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Background: Insulin resistance is a medical complication associated with obesity and metabolic syndrome in youth. Data have shown that pediatric obesity can stop or even decrease by an adequate clinical management of the insulin resistance-associated syndrome. Despite those new evidences, measurement of insulin resistance in youth remains quite low. Objective: The objective was to review and evaluate the proportion of pediatric obese patients referred to a 2nd line pediatric multidisciplinary obesity clinic among whom insulin resistance was screened or not. Material & Method: We have looked, retrospectively, at the initial blood tests among 133 obese patients (body mass index above 97th percentile with respect for age and sex) above 10 years of age, between July 2017 and April 2019. Sixty percent (60%) of our urban cohort is represented by 1st and 2nd generation immigrants. Hyperinsulinemia was defined as a value above 100 pmol/L. Pediatric obese patients were referred by general practitionniers or community pediatricians. Results: Among the 133 medical files revised, 91 patients shown hyperinsulinemia (68%). Of those 91 patients, 64 were not initially screened for hyperinsulinemia (70%). Interestingly, in the hyperinsulinemia pediatric group, mean HDL-cholesterol was lower, mean triglycérides were higher, as well as the mean alanine transaminase (ALT) compared to the normal insulin group (p smaller than 0.05). In the hyperinsulinemia group, 71,8% of our pediatric cohort was started on metformin therapy in addition to a multidisciplinary intensive educational family interventions as recommended by WHO. Conclusions: Fasting insulin can be variable among puberty stages and general guidelines for the use of metformin in the pediatric population are still to come. However, measurement of elevated fasting insulin among pre- and post-pubertal patients was previously associated with markers of cardiovascular and hepatic complications in obese young patients. Fasting insulin is a simple, cheap, easily accessible measure in all clinical settings. Multidisciplinary health care for pediatric obesity is still embryonic and difficult to access. Appropriate and complete initial clinical investigations, including fasting insulin measurement, should be performed in order not to delay its medical intensive multidisciplinary management both in 1st and 2nd lines practitioners.

Adequate evidence showed hormone therapy (HT) reduces the risk of new-onset diabetes in midlife women by decreasing fasting glucose and insulin. However, the improvement of these diabetic biomarkers varied with each individual in clinical observations. The objective of our study was to investigate potential baseline factors associated with the change of fasting glucose and insulin during HT. A retrospective cohort study was performed among 263 midlife participants aged 40 to 60 years with menopausal symptoms who have received 6-month individualized HT. Demographic information and laboratory indicators including reproductive hormone, lipid profiles, diabetic indicators were collected and measured at baseline and were followed-up. A series of statistical analyses were performed to confirm the effectiveness of HT and compare the baseline factors between participants with different glycemic or insulinemic response. Multivariable linear regression model with stepwise variable selection was further used to identify the associated factor with the change of fasting glucose and insulin. Of all participants, fasting glucose (P = .001) and fasting insulin (P

Background: A relationship between hyperthyroidism and insulin secretion in type 2 diabetes mellitus (T2DM) has been reported. Therefore, this study explored the use of first-phase insulin secretion in the differential diagnosis of thyroid diabetes (TDM) and T2DM. Methods: In total, 101 patients with hyperthyroidism were divided into hyperthyroidism with normal glucose tolerance (TNGT), hyperthyroidism with impaired glucose regulation (TIGR), and diabetes (TDM) groups. Furthermore, 96 patients without hyperthyroidism were recruited as control groups (normal glucose tolerance [NGT], impaired glucose regulation [IGR], and T2DM). The following parameters were evaluated: homeostasis model assessment (HOMA)-IR, HOMA-β, modified β-cell function index (MBCI), peak insulin/fasting insulin (IP/I0), AUCins-OGTT, and AUCins-OGTT/AUCglu-OGTT from the oral glucose tolerance test (OGTT) insulin release test were utilized to assess the second-phase insulin secretion, while the IP/I0, AIR0′~10′, and AUCins-IVGTT from the intravenous glucose tolerance test (IVGTT) insulin release test were used to assess the first-phase insulin secretion. Results: In the OGTT, the HOMA-β values of the TNGT and TDM groups were higher than those of the NGT and T2DM groups (all P < 0.05). In the hyperthyroidism groups, the MBCI of the TDM group was lower than that of the TNGT and TIGR groups (all P < 0.05). Among the control groups, the MBCI values of the IGR and T2DM groups were lower than that of the normal glucose tolerance (NGT) group (all P < 0.05). In the IVGTT, insulin secretion peaked for all groups at 2–4 min, except for the T2DM group, which showed a low plateau and no secretion peak. The IP values of the TNGT, TIGR, and TDM groups were higher than those of the NGT, IGR, and T2DM groups (all P < 0.05). The Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the TDM group were higher than those of the T2DM group but were lower than those of the TNGT, TIGR, NGR, and IGR groups (all P < 0.05). Compared with the other five groups, the Ip/I0, AIR0′~10′, and AUCins-IVGTT values of the T2DM group were significantly decreased (all P < 0.05). The Ip/I0 and AUCins-IVGTT values of the TNGT group were higher than those of the NGT group (all P < 0.05). Conclusions: β-cell function in TDM patients is superior to that in T2DM patients. First-phase insulin secretion could be used as an early diagnostic marker to differentiate TDM and T2DM.

