Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis.

BACKGROUND: Measures of insulin resistance (IR)/sensitivity (IS) are emerging tools to identify metabolic-associated fatty liver disease (MAFLD). However, the comprehensive assessment of the performance of various indicators is limited. Moreover, the utility of measures of IR/IS in detecting liver fibrosis remains unclear. AIMS: To evaluate the predictive ability of seventeen IR/IS and two beta cell function indices to identify MAFLD and liver fibrosis. METHODS: A cross-sectional study was conducted on individuals aged 25-75 years. Transient elastography was used to estimate liver stiffness and controlled attenuation parameter. The following measures were computed: homeostatic model assessment (HOMA/HOMA2) for IR, IS, and beta cell function; QUICKI; Bennett index; glucose/insulin; FIRI; McAuley index; Reynaud index; SPISE index; TyG; TyG-BMI; TyG-WC; TyG-WHtR; TG/HDL; and METS-IR. Subgroup analyses were performed according to age, gender, diabetes status, and body weight. RESULTS: A total of 644 individuals were included in our analysis. MAFLD and significant liver fibrosis were detected in 320 (49.7%) and 80 (12.4%) of the participants, respectively. All measures of IR/IS identified MAFLD and liver fibrosis. However, TyG-WC, TyG-BMI, and TyG-WHtR were the top three indicators that identified MAFLD. Measures that include insulin level in their mathematical calculation, namely, Raynaud index, HOMA-IR, HOMA 2-IR, FIRI, and QUICKI had the best performance in identifying liver fibrosis in the entire population, as well as among the study subgroups. CONCLUSIONS: TyG-WC, TyG-BMI, and TyG-WHtR were the best predictors of MAFLD. Insulin-based measures had better performances in the detection of advanced fibrosis. This was independent of age, gender, obesity, or diabetes status.

Glucagon-Like Peptide 1 (GLP-1) Receptor Variants and Glycemic Response to Liraglutide: A Pharmacogenetics Study in Iranian People with Type 2 Diabetes Mellitus.

INTRODUCTION: Pharmacogenetics studies suggest that genetic variants have a possible influence on the inter-individual differences in therapeutic response to glucagon-like peptide 1 receptor agonists (GLP-1 RAs). We aimed to examine the potential role of genetic variability of glucagon-like peptide 1 receptor (GLP-1R) on glycemic response to GLP-1 RAs in a population of Iranian people with type 2 diabetes mellitus (T2DM). METHODS: In this study, we analyzed the data from participants in a non-inferiority randomized clinical trial between 2019 and 2020. Patients received liraglutide 1.8 mg/day subcutaneously for 24 weeks. They were stratified by the baseline hemoglobin A1c (HbA1c) into four categories: 7-7.99, 8-8.99, 9-9.99, and ≥ 10%. In each category, subjects with HbA1c reduction greater than the median ΔHbA1c value for that group were defined as optimal responders. The pooled number of optimal/suboptimal responders in the four groups was used for the comparison. We evaluated two genetic variants of GLP-1R, rs6923761 and rs10305420, using Sanger sequencing. Logistic regression analyses were performed to examine the associations of the GLP-1R variants with the glycemic response in different genetic models. RESULTS: Out of 233 participants, 120 individuals were optimal responders. Median HbA1c reduction was - 2.5% in the optimal responder group compared with - 1.0% in the suboptimal responder group (P < 0.001). In genetic models, rs10305420 T allele homozygosity was associated with optimal glycemic response to liraglutide compared with heterozygous and wild-type homozygous states (recessive model: OR 3.28, 95% CI 1.41-7.65, P = 0.006; codominant model: OR 2.52, 95% CI 1.03-6.13, P = 0.04). No significant association was found between rs6923761 variant and HbA1c reduction. CONCLUSION: GLP-1R rs10305420 polymorphism can explain some of the inter-individual differences in glycemic response to liraglutide in a population of Iranian people with T2DM.

The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Body Composition in Type 2 Diabetes Mellitus: A Narrative Review.

