Predictive role of triglyceride-glucose index and HOMA index on development of arterial stiffening in non-diabetic men.

BACKGROUND AND AIMS: Insulin resistance (IR) is a major risk factor for cardiovascular disease. Recently, a novel index (triglyceride-glucose index-TyG) has been proposed as a surrogate marker of IR and a better expression of IR than the Homeostatic Model Assessment of IR (HOMA-IR) index. Few and heterogeneous data are so far available on the relationship between vascular damage and this novel index. Therefore, we aimed to estimate the predictive role of TyG, in comparison with the HOMA-IR, on the development of arterial stiffening (AS), defined as a pulse pressure>60 mmHg, in an 8-year follow-up observation of a sample of non-diabetic adult men (the Olivetti Heart Study). METHODS AND RESULTS: The analysis included 527 non-diabetic men, with normal arterial elasticity at baseline and not on antihypertensive or hypolipidemic treatment. TyG was significantly greater in those who developed AS than those who did not (p = 0.006). On the contrary, the HOMA-IR index was not different between the two groups (p = 0.24). Similar trends were shown by logistic regression analysis adjusting for main confounders. After the stratification by the optimal cut-off point, values of TyG >4.70 were significantly associated with the development of AS, also after adjustment for main confounders. On the contrary, the HOMA-IR index >1.90 was not associated with the risk of AS development in multivariate models. CONCLUSION: The results of this study indicate a predictive role of TyG on AS, independently of the main potential confounders. Moreover, the predictive power of TyG seems to be greater than that of the HOMA-IR index.

Relative Contribution of Metabolic Syndrome Components in Relation to Obesity and Insulin Resistance in Postmenopausal Osteoporosis.

Introduction. Osteoporosis (OP) affects 30% of postmenopausal women, often complicated by metabolic syndrome (MetS) with a still controversial role. We aimed to characterize MetS and its components in relation to bone mineral density (BMD), body mass index (BMI), and insulin resistance. Methods. Patients (n = 188) underwent DEXA scans, spine X-rays, and metabolic and hormonal investigations, including bone biomarkers, muscular strength, and physical performance tests, while insulin resistance was evaluated by the Homeostasis Model Assessment (HOMA-IR). Results. Patients with a normal BMD or osteopenia (n = 68) and with OP (n = 120) displayed 51.5% and 30.8% of MetS, but without differences in insulin resistance. When BMD was studied as a function of the cumulative MetS criteria and centiles of BMI, lower levels of BMD were observed beyond an inflection point of 27.2 kg/m2 for BMI, allowing for further stratification as lean and overweight/obese (OW/OB) subjects. In contrast with lean individuals (n = 74), in OW/OB patients (n = 46), MetS was associated with HbA1c (p < 0.0037, OR 9.6, 95% CI [1.64-55.6]) and insulin resistance (p < 0.0076, OR 6.7, 95% CI [1.49-30.8]) in the context where BMD values were lower than those predicted from BMI in non-OP subjects. In OP patients with fragility fractures (31% of MetS), glycemia also appeared to be the dominant factor for MetS (p < 0.0005, OR 4.1, 95% CI [1.63-10.39]). Conclusions. These data indicate a detrimental effect of insulin resistance in MetS on OP patients, while the prevalence of the syndrome depends on the proportion of obesity. These findings provide new insights into the pathogenic role of MetS and reveal the need to consider different strata of BMI and insulin resistance when studying postmenopausal OP.

Dietary Amino Acid Composition and Glycemic Biomarkers in Japanese Adolescents.

Protein intake reportedly increases the risk of diabetes; however, the results have been inconsistent. Diabetes in adulthood may be attributed to early life dietary amino acid composition. This study aimed to investigate the association between amino acid composition and glycemic biomarkers in adolescents. Dietary intake was assessed using a food frequency questionnaire, and fasting glucose and insulin levels were measured in 1238 eighth graders. The homeostatic model assessment (HOMA) indices (insulin resistance and ß-cell function) were calculated. Anthropometrics were measured and other covariates were obtained from a questionnaire. Amino acid composition was isometric log transformed according to the compositional data analysis, which was used as explanatory variables in multivariate linear regression models for glucose, insulin, and HOMA indices. Only the association between glucose and leucine was significant. In replacement of other amino acids with leucine, an increase of 0.1% of total amino acids correlated with a lower glucose level (-1.02 mg/dL). One-to-one substitution of leucine for isoleucine or methionine decreased glucose (-2.98 and -2.28 mg/dL, respectively). Associations with other biomarkers were not observed. In conclusion, compositional data analysis of amino acids revealed an association only with glucose in adolescents; however, the results of this study should be verified in other populations.

