Novel anthropometric indices for predicting type 2 diabetes mellitus.

BACKGROUND: This study aimed to compare anthropometric indices to predict type 2 diabetes mellitus (T2DM) among first-degree relatives of diabetic patients in the Iranian community. METHODS: In this study, information on 3483 first-degree relatives (FDRs) of diabetic patients was extracted from the database of the Endocrinology and Metabolism Research Center of Isfahan University of Medical Sciences. Overall, 2082 FDRs were included in the analyses. A logistic regression model was used to evaluate the association between anthropometric indices and the odds of having diabetes. Furthermore, a receiver operating characteristic (ROC) curve was applied to estimate the optimal cutoff point based on the sensitivity and specificity of each index. In addition, the indices were compared based on the area under the curve (AUC). RESULTS: The overall prevalence of diabetes was 15.3%. The optimal cutoff points for anthropometric measures among men were 25.09 for body mass index (BMI) (AUC = 0.573), 0.52 for waist-to-height ratio (WHtR) (AUC = 0.648), 0.91 for waist-to-hip ratio (WHR) (AUC = 0.654), 0.08 for a body shape index (ABSI) (AUC = 0.599), 3.92 for body roundness index (BRI) (AUC = 0.648), 27.27 for body adiposity index (BAI) (AUC = 0.590), and 8 for visceral adiposity index (VAI) (AUC = 0.596). The optimal cutoff points for anthropometric indices were 28.75 for BMI (AUC = 0.610), 0.55 for the WHtR (AUC = 0.685), 0.80 for the WHR (AUC = 0.687), 0.07 for the ABSI (AUC = 0.669), 4.34 for the BRI (AUC = 0.685), 39.95 for the BAI (AUC = 0.583), and 6.15 for the VAI (AUC = 0.658). The WHR, WHTR, and BRI were revealed to have fair AUC values and were relatively greater than the other indices for both men and women. Furthermore, in women, the ABSI and VAI also had fair AUCs. However, BMI and the BAI had the lowest AUC values among the indices in both sexes. CONCLUSION: The WHtR, BRI, VAI, and WHR outperformed other anthropometric indices in predicting T2DM in first-degree relatives (FDRs) of diabetic patients. However, further investigations in different populations may need to be implemented to justify their widespread adoption in clinical practice.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Reference range of testosterone and dehydroepiandrosterone sulfate levels in women during reproductive age in the Iranian population.

Backgrounds: To determine the average cutoff values of serum-free and total testosterone (FT, TT) and dehydroepiandrosterone sulfate (DHEAS) among healthy premenopausal women. Materials and Methods: Participants were women aged 18-55 years without signs and symptoms of hyperandrogenism (n = 489). Participants if Ferriman-Gallwey (FG) scores between 6 and 8 were considered a group located in the upper spectrum related to the normal hirsutism score (n = 30). DHEAS, TT, and FT levels were compared between different populations. Upper limits of 97.5 and 95 and lower limits of 5 and 2.5 percentiles were calculated to provide the reference intervals for DHEA, TT, and FT in the total sample and in the population with FG 6-8. Results: In the total population, the mean ± standard deviation (SD) serum FT, TT, and DHEAS levels were 1.40 ± 0.63 pg/mL, 0.42 ± 0.17 ng/mL, and 1.5 ± 0.97 µg/ml, respectively. The cutoff values of FT at 1.35 and TT at 0.49 were obtained for differentiating the patients with FG 6-8 scores from the normal population, with the corresponding specificity of 0.60, the sensitivity of 0.67, and area under the ROC curve (AUC) (confidence interval 95%) of 0.63 (0.52-0.73), P = 0.01 and 0.68 (0.58-0.78) P = 0.001, respectively. Conclusions: In our study, the mean ± SD serum FT level was 1.40 ± 0.63 pg/mL, the TT level was 0.42 ± 0.17 ng/mL, and the DHEAS level was 1.5 ± 0.97 µg/ml, in premenopausal women between 18 and 49 years of age. Furthermore, in a population with FG 6-8 score, a cutoff value of FT at 1.35 and TT at 0.49 was obtained. Although the irregular menstrual cycle did not change the reference range when compared with the normal group.

