Predictors of response to Radioactive Iodine Therapy in Intermediate and high risk patients with papillary thyroid carcinoma.

BACKGROUND: Radioactive iodine (RAI) therapy is the standard treatment approach after total thyroidectomy in patients with papillary thyroid carcinoma (PTC). We aimed to identify predictive factors of response to the treatment in intermediate and high-risk patients with PTC. In addition, the impact of multiple RAI treatments was explored. METHODS: In a 3-year retrospective study, data from intermediate and high-risk patients with PTC who received RAI therapy following total thyroidectomy, were analyzed by the end of year-one and year-three. Demographic data, tumor size, capsular/vascular invasion, extrathyroidal extension, local or distant metastasis, initial dose and cumulative dose of RAI, serum thyroglobulin(Tg), antithyroglobulin antibody(TgAb), and imaging findings were investigated. Patients with an excellent response to a single dose of RAI treatment, after three years of follow-up were classified as the "Responder group". Excellent response was defined as stimulated serum Tg less than 1 ng/ml, or unstimulated serum Tg less than 0.2 ng/ml in TgAb-negative patients with negative imaging scans. RESULTS: 333 patient records with a complete data set were analyzed in this study. After three years of initial treatment, 271 patients were non-responders (NR) and 62 were responders (R). At baseline, the median pre-ablation serum Tg level was 5.7 ng/ml in the NR group, and 1.25 ng/ml in the R group (P < 0.001). TSH-Stimulated serum Tg greater than 15.7 ng/ml, was associated with response failure even after multiple RAI therapy, AUC: 0.717(0.660-0.774), sensitivity: 52.5%, specificity: 89.47%, P < 0.001. On the other hand, multiple RAI therapy was associated with excellent response in 16.2% of the patients. The chance of ER was decreased by 74% if initial post-operation ultrasound imaging confirmed the presence of locoregional involvement, OR 0.26, (95% CI: 0.12-0.55), P < 0.001. CONCLUSION: Stimulated serum Tg and locoregional involvement after total thyroidectomy are predictive factors of non-response to RAI therapy in intermediate and high-risk patients with PTC. In addition, a minority of patients achieve excellent response after multiple RAI therapy.

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.

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.

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.

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.

COMPARISON OF CABERGOLINE VERSUS RALOXIFENE ADD-ON THERAPY TO LONG-ACTING SOMATOSTATIN ANALOGUE IN PATIENTS WITH INADEQUATELY CONTROLLED ACROMEGALY: A RANDOMIZED OPEN LABEL CLINICAL TRIAL.

OBJECTIVE: The present study aimed to evaluate the efficacy of add-on therapy of cabergoline versus raloxifene to long-acting somatostatin analogues (SAs) in patients with inadequately controlled acromegaly. METHODS: This was a prospective, randomized open label clinical trial. Forty-four patients (22 per group) completed the study; where participants received either cabergoline (3 mg/week) or raloxifene (60 mg twice daily) add-on therapy for 12 weeks in a parallel manner. The primary outcome was the rate of reduction in serum insulin-like growth factor 1 (IGF-1) from baseline. Secondary outcomes comprised normalization of serum IGF-1 for age and sex. RESULTS: Serum IGF-1 was significantly decreased in both the cabergoline (40.3 ± 25.6%, P<.001) and raloxifene (31.5 ± 24.6%, P<.001) groups, with no significant difference between arms ( P>.05). Normalization in serum IGF-1 values occurred in 40.9% of patients who were on cabergoline compared to 45.5% of those receiving raloxifene ( P = .76). The subsequent logistic regression analysis highlighted baseline IGF-1 as a significant predictor of IGF-1 normalization (odds ratio, 0.995; 95% confidence interval, 0.990-0.999; P = .02). Using the receiver operating characteristic (ROC) curve analysis for the entire group, the baseline IGF-1 value of 1.47 the upper limit of normal (ULN) was the best cut-off point to identify patients with normal IGF-1 at the end of the study (sensitivity: 52.6%, specificity: 84.0%, Yoden's index: 0.366). Full biochemical control of acromegaly was achieved in 22.7% of patients in the cabergoline group compared to 13.6% of those in the raloxifene group ( P = .43). CONCLUSION: Cabergoline and raloxifene add-on therapy could effectively decrease serum IGF-1 level in patients with inadequately controlled acromegaly. The efficacy profiles of both drugs are comparable. ABBREVIATIONS: DA = dopamine agonist; FBG = fasting blood glucose; GH = growth hormone; IGF1 = insulin-like growth factor-1; IQR = interquartile range; OR = odds ratio; ROC = receiver operating characteristic; SA = somatostatin analogue; SERM = selective estrogen modulator receptor; ULN = upper limit of normal.