Simple proxies of insulin resistance identify obese metabolic dysfunction-associated fatty liver disease subjects with advanced liver disease.

AIMS: Insulin resistance (IR) plays a pivotal role in the pathogenesis of Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD), which can progress to liver fibrosis. We examined the relationship of different IR scores with markers of MAFLD severity in obese individuals. MATERIALS AND METHODS: In this retrospective observational study, 346 non-diabetic, overweight/obese individuals with newly diagnosed MAFLD (age 50.2 ± 13.3 years, 34% females, BMI 30.8 ± 4.4 kg/m2 ) underwent liver stiffness (LS) and controlled attenuation parameter (CAP) measurements by Fibroscan® to assess liver fibrosis and steatosis. Biochemical data were collected to calculate surrogate markers of IR (Homoeostasis model assessment - insulin resistance index [HOMA-IR], triglyceride-glucose index, triglyceride by HDL ratio), liver fibrosis (Nonalcoholic Fatty Liver Diseases fibrosis score, fibrosis-4 score, Aspartate aminotransferase to platelet ratio index) and steatosis (fatty liver index, hepatic steatosis index). RESULTS: All three IR scores were associated with CAP, while only HOMA-IR positively correlated with LS (r = 0.275, p < 0.0001), independent of age and sex, BMI, transaminases, and fibrosis markers. Insulin-resistant individuals (HOMA-IR >2.5, n = 165) had higher liver enzymes, CAP and LS, with a 4-fold increased risk of severe liver disease (LS >9.7 kPa, OR 4.42[1.95-10.01], p = 0.0002). Among HOMA-IR components, fasting plasma insulin (FPI) was independently associated with LS (r = 0.270, p < 0.0001). ROC AUC for HOMA-IR and FPI to predict severe liver disease were virtually identical (0.748 and 0.758, respectively). CONCLUSIONS: HOMA-IR is independently associated with non-invasive markers of MAFLD severity in overweight/obese individuals. This relationship is largely mediated by hyperinsulinemia, regardless of BMI. Measuring insulin levels in MAFLD individuals might be useful to identify those at risk of liver fibrosis.

Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

BACKGROUND: Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk. METHODS: The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated. RESULTS: 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively (p < 0.001). The pubertal development (p < 0.03), systolic BP and diastolic BP z-scores (p = 0.002), heart rate (p < 0.001), and waist-to-height ratio (p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score (p = 0.001), heart rate (p < 0.01), and HOMA index (p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio. CONCLUSIONS: Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.

Multiple beneficial effects of 1-year nutritional-behavioral intervention on anthropometric and metabolic parameters in overweight and obese boys.

PURPOSE: Childhood obesity is on the rise worldwide increasing the risk for metabolic, cardiovascular and liver diseases in children. Eating habits and lifestyle changes are currently the standard of care for treating pediatric obesity. Our study aimed to determine the impact of a dietary intervention based on the Mediterranean Diet (MD) and the Health Eating Plate, on anthropometric and metabolic parameters in obese and overweight boys. METHODS: We studied 126 overweight/obese boys with anthropometric measurements, blood biochemistry and nutrient intakes evaluation by means of Food Frequency Questionnaire (FFQ) at baseline, at 6 and 12 months after a nutritional-behavioral intervention. RESULTS: We observed a significant reduction in energy, macronutrients and micronutrients intakes. BMI-SDS significantly decreased after 1 year with the proportion of obese boys decreasing by 33% and of overweight boys by 41%, while also all fat mass measures decreased both in obese and overweight individuals. In obese boys, ALT decreased significantly after 1-year nutritional intervention and these changes correlated with BMI-SDS reduction. Insulin-resistance and secretion indexes correlated with fat mass and BMI-SDS. In obese boys, significant changes were observed at 6 months for insulin concentrations, 1/HOMA-IR and QUICKI. With regard to the lipid profile, significant decreases were observed for total and LDL cholesterol in obese boys. CONCLUSION: Metabolic and anthropometric risk factors in overweight and obese boys can be improved by a nutritional-behavioral intervention of 1-year duration.

