Homeostatic Model Assessment Values Research Articles

The relationship and diagnostic efficacy of N-terminal propeptide type III collagen in pathological changes associated with non-alcoholic steatohepatitis.

This study delves into the role of N-terminal propeptide type III collagen (PIIINP) in the diagnosis and management of liver pathological changes associated with non-alcoholic steatohepatitis (NASH). We collected baseline information, pathological data, and serum PIIINP levels of 168 patients diagnosed with non-alcoholic fatty liver disease (NAFLD) via ultrasound imaging in our hospital. Based on the non-alcoholic fatty liver disease activity score (NAS), patients with different NAFLD patterns were divided into a Definite NASH group and a Not/borderline group. Differences in PIIINP levels and pathological features between the two groups were compared and analyzed. The diagnostic value of PIIINP for NASH was evaluated using the receiver operating characteristic (ROC) curve. Patients with NASH exhibited significantly higher values of homeostatic model assessment for insulin resistance (HOMA-IR), fibrosis biomarker fibrosis-4 (FIB-4), aminotransferase-to-platelet ratio index (APRI), and serum PIIINP levels than those classified as Not/borderline. A marked increase in the serum concentrations of PIIINP was observed with the severity of fatty degeneration, lobular inflammation, and hepatocellular ballooning. The AUC of PIIINP for diagnosing definite NASH was 0.766 (95% CI: 0.694, 0.839), APRI was 0.634 (95% CI: 0.549, 0.718), and FIB-4 was 0.621 (95% CI: 0.534, 0.708). The AUC of PIIINP for diagnosing definite NASH was significantly higher than that of APRI and FIB-4 (all p<0.05). Utilizing the predetermined threshold values for diagnostic parameters, the PIIINP measure demonstrated a sensitivity of 71.6% and a specificity of 73.6% in diagnosing definitive NASH when its value exceeded 7.72 ng/dL. This yielded a Youden index of 0.45. Similarly, when the APRI measure exceeded 0.21, it exhibited a sensitivity of 60.5% and a specificity of 63.2%, resulting in a Youden index of 0.24. Moreover, when the FIB-4 index surpassed 0.26, it showed a sensitivity of 46.9% and a specificity of 79.3%, culminating in a Youden index of 0.26. NASH patients in this study exhibited significantly elevated PIIINP serum levels, which were closely associated with hepatocyte pathological changes. PIIINP demonstrated superior competence in diagnosing NASH than APRI and FIB-4 and thus offers a viable alternative for the clinical diagnosis of NASH.

Vitamin D deficiency in adolescents: is there a difference according to the degree of obesity?

To analyze the frequency of vitamin D (VD) deficiency in adolescents with different degrees of obesity and its association with alterations in the metabolic profile. Cross-sectional, descriptive, and analytical study in 250 adolescents with different degrees of obesity, treated at the nutrition polyclinic of the Hospital Dr. Sotero del Río. Data on age, sex, weight, height, Tanner stage, 25-hydroxyvitamin D levels, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, basal insulin, and glycemia were collected. The following were used for statistical analysis: Student's test, chi-square, multiple linear regression analysis, and Pearson's correlation coefficient. 58% of the adolescents presented non-severe obesity and 42% severe obesity, the mean age was 12.4 ± 2.1 years, and 54% were male. 91% of the total sample presented VD deficiency, being more frequent among adolescents with severe obesity, reaching 95%. VD levels were significantly lower in winter. HOMA (homeostatic model assessment) values were higher among patients with severe obesity (6.3/4.2). Low HDL-c was more frequent in adolescents with severe obesity (78%/62%). An inverse correlation was found between VD and triglyceride levels (r = -0.20; p = 0.00) and total cholesterol (r = -0.15; p = 0.03). The VD deficiency among obese adolescents is worrying, reaching more than 90% of the study sample. Our results highlight the importance of timely prevention, detection, and treatment of VD deficiency in obese adolescents to prevent bone health deterioration and cardiometabolic risk in adulthood.

Prediction of type 2 diabetes using genome-wide polygenic risk score and metabolic profiles: A machine learning analysis of population-based 10-year prospective cohort study.

