Joint association of weight-adjusted-waist index and physical activity with insulin resistance in adolescents: a cross-sectional study.

BACKGROUND: The weight-adjusted waist index (WWI) is a recently developed obesity metric, and the aim of this study was to investigate the relationship between physical activity (PA) and WWI and the homeostasis model assessment of insulin resistance (HOMA-IR) in adolescents, as well as the joint association of HOMA-IR. METHODS: This study was based on the National Health and Nutrition Survey conducted between 2013 and 2016 and included 1024 adolescents whose median age was 15.4. Multivariate linear regression was used to examine the associations between HOMA-IR and PA and WWI. Using generalized additive models, a potential nonlinear link between WWI and HOMA-IR was evaluated. Subgroup analysis was also carried out. RESULTS: The fully adjusted model revealed a positive association (ß: 0.48, 95% CI: 0.43, 0.53) between the WWI and HOMA-IR. The HOMA-IR was lower in physically active (ß: -0.16, 95% CI: -0.26, -0.05) participants versus inactive participants. Participants who had higher WWI and were not physically active (ß: 0.69; 95% CI: 0.56, 0.82) had the highest levels of HOMA-IR compared to participants who had lower WWI and were physically active. Subgroup analysis revealed that these correlations were similar in males and females. CONCLUSION: Our results demonstrated that higher WWI and PA were associated with a lower HOMA-IR and that WWI and PA had a combined association with HOMA-IR. The findings of this study are informative for the preventing insulin resistance in adolescents.

A Nonlinear Relation between Body Mass Index and Long-Term Poststroke Functional Outcome-The Importance of Insulin Resistance, Inflammation, and Insulin-like Growth Factor-Binding Protein-1.

Both high serum insulin-like growth factor-binding protein-1 (s-IGFBP-1) and insulin resistance (IR) are associated with poor functional outcome poststroke, whereas overweight body mass index (BMI; 25-30) is related to fewer deaths and favorable functional outcome in a phenomenon labeled "the obesity paradox". Furthermore, IGFBP-1 is inversely related to BMI, in contrast to the linear relation between IR and BMI. Here, we investigated s-IGFBP-1 and IR concerning BMI and 7-year poststroke functional outcome. We included 451 stroke patients from the Sahlgrenska Study on Ischemic Stroke (SAHLSIS) with baseline measurements of s-IGFBP1, homeostasis model assessment of IR (HOMA-IR), BMI (categories: normal-weight (8.5-25), overweight (25-30), and obesity (>30)), and high-sensitivity C-reactive protein (hs-CRP) as a measure of general inflammation. Associations with poor functional outcome (modified Rankin scale [mRS] score: 3-6) after 7 years were evaluated using multivariable binary logistic regression, with overweight as reference due to the nonlinear relationship. Both normal-weight (odds-ratio [OR] 2.32, 95% confidence interval [CI] 1.30-4.14) and obese (OR 2.25, 95% CI 1.08-4.71) patients had an increased risk of poor functional outcome, driven by deaths only in the normal-weight. In normal-weight, s-IGFBP-1 modestly attenuated (8.3%) this association. In the obese, the association was instead attenuated by HOMA-IR (22.4%) and hs-CRP (10.4%). Thus, a nonlinear relation between BMI and poor 7-year functional outcome was differently attenuated in the normal-weight and the obese.

Triglyceride-glucose index: A surrogate marker of homeostasis model assessment of insulin resistance to predict diabetic nephropathy.