Background: Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of atorvastatin on insulin resistance in PCOS patients still remain controversial. Objective: The aim of this report was to evaluate the effects of atorvastatin therapy on the insulin resistance in the treatment of PCOS compared to that of placebo, in order to confer a reference for clinical practice. Methods: Randomized controlled trials (RCTs) of atorvastatin for PCOS published up to August, 2020 were searched. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was measured by the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: fasting glucose concentration, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) or body mass index (BMI) value. Results: Nine RCTs with 406 participants were included. The difference of fasting glucose concentration in PCOS patients between atorvastatin group and placebo group was not statistically significant (8 trials; SMD −0.06, 95% CI −0.31 to 0.20, P = .66). PCOS patients in atorvastatin group had lower fasting insulin level than those in placebo group (7 trials; SMD −1.84, 95% CI −3.06 to −0.62, P

Elevated levels of fasting glucose and fasting insulin precede the development type 2 diabetes (T2D). While T2D and cardiovascular disease share common risk factors, dysregulation of glucose metabolism is of particular concern because it can result in end-organ damage including the heart, nerves, kidneys, and eyes. The prevalence of diabetes is higher in American minority populations. Through genome-wide association studies, approximately 60 loci have been identified for fasting glucose, fasting insulin, and glycated hemoglobin. To better understand the genetic basis of glucose dysregulation, the Population Architecture using Genomics and Epidemiology (PAGE) Consortium genotyped 12,801 Hispanic/Latinos, 5,696 African Americans, 1,405 Native Hawaiians, 398 Native Americans, and 1,727 Asians without diabetes using the approximately 1.3 million variants on the Multi-Ethnic Global Array (MEGA), which is enriched for coding variation and ancestral diverse content. Through ancestry-combined single variant association testing with fasting glucose, fasting insulin, and glycated hemoglobin (HbA1c), we identified a novel potential association between decreased HbA1c and the minor A allele of rs11887523 ( p = 4.51x10 -9 , MFSD2B p.A60T, minor allele frequency (MAF) 7% in African Americans, MAF 2% in Hispanics). Other associations with HbA1c included hemoglobin genes, further highlighting the importance of considering variation in hemoglobin and red-blood cell lifespan when using HbA1c as a measure of glucose control. We also replicated several known associations including between fasting glucose and variants near G6PC2, GCKR, MTNR1B, and FOXA2 ; and between fasting insulin and the GRB14/COBLL1 locus. Further analyses including imputing the data out to 1000 Genomes phase3 and gene-based tests of rare variants are underway. These will increase power to detect associations with ancestry-specific rare variants.

To investigate metabolic differences between simple obese children and those comorbid with fatty liver disease.Obese children hospitalized in our center from 2014 to 2016 were included and divided into simple obese group and obese with fatty liver group by ultrasound-based diagnosis of fatty liver. Epidemiology data and serum biochemical studies were recorded. Body Mass Index (BMI) and homeostasis model insulin resistance index (HOMA-IR) were calculated accordingly.A total of 186 obese children were enrolled in this study, including 93 cases of obese children and 93 obese patients' comorbid with fatty liver. The proportion of male, age, waist circumference (WC), BMI, fasting blood-glucose (FBG), glycosylated hemoglobin A1c (HbA1c), fasting insulin (FINS), and HOMA-IR were significantly higher in obese patients with fatty liver (P 1, P