The association of type II diabetes with gut microbiota composition.

It is known that type 2 diabetes (T2D) in humans could be linked to the composition of gut microbiota. The aim of this study was to evaluate three faecal bacterial species, including Bacteroides fragilis, Bifidobacterium longum and Faecalibacterium prausnitzii in patients with T2D. This case control study included 18 patients with T2D and 18 matched persons without diabetes. The concentrations of B. fragilis, B. longum and F. prausnitzii were determined by quantitative Real-Time PCR. Quantitative PCR analysis revealed that the gut bacterial composition in patients with T2D was partially different from that in the healthy individuals. Faecalibacterium prausnitzii was significantly lower in patients with T2D (P-value = 0.038). Bacteroides fragilis was under-represented in the microbiota of the group with diabetes, but its difference between two groups was not significant (P-value = 0.38). No difference was observed for B. longum community between the both groups (P-value = 0.99). Characterization of specific species of intestinal microbiota shows some compositional changes in patients with T2D. The results may be valuable for developing strategies to control type 2 diabetes by modifying the intestinal microbiota. Long-term studies with emphasis on other bacterial groups are suggested to clarify the association of T2D with gut microbiota.

Comparison of gut microbiota in adult patients with type 2 diabetes and healthy individuals.

Recent studies indicate that inflammatory reactions leading to the development of type 2 diabetes mellitus (T2DM) may also contribute to variations in the composition of the intestinal microbiota, suggesting a relation between T2DM and bacterial residents in the intestinal tract. This case-control study was designed to evaluate the composition of the gut microbiota dominant bacterial groups in patients with T2DM compared to the healthy people. A total of 36 adult subjects (18 patients diagnosed with T2DM and 18 healthy persons) were included in the study. The intestinal microbiota composition was investigated by quantitative real-time polymerase chain reaction (qPCR) method using bacterial 16S rRNA gene. The quantities of two groups of bacteria were meaningfully different among T2DM patients and healthy individuals. While, the level of Lactobacillus was significantly higher in the patients with T2DM (P value < 0.001), Bifidobacterium was significantly more frequent in the healthy people (P value < 0.001). The quantities of Prevotella (P value = 0.0.08) and Fusobacterium (P value = 0.99) genera in faecal samples were not significantly different between the two groups. The significant alterations in dominant faecal bacterial genera found in T2DM patients participating in the current study highlight the link between T2DM disease and compositional variation in intestinal flora. These findings may be valuable for developing approaches to control T2DM by modifying the gut microbiota. More investigations with focus on various taxonomic levels (family, genus and species) of bacteria are necessary to clarify the exact relevance of changes in the gut microbial communities with the progression of T2DM disorder.

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.

Gut Microbiota and Their Associated Metabolites in Diabetes: A Cross Talk Between Host and Microbes-A Review.

Dysbiosis of the gut microbiota's composition and function is important in developing insulin resistance and diabetes. Diabetes has also been linked to changes in the circulating and fecal metabolites. Evidence suggests the associations between the gut microbiota and the aberrant diabetes-related metabolome. Metabolites play a crucial role in the host-microbiota interactions. Researchers have used a combination of metagenomic and metabolomic approaches to investigate the relationships between gut microbial dysbiosis and metabolic abnormalities in diabetes. We summarized current discoveries on the associations between the gut microbiota and metabolites in type 1 diabetes, type 2 diabetes, and gestational diabetes mellitus in the scoping review. According to research, the gut microbiota changes might involve in the development of diabetes through modulating the host's metabolic pathways such as immunity, energy metabolism, lipid metabolism, and amino acid metabolism. These results add to our understanding of the interplay between the host and gut microbiota metabolism.

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 between dietary glycemic index and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus.

Objective: Managing dietary glycemic index (GI) deserves further attention in the interplay between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). This study aimed to evaluate the relationship between dietary GI and the odds of NAFLD in patients with T2DM. Methods: A cross-sectional study was carried out between April 2021 and February 2022, including 200 participants with T2DM aged 18-70 years, of which 133 had NAFLD and 67 were in the non-NAFLD group. Cardiometabolic parameters were analyzed using standard biochemical kits and dietary intake was assessed using a validated food frequency questionnaire. Binary logistic regression was applied to explore odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD according to tertiles of dietary GI. Results: Highest vs. lowest tertile (< 57 vs. > 60.89) of energy-adjusted GI was not associated with the odds of having NAFLD (OR 1.25, 95% CI = 0.6-2.57; P-trend = 0.54) in the crude model. However, there was an OR of 3.24 (95% CI = 1.03-10.15) accompanied by a significant trend (P-trend = 0.04) after full control for potential confounders (age, gender, smoking status, duration of diabetes, physical activity, waist circumference, HbA1c, triglycerides, total cholesterol, dietary intake of total carbohydrates, simple carbohydrates, fat, and protein). Conclusion: High dietary GI is associated with increased odds of NAFLD in subjects with T2DM. However, interventional and longitudinal cohort studies are required to confirm these findings.