Objectives: To determine the association of triglyceride-glucose index with homeostasis model assessment of insulin resistance in type 2 diabetes mellitus patients, and to determine the association of triglyceride-glucose index with urinary albumin-to-creatinine ratio for predicting diabetic nephropathy. METHODS: The observational, cross-sectional study was conducted from September 2021 to September 2022 at the Department of Chemical Pathology, Pakistan Railway Hospital, Rawalpindi, Pakistan and comprised recently-diagnosed type 2 diabetes mellitus patients. Recorded data included age, gender, vitals, diabetes duration, body mass index and other pertinent demographic and clinical information. Measurements included spot urine albumin-to-creatinine ratio, triglycerideglucose index, homeostasis model assesment of insulin resistance as well as fasting serum insulin, fasting plasma glucose, glycosylated haemoglobin, triglycerides, total cholesterol and serum creatinine. On the basis of triglyceride-glucose index scores, the participants were divided into 4 quartiles; Q1=4.5-5, Q2=5.1-5.5, Q3=5.6-6, and Q4=>6. Data was analysed using SPSS 26. RESULTS: Of the 218 patients, 141(64.7%) were females and 77(35.3%) were males. The overall mean age was 49.22±11.46 years. There were 102(46.8%) overweight patients, 33(15.1%) obese and 82(37.2%) had normal weight. There were 58(26.6%) patients in Q1, 86(39.4%) in Q2, 46(21.1%) in Q3 and 28(12.8%) in Q4. Those in Q4 showed elevated fasting plasma glucose, glycated haemoglobin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and urine albumin-to-creatinine ratio (p<0.05), as well as low values for high-density lipoprotein cholesterol and estimated glomerular filtration rate(p<0.05). Fasting serum insulin was negatively linked to glycated haemoglobin (r=-0.12, p=0.07). Triglyceride-glucose index (r=0.76, p<0.001), homeostasis model assessment of insulin resistance (r=0.48, p<0.001), and urine albumin-to-creatinine ratio (r=0.10,p=0.05) positively correlated with glycated haemoglobin. Fasting serum insulin (r=-0.13, p=0.05), negatively correlated with triglyceride-glucose index, while homeostasis model assessment of insulin resistance (r= 0.32, p<0.001) and urine albumin-to-creatinine ratio (r=0.28, p=0.05) had a positive correlation. The estimated glomerular filtration rate was significantly positively linked with fasting serum insulin (r=0.05, p=0.05), and correlated significantly negatively with triglyceride-glucose index (r=-0.35, p=0.01), homeostasis model assessment of insulin resistance (r=-0.01, p=0.86) and urine albumin-to-creatinine ratio (r=-0.02, p=0.8). CONCLUSIONS: The triglyceride-glucose index showed a strong association with homeostasis model assessment of insulin resistance, and surpassed it in terms of predicting diabetic nephropathy in type 2 diabetes mellitus patients.

Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3-year prospective cohort study.

AIM: The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. METHODS: A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. RESULTS: Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. CONCLUSIONS: Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.

Association between experience of insulin resistance and long-term cardiovascular disease risk: findings from the Korean Genome and Epidemiology Study (KOGES).

PURPOSE: Although the correlation between insulin resistance (IR) and cardiovascular disease (CVD) risk is well-established, the impact of changes in IR status over time has received little attention. This study aimed to investigate the effect of IR on CVD risk in a large prospective cohort of middle-aged Korean adults. METHODS: We assessed 3597 participants from the Korean Genome and Epidemiology Study (KoGES). Participants were categorized as having IR if their HOMA-IR was ≥2.5 at least once during the exposure period. Multivariate Cox proportional hazards regression analysis was performed to assess hazard ratios (HRs) with 95% CIs for incident CVD after adjusting for confounders. RESULTS: Among a total of 3597 participants, 2259 did not have IR and 1138 had IR. The cumulative incidence rate of CVD in the IR group was significantly higher than that in the non-IR group (log-rank test, p = 0.015). Compared to the non-IR group, the HR and 95% CI for incident CVD in the IR group was 1.40 (1.07-1.83) in the unadjusted model. The presence of IR during the exposure period was significantly associated with a higher risk of incident CVD after adjusting for age, sex, body mass index, diabetes, hypertension, dyslipidemia, C-reactive protein, physical activity, alcohol intake, and smoking status (HR = 1.37; 95% CI: 1.01-1.84). CONCLUSION: Individuals who have experienced IR have a consistently higher likelihood of developing CVD than those who have never had IR. More intensive efforts should be made to prevent IR in middle-aged and older adults.

HOMA-IR is an effective biomarker of non-alcoholic fatty liver disease in non-diabetic population.