Body composition is related to cardiometabolic disorders and is a major driver of the growing incidence of type 2 diabetes mellitus (T2DM). Altered fat distribution and decreased muscle mass are related to dysglycemia and impose adverse health-related outcomes in people with T2DM. Hence, improving body composition and maintaining muscle mass is crucial in T2DM. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are novel glucose-lowering medications gaining popularity because of their cardiorenal-protective effects and weight-lowering characteristics. However, reports on myopathy secondary to SGLT2 inhibitor treatment raised a safety concern. The importance of maintaining muscle mass in people with T2DM necessitates further investigation to explore the impact of novel medications on body composition. In this review, we discussed current evidence on the impact of SGLT2 inhibitors on body composition in people with T2DM.

Non-alcoholic fatty liver disease and compromised endothelial function in people with type 2 diabetes.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) frequently coexists with type 2 diabetes mellitus (T2DM) and synergistically contributes to the development of atherosclerosis. Flow-mediated dilation (FMD) is a commonly used noninvasive test for assessing endothelial function. The main objective of this study was to explore FMD in patients with T2DM with and without NAFLD. METHODS: In this cross-sectional study, conducted on people with T2DM, NAFLD was defined as controlled attenuation parameter (CAP) score > 302 dB/m. Endothelial dysfunction was detected when arterial FMD of brachial artery was equal or less than 0.7%. Regression analyses were applied to assess factors associated with impaired FMD. RESULT: A total of 147 patients (72 with NAFLD and 75 without NAFLD) were included in the final analysis. Patients with NAFLD were more likely to develop FMD ≤ 7% (77.8% vs. 58.7%, P = 0.01). In multivariate analysis, NAFLD (OR = 2.581, 95% CI (1.18-5.62), P = 0.017) and hypertension (HTN) (OR = 3.114, 95% CI (1.31-7.35), P = 0.010) were associated with an increased risk of impaired FMD. However, female sex was associated with a decreased risk of impaired FMD (OR = 0.371, 95% CI (0.15-0.87), P = 0.024). CONCLUSION: NAFLD is associated with endothelial dysfunction in people with T2DM. This risk is comparable with the risk imposed by HTN, highlighting the importance of screening and management of NAFLD in these patients.

Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease. METHODS: This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM). RESULTS: In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01. CONCLUSION: Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .

Efficacy and Safety of a Biosimilar Liraglutide (Melitide®) Versus the Reference Liraglutide (Victoza®) in People with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Noninferiority Clinical Trial.

INTRODUCTION: Liraglutide effectively controls blood glucose level and reduces body weight. The aim of this study was to compare the efficacy and safety of a biosimilar liraglutide (Melitide®; CinnaGen, Tehran, Iran) to the reference liraglutide (Victoza®; Novo Nordisk, Bagsvaerd, Denmark) in people with type 2 diabetes mellitus (T2DM). METHODS: In this phase 3 clinical noninferiority trial, adult patients with inadequately controlled T2DM and with hemoglobin A1C (HbA1C) levels of 7-10.5% on at least two oral glucose-lowering drugs with stable doses for at least 3 months were randomized to receive Melitide® (n = 150) or Victoza® (n = 150) 1.8 mg/day for 26 weeks. The primary outcome was assessment of the noninferiority of Melitide® to Victoza® in terms of change in HbA1C level with a prespecified margin of 0.4%. The secondary outcomes were the assessment of additional efficacy parameters (including the proportion of patients achieving HbA1C levels of < 7%), the incidence of adverse events, and immunogenicity. RESULTS: Of the 300 participants enrolled in this study, 235 were included in the per-protocol analysis (112 in the Melitide® group and 123 in the Victoza® group). The mean (standard deviation) changes in HbA1C were - 1.76% (1.22) in the Melitide® group and - 1.59% (1.31) in the Victoza® group. The upper limit of the 95% one-sided confidence interval (CI) of the mean difference between Melitide® and Victoza® in lowering HbA1C was lower than the predefined margin (mean difference - 0.18, 95% CI - 0.5 to 0.15). Similar findings were obtained with the intention-to-treat analysis. No statistically significant differences were observed between the two study arms regarding the proportion of patients achieving HbA1C < 7% (p = 0.210), other efficacy parameters (p > 0.05), and reported adverse events (p = 0.916). Furthermore, none of the patients developed anti-liraglutide antibodies. CONCLUSION: The biosimilar liraglutide (Melitide®) was noninferior in efficacy and comparable in safety when compared with the reference liraglutide. TRIAL REGISTRATION: NCT03421119.