The association of exposure to air pollution with changes in plasma glucose indices, and incidence of diabetes and prediabetes: A prospective cohort of first-degree relatives of patients with type 2 diabetes.

Background: Increasing incidence rates of diabetes related to air pollution have been reported in high-income countries. However, few studies evaluated air pollution effect on plasma glucose indices, in addition to diabetes and prediabetes incidence in developing countries. This study investigated the association between exposure to common air pollutants and the changes plasma glucose indices over time. The incidence of type 2 diabetes (T2D) and prediabetes in future were also examined in association with exposure to air pollution. Materials and Methods: A total of 3828 first-degree relatives of patients with T2D who were prediabetes or had normal glucose tolerance (NGT) were enrolled in this study. Cox regression was used to assess the relationships between particulate matter (PM2.5 and PM10), nitrogen monoxide (NO), nitrogen dioxide, nitric oxides, sulfur dioxide (SO2), and ozone exposure and the incidence of T2D and prediabetes. We also applied a linear mixed model to assess the association between exposure to these air pollutants and changes in plasma glucose indices over time. Results: Air pollutants showed a significant positive association with changes in fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), and 2 h oral glucose tolerance (OGTT) in participants with NGT and prediabetes. The maximum increase in plasma glucose indices was associated with NO concentration. Our study also showed exposure to all air pollutants except SO2 was significantly associated with an increased risk of developing T2D and prediabetes (Hazard ratio > 1, P < 0.001). Conclusion: According to our results, exposure to air pollution increases the risk of T2D and prediabetes incidence in our population. The exposure to air pollutants was also associated with increasing trend in FPG, HbA1c, and OGTT levels in both groups of NGT and prediabetic participants.

The effect of linagliptin on microalbuminuria in patients with diabetic nephropathy: a randomized, double blinded clinical trial.

The aim of the present study was to investigate the effect of linagliptin on microalbuminuria in patients with diabetic nephropathy (DN). The present double-blind randomized placebo-controlled clinical trial was performed on 92 patients with DN who were divided into two groups. The intervention and control groups received linagliptin 5 mg and placebo for 24 weeks, respectively. Blood pressure, lipid profile, liver enzymes, fasting plasma glucose (FPG), and urine albumin-creatinine ratio (UACR) were assessed and recorded before, 12 weeks, and 24 weeks after the beginning of the intervention. The mean value of UACR decrease was significant over time in both groups, with higher decrease in linagliptin group, however, the differences between two groups were not, statistically significant (P > 0.05). However, the percentage of improvement in microalbuminuria (UACR < 30 mg/g) in the linagliptin group was significantly higher than that of the control group during 24 weeks of intervention (68.3% vs. 25%; P-value < 0.001). There was no statistically significant difference in the mean value of the UACR and other parameters between linagliptin treated and placebo treated patients with diabetic nephropathy. Further studies, with longer periods of follow-up are suggested to examine these patients' renal outcomes.

Effect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial.

To evaluate the effect of magnesium supplementation on insulin resistance and cardiovascular markers in people with prediabetes. A 12 week double-blind placebo-controlled randomized clinical trial was conducted at Isfahan Endocrine and Metabolism Research Center, Iran, on people with prediabetes (n = 86) to compare the effects of magnesium oxide 250 mg/day versus a placebo on anthropometric indices, blood pressure, fasting glucose, insulin, HOMA-IR index, C-reactive protein, uric acid and lipid profile. Both groups had similar distributions of anthropometric and biochemical variables at baseline. Those who received magnesium supplementation had significantly higher levels of HDL-cholesterol compared to the placebo group at the end of the study (49.7 ± 10.9 vs 43.6 ± 7.2 mg/dL, P = 0.003). The mean changes of HOMA-IR index, total cholesterol, LDL-cholesterol, triglyceride, uric acid and C-reactive protein levels as well as anthropometric indices and blood pressure in supplemented and placebo groups did not differ significantly. Magnesium supplementation increased HDL-cholesterol levels in people with prediabetes. However, other cardiometabolic markers were not improved by magnesium supplementation at the above dosage and duration.

TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis.

CONTEXT: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. OBJECTIVE: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. METHODS: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. RESULTS: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. CONCLUSION: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria.

Antioxidant effects of astaxanthin and metformin combined therapy in type 2 diabetes mellitus patients: a randomized double-blind controlled clinical trial.

Background and purpose: Since the critical role of oxidative stress in the pathogenesis and complications of type 2 diabetes mellitus (T2DM) has been proven, antioxidant therapy is considered an applicable strategy to control T2DM development. This study aimed at evaluating the effect of astaxanthin (AST) supplementation combined with metformin on oxidative indices and antioxidant defenses in T2DM patients. Experimental approach: In this randomized, double-blind placebo-controlled trial, 50 T2DM subjects receiving metformin were supplemented with 10 mg/day AST or placebo for 12 weeks. Malondialdehyde concentration and serum total antioxidant capacity (TAC) were assessed as oxidative indices. We also evaluated NF-E2-related factor2 (Nrf2) as the most critical transcription factor of antioxidant defense. Moreover, the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase were calculated. Findings/Results: AST supplementation-metformin combination caused a significant increase in SOD and catalase activities, as well as inducing Nrf2 protein expression compared to the placebo group. Significant changes in serum malondialdehyde and TAC between the AST group and placebo group after supplementation were not observed, although a significant increase was observed in TAC within the AST group after supplementation (32.67 ± 6.73) to before (25.86 ± 5.98). These results remained without change after adjustment for potential confounders. Conclusion and implications: Our study demonstrated that AST supplementation controlled oxidative stress through a synergistic effect with metformin and ameliorated overall antioxidant capacity by inducing Nrf2 transcription factor and activating SOD and catalase in T2DM patients. As a result, AST and metformin combination therapy can be considered beneficial in modifying oxidative stress and preventing T2DM complications.

Bacterial Profile and Antimicrobial Resistance Patterns of Infected Diabetic Foot Ulcers in Iran: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

Since infectious foot ulcers represent one of the major causes of lower-limb amputation, it calls for an appropriate action for early detection and sufficient treatment of diabetic foot infection (DFI). The present study aimed at investigating the bacterial epidemiology and antimicrobial resistance (AMR) patterns of DFIs in Iran. We have conducted a systematic search in PubMed, Embase, Web of Science, Scopus, Google Scholar, and Scientific Information Database to identify all articles reporting the proportion of different kinds of bacteria isolated from Iranian DFI samples. Quality was assessed using Joanna Briggs Institute tool. A pooled estimate of proportion with a corresponding 95% confidence interval (95% CI) was calculated using the random effect method. Fifteen studies were eligible, of which 1970 bacterial isolates were obtained from 1316 patients. The most predominant isolates recovered from DFIs was Staphylococcus aureus with a pooled proportion of 24.29% (95% CI: 20.25%, 28.57%) from which 55% (95% CI: 38%, 72%) were methicillin-resistant S. aureus (MRSA). Among Gram-negative strains, Escherichia coli had the highest proportion (17.19%; 95% CI: 13.96%, 20.68%) followed by Pseudomonas aeruginosa, 7.54% (95% CI: 4.56%, 11.14%). The highest pooled estimates of resistance against cotrimoxazole and ciprofloxacin were found in S. aureus 66% (95% CI: 48%, 82%) and E coli isolates 68% (95% CI: 51%, 84%), respectively. Our study revealed that AMR is at a high level in Iran and clinicians should be aware of bacterial resistance patterns to prescribe appropriate antibiotic regimens.