Role of Insulin Resistance as a Mediator of the Relationship between Body Weight, Waist Circumference, and Systolic Blood Pressure in a Pediatric Population.

Excess weight and high waist circumference (WC) are associated with increased blood pressure (BP), starting from the pediatric age. Insulin resistance is associated with elevated BP in childhood. The aim of the study was to assess the role of insulin resistance in mediating the relationship between body mass index (BMI), WC, and BP values in a pediatric population referred to a cardio-pediatric center for the presence of one or more cardiovascular risk factors. In 419 children (mean age 10.7 [standard deviation, SD 2.5] years), the following parameters were collected both in basal conditions and after 18.6 (SD 9.3) months of follow-up during which a treatment based on lifestyle and dietary modifications was given: systolic and diastolic BP (SBP and DBP), WC, plasma glucose, and insulin values. The HOMA (Homeostasis Model Assessment)-index was considered as an expression of insulin resistance. At baseline there was a significant correlation between HOMA-index and SBP z-score (ß = 0.081, p = 0.003), and insulin resistance was a mediator of the relationship between BMI and SBP z-score (p = 0.015), and between waist circumference to height (WtHr) and SBP z-score (p = 0.008). The effect of BMI z-score modifications on SBP z-score changes from baseline to follow-up was totally mediated by HOMA-index changes (p = 0.008), while HOMA-index only partially mediated the effect of WtHr modifications on SBP z-score changes (p = 0.060). Our study strongly suggests that, in a pediatric population at cardiovascular risk, the HOMA-index is an important mediator of the relationship between BMI, WC and SBP.

INSULIN RESISTANCE AND PATHOGENESIS OF POSTMENOPAUSAL OSTEOPOROSIS.

Osteoporosis (OP) is a disease predisposing postmenopausal women to fractures, and often accompanied by insulin resistance (IR) and metabolic syndrome (MetS). Previous studies provided contradictory results concerning prevalence of MetS in postmenopausal OP. To better understand the pathogenesis of IR, we reviewed cellular and molecular aspects and systematically reviewed studies providing homeostasis model assessment (HOMA) index. Bone is an active endocrine organ maintaining its integrity by orchestrated balance between bone formation and resorption. Both osteoblasts and osteoclasts contain receptors for insulin and insulin-like growth factor-1 (IGF-1) operating in skeletal development and in the adult life. Defects in this system generate systemic IR and bone-specific IR, which in turn regulates glucose homeostasis and energy metabolism through osteocalcin. Examination of genetic syndromes of extreme IR revealed intriguing features namely high bone mineral density (BMD) or accelerated growth. Studies of moderate forms of IR in postmenopausal women reveal positive correlations between HOMA index and BMD while correlations with osteocalcin were rather negative. The relation with obesity remains complex involving regulatory factors such as leptin and adiponectin to which the contribution of potential genetic factors and in particular, the correlation with the degree of obesity or body composition should be added.

Endocrine Evaluation and Homeostatic Model Assessment in Patients with Cornelia de Lange Syndrome.

Objective: The aim of this study was to expand knowledge about endocrine disorders in individuals with Cornelia de Lange syndrome (CdLS), a rare developmental genetic disorder with anomalies in multiple organs and systems. Methods: Hormone levels, clinical scores, anthropometric measurements, and molecular analysis were assessed in 24 individuals with CdLS. Results: Hyperprolactinemia was the most common endocrine disorder. Three patients showed subclinical hypothyroidism. In the gonadotropic axis, mildly delayed puberty was observed, as well as genital anomalies, such as cryptorchidism. Despite short stature, levels of insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 were normal, on average. Three prepubertal individuals without risk factors had higher than normal values for the homeostatic model assessment of insulin resistance (HOMA-IR) and for insulinemia, suggesting insulin resistance. Furthermore, two adults had elevated BMIs associated with HOMA-IR values over the cut-off values. Conclusion: CdLS can lead to dysregulation of the endocrine system, particularly in patients with high HOMA-IR values and insulinemia who are at risk of insulin resistance. Therefore, clinical follow-ups with hormonal assessments are proposed for individuals with CdLS.

Preoperative factors correlated with post-bariatric surgery weight loss.