OBJECTIVES: This study aimed to investigate the correlation between homeostasis model assessment of insulin resistance (HOMA-IR) and non-alcoholic fatty liver disease (NAFLD) in the non-diabetic population and establish its diagnostic efficacy. METHODS: This observational study involved participants divided into NAFLD and non-NAFLD groups, and baseline data were analyzed. Univariate and multivariate logistic regression analyses were used to correlate HOMA-IR with the risk of NAFLD. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of HOMA-IR for NAFLD. Subgroup analyses of non-obese individuals were performed. RESULTS: Overall, 2234 non-diabetic participants were included. The HOMA-IR was significantly higher in the NAFLD group than in the non-NAFLD group. Multivariate logistic regression analysis showed that HOMA-IR was a strong and independent risk factor for NAFLD after correcting for confounding factors. The area under the ROC curve (AUC) value of HOMA-IR for predicting NAFLD was 0.792. In the non-obese non-diabetic population, HOMA-IR was an independent risk factor for increased risk of lean NAFLD after correcting for confounding factors. The AUC value of HOMA-IR for predicting lean NAFLD was 0.770. CONCLUSIONS: HOMA-IR is independently associated with the risk of NAFLD in the non-diabetic and non-obese non-diabetic populations and has good diagnostic value.

Usefulness of SPISE Index for Screening and Detection of Early Stages of Insulin Resistance among Chilean Young Adults.

BACKGROUND: As the gold standard test to quantify insulin resistance (IR) involves intravenous insulin loading and repeated blood glucose monitoring, many indexes have been developed for IR assessment for convenience. OBJECTIVE: The objective of this study was to evaluate the agreement of the Single-Point Insulin Sensitivity Estimator (SPISE) by comparing it with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying IR. METHOD: Data came from the ongoing LIMACHE BIRTH COHORT. 1,948 individuals (aged 22-28 years) were studied. We performed an agreement plot called a Bangdiwala's Observer Agreement to evaluate patterns in departures from agreement in ordinal categorical variables. RESULTS: According to the Bangdiwala-Weighted statistics, we found that the agreement between both indexes was 0.14; this value would be considered a slight agreement. Thus, we found bias in the marginal distributions, and we noticed that the SPISE has a bias toward the central quintiles of the index. CONCLUSIONS: The identification of IR in young adult individuals by the SPISE index has slight agreement with HOMA-IR. Therefore, caution would be taken when considering SPISE index among young Chilean adults.

Variation in Clinical Presentation, Metabolic Profile, Hormonal Parameters and Inflammatory Markers in Polycystic Ovary Syndrome Women with and without Polycystic Ovary Morphology Appearance.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with a spectrum of presentation. Studies have reported considerably different rates in terms of the incidence of polycystic ovary morphology (PCOM) in patients with PCOS with inconsistent results regarding the effects of PCOM in them. Aims: The aim of this study was to determine the differences in clinical presentation, metabolic profile, hormonal parameters and inflammatory markers in PCOS women with and without PCOM on ultrasonography (USG). Settings and Design: A total of 70 PCOS women were recruited. To analyse the differences between various parameters, the patients were divided into two groups based on the presence or absence of PCOM on USG of the pelvis as per the Rotterdam criteria. Materials and Methods: A total of 37 patients had PCOM as per the diagnostic criteria for PCOS (Group 1), while 33 patients did not have PCOM on USG and were designated as Group 2. All participants underwent a detailed clinical evaluation and biochemical investigations, including high-sensitivity C-reactive protein, serum adiponectin, luteinising hormone, follicle-stimulating hormone, total testosterone and serum anti-Mullerian hormone. The homeostasis model assessment of IR (HOMA-IR) was calculated using standard equations. Statistical Analysis Used: The mean and Standard deviation were computed for all continuous variables. Frequencies and proportions were calculated for categorical variables. Comparisons of the mean scores between the study groups were assessed using the Unpaired Student's t-test. The mean score of the subgroups was also compared using the unpaired Student's t-test. P < 0.05 was considered significant for all statistical inferences. Results: The mean LDL and mean triglyceride were higher in Group 2, which was statistically significant (P = 0.004 and P ≤ 0.001, respectively). The mean hs-CRP was found to be higher in Group 2, which was statistically significant (P = 0.005). The mean AMH was higher in Group 1, which was statistically significant (P = 0.002). Group 1 had higher adiponectin levels, which was statistically significant (P = 0.04). Conclusion: The above findings suggest that patients without diagnostic PCO morphology have a worse metabolic profile compared to those with PCO morphology on USG. Obese patients without PCO morphology probably have a higher cardiovascular risk compared to obese patients with PCO morphology.