Previous work on predicting type 2 diabetes by integrating clinical and genetic factors has mostly focused on the Western population. In this study, we use genome-wide polygenic risk score (gPRS) and serum metabolite data for type 2 diabetes risk prediction in the Asian population. Data of 1425 participants from the Korean Genome and Epidemiology Study (KoGES) Ansan-Ansung cohort were used in this study. For gPRS analysis, genotypic and clinical information from KoGES health examinee (n=58,701) and KoGES cardiovascular disease association (n=8105) sub-cohorts were included. Linkage disequilibrium analysis identified 239,062 genetic variants that were used to determine the gPRS, while the metabolites were selected using the Boruta algorithm. We used bootstrapped cross-validation to evaluate logistic regression and random forest (RF)-based machine learning models. Finally, associations of gPRS and selected metabolites with the values of homeostatic model assessment of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) were further estimated. During the follow-up period (8.3±2.8 years), 331 participants (23.2%) were diagnosed with type 2 diabetes. The areas under the curves of the RF-based models were 0.844, 0.876, and 0.883 for the model using only demographic and clinical factors, model including the gPRS, and model with both gPRS and metabolites, respectively. Incorporation of additional parameters in the latter two models improved the classification by 11.7% and 4.2% respectively. While gPRS was significantly associated with HOMA-B value, most metabolites had a significant association with HOMA-IR value. Incorporating both gPRS and metabolite data led to enhanced type 2 diabetes risk prediction by capturing distinct etiologies of type 2 diabetes development. An RF-based model using clinical factors, gPRS, and metabolites predicted type 2 diabetes risk more accurately than the logistic regression-based model. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2019M3E5D1A02070863 and 2022R1C1C1005458). This work was also supported by the 2020 Research Fund (1.200098.01) of UNIST (Ulsan National Institute of Science & Technology).

Mesenchymal Stem Cells Ameliorate Hyperglycemia in Type I Diabetic Developing Male Rats

One of the most promising treatments for diabetes mellitus (DM) is stem cell therapy. This study is aimed at elucidating the antidiabetic effect of mesenchymal stem cells (MSCs) on streptozotocin- (STZ-) induced DM in developing male rats. Twenty-four male albino rats (4 weeks old) were divided into control, diabetic, diabetic+MSCs1 (received MSCs one week after STZ treatment), and diabetic+MSCs2 (received MSCs 4 weeks after STZ treatment). Diabetic rats showed marked impairment (p < 0.05) in serum levels of glucose, insulin, C-peptide, glycosylated hemoglobin (HbA1c), malondialdehyde (MDA), total antioxidant status (TAS), and total oxidant status (TOS) in addition to disruption of the calculated values of homeostatic model assessment of insulin resistance (HOMA-IR), pancreatic β cell function (HOMA-β), and oxidative stress index (OSI). These biochemical alterations were confirmed by the histopathological and ultrastructural assessments which showed marked destructive effect on pancreatic islet cells. MSC therapy in an early stage reversed most of the biochemical, histological, and ultrastructural alterations in the STZ-induced diabetic model and restored the normal cellular population of most acinar cells and islet of Langerhans. These results indicate that MSC therapy of STZ-induced diabetic developing rats during an early stage has the capacity of β cell restoration and the control of blood glycemic homeostasis.

Associations of accumulated selected persistent organic pollutants in adipose tissue with insulin sensitivity and risk of incident type-2 diabetes