The effects of melissa officinalis on depression and anxiety in type 2 diabetes patients with depression: a randomized double-blinded placebo-controlled clinical trial.

BACKGROUND: Depression is more common in diabetic patients, with a 1.5-fold increased risk of death.Melissa officinalis (M. officinalis) have anti-diabetic and anti-depression activities. The study aimed to determine the efficacy of M. officinalis extract on depression, anxiety, and sleep quality in patients with type 2 diabetes with depressive symptoms. METHODS: In this double-blind clinical trial, 60 volunteer patients (age range 20-65 years) with type 2 diabetes mellitus with symptoms of depression were randomized into the intervention (received 700 mg/day hydroalcoholic extract; n = 30) or control group (received 700 mg/day toasted flour; n = 30). Dietary intake, physical activity, anthropometric indices, FBS (Fasting blood sugar), hs-CRP(High-sensitivity C-reactiveprotein), depression, anxiety, and sleep quality were determined at the beginning and end of the study. Depression and anxiety were assessed by Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively; sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Sixty participants received M. officinalis extract or placebo, of which 44 patients completed the 12-week double-blind clinical trial. After 12-week the mean change of depression and anxiety scores were statistically significant between the two groups (p < 0.001 and p = 0.04, respectively), but no significant differences were observed in FBS, hs-CRP, anthropometric indices, sleep quality, and blood pressure.In the intervention group, there was a significant decrease in depression and anxiety severity(p < 0.001 and p = 0.01, respectively) at the end of the study compared to the baseline. TRIAL REGISTRATION: All protocols in this study were followed in accordance with the Helsinki Declaration (1989 revision). Ethical approval for this study was obtained from the Iran University of Medical Sciences Ethics committee (IR.IUMS.FMD.REC 1396.9413468004; research.iums.ac.ir). The study was registered at the Iranian Registry of Clinical Trials (IRCT201709239472N16); Registration date: 09/10/2017.

The association of dietary inflammatory index (DII) and central obesity with non-alcoholic fatty liver disease (NAFLD) in people with diabetes (T2DM).

Background & Objective: High prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus results in deleterious complications and morbidities related to both diseases. Thus, we aimed to investigate dietary and anthropometric risk factors for progression of Non-alcoholic Fatty Liver Disease (NAFLD) in diabetic people. Methods: Anthropometric, and dietary intakes, and hepatic steatosis and fibrosis were assessed in two hundred participants with type two diabetes (T2DM). Subjects with CAP score of more than 270 dB/m were considered to have NAFLD. Multivariable-adjusted ORs and 95% CIs were used to investigate the association between NAFLD and dietary inflammatory index (DII) score and anthropometric indices. Results: Participants in the highest tertile of DII had 2.41 (95% CI:1.16-4.97), 2,53 (95% CI: 1.04-6.16), 2.78 (95% CI: 1.09-7.13) times higher odds of developing NAFLD in comparison to the lowest tertile in crude, adjusted model 1 and 2, respectively. Among those with the highest relative to the lowest tertile of trunk-to-leg fat ratio (TLR), ORs and 95% CI were OR = 1.88, 95% CI = 0.9-3.91, and OR = 7.99, 95% CI = 2.43-26.26 in crude and full-adjusted models. Odds of NAFLD in the third tertile of metabolic score for visceral fat (METS-VF) was higher than the first tertile in crude (OR = 9.5, 95% CI = 4.01-22.46) and full-adjusted models (OR = 4.55, 95% CI = 1.46-14.2). Conclusions: In conclusion, this study highlighted an association between greater DII (pro-inflammatory diet) and higher NAFLD risk. Moreover, TLR and METS-VF are known as novel estimators of central obesity as a risk factor for NAFLD in diabetes.

Appropriateness of Intensive Statin Treatment in People with Type Two Diabetes and Mild Hypercholesterolemia: A Randomized Clinical Trial.