Biochemical and hormonal abnormalities in adult female acne.

BACKGROUND: Prevalence of adult patients with acne is increasing and women comprise majority of the cases. There is lack of data on biochemical and hormonal abnormalities in adult female acne (AFA). AIMS: To evaluate biochemical and hormonal parameters in 60 patients of AFA. METHODS: A cross-sectional observational study conducted from November 2018 to March 2020 in Dermatology outpatient department of a tertiary care hospital in North India. Adult females (age > 25 years) with a clinical diagnosis of acne were included in the study. RESULTS: 60 cases of AFA were included. The age ranged between 26-41 years with mean age at presentation being 29.45 years. 53.3% patients had persistent acne while 46.7% had late-onset acne. 50% patients had history of premenstrual flare-up of their acne. Raised FBG was found in 25% patients. 10% had raised serum insulin levels. HOMA-IR index was deranged in 55% patients. At least one lipid alteration was reported in 91.6% of patients. In hormonal parameters, raised TT was present in 6.7%, LH in 3.3%, FSH in 18.3%, prolactin in 3.3%, and TSH in 15%. No association was found between acne severity and biochemical and hormonal parameters. CONCLUSIONS: Our study highlighted the importance of measuring lipid profile in AFA and calculating HOMA-IR index for measuring insulin resistance rather than simply measuring serum insulin levels. In our study, additional parameter deranged in significant number of patients was FBG. Hence, we recommend routine screening of lipid profile, FBG and calculation of HOMA-IR index in AFA.

Maternal insulin resistance in pregnancy is associated with fetal fat deposition: findings from a longitudinal study.

BACKGROUND: Newborns exhibit substantial variation in fat mass accretion over gestation. These individual differences in newborn adiposity extend into infancy and childhood and relate to subsequent risk of obesity and metabolic dysregulation. Maternal glucose homeostasis in pregnancy has been proposed as an underlying mechanism; however, the timing in gestation when maternal glucose regulation influences the progression of fetal fat deposition remain unclear. OBJECTIVE: This study aimed to investigate the cross-sectional and longitudinal association of maternal insulin resistance in early, mid, and late pregnancy with fetal fat deposition in uncomplicated pregnancies. We hypothesized that maternal insulin resistance at early, mid, and late gestation is positively associated with fetal fat deposition, and that the magnitude of the association is greater for the mid and late gestation measures than for the early gestation measure. STUDY DESIGN: In a longitudinal study of 137 low-risk pregnancies, a fasting maternal blood sample was obtained and fetal ultrasonography was performed at ≈ 12, 20, and 30 weeks' gestation. Maternal insulin resistance was quantified using the homeostasis model assessment of insulin resistance (fasting insulin×fasting glucose/405). Estimated fetal adiposity was calculated by integrating measurements of cross-sectional arm and thigh percentage fat area and anterior abdominal wall thickness. The associations between maternal homeostasis model assessment of insulin resistance and estimated fetal adiposity and estimated fetal weight were determined by multiple linear regression adjusted for potential confounding factors including maternal age, parity, race and ethnicity, prepregnancy body mass index, gestational weight gain per week, fetal sex, and gestational age at assessments. RESULTS: Maternal homeostasis model assessment of insulin resistance at ≈ 12, 20, and 30 weeks was 2.79±1.79 (±standard deviation), 2.78±1.54, and 3.76±2.30, respectively. Homeostasis model assessment of insulin resistance at 20 weeks was positively associated with estimated fetal adiposity at 20 weeks (r=0.261; P=.005). Homeostasis model assessment of insulin resistance at 20 weeks (r=0.215; P=.011) and 30 weeks (r=0.285; P=.001) were also positively associated with estimated fetal adiposity at 30 weeks. These relationships remained significant after adjustment for confounding factors. There was no significant correlation between homeostasis model assessment of insulin resistance and estimated fetal weight at 20 and 30 weeks' gestation. CONCLUSION: In low-risk pregnancies, maternal insulin resistance at mid and late but not early pregnancy is significantly associated with fetal adiposity but not with fetal weight. Maternal insulin resistance in mid-gestation could provide a basis for risk identification and interventions that target child adiposity.

