Homeostasis Model Assessment Score Research Articles

Relationship Between Vitamin D Levels and β Cell Function and Insulin Resistance.

Background This study aimed to determine the relationship between vitamin D levels and β cell function and insulin resistance in patients with diabetes, glucose tolerance disorder, or impaired fasting glucose. Methodology A total of 75 outpatients (55 females and 20 males) between the ages of 30 and 65 years were included in the study. There were 25 healthy individuals, 25 individuals with prediabetes, and 25 individuals with diabetes. The Homeostasis Model Assessment (HOMA) score was used to evaluate insulin resistance. Results The mean levels ofvitamin 25(OH)D among the groups included in the study were 35 ± 16.9nmol/L in the control group, 44.5 ± 34.5nmol/L in the prediabetes group, and 35.7 ± 13.1nmol/L in the diabetes group. There were no significant differences. The mean level of vitamin 1.25(OH)2D3 was 15.95 ± 8 pg/mL in the control group, 18.4 ± 7.5 pg/mL in the prediabetes group, and 21.5 ± 7.9 pg/mL in the diabetes group. While the levels of vitamin 25(OH)D were similar between the groups, the levels of vitamin 1,25(OH)2D3 were significantly higher in the diabetes group. Considering all individuals, no significant difference was found between the vitamin 25(OH)D and glucose levels at minutes0, 30, 60, 90, and 120. While there was a significant positive relationship between the 1,25(OH)2D3 vitamin and glucose levels at minutes 0, 30, 60, and 90, there was no significant relationship between the levels at minute 120. When the 1,25(OH)2D3 vitamin and HOMA insulin resistance and HOMA β scores were compared, a significant positive relationship was found between the 1,25(OH)2D3 vitamin and HOMA β levels. Conclusions In our study, there was no significant difference between the groups (control, prediabetes, and diabetes) in 25(OH)D levels. Similarly, there was no significant relationship between the 25(OH)D levels and insulin sensitivity and resistance between the groups. The positive relationship identified between the 1,25(OH)2D3 vitamin levels and the glucose concentration at minutes 0, 30, 60, and 90 and the higher 1,25(OH)2D3 vitamin levels in the diabetes group compared to the control group in our study can be interpreted as the effort of the organism to prevent glucose-induced β-cell apoptosis.

Dental and Periodontal Health in Acute Intermittent Porphyria.

In the inherited metabolic disorder acute intermittent porphyria (AIP), high sugar intake prevents porphyric attacks due to the glucose effect and the following high insulin levels that may lower AIP disease activity. Insulin resistance is a known risk factor for periodontitis and sugar changes diabetogenic hormones and affects dental health. We hypothesized differences in homeostasis model assessment (HOMA) scores for insulin resistance in AIP cases vs. controls and in those with periodontitis. Our aim was to systematically study dental health in AIP as poor dental health was previously only described in case reports. Further, we aimed to examine if poor dental health and kidney failure might worsen AIP as chronic inflammation and kidney failure might increase disease activity. In 47 AIP cases and 47 matched controls, X-rays and physical examination of clinical attachment loss (CAL), probing pocket depth (PPD), and decayed missing filled teeth (DMFT) were performed. Dietary intake was evaluated through a diet logbook. Plasma cytokines and diabetogenic hormones were measured using multiplex technology and urine porphobilinogen and kidney and liver function by routine methods. An excel spreadsheet from the University of Oxford was used to estimate HOMA scores; beta cell function, HOMA%B (%B), insulin sensitivity, HOMA%S (%S), and insulin resistance HOMA-IR (IR), based on glucose and plasma (P) C-peptide. The Wilcoxon matched-pairs signed rank test, the Mann–Whitney U-test, and Spearman’s non-parametric correlation were used. Insulin (p = 0.007) and C-peptide (p = 0.006) were higher in the AIP cases with periodontitis versus those without. In AIP patients, the liver fibrosis index 4 correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.006); the estimated glomerular filtration rate correlated with DMFT (p < 0.001) and CAL ≥4 mm (p = 0.02). CAL ≥4 mm was correlated with chemokine ligand 11 and interleukin (IL)-13 (p = 0.04 for both), and PPD >5 mm was correlated with plasminogen activator inhibitor-1 (p = 0.003) and complement component 3 (p = 0.02). In conclusion, dental health in AIP cases was correlated with insulin resistance, inflammatory markers, and biomarkers of kidney and liver function, demonstrating that organ damage in the kidney and liver are associated with poorer dental health.