Continuous exposure to low doses of persistent organic pollutant (POPs), such as those occurring in the general population, might contribute to the burden of type 2 diabetes mellitus (T2DM). However, evidences from longitudinal studies are scarce. We aimed to explore the associations of accumulated POP exposure with the development of T2DM by means of 1) longitudinal associations with the 16-year incidence of the disease, and 2) complementary cross-sectional analyses with markers of glucose homeostasis at recruitment. Organochlorine pesticide and polychlorinated biphenyl (PCB) concentrations were analyzed in adipose tissue samples and incident T2DM cases were retrieved from clinical records. Homeostatic model assessment values of insulin sensitivity/resistance and β-cell function at recruitment were calculated. Linear and Cox-regression models were performed. In individuals with normal weight/overweight (n = 293), we observed positive dose–response relationships between the studied POPs and T2DM risk, particularly for hexachlorobenzene (HCB) [hazard ratio (HR): 3.96 for 4th quartile versus 1st quartile (Q1); confidence interval (CI) 95%: 0.79, 19.71]. PCB-180 showed a positive but seemingly non-linear association with T2DM risk [HR of 3er quartile (Q3) versus Q1: 6.48; CI 95%: 0.82, 51.29]. Unadjustment for body mass index considerably increased the magnitude of the associations. In the cross-sectional study (n = 180), HCB and PCB-180 were inversely associated with insulin sensitivity and positively associated with insulin resistance parameters. Our results suggest that a higher burden of specific POPs in adipose tissue may disrupt glucose homeostasis, possibly contributing to increase T2DM risk, especially in non-obese adults.

Alleviation of diabetes mellitus through the restoration of β-cell function and lipid metabolism by Aloe vera (L.) Burm. f. extract in obesogenic WNIN/GR-Ob rats

Ethnopharmacological relevanceAloe vera (L.) Burm. f. extract has been medicinally used for over 5000 years in different cultures for its curative and therapeutic properties ranging from dermatitis to diabetes. It has been demonstrated to alleviate diabetes through its protective effects on pancreatic islets and by improving insulin secretion. Aim of the studyTo investigate the simultaneous effect of ethanolic A. vera gel extract on diabetes and obesogenic milieu in Streptozotocin-induced WNIN/GR-Ob mutant obese rats. Materials and methodsA total of 30 rats were grouped equally into WNIN/GR-Ob control (received water as a vehicle), WNIN/GR-Ob Diabetic rats (Streptozotocin-35 mg/kg bw), WNIN/GR-Ob Diabetic rats + Sitagliptin (10 mg/kg bw), WNIN/GR-Ob Diabetic rats + A. vera (300 mg/kg bw) and GR-Ob control + A. vera (300 mg/kg bw). After 4 weeks of treatment, fasting blood glucose, serum insulin, Homeostatic Model Assessment - Insulin Resistance and β-cell function, glucose-stimulated insulin secretion, Dipeptidyl peptidase-IV activity, and lipid profiles were studied. In addition, ultrastructural analysis of isolated islets and dual-energy X-ray absorptiometry analysis for body composition were also carried out. ResultsThe A. vera treated group showed a significant reduction (p < 0.05) in triglyceride, Very low-density lipoprotein levels, Triglyceride to High-density lipoprotein ratio as well as fasting blood glucose levels and DPP-IV activity with a concomitant increase in the serum insulin levels. The increase in IR was observed in both WNIN/GR-Ob control and diabetic rats with a significant decrease in β-cell function in the diabetic rats as per Homeostatic Model Assessment values. Oral administration of A. vera was effective in both reducing Homeostatic Model Assessment-Insulin Resistance and increasing Homeostatic Model Assessment-β values. Also, the treated group demonstrated preservation of islets and a significant increase (p < 0.05) in the diameter of β-cell as evident through Scanning electron microscope analysis. The increase in lean body mass was manifested in the treated group with a reduction in Fat percent in comparison with other groups. ConclusionThe beneficial effects of A. vera in WNIN/GR-Ob strain may be attributed to its ability to lower lipid profile thus improve insulin sensitivity and/or modulating β-cell function. Thus, it has great therapeutic potential as an herbal remedy for the treatment of diabetes and associated adverse effects such as obesity. The exact mechanism underlying the observation needs to be investigated further to explore the anti-obesity and anti-diabetic properties of A. vera and advocate its potential application as alternative medicine.

Could SCGF-Beta Levels Be Associated with Inflammation Markers and Insulin Resistance in Male Patients Suffering from Obesity-Related NAFLD?