Correlation of Markers of Inflammation with Hormonal, Metabolic Parameters, Insulin Resistance and Adiposity Indices in First-Degree Relatives of Patient with Polycystic Ovary Syndrome.

Background: Polycystic ovary syndrome (PCOS) is a state of chronic low-grade inflammation. Low-grade inflammation has been linked to the development of cardiovascular disease (CVD). There is evidence of clustering for metabolic syndrome, hypertension, dyslipidaemia in type 2 diabetes mellitus and insulin resistance (IR) in mothers, fathers, sisters and brothers of women with PCOS. Aims: The aim is to study the levels of inflammatory markers and IR in first-degree relatives of patients with PCOS and find any correlation with hormonal parameters, metabolic parameters and adiposity indices in them. Settings and Design: A total of 66 first-degree relatives of a patient with PCOS were included in this cross-sectional study. Materials and Methods: All participants underwent detailed clinical evaluation and biochemical investigations, including high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), luteinising hormone (LH), follicle-stimulating hormone (FSH) and total testosterone (only in females). Homeostasis model assessment of IR (HOMA-IR), lipid accumulation product and visceral adiposity index were calculated using standard equations. Visceral adipose tissue thickness and subcutaneous adipose tissue thickness were assessed using ultrasonography. Statistical Analysis Used: Spearman's and Pearson's correlation coefficients were used to analyse the correlation between different non-parametric and parametric data, respectively. Multiple linear regression was used to correlate multiple dependent factors. Results: The mean hs-CRP level was 2.4 ± 1.1 mg/L, which is greater than the cut-off of 2 mg/L and hs-CRP >2 mg/L was found in 62% (n = 41) participants. The mean IL-6 (3.5 ± 1.1 pg/ml) and total white blood cell count (7244 ± 2190/mm3) were in the normal range. The mean HOMA-IR was 2.35 ± 0.76, which is elevated, considering HOMA IR >2 as a predictor of IR and metabolic syndrome. HOMA IR >2 was found in 64% (n = 42) of the participants. Inflammatory markers were significantly correlated with LH and HOMA IR, even after multiple linear regression was fitted for each marker individually. Conclusion: Apparently, healthy first-degree relatives of PCOS patients had evidence of chronic low-grade inflammation. The chronic inflammation in them correlated well with HOMA-IR and LH but was independent of body mass index. This low-grade inflammation may predispose the first-degree relatives of PCOS to CVD.

A Non-Obese Hyperglycemic Mouse Model that Develops after Birth with Low Birthweight.

The number of low birthweight (LBW) infants weighing below 2500 g has not decreased in Japan. This study aimed to develop an adult non-obese hyperglycemic mouse model born with LBW to study the pathogenesis. At 16.5 days of gestation, transient intrauterine ischemia (blocked blood flow in both uterine arteries for 15 min) was performed in a subgroup of pregnant mice (group I). Non-occluded dams were used as sham controls (group C). After birth, female pups in each group were weaned at 4 weeks of age and reared on the normal diet until 8 weeks of age (n = 7). Fasting blood glucose levels, serum immunoreactive insulin (IRI), and body composition were then measured. Metabolite analyses was performed on the liver tissues. Birthweight was significantly lower in group I compared with group C. Pups from group I remained underweight with low fat-free mass and showed hyperglycemia with high serum IRI and homeostasis model assessment of insulin resistance levels, indicating insulin resistance. Metabolite analyses showed significantly reduced adenosine triphosphate and nicotinamide adenine dinucleotide production and increased lactic acid in group I. The pathogenesis of our non-obese hyperglycemic mouse model may be due to increased myogenic insulin resistance based on mitochondrial dysfunction and reduced lean body mass.

Evaluating Triglyceride and Glucose Index as a Simple and Easy-to-Calculate Marker for All-Cause and Cardiovascular Mortality.