Glucose and insulin levels’ linkages with breast cancer factors

Serum lipid and glucose metabolisms are considered as the intermediary mechanisms for connecting obesity and Breast Cancer (BC). The article aims to identify the linkages between diabetes biochemical factors such as glucose &amp; insulin and BC biochemical factors such as Monocyte Chemoattractant Protein-1 (MCP-1), adiponectin, Homeostasis Model Assessment score Insulin Resistance (HOMA-IR), resistin, leptin. These objectives can be focused on the two separate statistical models of glucose &amp; insulin based on the remaining factors. From the mean model of glucose, it is observed that mean glucose level is directly linked with BC women (P= 0.023), leptin (P&lt;0.001), HOMA-IR (P&lt;0.001), while it is inversely linked with the interaction effects between HOMA-IR &amp; leptin (i.e., HOMA-IR*leptin (P&lt;0.001)) and adiponectin &amp; leptin (i.e., adiponectin* leptin (P= 0.088)). Similarly, from the mean model of insulin, it is observed that mean insulin level is directly linked with HOMA-IR (P&lt;0.001), leptin (P&lt;0.001), and the interaction effects Age*MCP-1 (P= 0.091), glucose*adiponectin (P= 0.043), glucose*resistin (P&lt;0.001), MCP-1*HOMA-IR (P&lt;0.001), while it is reciprocally linked with MCP-1 (P= 0.026), resistin (P&lt;0.001), adiponectin (P= 0.078), HOMA-IR*body mass index (BMI) (P&lt;0.001), glucose*HOMA-IR (P&lt;0.001), leptin*adiponectin (P= 0.071). There are more linkages of the variances of insulin and glucose with the BC biochemical factors. Based on the summarized results it is interpreted that diabetes biochemical factors such as insulin and glucose are highly linked with BC biomarkers such as MCP-1, HOMA-IR, leptin, resistin, and adiponectin.

The glucose level linkages with breast cancer markers

The glucose level linkages with breast cancer (BC) biomarkers are focused in the article adopting probabilistic modeling with a real data set surveyed from 64 BC women and 52 normal women along with 10 interested study factors. It is derived that mean glucose levels are over for BC women (P=0.02224) than normal. Mean glucose levels are inversely linked with insulin (P&lt; 0.00001), interaction effects of leptin and adiponectin (leptin*adiponectin) (P=0.08834), homeostasis model assessment score insulin resistance (HOMA-IR) and leptin (HOMA-IR*leptin) (P&lt;0.00001), while they are directly linked with HOMA-IR (P&lt;0.00001) and leptin (P&lt;0.00001). The variance of glucose levels is inversely linked with leptin (P=0.00022), insulin (P=0.01365), monocyte chemoattractant protein-1 (MCP-1) (P=0.01153), insulin*HOMA-IR (P=0.00022), age*resistin (P=0.03974), age*HOMA-IR(P=0.03102), while it is directly linked with HOMA-IR (P&lt;0.00001), resistin (P=0.02182) and age (P=0.00133). Glucose levels are higher for BC women, and they increase along with the increased levels of HOMA-IR, leptin, and the decreased levels of insulin, HOMA-IR*leptin, leptin*adiponectin.

Effect of Reduction Mammoplasty on Insulin and Lipid Metabolism in the Postoperative Third month: Compensatory Hip Enlargement.