BACKGROUND: The aim of this study was to compare moderate- versus high-intensity statin therapy in patients with type 2 diabetes and low-density lipoprotein (LDL) cholesterol less than 130 mg/dL. METHODS: This was a randomized, open-label, parallel design trial comprised of 79 patients randomly allocated into two groups receiving high-intensity [atorvastatin 40 mg (A40) or rosuvastatin 20 mg (R20) daily] or moderate-intensity [atorvastatin 20 mg (A20) or rosuvastatin 10 (R10) mg daily] statins for eight weeks. The variables investigated were lipid profile, high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6). RESULTS: The percentage of decrease in LDL levels (±SD) for the high-intensity group (-35.5±25.5) was significantly greater than the moderate-intensity group (-24.6±23.5) (P=0.04). While 38.1% (n:8) of patients receiving A20 and 55% (n:11) of those being on R10 achieved the targets of≥30% reduction in the LDL level, these figures were 63.2% (n=12) and 73.8% (n=14) for A40 and R20 subgroups, respectively. Subsequently, the likelihood of achieving LDL reduction≥30%, was significantly greater with high-intensity statin therapy (OR: 3.1, 95% CI: 1.09, 8.90, P=0.03). Logistic regression analysis also showed that for every 1 mg/ dL increase in the baseline LDL level, the odds of achieving the LDL reduction≥30% increased by 1.04 times [95% CI: (1.01, 1.07), P=0.003]. CONCLUSION: Despite the general conception, moderate-intensity statins are not adequate for the majority of patients with T2DM and mild hyperlipidemia and greater numbers of patients could reach the LDL cholesterol target with high-intensity statin therapy.

Association of monocyte/high-density lipoprotein cholesterol ratio and the carotid intima-media thickness in diabetic patients.

OBJECTIVES: The goal of this study was to see whether there was a link between the monocyte/high-density lipoprotein cholesterol ratio (MHR) and carotid intima-media thickness (CIMT) in people with type 2 diabetes. METHODS: Duplex ultrasonography parameters and demographic, physical, and paraclinical assessments were recorded. Using the t-test, the MHR and CIMT were compared between the two groups. Regression models were also constructed. RESULTS: A total of 118 diabetics and 126 non-diabetics were included in the cross-sectional research. According to the stated diabetes duration, the observed age difference of 7 years might be considered. The MHR and CIMT were not substantially different between the two groups. In the DM and non-DM groups, the Spearman correlations between MHR and CIMT were 0.32 and - 0.08, respectively (p-values = 0.001 and 0.379). Thus, regression models (stratified for DM/non-DM and male/female) revealed that the MHR is a significant predictor of CIMT, but only in the case of male DM individuals, when crudely adjusted for confounders. CONCLUSIONS: In diabetes mellitus, the current investigation found a direct link between MHR and CIMT. In addition, in male diabetic subjects, MHR was demonstrated to be a predictor of CIMT.

Predictive ability of six obesity measures to identify 7-year fatal and non-fatal cardiovascular events: A population-based cohort study.

Background: Globally, most people die from cardiovascular diseases. We aimed to compare predictive ability of six obesity indices, including body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio, conicity index, and abdominal volume index, to identify people at risk of fatal and non-fatal cardiovascular events, in a cohort study. Methods: We studied 5147 participants in a baseline population-based cohort study conducted in northern Iran. The obesity measures were calculated in enrollment phase (2009-2010), and the cardiovascular events were recorded during a 7-year follow-up phase (2010-2017). Receiver operating characteristic (ROC) analyses and Cox hazard regression models were applied, considering the obesity measures as predictors, and the 7-year cardiovascular events as outcomes. Multiple Cox models were adjusted by age, prior history of cardiovascular diseases, chronic kidney diseases, insulin resistance, diabetes mellitus, dyslipidemia, hypertension, and smoking status. Results: Conicity index showed the highest performance in predicting 7-year fatal and non-fatal cardiovascular events with areas under the ROC curve of 0.77 [95% confidence interval: 0.71-0.82], and 0.63 [0.59-0.68] in men, and 0.80 [0.74-0.87], and 0.65 [0.60-0.71] in women, respectively. In multiple Cox models, the obesity measures had no significant associations with cardiovascular events in women. In men, only waist-to-height ratio was independently associated with 7-year non-fatal cardiovascular events (hazard ratio: 1.19 [95% confidence interval: 1.01-1.38]). Conclusions: Although waist-to-height ratio had an independent association with 7-year non-fatal cardiovascular events in men, conicity index showed the best ability to predict 7-year fatal and non-fatal cardiovascular events in our study.