Whether preoperative parameters can predict weight loss following bariatric surgery is a matter of debate. We conducted a longitudinal and prospective pilot study on 35 patients that underwent bariatric surgery, with a 12-month follow-up. In the preoperative period, a high HOMA-beta index, lower fasting blood glucose, and lower HbA1c were correlated with a lower BMI at 12 months. Traditional preoperative factors, such as weight and BMI, were correlated with the postoperative BMI values. The presence of well-controlled diabetes may influence weight loss after surgery.

Association of obesity phenotypes with left ventricular mass index and left ventricular hypertrophy in children and adolescents.

It has been argued that metabolically healthy obesity (MHO) does not increase the risk of cardiovascular disease. The aim of this study is to evaluate whether, in a population of obese children/adolescents, the metabolically unhealthy obesity (MUO) phenotype is associated with higher left ventricular mass index and/or higher prevalence of left ventricular hypertrophy than the MHO phenotype. We also tested whether the addition of an insulin resistance index (HOMA-index >90th percentile by sex and age) and the presence of hyperuricemia (serum uric acid >90th percentile by sex and age) to the definition of MUO better identified obese children with early cardiac damage. Left ventricular hypertrophy was defined as the presence of left ventricular mass index greater than or equal to the age- and sex-specific 95th percentile. The study population included 459 obese children (males 53.2%, mean age 10.6 [standard deviation, 2.6] years), of whom 268 (58.4%) were MUO. The left ventricular mass index was higher in MUO children than in MHO children (37.8 vs 36.3 g/m2.7, p=0.015), whereas the percentage of MUO children presenting left ventricular hypertrophy was only slightly higher in MUO children (31.1 vs 40%, p=0.06). Multiple linear regression analyses showed that the variables significantly associated with higher left ventricular mass index were male gender (p<0.01), Body Mass Index z-score (p<0.001) and Waist-to-Height-ratio (p<0.001). Multiple logistic regression analyses showed that the presence of left ventricular hypertrophy was only significantly associated with higher Body Mass Index z-score (p<0.05) and Waist-to-Height-ratio (p<0.05). In spite of the higher left ventricular mass index of MUO as compared to MHO children, the MUO phenotype was not a significant predictor of either higher left ventricular mass index or higher left ventricular hypertrophy prevalence. The MUO phenotype had a low predictive ability on the presence of left ventricular hypertrophy. The area under the receiver operating characteristic curve was 0.57 (sensitivity 0.64, 1-specificity 0.55). The addition of insulin resistance and hyperuricemia to the definition of MUO did not change the results observed with the standard definition of MUO at multivariable analysis. The MUO phenotype appears to be of little usefulness in identifying the early presence of cardiac damage in a large population of obese children and adolescents. Excess weight and abdominal obesity are confirmed as an important determinant of early organ damage in obese children.

Elevated heart rate as sympathetic biomarker in human obesity.

BACKGROUND AND AIM: The present study was aimed at determining whether and to what extent a specific heart rate (HR) cutoff value allows to identify in obeses a more pronounced level of adrenergic overdrive. METHODS AND RESULTS: In 86 obese subjects aged 44.7 ± 0.9 (mean ± SEM) years and in 45 heathy lean controls of similar age we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the subjects in 3 different groups according to their resting clinic and 24-h HR values (<70, 70-79 and 80-89 beats/minute). MSNA and plasma NE values detected in the three obese groups were almost superimposable each other, no significant difference between groups being observed. A similar behavior was observed when HR values were assessed during the 24-h Holter monitoring. In the group as a whole no significant relationship was detected between MSNA, plasma NE and clinic HR, this being the case also when 24-h HR replaced clinic HR in the correlation analysis. In contrast lean controls displayed a progressive significant increase in MSNA values form the group with clinic (and 24 Holter) values below 70 beats/minute to the ones with HR values between 70 and 79 and above 80 beats/minute. CONCLUSIONS: In the obese state measurement of resting HR may allow to provide some general information on the functional status of the adrenergic cardiovascular drive. When the information required, however, are more subtle the sensitivity of the approach appears to be reduced and HR cannot be regarded as a faithful sympathetic biomarker.

Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS.

