulinemia were positively associated with increased pancreatic cancer mortality. Specifically, the multivariable-adjusted hazard ratio (95% confidence intervals) for pancreatic cancer mortality comparing the homeostatic model assessment of insulin resistance ≥75th percentile to the <75th percentile was 1.49 (1.08-2.05), and the corresponding hazard ratio comparing the insulin ≥75th percentile to the <75th percentile was 1.43 (1.05-1.95). These associations remained significant when introducing changes in insulin resistance, hyperinsulinemia, and other confounders during follow-up as time-varying covariates. DISCUSSION: Glycemic status, insulin resistance, and hyperinsulinemia, even in individuals without diabetes, were independently associated with an increased risk of pancreatic cancer mortality.

Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine and Head and Neck Disease Site Working Group, Part 2 of 2: Perioperative Management and Outcomes of Pheochromocytoma and Paraganglioma.

This is the second part of a two-part review on pheochromocytoma and paragangliomas (PPGLs). In this part, perioperative management, including preoperative preparation, intraoperative, and postoperative interventions are reviewed. Current data on outcomes following resection are presented, including outcomes after cortical-sparing adrenalectomy for bilateral adrenal disease. In addition, pathological features of malignancy, surveillance considerations, and the management of advanced disease are also discussed.

NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells.

BACKGROUND: The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progression of breast cancer. Nuclear receptor subfamily 2, group F, member 2 (NR2F2) has been implicated in the development of breast cancer, however its contribution to insulin-induced EMT in breast cancer remains unclear. METHODS: Overexpression and knockdown of NR2F2 were used in two breast cancer cell lines, MCF-7 and MDA-MB-231 to investigate potential mechanisms by which NR2F2 leads to insulin-mediated EMT. To elucidate the effects of insulin and signaling events following NR2F2 overexpression and knockdown, Cells' invasion and migration capacity and changes of NR2F2, E-cadherin, N-cadherin and vimentin were investigated by real-time RT-PCR and western blot. RESULTS: Insulin stimulation of these cells increased NR2F2 expression levels and promoted cell invasion and migration accompanied by alterations in EMT-related molecular markers. Overexpression of NR2F2 and NR2F2 knockdown demonstrated that NR2F2 expression was positively correlated with cell invasion, migration and the expression of N-cadherin and vimentin. In contrast, NR2F2 had an inverse correlation with E-cadherin expression. In MDA-MB-231, both insulin-induced cell invasion and migration and EMT-related marker alteration were abolished by NR2F2 knockdown. CONCLUSIONS: These results suggest that NR2F2 plays a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT.

Metabolic syndrome and pre-eclampsia.

OBJECTIVE: To evaluate the association between different pre-eclampsia (PE) phenotypes and the development of metabolic syndrome postpartum, in order to identify the subgroup of formerly pre-eclamptic women with a worse cardiovascular risk profile requiring tailored postpartum follow-up. METHODS: This was a cohort study of 1102 formerly pre-eclamptic women in whom cardiovascular and cardiometabolic evaluation was performed at least 3 months postpartum. Women were divided into four subgroups based on PE resulting in delivery before 34 weeks (early-onset (EO)) or at or after 34 weeks (late onset (LO)) of gestation and whether they delivered a small-for-gestational-age (SGA) neonate. Metabolic syndrome was diagnosed as the presence of hyperinsulinemia along with two or more of: body mass index ≥ 30 kg/m2 ; dyslipidemia; hypertension; and microalbuminuria or proteinuria. Data were compared between groups using ANOVA after Bonferroni correction. Odds ratios (OR) were calculated using logistic regression to determine the association between metabolic syndrome and the four subgroups. We constructed receiver-operating characteristics curves and computed the area under the curve (AUC) to quantify the ability of different obstetric variables to distinguish between women who developed metabolic syndrome and those who did not. RESULTS: The prevalence of metabolic syndrome was higher in women with EO-PE and SGA (25.8%) than in those with EO-PE without SGA (14.7%) (OR 2.01 (95% CI, 1.34-3.03)) and approximately five-fold higher than in women with LO-PE with SGA (5.6%) (OR 5.85 (95% CI, 2.60-13.10)). In women with LO-PE, the prevalence of metabolic syndrome did not differ significantly between women with and those without SGA. Multivariate analysis revealed that a history of SGA, a history of EO-PE and systolic blood pressure at the time of screening are the best predictors of developing metabolic syndrome postpartum. The AUC of the model combining these three variables was 74.6% (95% CI, 70.7-78.5%). The probability of the presence of metabolic syndrome was calculated as: P = 1/(1 + e-LP ), where LP is linear predictor = -8.693 + (0.312 × SGA (yes = 1)) + (0.507 × EO-PE (yes = 1)) + (0.053 × systolic blood pressure). CONCLUSIONS: The incidence of metabolic syndrome postpartum was associated more strongly with EO-PE in combination with SGA as compared with LO-PE or EO-PE without SGA. Both time of onset of PE and fetal growth affect the risk of metabolic syndrome after a pre-eclamptic pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Temporal relationship between body mass index and triglyceride-glucose index and its impact on the incident of hypertension.