BackgroundsThe positive effects of reduction mammoplasty on metabolic profile have been shown in a limited number of studies. This study objective to reveal the effects of reduction mammoplasty on metabolic profile and anthropometric measurements.Subjects and MethodThe study was prospectively conducted on 42 patients who were operated between April 2019 and March 2020. Fasting plasma glucose, fasting plasma insulin, total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein cholesterol, HgA1c, homeostasis model assessment scores, adiponectin, leptin, and resistin levels were evaluated. In addition, age, height, weight, body mass index; breast, chest, waist, hip circumference; waist-hip ratio, and bilateral breast resection tissue weights were recorded. Data and blood samples were collected one hour before the operation, 6 and 12 weeks after the operation.ResultThe patients' mean age was 43.14±10.24, and their average height was 159.42±4.96 cm. The excised bilateral dermo fatty tissue weight was 1435.85±721.16 g. At the postoperative 40th day a decrease in leptin (p = 0.001), resistin (p =0.008), glucose (p = 0.021) and insulin resistance values (p=0.013) stated. There was an increase in adiponectin (p < 0.001) and HDL (p = 0.013) levels at the postoperative 40th day. In the postoperative third month, these data returned to the previous levels that were measured before operations. However, an increase in hip circumference (p = 0.034) and a decrease in waist-hip ratio (p < 0.001) was detected in third month. Also, there was no difference in body mass index and weight compared to pre-operation.ConclusionAfter reduction mammoplasty, compensatory fat growth in the hip area, an increase in the hip circumference, and a decrease in the waist-hip ratio were observed in the postoperative third month.Level of EvidenceThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Abstract 3721: Relationship between insulin resistance and chemosensitivity of high grade bone sarcoma

Abstract Background: Neoadjuvant chemotherapy with intercalated surgery is the standard of care for resectable high-grade bone sarcoma (BS) but identification of biomarkers for chemosensitivity prediction is still needed. Insulin-like Growth Factor (IGF) pathway was first linked with sarcoma biology approximately 30 years ago (El-Brady OM, 1990). Methods: We recruited 138 pts with newly diagnosed primary localized or metastatic BS. We measured fasting blood glucose and insulin, body mass index (BMI). The HOMA-IR (Homeostasis Model Assessment) score ((Glucose (mmol/l) x Insulin) / 22.5), which has been proven to reliably detect insulin resistance IR was calculated, and patients with HOMA-IR &amp;gt; 2.6 were considered as IR. We collected characteristics usually associated with insulin resistance: age, obesity, diabetes, dyslipidemia and hypertension. Results: Out of 138 pts, 50 (36%) were insulin resistant: HOMA-IR &amp;gt;2.6. Thirty-two IR patients (64%) had no cardiovascular risk factor. In univariate analysis, IR was associated with obesity (BMI &amp;gt; 30 kg/m2)(22% vs 3%, p=0.0015), but not with age (median 36,8 vs 41 years, p=0.19). IR was more prevalent in Ewing sarcoma (14/29; 48%) and chondrosarcoma (7/16; 44%) followed by osteosarcoma (25/67; 37%) and other rare bone sarcomas (4/26; 15.3%), but not significantly (p=0.097). After neoadjuvant chemotherapy and surgery of Ewing tumor and osteosarcoma, pathologic tumor necrosis was higher in IR pts (88.9 vs 75%, p= 0.028). Conclusion: Our results suggest that metabolic profile may help to discriminate best candidates for neoadjuvant chemotherapy in high-grade bone sarcomas. Further studies are needed to confirm and explain these results. Citation Format: Pascaline Boudou-Rouquette, Ithar Gataa, Sixtine De Percin, Camille Tlemsani, David Biau, Valerie Dumaine, Virginie Audard, Frédérique Larousserie, Philippe Anract, Anne Jouinot, François Goldwasser. Relationship between insulin resistance and chemosensitivity of high grade bone sarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3721.

A new inflammatory marker in overweight patients: triggering receptor expressed on myeloid cells-1.