OBJECTIVE: The triglyceride and glucose (TyG) index is a useful marker of insulin resistance and is a predictor of several metabolic diseases. The aim of this study was to evaluate the association between the TyG index and all-cause or cardiovascular mortality using a large population-based cohort study database. METHODS: A total of 255,508 subjects in the Kangbuk Samsung Health Study cohort were enrolled. Cox proportional hazards models were used to analyze the risk of mortality. RESULTS: During a median 5.7-year follow-up, the cumulative all-cause and cardiovascular mortality was 0.47% and 0.07%. There was a nonlinear relationship between the TyG index and death, and moving from moderate to high, the TyG index levels were associated with an increase in the risk of death. The hazard ratio (HR) for all-cause and cardiovascular mortality of the TyG index was 1.21 [95% confidence interval (CI) 1.14-1.28] and 1.45 (95% CI 1.26-1.66) in the unadjusted model, respectively. After adjustment for covariates, the association between the TyG index and all-cause and cardiovascular mortality was attenuated. In the multivariable-adjusted model, the TyG index was associated with an elevated risk of all-cause mortality in women (HR 1.13, 95% CI 1.02-1.26) and a decreased risk in men (HR 0.92, 95% CI 0.85-0.99). The association between cardiovascular mortality and the TyG index was not statistically significant among either men or women in the multivariable-adjusted model. CONCLUSIONS: The TyG index in a young, relatively healthy, population is associated with an elevated risk of all-cause and cardiovascular mortality. This association between the TyG index and all-cause mortality persists in women after multivariable adjustment.

Renal Cell Carcinoma-Associated Diabetes Mellitus Due to Paraneoplastic Syndrome in Maintenance Hemodialysis: A Case Report.

A 59-year-old Japanese woman with a 22-year history of long-term hemodialysis was admitted to our hospital for further examination of hyperglycemia and anemia. Five months before hospitalization, her fasting plasma glucose value was 99 mg/dL and her glycated hemoglobin was 5.7%. On admission, her fasting plasma glucose value was 873 mg/dL, glycated hemoglobin was 16.2%, C-peptide reactivity was 22.3 ng/mL (reference range, 0.5-3.0), and homeostasis model assessment of insulin resistance (HOMA-IR) was 10.6 (reference range, <2.0); the high HOMA-IR indicated high insulin resistance. Intensive insulin therapy was started for hyperglycemia, which required more than 40 units/day. Computed tomography showed a hypervascular lesion 2.2 cm in diameter on the right kidney; therefore, right nephrectomy was performed. Complete resection was confirmed, and the lesion was diagnosed as a clear cell type of renal cell carcinoma (RCC). Immediately after nephrectomy, glycemic control normalized and administration of insulin was discontinued. Fourteen days after nephrectomy, the HOMA-IR decreased to 2.96. RCC that develops in patients receiving long-term hemodialysis has been reported to be dialysis-related RCC, but there have been no reports suggesting a relationship between dialysis-related RCC and diabetes. To our knowledge, this is the first report of RCC presenting with the paraneoplastic syndrome of acute-onset diabetes because of insulin resistance.

Abnormal Glucose Metabolism Parameters and the Aggressiveness of Differentiated Thyroid Carcinoma: A Hospital-Based Cross-Section Study in China.

Purpose: The correlation of abnormal glucose metabolism and thyroid carcinoma, especially the aggressiveness of thyroid cancer, still remains controversial. We conducted this study to investigate the relationship between abnormal glucose metabolism parameters and differentiated thyroid carcinoma (DTC) in the Chinese population. Materials and Methods: The study was designed as a hospital-based case-control study and was approved by the Ethics Committee of our hospital and registered in the Clinical Trial Protocol Registration and Results System (Registration code: NCT03006289). From January 1, 2018 to June 30, 2021, a total of 377 DTC patients were enrolled in the study. Demographic and general characteristics, details of thyroid surgery and histopathological results, hematological test indicators were collected. Glucose metabolism parameters were calculated. Variables were analyzed by t-test, ANOVA, chi-squared analysis and Fisher's exact test. Pearson bi-variate correlation and Spearman's correlation analysis were used for bi-variate analysis. Results: More than 40% of patients with DTC were multifocality, more than half were extra-glandular invasion, and nearly 85% complied by lymph node metastasis. The prevalence of diabetes mellitus (DM) was about 10.08% in DTC patients. It was found that the proportion of postprandial 2 h blood glucose ≥11.1mmol/L and HbA1c ≥6.5% was significantly higher than the known proportion of DM (17.8%, 16.7% vs. 10.08%). Additionally, 87.3% of the DTC patients in this study had varying degrees of insulin resistance. Further analysis found that higher T staging was associated with higher levels of area under curve of C-peptide (P = 0.029), insulin sensitivity index (P = 0.012) and C-peptide sensitivity index (P = 0.016). A delayed peak of insulin secretion was found to be positive related with capsule invasion (r = 0.206, P = 0.004). In patients without a DM history, homeostasis model assessment of insulin resistance (P = 0.017), insulin sensitivity index (P = 0.019) and C-peptide sensitivity index (P = 0.020) were statistic associated with T staging. Also, the glucose metabolism parameter at 3-hour after a meal was related to a larger number of metastatic lymph nodes. Conclusion: Abnormal glucose metabolism, namely, DM, hyperinsulinemia and insulin resistance, were significantly associated with the carcinogensis and aggressiveness of DTC.