A Thyroid Stimulating Hormone Reference Range: Iranian Thyroid Cohort study.

BACKGROUND: Current reference values for thyroid function tests are derived from data from different ethnicities and geographical areas. In this article, we aim to select criteria from the guidelines proposed by the National Academy of Clinical Biochemistry (NACB) and to determine the TSH and T4 reference limits in the iodine-sufficient area of Isfahan, a metropolitan city in Iran. MATERIALS AND METHODS: This study was conducted within the framework of "Isfahan Thyroid Study (ITS)", an ongoing prospective cohort that started in 2006 (n=2523) until 2011 (n=711) and included participants above the age of twenty. We measured TSH, total T4, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). RESULTS: Recruitment was based on the NACB criteria, 1899 participants were included in 2006(58.5% male) and 377 in 2011(62.3% male). The mean± SD age was 39.66 ±12.71 and 48.96±12.35 years in 2006 and 2011, respectively. The mean± SD for TSH was 2.0±1.19 and 2.11±1.11 mU/L and T4 was 6.67±1.47 and 8.3±2.95 µg /dl in 2006 and 2011, respectively. In 2006, the 2.5th percentile of serum TSH levels was 0.4 mU/L (males: 0.4 mU/L, females: 0.5 mU/L) and the 97.5th percentile of serum TSH was 4.96 mU/L (males: 4.72 mU/L, females: 5. 3 mU/L). In 2011, the 2.5th percentile of serum TSH levels was 0.7 mU/L (males: 0.6 mU/L, females: 0.77 mU/L) and 97.5th percentiles of serum TSH was 4.9 mU/L (males: 5.7 mU/L, females: 5. 57 mU/L). CONCLUSION: This study determined age and sex specific TSH and T4 reference ranges in the Isfahanian population, which could theoretically enable clinicians to classify patients more accurately. (www.actabiomedica.it).

The effect of alendronate on lipid profile of postmenopausal women with osteopenia and prediabetes: A randomized triple-blind clinical trial.

BACKGROUND: Prediabetes is a high-risk state for developing diabetes at an annual rate of 5%-10%. Early intervention can prevent further complications, including metabolic syndrome. Bisphosphonates are commonly used for osteoporotic postmenopausal women. The purpose of this study was to assess the effects of bisphosphonates on lipid profile including triglyceride (TG), total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) of prediabetic postmenopausal women with osteopenia. MATERIALS AND METHODS: In this triple-blind randomized controlled trial, sixty prediabetic, postmenopausal women with sufficient Vitamin D and osteopenia, aged 45-60 years, were randomly enrolled in two groups of intervention (receiving 70-mg alendronate for 12 weeks [duration for maximum metabolic effect of bisphosphonates], n = 30) and control (receiving placebo, n = 30) according to a randomized block procedure of size 2 and 1:1 allocation ratio. The primary outcome of the study, the lipid profile, was evaluated before and after the interventions. The effect of the intervention was assessed using analysis of covariance. RESULTS: The lipid profiles showed no significant differences to the mean values at the baseline in both the groups (all P > 0.05). At the end of the study, the differences between the groups were not significant for 25(OH) D3 (mean difference: -11.09, 95% confidence interval: -32.43-10.25), T (4.19, -30.58-38.97), cholesterol (8.13, -13.07-29.33), LDL-cholesterol (5.07, -10.18-20.31), and HDL-cholesterol (-0.86, -6.04-4.31) when the baseline values and confounders were adjusted (all P > 0.05). CONCLUSION: No statistically significant difference was detected in the serum lipid profile of prediabetic postmenopausal women with osteopenia as a result of alendronate intervention. More studies with larger sample sizes and longer intervention periods are recommended.

Isfahan Thyroid Cohort Study (ITCS).