The prevalence of glucose abnormalities (GAs) and the diagnostic value of fasting plasma glucose and insulin in detecting impaired glucose tolerance (IGT) and diabetes mellitus (DM) were determined in urban Latin Americans. An oral glucose tolerance test was conducted in 592 subjects after administration of 75 g of glucose. Employing American Diabetes Association (ADA) and World Health Organization guidelines, GAs were found in 34% of the subjects, defined as impaired fasting glucose (IFG) (13.3%), IGT (6.9%), combined IFG + IGT (7.8%), and newly diagnosed type-2-DM (6.5%). All newly diagnosed diabetics had 2-hour glucose levels ≥200 mg/dL, but only 46.1% had fasting glucose ≥126 mg/dL. In addition, nearly half of the subjects with IGT (47%) had fasting glucose levels

Elevated serum fetuin-B is suggested to be associated with insulin resistance, but it is unknown if this association is causal. The aim of this study was to explore the potential causal relationship between fetuin-B and insulin resistance. We used Mendelian randomization analysis by incorporating information of genetic variants in FETUB and serum fetuin-B concentrations with insulin resistance in 1148 obese Chinese adults. Common genetic variants (FETUB rs4686434, rs6785067, and rs3733159) were significantly associated with serum fetuin-B concentrations but not with insulin resistance. Higher serum fetuin-B levels were significantly associated with increased homeostasis model assessment of insulin resistance (HOMA-IR) (0.17 [95%CI: 0.01 to 0.32, P = .037] 10−6 mol IU L−2 higher per SD). However, Mendelian randomization analysis using 3 single-nucleotide polymorphisms as instrumental variables did not support a significant association between genetically predicted fetuin-B levels and HOMA-IR (−0.09 [95%CI: −0.62 to 0.44, P = .738] 10−6 mol IU L−2 lower per SD). The regression coefficients for measured and genetically predicted fetuin-B concentrations on HOMA-IR were significantly different (P

Background: Effects of dietary factors on cardiometabolic risk are often studied in isolation. Yet, multiple dietary components are often consumed together, which may alter effects of individual dietary factors. Objective: To quantify effects of 7 diet components (fruits, vegetables, nuts/seeds, whole grains, fish, dietary fiber) when consumed within the context of overall dietary patterns on major metabolic risks. Methods: Using MOOSE and PRISMA guidelines, we systematically searched multiple databases to identify randomized controlled feeding studies evaluating effects of diet patterns on cardiometabolic risk factors. We focused on trials evaluating major diet patterns that included fruits, vegetables, nuts/seeds, whole grains, fish, and dietary fiber as major components and tested effects on BP, lipids, BMI or waist circumference, or glucose-insulin homeostasis (fasting glucose, HbA1c, oral glucose tolerance test, postprandial glucose, fasting insulin). Studies were excluded if Results: Meta-regression analyses of 6 intervention arms in 3 large dietary pattern trials demonstrated significant effects of several individual components (Table) Pooled results including additional dietary pattern trials and results for adiposity and glucose/insulin homeostasis are to be shown. Conclusions: This systematic assessment quantifies the impact of individual dietary factors on cardiometabolic risks within the context of overall diet patterns, more accurately reflecting complementary effects of multiple components and informing magnitudes of benefits for preventive policies and interventions.

Objective This study examined how cholesterol and fasting insulin levels are related to blood pressure reactivity to behavioral stressors. Methods Subjects (N = 116) were 20 to 52 years old, at 80% to 150% of ideal weight, and had an average fasting cholesterol level of 183 mg/dl. Stressor tasks included mirror star tracing and a videotaped speech task. Changes from baseline were calculated for systolic and diastolic blood pressure. Results Neither cholesterol nor insulin was independently related to blood pressure change scores. However, after controlling for body mass, a two-way analysis of variance revealed a significant cholesterol-by-insulin interaction for change in diastolic blood pressure (p = .022). Subjects in the high-cholesterol/high-insulin group showed the greatest increase in diastolic blood pressure reactivity. Conclusions In a general population, people with a below-average cholesterol level experience only moderate cardiovascular reactivity to mental stressors regardless of their fasting insulin level. However, for people with an above-average cholesterol level, fasting insulin level is an important factor in determining potential reactivity to mental stressors. These findings highlight the importance of adequate sample size to allow for the analysis of such interactions in future studies of cholesterol, insulin, and blood pressure reactivity.