Triggering receptor expressed on myeloid cells 1 (TREM-1) is secreted by phagocytes in adipose tissue and it also upregulates the expression of genes involved in the inflammatory response and atherosclerotic conditions. This study was aimed to investigate the serum TREM-1 levels in overweight patients. Twenty-eight subjects in the overweight group (OG) and 20 age-matched healthy subjects in the control group (CG) (BMI 27.6±1.2 vs 23.1±2.17 kg/m2, respectively, p<0.001) were included in the study. The serum sTREM-1 level was measured by ELISA. The homeostasis model assessment score (HOMA-IR) was also calculated. The mean TREM-1 levels were significantly higher in OG than in CG (407.3±323.7 vs 150.3±152.7 pg/mL, respectively, p<0.001). The HOMA-IR score was also significantly higher in OG than in CG (3.42±3.63 vs 2.77±1.61, respectively). A positive correlation was detected between TREM-1 and BMI (r=0.318, p=0.028). This study mainly demonstrated that a high serum TREM-1 level might be an early inflammatory marker in overweight patients. We found that TREM-1 might be associated with BMI in overweight patients regardless of insulin resistance (Tab. 1, Ref. 21). Text in PDF www.elis.sk.

Effect of HCV treatment response on insulin resistance: A systematic review and meta-analysis.

Sustained virological response (SVR) in hepatitis C virus (HCV) patients treated with pegylated interferon α-2a and ribavirin is associated with reduced insulin resistance (IR), measured as a reduction of homeostasis model assessment (HOMA) scores after 24 weeks of therapy, and reduced fasting serum insulin and serum glucose levels. The present meta-analysis aimed to evaluate the effect of HCV treatment response on IR in HCV patients who achieved SVR and those who did not (non-SVR) after receiving interferon (IFN)-based therapy. The PubMed, Cochrane and Embase databases were searched using combinations of the following search terms: ‘HCV’, ‘hepatitis C’, ‘interferon’, ‘antiviral’, ‘treatment response’ and ‘insulin resistance’. The incidence of IR, HOMA-IR and HOMA-β, as well as fasting glucose and fasting insulin levels, were summarized in terms of basal values and values after the end of treatment for each study. A total of 8 studies were included in the final analysis. There was no significant difference in the reduction in IR between the SVR and non-SVR groups (odds ratio, 0.995; 95% CI=0.613–1.616; P=0.984). However, the SVR group had a significantly higher mean reduction in HOMA-IR (difference in means=−0.485; 95%CI=−0.713 to −0.256; P<0.001) and HOMA-β (difference in means=−15.448; 95%CI=−23.326 to −7.570; P<0.001) compared to the non-SVR group. In conclusion, HCV patients who achieved SVR after IFN-based therapy exhibited improvement in HOMA-IR and HOMA-β. The present results suggest that clinical management of IR and serum glucose levels may be an important way to impact the therapeutic response in HCV patients.

Insulin resistance in prostate cancer patients and predisposing them to acute ischemic heart disease.

Lack of insulin or insulin resistance (IR) plays a central role in diabetes mellitus and makes diabetics prone to acute ischemic heart disease (AIHD). It has likewise been found that many cancer patients, including prostate cancer patients die of AIHD. Previously it has been delineated from our laboratory that dermcidin could induce anomalous platelet aggregation in AIHD and also impaired nitric oxide and insulin activity and furthermore dermcidin was also found in a few types of cancer patients. To determine the role of this protein in prostatic malignancy, a retrospective case–control study was conducted and blood was collected from prostate cancer patients and healthy normal volunteers. So, we measured the level of dermcidin protein and analyzed the IR by Homeostasis Model Assessment (HOMA) score calculation. Nitric oxide was measured by methemoglobin method. HDL, glycated hemoglobin (HbA1c), BMI, hs-cTroponin-T were measured for the validation of the patients’ status in the presence of Dermcidin isoform-2 (DCN-2). Multiple logistic regression model adjusted for age and BMI identified that the HOMA score was significantly elevated in prostate cancer patients (OR = 7.19, P<0.001). Prostate cancer patients are associated with lower level of NO and higher level of both proteins dermcidin (OR = 1.12, P<0.001) and hs-TroponinT (OR = 1.76, P<0.001). From the results, it can be interpreted that IR plays a key role in the pathophysiology of prostate cancer where dermcidin was the cause of IR through NO inhibition leading to AIHD was also explained by high-sensitive fifth generation cTroponin-T (hs-cTroponinT) and HbA1c level which are associated with endothelial dysfunction.