BACKGROUND: The Isfahan Thyroid Cohort Study (ITCS) is one of the few population-based epidemiological studies in Iran that investigates the prevalence and incidence of thyroid disorders including hypothyroidism, hyperthyroidism, goiter, nodule, and iodine status. METHODS: This cohort is located in Isfahan, Iran. The first phase was initiated in 2006 with 2523 participants (1275 males, 1248 females). The participants were selected using multi-stage cluster sampling from the general residents of Isfahan, Iran. The study had two phases (2006 and 2011) and its third stage is planned for 2020-2021. RESULTS: The prevalence of thyroid function states was euthyroid (89.3%, 95% CI: 88%-90%), overt hypothyroidism (2.8%, 95% CI: 2%‒3%), subclinical hypothyroidism (5.8%, 95% CI: 4%-6%), overt hyperthyroidism (0.8%, 95% CI: 0.4%‒1%), and subclinical hyperthyroidism (0.99%, 95% CI: 0.6%-1%). Hypothyroidism and hyperthyroidism were significantly associated with goiter. The incidence of thyroid dysfunction was reported as follows: overt hypothyroidism (2.7, 95% CI: 1.6-3.7), subclinical hypothyroidism (20.6, 95% CI: 18-23), overt hyperthyroidism (1.9, 95% CI: 1-2.7) and subclinical hyperthyroidism (2.7, 95% CI: 1.6-3.7) per 1000 (person-year). CONCLUSION: We assessed the prevalence and incidence of thyroid disorders in Isfahan in the first and second phase, respectively. We are conducting the third phase of the ITCS in order to study the associations between thyroid peroxidase antibody (TPOAb) level and environmental factors such as infection.

Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level.

A concern was raised 1 regarding the number of pregnant women in the analysis of reference range for the thyroid hormones in pregnancy 2, where we reported 185 cases and it was believed to be 145 cases.

A 16-year prospective cohort study to evaluate effects of long-term fluctuations in obesity indices of prediabetics on the incidence of future diabetes.

This study aimed to evaluate the patterns of changes in obesity indices over time in prediabetic subjects and to classify these subjects as either having a low, moderate, and high risk for developing diabetes in the future. This study was conducted among 1228 prediabetics. The patterns of changes in obesity indices based on three measurements including first, mean values during the follow-up period, and last visit from these indices were evaluated by using the latent Markov model (LMM). The mean (standard deviation) age of subjects was 44.0 (6.8) years and 73.6% of them were female. LMM identified three latent states of subjects in terms of change in all anthropometric indices: a low, moderate, and high tendency to progress diabetes with the state sizes (29%, 45%, and 26%), respectively. LMM showed that the probability of transitioning from a low to a moderate tendency to progress diabetes was higher than the other transition probabilities. Based on a long-term evaluation of patterns of changes in obesity indices, our results reemphasized the values of all five obesity indices in clinical settings for identifying high-risk prediabetic subjects for developing diabetes in future and the need for more effective obesity prevention strategies.

Alleviating neuropathy of diabetic foot ulcer by co-delivery of venlafaxine and matrix metalloproteinase drug-loaded cellulose nanofiber sheets: production, in vitro characterization and clinical trial.

BACKGROUND: The objective of the present study was co-delivery of venlafaxin (VEN) and doxycycline (DOX), a matrix metalloproteinase inhibitor drug, for alleviating inflammation and neuropathy in diabetic foot ulcer (DFU). METHODS: Bacterial cellulose nanofiber sheets (BCNS) were loaded with DOX and VEN and categorized by their loading efficiency, release profiles and ex vivo permeation throughrat skin. The optimized nanofibers were used in patients with DFU to compare with the standard wound care regimen during a 12-week trial. Wound area was measured every 2 weeks. Biochemical parameters and microscopic studies of the skin were examined prior and at the end of the treatment. The Michigan Neuropathy Screening Instrument (MNSI) questionnaire was utilized to assess diabetic neuropathy. RESULTS: The optimum formulation showed loading efficiency of 37.8 ± 1.6% for DOX and 48 ± 1.9% for VEN. Rat skin permeation was 40% for DOX after 7-29 h and 83% for VEN during 105 h. Patients treated with BCNS showed no significant difference in their biochemical parameters before and after intervention. The ulcer size showed faster reduction after 12 weeks in the treatment group compared to the control group. The abnormal responses in the MNSI questionnaire decreased and pain-free walking distance increased significantly in the treatment group compared with the control group (p < 0.001). Microscopic studies of the skin after using nanofibers showed a large number of polymorphonuclear chronic inflammatory cells and formation of new capillary beds. CONCLUSIONS: The BCNS loaded with DOX and VEN may expedite healing and reduce neuropathy in the DFU of diabetic patients.