One of the pathologic hallmarks of obesity is macrophage infiltration of adipose tissue that has been confirmed as source of multipotent adult stem cells. Stem cell growth factor-beta (SCGF-β) shows activity on granulocyte/macrophage progenitor cells in combination with granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Obesity-associated inflammation induces insulin resistance (IR), which is central to nonalcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). We searched for relationship between levels of SCGF-β and those of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-β (TNF-β), interleukin-12p40 (IL-12p40), interleukin-10 (IL-10), ferritin, GM-CSF and M-CSF and between SCGF-β concentrations and IR in obese patients with HS. Eighty obese patients were retrospectively studied. Serum cytokines levels were appreciated by magnetic bead-based multiplex immunoassays. IR was evaluated by homeostatic model assessment (HOMA), HOMA-derived β-cell function (HOMA-B%), quantitative insulin sensitivity check Index (QUICKI) and single point insulin sensitivity estimator (SPISE). HS and spleen volume were assessed by ultrasonography (US). SCGF-β and IL-6 levels predicted HOMA values (p = 0.032 and 0.041, respectively) only in males. In male patients, CRP and IL-6 levels (p = 0.007) predicted SCGF-β concentrations (p = 0.03 and 0.007, respectively), which in turn predicted HS at US, p = 0.037. SCGF-β levels were linked to IR and HS severity with the mediation role of CRP. IL-10 levels negatively predicted SCGF-β concentrations (p = 0.033). M-CSF levels predicted serum concentration of both TNF-β and IL-12p40 (p = 0.00), but did not predict serum IL-10 (p = 0.30). Prediction of HOMA values by SCGF-β levels, likely mediated by markers of inflammation, characterizes this study, shedding some light on mechanisms inducing/worsening IR of male patients with obesity-related NAFLD.

Hypoxic exposure can improve blood glycemic control in high-fat diet-induced obese mice.

[Purpose]Blood glucose and insulin resistance were lower following hypoxic exposure in previous studies. However, the effect of hypoxia as therapy in obese model has not been unknown.[Methods]Six-week-old mice were randomly divided into chow diet (n=10) and high-fat diet (HFD) groups (n=20). The chow diet group received a non-purified commercial diet (65 % carbohydrate, 21 % protein, and 14 % fat) and water ad libitum. The HFD group was fed an HFD (Research Diet, #D12492; 60% kcal from fat, 5.24 kcal/g). Both groups consumed their respective diet for 7 weeks. Subsequently, HFD-induced mice (12-weeks-old) were randomly divided into two treatment groups : HFD-Normoxia (HFD; n=10) and HFD-Hypoxia (HYP; n=10, fraction of inspired=14.6%). After treatment for 4 weeks, serum glucose, insulin and oral glucose tolerance tests (OGTT) were performed.[Results]Homeostatic model assessment values for insulin resistance (HOMA-IR) of the HYP group tended to be lower than the HFD group. Regarding the OGTT, the area under the curve was 13% lower for the HYP group than the HFD group.[Conclusion]Insulin resistance tended to be lower and glucose uptake capacity was significantly augmented under hypoxia. From a clinical perspective, exposure to hypoxia may be a practical method of treating obesity.

Pulmonary function tests in type 2 diabetes mellitus and their association with glycemic status and insulin resistance

Type 2 diabetes mellitus (T2DM) is associated with long-term complications in different organs, and this is attributable to macrovascular and microvascular changes as reported by Fowler. Pulmonary complications, however, have been poorly characterised. The present study was a case–control study done at SRN Hospital, Prayagraj to correlate the pulmonary functions with glycemic status and insulin resistance in 100 patients with diabetes (cases) and compare these parameters in patients without diabetes (controls). Baseline values of fasting plasma glucose (FPG), prandial plasma glucose (PPG) and glycated hemoglobin (A1C) were significantly increased in cases as compared with controls. Forced expiratory volume (FEV1) (78.71% compared with 88.15%) and forced vital capacity (FVC) (67.48% compared with 96.58%) were both decreased in cases compared with controls but as decline in FVC was more compared with FEV1; their ratio, FEV1/FVC (121.70 as compared to 90.19), was increased in cases. FVC decreased with increase in A1C values (96.2%, 84.2%, 71.2% for A1C values 5.7%, 5.7–6.4% and > 6.4% respectively). FVC was also decreased for greater values of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (98.2% for HOMA-IR 2.5). The ratio of FEV1/FVC was more with higher values of A1C (103.3 for A1C > 2.5 and 91.1 for A1C < 2.5). FVC also decreased with increasing values of FPG (97.4%, 91.1% and 71.2% for FPG values of < 100 mg%, 100–125 mg% and ≥ 126 mg%). A total of 65% of patients had abnormal pulmonary function tests with predominance of restrictive pattern. This restrictive decline is significantly associated with increasing dysglycemia and insulin resistance. However, it is unrelated to levels of low-density lipoprotein (LDL) and duration of T2DM.