Adiponectin is Inversely Associated with Insulin Resistance in Adolescents with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Insulin Resistance (IR) is confirmed as a key feature of Nonalcoholic Fatty Liver Disease (NAFLD) in children and adolescents. Numerous studies report that adiponectin (APN) levels are inversely associated with the status of IR in adults with NAFLD. This study aimed to investigate the relationship between serum total APNand Homeostasis Model Assessment Insulin Resistance (HOMA-IR) in adolescents with NAFLD. METHODS: 382 newly-diagnosed NAFLD adolescents, aged 9-16 years old, were enrolled and divided into three subgroups according to the APNtertile. Simple and multiple linear regression analyses were performed to assess the correlation between HOMA-IR and APN in boys and girls, respectively. RESULTS: The HOMA-IR values tended to decrease in boys according to APN tertiles: 5.6(4.4-7.3) vs. 5.2(4.6-6.9) vs. 4.9(4.1-5.8) (p<0.01), and there was a significant difference in the HOMA-IR values among three APN tertile subgroups in girls (p<0.01). Univariate analysis showed that body mass index, waist circumference, weight-to-height ratio, fasting blood glucose, insulin, triglyceride, and APN were significantly associated with HOMA-IR in boys (p<0.05). In girls, body mass index, fasting blood glucose, insulin, total cholesterol, triglyceride, and APN were significantly associated with HOMA-IR (p<0.05).APN was found to be a significant determinant for HOMA-IR only in boys (ß=-0.147, p<0.01). CONCLUSION: Our findings showed that APN was an independent and significant determinant for increased HOMA-IR in boys with NAFLD. Further studies are needed to explore the underlying mechanisms.

Subtypes of gestational diabetes and future risk of pre-diabetes or diabetes.

BACKGROUND: Recent studies have suggested that gestational diabetes (GDM) is a heterogeneous condition with distinct subtypes determined by whether the predominant metabolic abnormality is impaired insulin sensitivity or deficient insulin secretion. However, it is not known if the elevated future risk of pre-diabetes/diabetes associated with GDM varies according to these subtypes. Thus, we sought to evaluate maternal metabolic function in the 1st year postpartum in relation to GDM subtypes. METHODS: In this prospective cohort study conducted in Toronto, Canada, 613 women underwent GDM screening by oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at both 3-months and 12-months postpartum between 09/2003 and 03/2016. The antepartum OGTT identified 3 groups of women: GDM with predominant sensitivity defect (GDM-sensitivity), GDM with predominant secretion defect (GDM-secretion), and non-GDM. FINDINGS: Antepartum findings persisted after pregnancy, with lower insulin sensitivity in GDM-sensitivity (Matsuda index; HOMA-IR) and lower insulin secretion in GDM-secretion (Stumvoll first-phase; insulinogenic index (IGI)) at both 3-months and 12-months (all p<0.005). Beta-cell compensation (Insulin Secretion-Sensitivity Index-2; IGI/HOMA-IR) was lower in both GDM subtypes compared to non-GDM (all p<0.0005) but did not differ between GDM-sensitivity and GDM-secretion. Similarly, both subtypes exhibited higher post-challenge glycemia on OGTT at 3-months and 12-months than non-GDM (all p<0.0005) but did not differ from one another. The prevalence of pre-diabetes/diabetes was higher in both GDM-sensitivity (30.9%; 95%CI: 21.7-41.2) and GDM-secretion (27.6%; 16.7-40.9) than in non-GDM (10.4%; 7.7-13.6) at 12-months (both p<0.005), with no difference between GDM subtypes (p = 0.75). INTERPRETATION: Beta-cell dysfunction, glycemia and incident pre-diabetes/diabetes do not vary between GDM subtypes in the 1st year postpartum. FUNDING: Canadian Institutes of Health Research; Diabetes Canada.