Evaluation of changing the pattern of CTRP5 and inflammatory markers levels in patients with coronary artery disease and type 2 diabetes mellitus.

PURPOSE: It has recently found that adipokines, play a numerous functional roles in inflammation, lipids and glucose metabolism and in the pathogenically conditions such as atherosclerosis and insulin resistance. Therefore, for the first time we aimed the present study to evaluating serum levels of CTRP5 and inflammatory cytokines patients with CAD and T2DM in comparison with controls. METHODS: This study was done on 44 patients with CAD, 45 type 2 diabetes mellitus (T2DM), 41 CAD + T2DM and 41 controls. Serum levels of TNF-α, IL-6, MCP-1 and CTRP5 were investigated by ELISA method. RESULTS: The CTRP5 levels of all patients groups were lower in comparison with control group. There was a significant negative relationship between CTRP5 levels and cytokines concentration in the studied patients. CONCLUSIONS: Our findings suggested a potential role of CTRP5 in inflammatory process of underlying atherosclerosis and diabetes; however, more studies are needed to support these finding.

Post-treatment heterogeneity of cardiometabolic risk in patients with acromegaly: The impact of GH and IGF-1.

BACKGROUND: Metabolic abnormalities are frequently seen in patients with acromegaly. However, it is not clear to what extent growth hormone/insulin-like growth factor-1 (GH/IGF-1) contributes to the development of these abnormalities. OBJECTIVE: This study aimed to explore the impact of postoperative GH/IGF-1 on different aspects of metabolic abnormalities in patients with acromegaly. METHODS: This retrospective, registry-based study conducted on 102 patients with acromegaly. The impact of GH/IGF-1 on the cardiometabolic risk factors at 3-12 months after surgery has been investigated using linear and logistic regression models. RESULTS: In this study, each 1 ng/ml increase in the level of GH was significantly associated with a 2 mg/dl increase in the level of fasting blood glucose (FBG), a 0.5 mmHg increase in the level of systolic blood pressure (SBP), and a 0.9 mmHg increase in the level of diastolic blood pressure (DBP). Upon multivariate analysis, GH, but not IGF-1, significantly increased the odds of diabetes mellitus (DM) (OR; 1.2, 95% CI; 1.0-1.4, p = .025). CONCLUSIONS: Our findings indicated at early postoperative stage, GH is significantly associated with the levels of FBG, SBP, and DBP. Moreover, GH, but not IGF-1, appears as a predictive factor for the presence of DM. However, neither GH nor IGF-1 could predict the presence of hypertension HTN, or dyslipidemia in this study. ABBREVIATIONS: CVD: Cardiovascular disease; GH: Growth hormone; IGF-1: Insulin-like growth factor 1; BMI: Body mass index; HTN: hypertension; IPTR: Iran Pituitary Tumor Registry; WC: Waist circumference; MRI: Magnetic resonance imaging; FBG: Fasting blood glucose; HbA1C: Glycated hemoglobin; TG: Triglyceride; LDL: Low density lipoprotein; HDL: High density lipoprotein; SBP: Systolic blood pressure; DBP: Diastolic blood pressure.

Visceral Adipose Tissue and Non-alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes.