A Diet-Induced Pediatric Model of Non Alcoholic Fatty Liver Disease Using Neonatal Iberian Pigs (OR26-02-19)

ObjectivesThe prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high-fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. MethodsAnimals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n = 8), 22 g fructose, 16 g fat and 300 kcal (HFF-N; n = 6), CON + probiotic (CON-P; n = 6), or HFF + probiotic (HFF-P; n = 6) every 6 h for 70 d. The probiotic mixture (6.2 × 104cfu/mL) contained Pediococcus, Lactobacillus and Bacillus. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver tissue was collected on d 70 for histology, triacylglyceride (TG) quantification, and gene expression of tumor necrosis factor (TNF) α, tumor growth factor (TGF) β, interleukin (IL) 1α, peroxisome proliferator-activated receptor (PPAR) γ, carbohydrate-responsive element-binding protein (ChREBP) and sterol regulatory element-binding protein (SREBP) 1c. ResultsBody weight was higher in CON-P, and insulin and HOMA values in HFF-P and CON-P (P ≤ 0.05). Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF-N and HFF-P. Livers in HFF-P and HFF-N had higher relative weight and TG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). ConclusionsIberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. Funding SourcesARI, AcornSeekers.

Effect of high-dose dexamethasone on patients without diabetes during elective neurosurgery: a prospective study.

The peri-operative use of high-dose dexamethasone to reduce cerebral oedema may result in worsening glycaemic control in people with diabetes and glucocorticoid-induced diabetes in susceptible individuals. This study aims to examine the incidence of glucocorticoid-induced diabetes in a cohort of neurosurgical patients receiving high-dose dexamethasone peri-operatively. Adult non-diabetic neurosurgical patients receiving high-dose dexamethasone were prospectively studied. Exclusion criteria included pregnancy, HbA1c > 6.0%, and use of anti-diabetes therapies. The following data were collected: Family history of diabetes, body mass index, fasting glucose, insulin, C-peptide, and HbA1c (prior to surgery and 6 weeks after last dose of dexamethasone). Homeostatic model assessment values were calculated. Peri-operative glucose readings were recorded and 75g oral glucose tolerance tests performed at the end of 6weeks. Paired student t tests and multiple linear regressions were used. Data from 21 participants (11 women) were available. The mean total dose of dexamethasone was 96 ± 34mg, and treatment duration was 17 ± 7days. A total of 105 random blood glucose levels were documented peri-operatively (mean 7.0 ± 1.0mmol/L). Six weeks following cessation of dexamethasone course, none of the participants developed diabetes, defined either by fasting glucose or by 75g OGTT. There was a statistically significant increase in the mean HOMA-β from 81.5 to 102.1% (p = 0.01) and a significant decrease in the mean fasting glucose from 5.7 to 4.8mmol/L (p = 0.001). The use of high-dose dexamethasone in this cohort of neurosurgical patients did not result in glucocorticoid-induced diabetes. Hyperglycaemia was transient and had resolved by 6weeks.

Influence of vitamin D levels on the cardiovascular profile of hypogonadal men.