Thyroid hormones are normally involved in glycaemic control, but their excess can lead to altered glucose metabolism and insulin resistance (IR). Since hyperthyroidism-linked increase in ROS results in tissue oxidative stress that is considered a hallmark of conditions leading to IR, it is conceivable a role of ROS in the onset of IR in hyperthyroidism. To verify this hypothesis, we evaluated the effects of vitamin E on thyroid hormone-induced oxidative damage, insulin resistance, and on gene expression of key molecules involved in IR in the rat liver. The factors involved in oxidative damage, namely the total content of ROS, the mitochondrial production of ROS, the activity of antioxidant enzymes, the in vitro susceptibility to oxidative stress, have been correlated to insulin resistance indices, such as insulin activation of hepatic Akt and plasma level of glucose, insulin and HOMA index. Our results indicate that increased levels of oxidative damage ROS content and production and susceptibility to oxidative damage, parallel increased fasting plasma level of glucose and insulin, reduced activation of Akt and increased activation of JNK. This last result suggests a role for JNK in the insulin resistance induced by hyperthyroidism. Furthermore, the variation of the genes Pparg, Ppara, Cd36 and Slc2a2 could explain, at least in part, the observed metabolic phenotypes.

The Interaction Between Dietary Total Antioxidant Capacity and MC4R Gene and HOMA-IR in Metabolically Healthy and Unhealthy Overweight and Obese Women.

Introduction: The current prevalence of the metabolically healthy obesity is about 3%. Genetic and nutrition are influencers of such phenotypes. The main goal of this study was to assess the interaction between Dietary Total Antioxidant Capacity (DTAC) and the genotypes of MC4R and Insulin resistance in metabolically healthy/unhealthy overweight and obese women in Iran. Material And Methods: This cross-sectional study was conducted on 237 overweight-obese women with a mean age of 36. The value of Dietary total antioxidant capacity (DTAC) was calculated using the following indices: Total reactive antioxidant potential (TRAP), Trolox equivalent antioxidant capacity (TEAC), and ferric reducing ability of plasma (FRAP). The Metabolic health status was evaluated using the Karelis criteria. Melanocortin 4 receptor single nucleotide polymorphisms were determined by the restriction fragment length polymorphism (PCR-RFLP) method. Also, insulin resistance was evaluated through homeostasis model assessment (HOMA). Result: Our data noted that 72.96% of participants presented Unhealthy Metabolically and 26.94% Healthy Metabolically including 33.5% of the total had T/T genotype, 23.8% had the C/T genotype, and 42.5% had the C/C genotype (P = .05). A linear regression model test showed that the probability of metabolically healthy obesity was significantly higher in patients with the T/C genotype. The test value was statistically significant (95% CI: 0.000-0.001; P = .056, ß = 0). No statistically significant relation was observed between study parameters and DTAC values. HOMA-Index was higher in all unhealthy subjects significantly. Conclusions: The findings indicated that there are significant associations between genotypes of rs1333048 SNP and DTAC. The C/C genotype subjects with higher DTAC had a better lipid profile and were metabolically healthier.

THE ROLE OF LEPTINRESISTANCE IN THE PATHOGENESIS OF OBESITY IN PREGNANT WOMEN.

OBJECTIVE: The aim: To investigate the relationship between leptin resistance, lipid and carbohydrate metabolism, blood pressure in obese pregnant women. PATIENTS AND METHODS: Materials and methods: Under observation were 65 women (main group) with obesity (I degree -27 women, II degree - 24 women, III degree - 14 women) in the II trimester of pregnancy, who were hospitalized in the Department of Pathology of Pregnancy KNP «Maternity Clinical house №1 "in Lviv during 2017-2020 on preeclampsia of varying severity, which were sent for inpatient treatment by women's clinics. The control group consisted of 30 healthy pregnant women without obesity. RESULTS: Results: Serum leptin in obese women was directly correlated with BMI (r = 0.66, p<0.001), body weight (r = 0.29, p<0.05), total cholesterol (cholesterol) (r = 0, 37, p<0,009), low density lipoproteins (LDL cholesterol) (r = 0.33, p<0.05) and inversely with high density particles (HDL cholesterol) (r = -0.37, p<0.02 ). Studies of carbohydrate metabolism indicate the following correlation coefficients of BMI with glucose level r = 0.351; p<0,001, BMI with the level of C-peptide r = 0,450; p<0,001, BMI with HOMA index r = 0,1504; p = 0.036. Inverse correlations of C-peptide were detected with the level of P (r = -0.169; p = 0.025). CONCLUSION: Conclusions: The discovery of the relationship between leptin resistance, lipid and carbohydrate metabolism, blood pressure indicates the possibility of using signs of leptin resistance to prevent complications during pregnancy in the second trimester.