Dietary total antioxidant capacity is inversely associated with the odds of non-alcoholic fatty liver disease in people with type-2 diabetes.

Background: This study was conducted to evaluate possible associations between Dietary Total Antioxidant Capacity (DTAC) and odds of non-alcoholic fatty liver disease (NAFLD) in people with type-2 diabetes mellitus (T2DM). Materials and methods: We recruited two hundred people with T2DM, and evaluated their liver steatosis using Fibroscan. Dietary intakes of participants were assessed using a validated food frequency questionnaire. DTAC was computed via ferric reducing antioxidant power (FRAP). Results: In the crude model, no statistically significant association was found between DTAC and the odds of NAFLD in people with diabetes. However, after adjustment for potential confounders including age, gender, diabetes duration, smoking status, physical activity, BMI, waist circumference, and energy, the most reduced adjusted OR was indicated for the third tertile vs. the first one (OR: 0.28, 95% CI: 0.09-0.81, P = 0.02), meaning that diabetic patients in the third tertile of DTAC had 72% decreased risk of NAFLD in comparison to those in the first one. The relationship was remained significant after additional adjustment for HOMA-IR, HbA1c, serum Triglyceride (TG), and low-density lipoprotein-cholesterol (LDL) levels (OR: 0.29, 95% CI: 0.09-0.93, P = 0.03). Importantly, a dose-response pattern was demonstrated for DTAC and risk of NAFLD (P = 0.04). Conclusion: Higher DTAC was related with a decreased risk of NAFLD in individuals with diabetes.

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.

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.

Triglyceride Glucose Index and Related Parameters (Triglyceride Glucose-Body Mass Index and Triglyceride Glucose-Waist Circumference) Identify Nonalcoholic Fatty Liver and Liver Fibrosis in Individuals with Overweight/Obesity.

Background: The triglyceride glucose (TyG) index has been proposed as a reliable surrogate marker for nonalcoholic fatty liver disease (NAFLD). Furthermore, NAFLD is strongly related with obesity. This study aimed to compare TyG index and its related parameters (TyG-waist circumference [WC] and TyG-body mass index [BMI]), comprising TyG and obesity markers, in predicting NAFLD and liver fibrosis in overweight/obese individuals without diabetes. Methods: This was a cross-sectional study consisting of 184 overweight/obese people (96 with and 88 without NAFLD), 30-65 years of age. TyG, TyG-BMI, and TyG-WC were computed using the established formula. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were determined by transient elastography (FibroScan). Results: In correlation analyses, CAP and LSM were significantly associated with WC, BMI, TyG, TyG-BMI, and TyG-WC. Regression analyses highlighted TyG-WC as a significant predictor of NAFLD, with the highest standardized odds ratio (2.25, P < 0.001); while liver fibrosis was associated more strongly with TyG-BMI. In receiver operating characteristic (ROC) analysis, TyG-WC showed the largest area under the ROC curve (AUC) for detection of NAFLD (0.693, 95% confidence interval [CI]: 0.617-0.769). However, TyG-BMI was a better discriminator of liver fibrosis (AUC: 0.635, 95% CI: 0.554-0.714). TyG-WC value of 876 (sensitivity: 81.3%, specificity: 52.3%) and TyG-BMI value of 259 (sensitivity: 78.3%, specificity: 51.3%) were the optimal cutoff points to predict NAFLD and liver fibrosis, respectively. Conclusions: The results highlight the significant associations of TyG and its related indices with NAFLD, with TyG-WC being a better indicator. TyG-BMI and TyG-WC could reliably predict liver fibrosis in this population. These indices appear to be simple, practical, and affordable tools for screening NAFLD and liver fibrosis in clinical settings.

The optimal vitamin D cut-off value associated with hyperglycemia in an Iranian population.