A large body of evidence suggests a role for vitamin D in conditioning cardiovascular risk. Therefore, it can be hypothesized that vitamin D might also play a role in influencing the metabolic profile of hypogonadal men. In this work, we aimed at evaluating if any relationship exists between vitamin D levels and cardiovascular parameters in male hypogonadism. Hypogonadal patients attending our andrology unit were retrospectively reviewed. Clinical and biochemical parameters were evaluated. 103 patients were studied (51 non-diabetic and 52 diabetic subjects). Mean age of the whole sample was 65years (standard error of the mean: 0.62). Significant correlations of age, total testosterone, parathyroid hormone (PTH), calcemia, and 25-OH vitamin D with the metabolic profile were found. In logistic regression models including age, total testosterone, PTH, calcemia and 25-OH vitamin D as independent variables, lower levels of 25-OH vitamin D were associated with high values of body mass index (BMI) [odds ratio (OR) 0.910, p 0.019], insulin (OR 0.918, p 0.034), homeostatic model assessment (HOMA) index (OR 0.918, p 0.030), total cholesterol (OR 0.819, p<0.001), triglycerides (OR 0.820, p<0.001), and low-density lipoprotein cholesterol (OR 0.923, p 0.034). In non-diabetic subjects, lower levels of 25-OH vitamin D were associated with high values of BMI, insulin, HOMA, triglycerides, systolic, and diastolic blood pressure. On the other hand, in diabetic subjects, lower levels of 25-OH vitamin D were associated with high values of total cholesterol and triglycerides. Our work shows the influence of vitamin D on cardiovascular profile in male hypogonadism. This effect seems to be more relevant in non-diabetic subjects. If these data were to be confirmed, vitamin D assessment might become mandatory in the clinical evaluation of cardiovascular profile in male hypogonadism.

Effects of thyroid hormone withdrawal on metabolic and cardiovascular parameters during radioactive iodine therapy in differentiated thyroid cancer.

ObjectiveTo investigate the cardiometabolic effects of a severe hypothyroid state induced by withdrawal of thyroid hormone replacement before radioactive iodine therapy.MethodsPatients with thyroid cancer who were scheduled to receive radioactive iodine ablation were enrolled. Cardiometabolic parameters were measured using blood samples taken immediately before levothyroxine withdrawal, 4 weeks following withdrawal (on radiotherapy day), and 4 weeks following reinstitution of levothyroxine.ResultsOut of 48 patients (age 49.4 ± 10.5 years; 77.1% [37/48] female), the severe hypothyroid state induced by levothyroxine withdrawal significantly aggravated the majority of lipid parameters, particularly in patients with a greater number of metabolic syndrome components. Fasting plasma glucose levels and homeostatic model assessment values for insulin resistance and β-cell function significantly decreased following levothyroxine withdrawal. Serum high-sensitivity C-reactive protein, fibrinogen and cystatin C levels significantly decreased, and homocysteine levels increased during the severe hypothyroid state. All of these changes were reversed by levothyroxine reinstitution.ConclusionsSevere hypothyroid state induced pronounced changes in cardiometabolic parameters. Further studies should identify the long-term effects of changes in these parameters on cardiovascular morbidity and mortality in relation to thyroid disease.

Metabolic changes in normal- and underweight children with obstructive sleep-disordered breathing

ObjectiveThis study evaluates the metabolic profile of normal- and underweight children with sleep-disordered breathing (SDB) due to adenotonsillar hypertrophy. MethodsA total of 39 children aged 3–15 years with SDB and 28 age- and gender-matched controls were included in the study. Body mass index z score, blood pressure, and fasting serum levels of triglycerides (TGs), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, very-low-density lipoprotein (VLDL), blood glucose, plasma insulin, and homeostatic model assessment (HOMA) were determined in both case patients and controls. ResultsWe observed significantly lower levels of fasting blood glucose (p = 0.015) and higher levels of HDL (p = 0.002), LDL (p = 0.002), and cholesterol (p = 0.001) in case patients than in controls. The mean values of fasting insulin and HOMA were higher in case patients (6.42 ± 6.47 and 1.40 ± 1.48) than in controls (5.31 ± 3.40 and 1.20 ± 0.84) respectively. No direct correlation between indices of severity of SDB and various metabolic and blood pressure parameters was found. When the effect of body weight was studied by subgrouping case patients according to normal weight and underweight, significant increases in the levels of fasting insulin (p = 0.039), HOMA (p = 0.017), and fasting blood glucose (p = 0.021) were observed. Also, a significant correlation was observed between the duration of illness and fasting insulin (p = 0.023), HOMA (p = 0.020), fasting glucose (p = 0.004), and diastolic blood pressure (p = 0.030). ConclusionThis study shows an independent effect of body weight and duration of illness on various metabolic and blood pressure parameters in normal- and underweight children with SDB

Dairy consumption and insulin resistance: the role of body fat, physical activity, and energy intake.