Insulin resistance is not a risk factor for oesophageal varices development in hepatitis C.

Chronic hepatitis C (HCV) patients commonly have insulin resistance which is a risk factor for disease progression. Oesophageal varices may bleed with high mortality. We aimed to assess the relationship between insulin resistance and oesophageal varices. HCV-related compensated liver cirrhosis patients (n = 146) underwent gastroscopy and homeostasis model assessment (HOMA)-IR, HOMA-β and HOMA-S calculations. Their average age was 54.98 years; most (84.9%) patients were men and non-diabetic (60.3%). Patients with oesophageal varices had higher median Model for End-Stage Liver Disease (MELD) scores and comparable Child-Pugh class. Patients with and without oesophageal varices had comparable (P > 0.05) HOMA scores and insulin resistance percentage of 82.9% versus 85.5%. We therefore conclude that insulin resistance is unrelated to the presence of oesophageal varices.

Metabolic profile and neoadjuvant chemotherapy sensitivity in high-grade bone sarcoma.

e22506 Background: Neoadjuvant chemotherapy with intercalated surgery is the standard of care for resectable high-grade bone sarcoma (BS) but identification of biomarkers for chemosensitivity prediction is still needed. Methods: We recruited 121 pts with new primary localized or metastatic BS, measured fasting blood glucose and insulin, body mass index (BMI). The HOMA-IR (Homeostasis Model Assessment) score ((Glucose (mmol/l) x Insulin) / 22.5), which has been proven to reliably detect insulin resistance was calculated, and patients with HOMA-IR &gt; 2.6 were considered as insulin resistant (IR). We collected characteristics usually associated with insulin resistance (IR): age, obesity, diabetes, dyslipidemia and hypertension. Results: Out of 121 pts, 48 (40%) were IR: HOMA-IR &gt; 2.6. Thirty IR patients (62%) had no cardiovascular risk factor. In univariate analysis, IR was associated with obesity (BMI &gt; 30 kg/m2)(23% vs 3%, p = 0.0013), but not with age (median 38.4 vs 43.3 years, p = 0.15). IR was more prevalent in Ewing sarcoma (12/21; 57%) and chondrosarcoma (7/13; 54%) followed by osteosarcoma (25/61; 41%) and other rare bone sarcomas (4/26; 15.3%)(p = 0.037). After preoperative chemotherapy and surgery of Ewing tumor and osteosarcoma, pathologic tumor necrosis was higher in IR pts (85.8 vs 69.3%, p = 0.012). Using multivariate linear regression models, IR was independently associated with pathologic tumor necrosis (p = 0.042) but not with obesity (p = 0.55). Conclusions: Our results suggest that tumor-induced metabolic profile may help to discriminate best candidates for preoperative chemotherapy in high-grade bone sarcomas. Further studies are needed to confirm and explain these results.

Relationship of body mass index with diabetes and breast cancer biomarkers

Body mass index (BMI=Weight(kg)/Height(m2) is generally computed for each patient under some clinical studies, considering that it may be related with the disease. The report has derived the effects of BMI on diabetes & breast cancer markers for some cancer patients with the help of probabilistic modeling. It has been obtained that mean BMI is positively associated with fasting glucose (p=0.0753), insulin (p=0.0002), leptin (p<0.0001), monocyte chemoattractant protein-1 (MCP-1) (p=0.0002), and it is negatively associated with homeostasis model assessment score (HOMA) (p<0.0001), adiponectin (p=0.0003), and class of patients (p=0.0116). The variance of BMI is partially positively associated with age (p=0.1751), and it is negatively associated with resistin (p=0.1450) and insulin (p=0.2413). These three variance explanatory factors are known as confounder according to Epidemiology. Therefore, high BMI increases glucose, insulin, leptin, MCP-1, and it decreases HOMA & adiponectin.