Patterns of changes in fasting plasma glucose, hemoglobin A1c and the area under the curve during oral glucose tolerance tests in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

AIM: This study aimed to identify the patterns of changes in glycemic indices over time in prediabetics and to classify these subjects as either having a high or low risk for developing diabetes in future. METHODS: This prospective 16-year cohort study was conducted among 1228 prediabetic subjects. Three measurements including first visit, mean values during the follow-up period, and last visit from fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), and area under the curve during an oral glucose tolerance test (OGTT AUC) were used to evaluate the patterns of changes by using the latent Markov model (LMM). RESULTS: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The LMM identified 2 latent states of subjects in terms of changes in FPG, HbA1c, OGTT AUC, and the combination of these glycemic measures: a low tendency to progress diabetes and a high tendency to progress diabetes with the latent state sizes (87, 13%), (94, 6%), (57, 43%), and (84, 16%), respectively. The LMM showed that the probability of transitioning from a low tendency to a high tendency to progress diabetes was higher than the probability of transitioning in the opposite direction. CONCLUSION: Based on a long-term evaluation of patterns of changes in glycemic indices, we classified prediabetic subjects into 2 groups (high or low risk to progress diabetes states in future). Also, the method used enabled us to estimate the transition probabilities from low- to high-risk states and vice versa. Our results reemphasized the values of all 3 glycemic measures in clinical settings for identifying prediabetic people with a high risk of progressing diabetes and the need for more effective prevention strategies, which should be conducted as urgently in prediabetic life as high-risk subjects.

Patterns of changes in serum lipid profiles in prediabetic subjects: results from a 16-year prospective cohort study among first-degree relatives of type 2 diabetic patients.

BACKGROUND: Lipid abnormality pervasively is associated with the risk of type 2 diabetes mellitus. To the best of our knowledge, there is no study that has examined the longitudinal changes in a wide range of serum lipid profiles in prediabetic subjects in association with the risk of developing type 2 diabetes mellitus in the future. This study aimed to identify the patterns of changes in lipid profiles over time in prediabetic patients and to classify these subjects in order to highlight which patients are at high risk for future diabetes. METHODS: This prospective 16-year (2003-2019) cohort study was conducted among 1228 prediabetic subjects. The study subjects were followed, and the changes in their lipid profiles, including triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, were evaluated. The latent Markov model was used for data analysis. RESULTS: The mean (standard deviation) age of subjects was 44.0 (6.8) years, and 73.6% of them were female. The latent Markov model identified two latent states of subjects in terms of changes in lipid profiles: a low tendency to progress diabetes / high tendency to progress diabetes (74, 26%). The latent Markov model showed that the transition probability from a "low tendency to progress diabetic" state to a "high tendency to progress diabetic" state was lower than the transition probability from "high tendency to progress diabetic" state to "low tendency to progress diabetic" state. CONCLUSIONS: The present study showed that more than half of the first-degree relatives of T2DM had approximately normal lipid profiles and that these patients are more inclined to transition from a higher- to a lower-tendency diabetic state. These findings confirm the value of regular screening of first-degree relatives of T2DM. Moreover, preventive intervention strategies are recommended to reduce their risk of developing T2DM.