BACKGROUND AND AIMS: Obesity and insulin levels can influence each other by metabolism. However, their temporal sequences and influence on hypertension are generally unknown, especially in Chinese adults. Recently, some scholars have proposed that triglycerides-glucose index (TyG) is an important indicator of insulin resistance. The study aims to describe the relationship between body mass index (BMI) and TyG index and its impact on hypertension. METHODS AND RESULTS: A total of 4081 adults (56.33% women) without antihypertensive, hypoglycemic or lipid-lowering medications were selected for the present study. Measurements of BMI and TyG index were obtained twice from 2012 to 2017. Cross-lagged panel analysis was used to describe the temporal sequences between BMI and TyG index, and the effect of their temporal relationship patterns on hypertension was explored through mediation analysis. After adjusting for confounding factors (age, sex, ethnicity et al.), the cross-lagged path coefficient from baseline BMI to follow-up TyG (ρ2 = 0.135, P < 0.001) was significantly greater than the path coefficient from baseline TyG to follow-up BMI (ρ1 = 0.043, P < 0.001), and P < 0.001 for the difference between ρ1 and ρ2. Furthermore, the sensitivity analyses between women and men revealed identical findings. In addition, TyG index mediation effect on BMI-hypertension was estimated to be 38.45% (P < 0.001) in total population, 25.24% in women and 57.35% in men. CONCLUSION: These results provided evidence that the temporal relationship between BMI and insulin resistance is reciprocal and a higher BMI precedes hyperinsulinemia in Chinese adults. This relationship plays an essential role in the development of hypertension, while there is a difference between women and men.

Hyperinsulinemia and thyroid peroxidase antibody in Chinese patients with papillary thyroid cancer.

This study aimed to investigate if hyperinsulinemia and/or insulin resistance was correlated with the occurrence of papillary thyroid cancer (PTC) in a group of Chinese patients. 258 inpatients were included in the study. According to the postoperative pathology results, all subjects were divided into PTC (n = 153) and control groups (with benign thyroid nodules, n = 105). Body mass index (BMI), fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid-stimulating hormone (TSH), FT4, FT3, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb), serum uric acid (UA), and lipid levels. Fasting insulin levels, HOMA-IR values, TPOAb levels, serum TSH levels, and serum uric acid levels in the PTC group were higher than those in the control group (p < 0.05). However, no significant differences in age, gender, BMI, history of hypertension, and the levels of fasting plasma glucose, FT3, FT4, TGAb, total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were observed between the two groups (p > 0.05). After the multiple logistic regression analysis, the occurrence of PTC was positively associated with fasting insulin (odds ratio [OR] = 1.048, 95% confidence interval [CI]: 1.003-1.096, p = 0.037) and TPOAb levels (OR = 1.001, 95% CI: 1.000-1.002, p = 0.032). Moreover, TPOAb level was positively correlated with vague margin (r = 0.126, p = 0.045) and negatively correlated with homogeneous echo (r = -0.179, p = 0.004). However, fasting insulin levels were not correlated with pathological characteristics of PTC. Hyperinsulinemia and higher TPOAb levels might be the risk factors of PTC, but not disease severity in Chinese patients.

Endocrinopathies in paediatric-onset neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4) antibody.

The involvement of the diencephalic regions in neuromyelitis optica spectrum disorder (NMOSD) may lead to endocrinopathies. In this study, we identified the following endocrinopathies in 60% (15/25) of young people with paediatric-onset aquaporin 4-Antibody (AQP4-Ab) NMOSD: morbid obesity ( n = 8), hyperinsulinaemia ( n = 5), hyperandrogenism ( n = 5), amenorrhoea ( n = 5), hyponatraemia ( n = 4), short stature ( n = 3) and central hypothyroidism ( n = 2) irrespective of hypothalamic lesions. Morbid obesity was seen in 88% (7/8) of children of Caribbean origin. As endocrinopathies were prevalent in the majority of paediatric-onset AQP4-Ab NMOSD, endocrine surveillance and in particular early aggressive weight management is required for patients with AQP4-Ab NMOSD.

Impact of cigarette smoking on the relationship between body mass index and insulin: Longitudinal observation from the Bogalusa Heart Study.

OBJECTIVES: Despite the inverse association between cigarette smoking and body mass index (BMI), it is unknown whether the effect of smoking on insulin is mediated through decreased BMI. This study aims to examine the temporal relationship between BMI and insulin, the impact of smoking on this relationship and the mediation effect of BMI on the association between smoking and insulin levels. METHODS: The longitudinal cohort consisted of 1121 adults (807 white and 314 black participants, mean age, 42.0 years at follow-up) for whom BMI and fasting insulin were measured twice, with an average follow-up period of 17.1 years. Cross-lagged panel and mediation analysis models were used to examine the temporal relationship between BMI and insulin, and the mediation effect of BMI on the smoking-insulin association. RESULTS: Smoking was inversely associated with insulin (regression coefficient, -0.073; P = .015 at baseline and -0.121; P < .001 at follow-up), adjusting for age, race and gender. After additional adjustment for follow-up periods, the cross-lagged path coefficient from BMI to insulin (ß, 0.226; P < .001) was significantly greater than that from insulin to BMI (ß, -0.029; P = .208), with P < .001 for the difference. The path coefficient from BMI to insulin was significantly greater in non-smokers (ß, 0.273; P < .001) than in smokers (ß, 0.122; P = .046), with P = .013 for the difference. The mediation effect of BMI on the smoking-insulin association was estimated at 53.4% (P = .030) at baseline and 58.7% (P < .001) at follow-up. CONCLUSIONS: These findings suggest that cigarette smoking has a significant impact on the one-directional relationship from BMI to insulin. The insulin-lowering effect of smoking is predominantly mediated through decreased BMI as the result of smoking.