BACKGROUND: Vitamin D deficiency may accelerate the risk of type 2 diabetes mellitus. The association of vitamin D with hyperglycemia may be influenced by lifestyle. OBJECTIVE: To evaluate the relationship between vitamin D status and hyperglycemia among the workers' population. METHODS: This was a medical records review of 7054 Iranian factory workers participating in an annual health check-up for employees. Of those, potential participants were included in this analysis if data for serum 25-hydroxyvitamin D [25(OH) D] levels were also available. RESULTS: Data of 429 male participants were used for this analysis. Of those, 61.07% had serum 25(OH)D concentrations lower than the sufficient level [≥20 ng/ml]. Hyperglycemic participants had significantly lower 25(OH)D than those with normal fasting blood glucose (FBG). Regression analyses highlighted serum 25(OH)D as a significant determinant of hyperglycemia [OR: 0.943(0.901, 988); p = 0.01]. The association between 25(OH)D and FBG remained significant after adjustment for potential confounders (p = 0.008). Using the ROC analysis, the serum 25(OH)D value of 14.7 ng/ml was the optimal cut-off point to predict hyperglycemia in this population (sensitivity: 63.6%, specificity: 62.3%, p = 0.01). CONCLUSION: Our results revealed a considerable proportion of participants with serum 25(OH)D below the optimal level as well as a significant inverse association between vitamin D status and hyperglycemia among the factory workers. These findings highlight the importance of including the evaluation of vitamin D status as a part of annual health examinations for employees, and may help health policy- makers prevent or delay type 2 diabetes mellitus among the workers' population.

High-dose thiamine supplementation may reduce resting energy expenditure in individuals with hyperglycemia: a randomized, double - blind cross-over trial.

BACKGROUND: Despite the crucial role of thiamine in glucose and energy metabolism pathways, there has been no published study examining the impact of thiamine on energy metabolism in humans. OBJECTIVE: To assess the effects of thiamine supplementation on resting energy expenditure (REE) in individuals with hyperglycemia. METHODS: Twelve hyperglycemic patients completed this double-blind, randomized trial, where all participants received both thiamine (300 mg/day) and matched placebo for 6 weeks in a cross-over manner. REE was assessed by indirect calorimetry. Anthropometric measurements, fasting and 2-h plasma glucose, and glucose-induced thermogenesis were also assessed at the beginning and on the completion of each six-week phase. RESULTS: Participants consuming thiamine supplements experienced a significant decrease in the REE assessed at week six compared to the baseline [mean (SE): 1478.93 (73.62) vs.1526.40 (73.46) kcal/d, p = 0.02], and the placebo arm (p = 0.002). These results did not change significantly after adjusting for the participants' body weight and physical activity as potential confounders. Six-week intervention had no significant effect on the participants' body weight or waist circumference, in either supplement or placebo arms (all p values>0.05). However, correlation analysis highlighted significant positive relationships between the changes in REE, and those in fasting (rs = 0.497, p = 0.019) and 2-h plasma glucose (rs = 0.498, p = 0.018) during the six-week intervention period. CONCLUSION: Supplementation with high-dose thiamine may attenuate REE in patients with impaired glucose regulation. Our findings suggest that the impact of thiamine on REE may in part be explained by improved glycemic control. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12611000051943. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12611000051943.

Ethnic Variations in Adiponectin Levels and Its Association with Age, Gender, Body Composition and Diet: Differences Between Iranians, Indians and Europeans Living in Australia.

Adiponectin is an adipocyte-derived protein with anti-diabetic, anti-atherogenic and anti-inflammatory action, but there are few studies on its association with cardiovascular and metabolic risk factors in different ethnic groups in Australia. This cross-sectional study evaluated ethnic differences in adiponectin levels and its association with age, gender, body composition and diet in 89 adult Australians of European (n = 28), Indian (n = 28) and Iranian (n = 33) ancestries. Different measures of adiposity were assessed using the method of whole body dual energy X-ray absorptiometry (DEXA). Total adiponectin levels determined in Indians and Iranians were significantly lower than those in Europeans (p values < 0.001). There was no significant difference between the adiponectin levels in Indians and Iranians (p value > 0.05). There was no substantial change in the results after adjustment for potential confounders. Circulating levels of adiponectin was associated with age, truncal fat percentage, dietary glycemic index, glycemic load and carbohydrate intake, by correlation analysis (p values < 0.05). Using multiple linear regression analysis, a model including truncal fat percentage (p < 0.001), ethnicity (p = 0.001), age (p = 0.001) and dietary glycemic index (p = 0.04) could predict 50% of the variance in adiponectin levels (R2 = 0.504). Among different variables assessed, truncal fat percentage (in Indian and Iranian groups) and glycemic index (in European group) were the strongest predictors of serum adiponectin when data were analysed for three ethnic groups, separately. In conclusion, individuals with Iranian or Indian ancestries may have lower adiponectin levels compared to Europeans. Ethnicity was found as an independent factor affecting adiponectin levels. Our results also highlighted age, truncal adiposity and dietary glycemic index as other determinants of serum adiponectin, however the extent to which these factors influence adiponectin concentrations may vary across ethnicities.