AIM: To explore the association of visceral adipose tissue (VAT) area and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study comprising 100 patients with T2DM and 100 non-T2DM individuals, matched for age, sex, and body mass index (BMI). Transient elastography was used to assess hepatic steatosis and liver stiffness measurements (LSM). Controlled attenuation parameter (CAP) was used to quantify hepatic steatosis. To distinguish grades of hepatic steatosis, cutoff values were as follows: S1 ≥ 302, S2 ≥ 331, and S3 ≥ 337 dB/m. Moreover, VAT area was measured by dual-energy X-ray absorptiometry in accordance with validated protocols. RESULTS: CAP score was significantly higher in participants with T2DM (294.61 ± 3.82 vs. 269.86 ± 3.86 dB/ m; P < 0.001). Furthermore, 42% of participants with T2DM had hepatic steatosis (S > S1: 302 dB/m), while this figure was 26% in non-T2DM group (P < 0.003). The mean liver stiffness measurement was also significantly higher in patients with T2DM (5.53 vs. 4.79 kPa; P < 0.001). VAT area was greater in patients with T2DM compared to non-T2DM individuals: 163.79 ± 47.98 cm2 versus 147.49 ± 39.09 cm2, P = 0.009. However, total and truncal fat mass were not different between the two groups. Age, BMI, waist circumference, ALT, CAP, and LSM were significantly associated with VAT area. BMI and VAT area were the important determinants of steatosis in both groups of participants with and without T2DM. Moreover, the VAT area was associated with the severity of hepatic steatosis and liver stiffness, independent of anthropometric measures of obesity. CONCLUSION: VAT area is a major determinant of the severity of hepatic steatosis and liver stiffness in patient with T2DM.

Gestational diabetes mellitus: Major risk factors and pregnancy-related outcomes: A cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major pregnancy endocrine problem that has several confirmed risk factors and is associated with adverse pregnancy-related outcomes (PRO). OBJECTIVE: To evaluate the relationship between GDM diagnosis and the associated risk factors of PRO (maternal, intrapartum, perinatal, and neonatal) in accordance with International Association of Diabetes and Pregnancy Study Groups criteria. MATERIALS AND METHODS: This prospective cohort study was performed with 531 singleton parturient (265 GDM and 266 non-GDM). They were selected consecutively from referral hospitals, and the maternal, intrapartum, perinatal, and neonatal outcomes were assessed. RESULTS: The major risk factors influencing the GDM diagnosis were maternal age, obesity, family history of diabetes, previous history of GDM, and previous history of macrosomia. In the comparison of PRO between the groups, significant associations were detected for emergency cesarean delivery, preeclampsia, polyhydramnios, premature rupture of membrane, preterm delivery, and neonatal hyperbilirubinemia in the GDM group. In the multivariate logistic regression analysis, a previous history of stillbirth was significantly associated with maternal and perinatal outcomes. The odds ratios (CI 95%) of the PRO in the women with a GDM diagnosis were: maternal = 2.43 (1.51-3.90), intrapartum = 2.05 (1.35-3.11), perinatal = 2.00 (1.29-3.10), and neonatal = 1.68 (1.08-2.62). The PRO was significantly correlated with GDM diagnosis, but not with the risk factors. CONCLUSION: The adverse pregnancy outcomes were significantly correlated with GDM diagnosis, and the outcomes were not directly affected by the risk factors. Given the related adverse outcomes for mothers and offspring, early screening and management of GDM is necessary especially in Asians and in low-/middle-income countries.

Triglyceride glucose-waist to height ratio: a novel and effective marker for identifying hepatic steatosis in individuals with type 2 diabetes mellitus.

BACKGROUND: The triglyceride-glucose index (TyG), and TyG-driven parameters incorporating TyG and obesity indices have been proposed as reliable indicators of insulin resistance and its related comorbidities. This study evaluated the effectiveness of these indices in identifying hepatic steatosis in individuals with Type 2 diabetes (T2DM). METHODS: This was a cross-sectional study consisting of 175 patients with T2DM (122 with and 53 without NAFLD). TyG index, triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist-to-height ratio (TyG-WHtR) were determined using standard formulas. Controlled attenuation parameter (CAP) was measured by transient elastography (FibroScan). RESULTS: Among obesity parameters, CAP showed the strongest correlation with WHtR, followed by BMI and WC (all P < 0.001). Regression analyses demonstrated TyG-WHtR as a significant predictor of NAFLD with the highest odds ratio, reaching 10.69 (95% CI: 1.68-68.22) for the top quartile (Q4) compared to the first quartile (P = 0.01), followed by TyG-BMI (Q4: 6.75; 95% CI: 1.49-30.67) and TyG-WC (Q4: 5.90; 95% CI: 0.99-35.18). Moreover, TyG-WHtR presented the largest AUC for detection of NAFLD (0.783, P < 0.001) in ROC analysis, followed by TyG-BMI (AUC: 0.751, P < 0.001), TyG-WC (AUC: 0.751, P < 0.001), and TyG (AUC: 0.647, P = 0.002). TyG-WHtR value of 5.58 (sensitivity: 79%, specificity: 68%, P < 0.001) was the best cut-off point to identify hepatic steatosis in this population. CONCLUSIONS: This study confirmed that the TyG-related indices comprising TyG and obesity parameters can identify hepatic steatosis more successfully than TyG alone. Furthermore, our results highlighted TyG-WHtR as a simple and effective marker for screening fatty liver in patients with T2DM, which may be used practically in clinical setting.

Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.

BACKGROUND: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC. METHODS: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews. RESULTS: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported. CONCLUSION: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42019125245 .

Warning signals of elevated prediabetes prevalence in the modern Iranian urban population.

BACKGROUND: We sought to estimate the prevalence of diabetes mellitus (DM) and pre-DM and their associated factors among a sample of the Iranian urban population between 2017 and 2019. METHODS: The present investigation is a sub-study on the HAMRAH cohort study, a longitudinal population-based cohort study to assess the 10-year risk of cardiovascular diseases and their related risk factors in the adult population of the Iranian capital, Tehran. Via a multistage cluster randomized sampling method, 2123 adults aged between 30 and 75 years who had no history of cardiovascular diseases were selected for the study. With the aid of the 2010 American Diabetes Association criteria for the definition of DM and pre-DM, age and sex-specific prevalence rates were estimated. RESULTS: The estimated overall prevalence of DM was 14.3% (95% CI: 13.1%-15.8%): 10.4% known DM (95% CI: 9.1%-11.8%) and 4% newly diagnosed DM (95% CI: 3.1%-5.1%). Pre-DM was detected in about 29.2% of the study participants (95% CI: 22.9-36.3%). Our logistic regression analysis revealed that increasing age, higher systolic blood pressure, higher levels of triglycerides, and lower levels of high-density lipoprotein were significantly associated with DM. CONCLUSIONS: DM and pre-DM follow a notable incremental pattern among the Iranian urban population. This finding underscores the significance of the need to improve prevention and screening strategies in the Iranian urban population.

Hepatic Steatosis and Fibrosis in Type 2 Diabetes: A Risk-Based Approach to Targeted Screening.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common in people with type 2 diabetes mellitus (T2DM). We aimed to explore predictive factors of NAFLD in T2DM and identify high risk subgroups. METHODS: This was a cross-sectional study including 100 individuals with T2DM and 100 without diabetes matched for age, sex, and body mass index (BMI). Hepatic steatosis grades (calculated by controlled attenuation parameters-CAP score-3), and liver fibrosis stages (F0-F4) were determined using transient elastography. RESULTS: The frequency of NAFLD was comparable between the two study groups. However, CAP scores were significantly higher in individuals with diabetes (294.90 ± 53.12 vs. 269.78 ± 45.05 dB/m; P < 0.001). Fifty percent of individuals with diabetes had severe steatosis (S3), while this figure was 31.6% in those without diabetes (P < 0.05). Significant fibrosis (F2-F4) was more frequent in individuals with T2DM (13% vs. 4.1%, P = 0.02). Individuals with T2DM and advanced fibrosis had significantly higher BMI, waist circumference (WC), waist-hip ratio (WHR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and CAP score compared to those without fibrosis (P < 0.05). In the regression analysis, a model including BMI, WHR, AST and female gender explained 50% of the variation in CAP score in patients with diabetes (all P < 0.05, adjusted R2 : 0.508). CAP scores were also the major determinant of liver fibrosis in this group (OR: 1.04; CI: 1.017-1.063; P = 0.001). CONCLUSION: Individuals with diabetes are more likely to have severe fibrosis. Obesity (especially central obesity), the female gender, elevated liver enzymes, and higher degree of insulin resistance are associated with more advanced liver disease in individuals with T2DM.

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

INTRODUCTION: To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). METHODS: In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score. RESULTS: A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: - 29.6 dB/m (- 39.5 to - 19.6) versus - 16.4 dB/m (- 25.0 to - 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: - 0.77 kPa (- 1.45, - 0.09), p = 0.02, versus 0.01 kPa (95% CI - 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group. CONCLUSION: Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3.