The verification of the reliability of a triglyceride-glucose index and its availability as an advanced tool.

BACKGROUND: The triglyceride-glucose (TyG) index has been considered as insulin resistance (IR) assessment index. The current study aimed to verify the reliability of the TyG index as an IR assessment marker; the study of plasma fatty acids and body fat composition to determine potential metabolic syndrome (MetS) participants with a body mass index (BMI) of between 25.0 and 29.9 kg/m2. METHODS: The study included 378 overweight participants with a body mass index of between 25.0 and 29.9 kg/m2. They were divided into tertiles according to the homeostasis model assessment of IR (HOMA-IR) or the TyG index. The role of the IR assessment index and the relationship with IR-related diseases and the risk factors using gas chromatograph-mass spectrometry, computed tomography, and dual energy X-ray absorptiometry, was investigated. RESULTS: It was only in the TyG index tertile that the higher TyG index participants showed considerably higher LDL-cholesterol levels. More markedly, a close relationship was observed between the TyG index and the omega-6 polyunsaturated fatty acids compared with the HOMA-IR. Unlike HOMA-IR, with regard to the risks of developing chronic diseases, the MetS, the third tertile of the TyG index, showed an approximately 33.7 times greater odds ratio (OR) of the MetS occurring, compared with the first tertile of the TyG index. CONCLUSIONS: The TyG index may be considered as an IR assessment index. In addition, the TyG index is an advanced tool that reflects the relevance of pro-inflammation levels and the presence of IR-related chronic diseases.

Mechanisms Involved in the Relationship between Vitamin D and Insulin Resistance: Impact on Clinical Practice.

Recent evidence has revealed anti-inflammatory properties of vitamin D as well as extra-skeletal activity. In this context, vitamin D seems to be involved in infections, autoimmune diseases, cardiometabolic diseases, and cancer development. In recent years, the relationship between vitamin D and insulin resistance has been a topic of growing interest. Low 25-hydroxyvitamin D (25(OH)D) levels appear to be associated with most of the insulin resistance disorders described to date. In fact, vitamin D deficiency may be one of the factors accelerating the development of insulin resistance. Vitamin D deficiency is a common problem in the population and may be associated with the pathogenesis of diseases related to insulin resistance, such as obesity, diabetes, metabolic syndrome (MS) and polycystic ovary syndrome (PCOS). An important question is the identification of 25(OH)D levels capable of generating an effect on insulin resistance, glucose metabolism and to decrease the risk of developing insulin resistance related disorders. The benefits of 25(OH)D supplementation/repletion on bone health are well known, and although there is a biological plausibility linking the status of vitamin D and insulin resistance supported by basic and clinical research findings, well-designed randomized clinical trials as well as basic research are necessary to know the molecular pathways involved in this association.

Calcium-Deficiency during Pregnancy Affects Insulin Resistance in Offspring.

Prenatal malnutrition is known to affect the phenotype of the offspring through changes in epigenetic regulation. Growing evidence suggests that epigenetics is one of the mechanisms by which nutrients and minerals affect metabolic traits. Although the perinatal period is the time of highest phenotypic plasticity, which contributes largely to developmental programming, there is evidence of nutritional influence on epigenetic regulation during adulthood. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. Cortisol, the most important glucocorticoid, is considered to lead to insulin resistance and metabolic syndrome. 11ß-hydroxysteroid dehydrogenase-1 is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. This brief review aims to identify the effects of Ca deficiency during pregnancy and/or lactation on insulin resistance in the offspring. Those findings demonstrate that maternal Ca deficiency during pregnancy may affect the epigenetic regulation of gene expression and thereby induce different metabolic phenotypes. We aim to address the need for Ca during pregnancy and propose the scaling-up of clinical and public health approaches that improved pregnancy outcomes.