Dietary Magnesium Intake Affects the Vitamin D Effects on HOMA-ß and Risk of Pancreatic ß-Cell Dysfunction: A Cross-Sectional Study.

Background: Some studies have shown that, the circulating vitamin D (Vit D) concentration in the body exerts a crucial role in regulating the pancreatic ß-cell function. Meanwhile, the role of magnesium is important in the synthesis of Vit D, since it is an essential element for activating Vit D. Nevertheless, there remains insufficient studies concerning whether dietary Magnesium intake influences the association between Vit D and risk of pancreatic ß-cell dysfunction. Hence, this cross-sectional study aimed to assess the effect of Magnesium intake alterations on the association between serum Vit D levels and the risk of pancreatic ß-cell dysfunction. Methods: This large-scale cross-sectional study involves four cycles of National Health and Nutrition Examination Survey (NHANES) (2007-2014), with totally 4,878 participants. Groups were divided depending on the median daily intake of Magnesium, namely, the low intake group (Magnesium intake <267 Magnesium/d) and the high intake group (Magnesium intake ≥ 267 Magnesium/d). By constructing multiple multivariate linear and logistics regression models, the associations between serum Vit D levels and HOMA-ß, as well as between serum Vit D levels and the risk of pancreatic ß-cell dysfunction were explored at different Magnesium intakes. Results: In this cross-sectional study, the serum Vit D level is independently correlated with the HOMA-ß index [ß: 0.65 (0.40-0.90)] and the risk of pancreatic ß-cell dysfunction [OR: 0.95 (0.92-0.98)]. Moreover, such correlations are affected by different dietary Magnesium intakes (P for interaction < 0.001). Conclusion: According to the results of this study, the dietary Magnesium intake influences the associations of serum Vit D levels with HOMA-ß index and pancreatic ß-cell dysfunction. Besides, the finding requires validation through more RCT or cohort studies.

First Year Metabolic and Hormonal Behavior Define two Different Populations of SGA Newborn for Weight or Height.

Context: Small-for-gestational-age (SGA) children have a particular metabolic and hormonal pattern at birth that changes rapidly. Objective: To evaluate the linear and weight growth in the first year of life in SGA children. Design: Prospective, monocentric cohort study. Setting: Real-world data collected from April 2012 to January 2016. Patients: SGA newborns uniformly defined by either growth or length lower than -2 SDs for gestational age. Interventions: All children were evaluated for 1 year after birth, at 3 days of life, then 3, 6, and 12 months after birth. Main outcome measures: Anthropometric parameters and biochemical variables, such as blood glucose, insulin, leptin, IGF-1, IGF binding protein-3 (IGFBP-3), and homeostasis model assessment - insulin resistance (HOMA-IR) index. Results: A total of 133 SGA children were enrolled. Length significantly improved 1 month after birth, whereas weight significantly increased only at 3 months after birth. Biochemical variables increased during the first year of life, showing a prediction by IGFBP-3 and HOMA-IR index. Then, the variables were divided considering either weight, length, or both, showing a different incidence. The biochemical variable changes recorded in the first step were maintained considering SGA children for weight or length, whereas they disappeared when weight and length were considered together. Conclusions: Our study shows a specific catchup growth for weight and length in SGA children. Moreover, we highlight that weight and length should be considered as independent parameters in SGA children, defining 2 different metabolic-hormonal populations with different conceivable predictive role in early catchup growth and in later growth and metabolic status.

HOMA Index, Vitamin D Levels, Body Composition and Cardiorespiratory Fitness in Juvenile Obesity: Data from the CHILT III Programme, Cologne.