The association between serum zinc levels and insulin resistance among polycystic ovary syndrome patients in Duhok City, Kurdistan Region, Iraq

Background: Polycystic ovary syndrome (PCOS) is a relatively common endocrine and metabolic problem. Patients with PCOS are known to have a higher incidence of insulin resistance. The homeostasis model assessment (HOMA) is an indirect, rapid, accurate, and cost-effective method of assessing insulin resistance based on patient's fasting plasma insulin and glucose concentrations. Several studies have reported a significant correlation between HOMA and the traditional hyperinsulinemic-euglycemic clamp method. Zinc deficiency promotes insulin resistance, and that zinc supplementation can prevent or, at least, alleviate insulin resistance in selected patient populations. Objective: The current study primarily aims at defining the association between insulin resistance and zinc deficiency among both PCOS and selected controls. It also looks at certain risk factors associated with obesity among the study population in Duhok City, Kurdistan Region, Iraq. Materials and Methods: The current case–control study was performed at Azadi Teaching Hospital/Gynecological Outpatient Clinic in Duhok City/Kurdistan Region/Iraq. The study included 80 women (40 cases with PCOS and 40 controls of healthy women). Results: There was no age difference between both groups (Mean = 26.77 years, standard deviation [SD] = 6.42 years for PCOS cases versus mean and SD of 27.57 years and 6.45 years, respectively; P= 0.48). Likewise, there was no difference in the serum zinc levels between cases and controls. However, patients with PCOS had significantly higher Body mass index and HOMA scores compared to the controls (P = 0.005 and 0.007, respectively). Conclusion: Higher serum zinc levels are independently associated with lower HOMA. Patients with PCOS had significantly higher insulin resistance when compared to the controls of similar age and zinc level.

Chemerin as a biomarker at the intersection of inflammation, chemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer

ObjectivesChemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. Materials and MethodsIn a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). ResultsNSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09–4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. ConclusionChemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.

Influence of pegylated interferon and ribavirin on insulin resistance and metabolic factors in chronic hepatitis C

Abstract Background In this study it was aimed to evaluate the effect of pegylated interferon alfa-2a/2b and ribavirin, which are used for treatment of chronic hepatitis C (CHC), on insulin resistance and metabolic factors. Materials and methods A total of 104 CHC patients aged 20–75 years with available serum insulin data at 0 and 48 weeks, and hepatitis C virus (HCV)-RNA data at 0, 12, 24, 48 and 72 weeks were included in the study. All clinical para-meters were assessed according to the therapy response. Results Among 104 patients, sustained virologic response (SVR) was achieved in 55 cases. A statistically significant difference was noted between SVR and non-SVR groups regarding γ-glutamyltranspeptidase (GGT), insulin level plus homeostasis model assessment (HOMA) score and insulin resistance at week 48, log HCV-RNA and stage of fibrosis. Conclusion Insulin resistance is accepted to have a negative effect on SVR. Insulin resistance may improve once SVR is achieved. Presence of IR at week 48 has been found associated with SVR. In this context, it can be advocated that insulin resistance at week 48 may be a predictive factor for prediction of SVR at week 72.

Candesartan targeting of angiotensin II type 1 receptor demonstrates benefits for hypertension in pregnancy via the NF‑κB signaling pathway.