The relationship between dairy consumption and insulin resistance was ascertained in 272 middle-aged, nondiabetic women using a cross-sectional design. Participants kept 7-day, weighed food records to report their diets, including dairy intake. Insulin resistance was assessed using the homeostatic model assessment (HOMA). The Bod Pod was used to measure body fat percentage, and accelerometry for 7 days was used to objectively index physical activity. Regression analysis was used to determine the extent to which mean HOMA levels differed across low, moderate, and high dairy intake categories. Results showed that women in the highest quartile of dairy consumption had significantly greater log-transformed HOMA values (0.41 ± 0.53) than those in the middle-two quartiles (0.22 ± 0.55) or the lowest quartile (0.19 ± 0.58) (F = 6.90, P = 0.0091). The association remained significant after controlling for each potential confounder individually and all covariates simultaneously. Adjusting for differences in energy intake weakened the relationship most, but the association remained significant. Of the 11 potential confounders, only protein intake differed significantly across the dairy categories, with those consuming high dairy also consuming more total protein than their counterparts. Apparently, high dairy intake is a significant predictor of insulin resistance in middle-aged, nondiabetic women.

Association Between Markers of Glucose Metabolism and Risk of Colorectal Adenoma

Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location. In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma. Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P= .04) for fasting glucose, 1.07 (0.99-1.15; P=.10) for insulin, 1.09 (1.02-1.18, P= .02) for HOMA, 1.09 (1.01-1.17; P= .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P= .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P= .08), 1.10 (0.98-1.24; P= .12), 1.15 (1.02-1.29; P= .02), 1.14 (1.01-1.28; P= .03), and 1.20 (1.05-1.37; P= .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P= .11), 1.23 (0.87-1.75; P= .24), 1.30 (0.92-1.85; P= .14), 1.13 (0.79-1.61; P= .50), and 1.67 (1.15-2.42; P=.007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P< .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P= .002). Associations were similar for adenomas located in the distal versus proximal colon. Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism.

Association of adiponectin (ADIPOQ) rs2241766 polymorphism and dyslipidemia in HIV/HCV‐coinfected patients

The adiponectin (ADIPOQ) rs2241766 polymorphism is related to metabolic abnormalities. The aim of this study was to evaluate the association of the ADIPOQ rs2241766 polymorphism with serum dyslipidemia and insulin resistance (IR) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We carried out a cross-sectional study on 262 patients. ADIPOQ rs2241766 polymorphisms were genotyped by GoldenGate® assay. Generalized linear models (GLMs) were used to compare continuous outcome variables (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C and homeostatic model assessment (HOMA)) and categorical outcome variables (TC≥200 mg/dL, TG≥170 mg/dL, LDL-C≥100 mg/dL, HDL-C≤35 mg/dL, non-HDL-C≥120 mg/dL and HOMA≥3·8) according to ADIPOQ genotype under a dominant inheritance model. Patients with the rs2241766 GG/GT genotype had significantly lower serum TC levels (P=0·038) and percentages of TC≥200 mg/dL (P=0·022) than rs2241766 TT carriers. When adjusted GLM was performed, rs2241766 GG/GT was associated with low serum TC levels (arithmetic mean ratio (AMR)=0·92 [(95% CI=0·85; 0·99) P=0·024]) and low likelihood of TC≥200 mg/dL (odds ratio (OR)=0·32 [(95% CI=0·11; 0·88) P=0·027]. When stratifying by steatosis, no significant values were found for patients without steatosis. However, for patients with steatosis, rs2241766 GG/GT genotypes were related to low TC serum values of TC (AMR=0·89; P=0·027), LDL-C (AMR=0·85; P=0·039) and non-HDL-C (AMR=0·86; P=0·015). No significant associations were found between rs2241766 and HOMA values. The presence of the ADIPOQ rs2241766 G allele (GG/GT genotype) was associated with a protective effect against dyslipidemia, primarily in HIV/HCV-coinfected patients with steatosis.