Introduction: Common variants in the gene encoding insulin receptor substrate 1 ( IRS1 ) and nearby on 2q36.3 have been associated with levels of fasting insulin (FI). We hypothesized that a greater burden of rare variants in these regions is associated with higher FI. Methods: CHARGE-S sequenced (average coverage >60x) the IRS1 and 2q36.6 regions (totaling 185 kb) in 3,539 individuals on the SOLiD platform. FI information among non-diabetics was available in 3 studies: Framingham Heart Study ( N =811), Cardiovascular Heart Study ( N =967) and Atherosclerosis Risk in Communities Study ( N =1761). We analyzed rare variants (MAF < 1%) using a weighted sum test, similar to Madsen-Browning (powerful to detect an association if effects of casual rare variants are in the same direction), and the SKAT test (preferred method if variant effects are in opposite directions). Meta-analyses of weighted rare variants results used the inverse-variance method while SKAT results used a similar approach. For multi-variant tests, the threshold for significance was considered to be α = 0.05. Coding annotation predictions were obtained from the dbNSFP database which includes functional predictions from SIFT, MutationTaster, Polyphen-2, Phylo-P and LRT. Non-coding annotation information (protein binding regions, transcription factor binding sites, DNase hypersensitivity sites, conservation scores) was obtained from ENCODE and ORegAnno databases. From these annotations, we grouped different types of variants together (possible loss of function; possibly regulatory) in order to determine specific variants contributing most to the effect. Results: Sequencing found 4,534 variants in two regions, 86.7% of which were rare and novel, not seen in 1000 genomes or dbSNP. Approximately 20% of variants had annotation information available; of these, 34 variants were possibly damaging. We found suggestive association with FI ( p =0.03) for all rare variants in the meta-analysis of weighted-sum tests at 2q36.3 but not at IRS1 . At IRS1 (but not at 2q36.3), SKAT meta-analysis tests showed evidence for all rare variants associated with FI ( p =0.03). SKAT tests restricted to N =365 possibly damaging variants at IRS1 suggested an association with FI in coding ( p =0.06) and in non-coding ( p =0.02) variants. Conclusion: Large scale deep sequencing in the IRS1 and 2q36.3 regions found very large numbers of new, rare variants. Multi-variant tests suggest that rare variation in these regions influence FI levels, with individuals with more and rarer variants having higher FI. Further investigation is warranted to address why weighted sum and SKAT tests provide different levels of evidence for association in the two regions. Also, conditional analyses will test whether new rare variants at IRS1 or 2q36 explain observed GWAS associations.

There is a concern around the world, including the Arabic countries, of young people's lifestyle and its effect on health later in life. Early markers for a possible elevated risk to develop metabolically related chronic diseases are sought for but it is still unknown which of them is the most sensitive. Moreover, the primary life style factor focused on, has been nutrition and overweight with only little attention being paid to physical inactivity and low maximal oxygen uptake.PURPOSE: To screen for a large number of "metabolic" markers in the blood in young Qatari boys with concomitant measures of body composition and maximal oxygen uptake.METHODS: Forty, 10-13 years old boys were studied. A fasting blood sample was taken and in addition to their height and weight a DEXA scan was used to assess body composition. A step test was performed to exhaustion to measure aerobic fitness.RESULTS: The BMI ranged from 14 to 36 kg/m2 with a mean of 22 kg/m2 (median 20) and the aerobic fitness ranged from 14 to 36ml/kg/min with mean value of 30 ml/kg/min (median 32). Equally strong and significant correlations were found for both BMI and aerobic fitness and fasting insulin level with a four fold difference comparing the 20% "worst" and the 20% "best" (4 vs16 microU/ml. The 20% in the middle were in between (8 microU/ml). Also the CRP levels were significantly correlated with BMI and aerobic fitness, with a slightly stronger link to BMI. However the difference in absolute values between those with the highest and lowest BMI and aerobic fitness was 4 fold (2 vs 8 mg/l) and with the middle group being similar to the fit and non-obese boys. The pattern and strength for the correlations were the same for fat % and BMI. No relationships were found for measures of body composition and aerobic fitness to any of the other markers studied (chol, LDL- and HDL-chol, TG, glucose, HbA1c, homocysteine).CONCLUSIONS: Fasting insulin and to some extent CRP may be sensitive early markers of an emerging metabolic deterioration but in this group of boys it is impossible to dissociate between overweight and a low aerobic fitness playing the largest role. Longitudinal studies are needed to track the long term effect of these factors upon metabolic deterioration.©2008The American College of Sports Medicine