Hypertensive disorders may be a complication of pregnancy and are characterized by the high blood pressure. Evidence suggests that alterations in the renin-angiotensin-aldosterone system and the sympathetic nervous system are associated with gestational hypertension. Angiotensin II type 1 receptor (Ang-IITR) is a potential target in the progression of gestational hypertension. Candesartan is selective Ang-IITR antagonist that may act against vasoconstriction and reduces peripheral vascular resistance. The aim of the present study was to evaluate the efficacy of Candesartan and the underlying molecular mechanism of the nuclear factor-κB (NF-κB) signaling pathway in the progression of gestational hypertension in a mouse model. Expression and activity of Ang-IITR was evaluated in a mouse model of gestational hypertension prior to and post-treatment of Candesartan both in vitro and in vivo. It was determined whether Candesartan treatment reduces higher blood pressure activated the renal renin-angiotensin system and a prognostic marker, soluble endoglin, and its associated gene in mice with gestational hypertension. Angiotensin-converting enzyme plasma levels and activity were also evaluated in the present study. Cytoplasmic and nuclear immunostaining of NF-κB and associated proteins transforming growth factor β (TGF-β) and endoglin was enhanced in vascular endothelial cells and mice with gestational hypertension. Soluble fms-like tyrosine kinase 1 (sFlt-1), insulin resistance homeostasis model assessment score and associated cardiovascular risk factors also were measured. Results demonstrated that angiotensin and Ang-IITR expression levels were upregulated in mice with gestational hypertension and were downregulated by Candesartan treatment. Renal renin-angiotensin and soluble endoglin were also improved in mice in the Candesartan-treated group. In addition, Candesartan treatment enhanced NF-κB activity, as well as TGF-β and vascular endothelial growth factor expression which led to improved levels of sFlt-1, insulin resistance homeostasis and associated cardiovascular risk factors. Gestational hypertension was markedly improved by treatment of Candesartan compared with the control. In conclusion, the findings of the present study suggested that the NF-κB signaling pathway may be involved in with Candesartan-mediated Ang-IITR for the treatment of gestational hypertension.

Increased prevalence of obstructive sleep apnea in patients with Cushing's syndrome compared with weight- and age-matched controls.

Diabetes mellitus and obesity are well-known risk factors associated with obstructive sleep apnea (OSA). Cushing's syndrome (CS) is also characterized by obesity and diabetes mellitus. However, the association between CS and OSA remains unclear. Therefore, we investigated the possible associations between CS and OSA in this study. Thirty female patients with newly diagnosed active CS and 30 age-, gender- and body mass index (BMI)-matched controls were included in this study. All participants were evaluated by overnight polysomnography. OSA was defined as having an apnea-hypopnea index (AHI) score of ≥5 events/h. Insulin resistance was calculated by homeostasis model assessment (HOMA) scores. Fasting serum cortisol was also determined. The prevalence of OSA was higher (50% vs 23%, P = 0.003) in patients with CS compared with the control subjects. The mean HOMA (P = 0.046) and AHI (P = 0.028) scores were higher in patients with CS compared with the control subjects. AHI was positively correlated with the HOMA scores (r = 0.281, P = 0.046) in both groups. Linear regression analysis showed that serum cortisol remained as an independent predictor for AHI after controlling for BMI and HOMA score (P < 0.001). The prevalence of OSA increased in patients with CS compared with control subjects with similar ages and BMI levels. Hypercortisolemia is an independent risk factor for developing OSA. The presence of OSA needs to be considered in patients with CS.

Effect of Continuous Positive Airway Pressure on Glycemic Control in Patients with Obstructive Sleep Apnea and Type 2 Diabetes. A Randomized Clinical Trial.