Red but not white meat consumption is associated with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men

The influence of diet on metabolic syndrome and oxidative stress are not completely known. This cross-sectional study assessed the association of red meat and white meat consumption with metabolic syndrome, insulin resistance and lipid peroxidation in Brazilian middle-aged men. A total of 296 subjects (age: 50.5 ± 5.0 years, body mass index: 25.8 ± 3.5 kg/m(2)) were evaluated. Anthropometry, lifestyle features, blood biochemical parameters, diagnosis of metabolic syndrome, homeostatic model assessment for insulin resistance, a lipid peroxidation marker (oxidized low-density lipoprotein) and triglycerides:high-density lipoprotein cholesterol ratio were assessed. Dietary intake was estimated by a food frequency questionnaire. The subjects included in the highest tertile red meat (≥81.5 g/d) and saturated fatty acid from red meat consumption (≥4.3 g/d) had higher occurrence of central obesity (nearly 60%, p < 0.01), hypertriglyceridaemia (nearly 43%, p < 0.01) and metabolic syndrome (35%, p < 0.01). They also had higher values of homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein, and triglycerides:high-density lipoprotein cholesterol ratio, regardless of interfering factors. There were no associations of highest white meat tertile (≥39.4 g/d) and saturated fatty acid from white meat (≥1.0 g/d) consumption with the assessed parameters (p > 0.05). Red meat consumption was cross-sectionally associated with the occurrence of central obesity, hypertriglyceridaemia, and metabolic syndrome as well as with higher homeostatic model assessment for insulin resistance, oxidized low-density lipoprotein concentrations and triglycerides:high-density lipoprotein cholesterol ratio. The content of saturated fatty acid from red meat consumption may be a factor that contributed to this relationship, while white meat consumption was not associated with metabolic syndrome and the assessed biomarkers.

The Severity of Menstrual Dysfunction as a Predictor of Insulin Resistance in PCOS

The objective of the study was to evaluate the relationship between the severity of menstrual disturbances and the degree of insulin resistance in women with polycystic ovary syndrome (PCOS). This was a cross-sectional study. The study was conducted at a tertiary care academic medical center. Four hundred ninety-four women diagnosed with PCOS by the Rotterdam criteria and 138 eumenorrheic, nonhirsute, control women participated in the study. INTERVENTIONS in the study included history and physical examination and blood sampling. Physical assessment and total and free T, dehydroepiandrosterone sulfate, fasting glucose, and insulin levels and calculated homeostatic model assessment values for insulin resistance (HOMA-IR) were measured. Overall, 80% of PCOS subjects included had clinically evident oligomenorrhea. The remainder demonstrated vaginal bleeding intervals of fewer than 35 days (ie, with either polymenorrhea or clinically apparent eumenorrhea). Only 10% of PCOS subjects studied were ovulatory. After adjusting for body mass index, age, and race, all PCOS subjects with menstrual cycles longer than 35 days had significantly higher mean HOMA-IR levels than controls, and those with cycles longer than 3 months had the highest HOMA-IR levels. There was no difference in mean HOMA-IR levels between PCOS with regular vaginal bleeding (apparent eumenorrhea), regardless of whether they were anovulatory or not, or those with cycles fewer than 26 days, when compared with controls. Women with PCOS and overt oligomenorrhea comprise the vast majority of PCOS subjects seen clinically and have significantly more insulin resistance than controls. About 20% of PCOS women seen reported vaginal bleeding intervals of fewer than 35 days in length and did not generally have overt insulin resistance, regardless of whether they were ovulatory or not. Overall, the presence of clinically evident menstrual dysfunction can be used to predict the presence and possibly the degree of insulin resistance in women with PCOS.

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV‐coinfected patients

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n=65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P=0.024), as well as the subgroups of patients with significant fibrosis (P=0.047) and infected with HCV genotype 3 (P=0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR)=2.02; P=0.034), in patients with significant fibrosis (aOR=2.86; P=0.039) and HCV genotype 3 patients (aOR=4.89; P=0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.