Juvenile obesity is associated with insulin resistance, among other comorbidities. In the pathogenesis of insulin-resistance-related diseases, including obesity and diabetes, Vitamin D deficiency is very common. Therefore, the relationship between insulin resistance, body composition, vitamin D level, and cardiorespiratory fitness in obese children and youth were analyzed based on the Children's Health InterventionaL Trial III project, Germany. Data on vitamin D levels and homeostatic model assessment (HOMA) indices were available from 147 participants (52.4% female; 90.5% obese; 12.3 ± 2.3 years, BMI: 30.5 ± 5.2 kg/m2, BMI standard deviation score (BMI-SDS): 2.52 ± 0.46). Vitamin D levels correlated negatively with the HOMA index, BMI, BMI-SDS, abdominal circumference, and body fat percentage but positively with relative cardiorespiratory fitness (p < 0.05 in each case). In the backward stepwise linear regression analysis, body fat (in kg; ß = 0.403) and vitamin D levels (ß = -0.154) explained 21.0% of the variance in the HOMA index. In summary, increased body fat and lower vitamin D levels are associated with increased HOMA indices in overweight and obese children and adolescents. In order to prevent potential negative consequences, including the development of manifest Type 2 diabetes, a healthy lifestyle with a vitamin-D-enriched diet and more time spent outdoors should be promoted.

Effects of delta-tocotrienol supplementation on glycaemic control in individuals with prediabetes: A randomized controlled study.

OBJECTIVE: To study the effects of delta-tocotrienol on glycaemic control parameters in individuals with pre-diabetes. METHODS: The randomised control trial was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from July 15 to November 15, 2019, and comprised individuals aged 18-60 years having fasting plasma glucose of 5.6 to 6.9 mmol/L or glycosylated haemoglobin of 5.7 to 6.4%. They were randomised into group A receiving 300mg delta-tocotrienol and group B receiving a placebo once daily for 12 weeks. Weight, height, waist circumference, fasting plasma glucose, insulin and glycosylated haemoglobin were measured at the beginning and end of the trial to assess any change. Body mass index and homeostatic model assessment-insulin resistance were also calculated. Data was analysed using SPSS 21. RESULTS: Of the 77participants, 40(52%) were in group A and 37(48%) in group B. Group A showed significantly greater reduction in terms of fasting plasma glucose, glycosylated haemoglobin, insulin and homeostatic model assessment-insulin resistance index (p≤0.001) post-intervention. CONCLUSIONS: Delta-tocotrienol supplementation was found to have a significant effect in improving glycaemic control parameters in persons with pre-diabetes. Futures larger scale clinical trials are needed to confirm these findings. CLINICAL TRIAL NUMBER: SLCTR/2019/024.

Correlation of Surrogate Markers of Insulin Resistance with Fasting Insulin in Type 2 Diabetes Mellitus Patients: A Study of Malwa Population in Punjab, India.

Context Insulin resistance (IR) and abnormal insulin secretion play a key role for the development of type 2 diabetes mellitus (DM). Aims We investigated the surrogate markers of IR, i.e., Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), McAuley, and Fasting Insulin Resistance Index (FIRI) in type 2 DM patients. Also, fasting insulin (FI) levels were estimated in type 2 diabetics. Further, the correlation of FI with other surrogate markers of IR in type 2 DM was done. Settings and Design A hundred newly diagnosed patients with type 2 DM from Malwa population, Punjab, were considered for evaluation. Another 100 healthy individuals (age and sex-matched) were examined as controls. Methods and Material Fasting blood glucose, FI, and lipid profile were estimated, and IR was calculated using McAuley index (McA), HOMA, QUICKI, and FIRI. Statistical Analysis Used The statistical analysis was performed on the above-mentioned clinical interpretations. The Cohen's kappa test was used to affirm the agreement. Results FI levels in patients with type 2 diabetes were significantly higher (20.8 ± 9.05 µIU/L) than controls (7.93 ± 1.01 µIU/L). IR by surrogate markers was found significant in the study group. The 76% patients with type 2 diabetes ended up as resistant to insulin by FI measurement, almost equivalent to McA, 80%; HOMA, 88%; FIRI, 88%; and QUICKI, 90%. A notable correlation was highlighted between FI and McA manifesting IR ( p < 0.01, r = -0.85). We calculated the statistical correlation of FI with HOMA, QUICKI, and FIRI indices ( p < 0.01, r = 0.93; p < 0.01 r = -0.92; and p < 0.01, r = +0.93, respectively). The agreement visible from Cohen's kappa test also affirms the same ( k = 0.9 for McA). Conclusion We concluded that all the surrogate markers for IR were specific when compared with FI, but in terms of sensitivity McA was found to be more sensitive as it includes markers of dyslipidemia, which is the precipitating factor of metabolic derangements so as the IR in type 2 DM.