Obstructive sleep apnea (OSA) is a risk factor for type 2 diabetes that adversely impacts glycemic control. However, there is little evidence about the effect of continuous positive airway pressure (CPAP) on glycemic control in patients with diabetes. To assess the effect of CPAP on glycated hemoglobin (HbA1c) levels in patients with suboptimally controlled type 2 diabetes and OSA, and to identify its determinants. In a 6-month, open-label, parallel, and randomized clinical trial, 50 patients with OSA and type 2 diabetes and two HbA1c levels equal to or exceeding 6.5% were randomized to CPAP (n = 26) or no CPAP (control; n = 24), while their usual medication for diabetes remained unchanged. HbA1c levels, Homeostasis Model Assessment and Qualitative Insulin Sensitivity Check Index scores, systemic biomarkers, and health-related quality of life were measured at 3 and 6 months. After 6 months, the CPAP group achieved a greater decrease in HbA1c levels compared with the control group. Insulin resistance and sensitivity measurements (in noninsulin users) and serum levels of IL-1β, IL-6, and adiponectin also improved in the CPAP group compared with the control group after 6 months. In patients treated with CPAP, mean nocturnal oxygen saturation and baseline IL-1β were independently related to the 6-month change in HbA1c levels (r(2) = 0.510, P = 0.002). Among patients with suboptimally controlled type 2 diabetes and OSA, CPAP treatment for 6 months resulted in improved glycemic control and insulin resistance compared with results for a control group. Clinical trial registered with www.clinicaltrials.gov (NCT01801150).

Legume consumption and its association with fasting glucose, insulin resistance and type 2 diabetes in the Indian Migration Study.

Legume consumption is associated with lower fasting glucose (FG) and insulin levels in nutrition trials and lower CVD mortality in large-scale epidemiological studies. In India, legumes are widely consumed in various preparations, yet no epidemiological study has evaluated the association of legumes with FG levels, insulin resistance and diabetes risk. The present study aimed to fill this gap. Fasting blood samples, in-person interviews to obtain information on demographic/socio-economic factors, physical activity, alcohol and tobacco use, and anthropometric measurements were collected. Dietary intakes were assessed by an interviewer-administered, validated, semi-quantitative FFQ. Lucknow, Nagpur, Hyderabad and Bangalore, India. Men and women (n 6367) aged 15-76 years - urban residents, urban migrants and their rural siblings. In multivariate random-effects models adjusted for age, BMI, total energy intake, macronutrients, physical activity and rural/migration status, daily legume consumption was not associated with FG (P-for-trend=0·78), insulin resistance (homeostasis model assessment score; P-for-trend=0·73) or the prevalence of type 2 diabetes mellitus (P-for-trend=0·41). Stratified analyses by vegetarian diet and migration status did not change the findings. Inverse associations between legumes and FG emerged for participants with lower BMI and higher carbohydrate, protein, fat and sugar intakes. Although legumes are essential in traditional Indian diets, as well as in prudent and Mediterranean diets in the West, we did not find an association between legumes and markers of glycaemic control, insulin resistance or diabetes, except for subgroups based on BMI and macronutrient intake. The ubiquitous presence and complexity of legume preparations in Indian diets may contribute to these findings.

Ovaries are more vulnerable than hepatocytes for insulin resistance and hyperinsulinemia

Non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are common metabolic disorders. We aimed to evaluate the underlying mechanisms in the development of NAFLD and PCOS. Thirty female patients with NAFLD and without PCOS; 12 female patients with PCOS; and a control group with 17 healthy females were included. Pancreatic homeostatic model assessment-Beta cell function was measured by the homeostasis model assessment (HOMA)-B test. The body mass index (BMI) of the NAFLD patients was higher than that of the PCOS patients (29.4±3.8 kg/m² vs 25.6±5.2 kg/m², p<0.05). There was no significant difference between the PCOS patients and controls with respect to BMI. The fasting insulin levels of the NAFLD patients were higher than those of the PCOS patients (5.06 unit more than PCOS, p<0.05) and 12.8 unit more than controls (p<0.001). The HOMA scores of the NAFLD patients were more than those of the PCOS patients (1.41 unit more than PCOS, p<0.05) and 2.95 unit more than controls (p<0.001). The HOMA-B score was higher in the NAFLD patients than in the PCOS patients. There was no statistical difference among the groups for serum triglyceride (p>.05) and cholesterol (p>.05). This study showed that rather than pancreatic beta-cell hyperfunction, insulin resistance plays a central role in the development of ovarian abnormalities.