Interrelationship between thyroid hormones and reduced renal function, a review article.

BACKGROUND: Understanding the relationship of thyroid hormones with the development of chronic kidney disease (CKD) has important clinical implications for managing patients with both thyroid and kidney dysfunction. In this review, our purpose was to provide a thorough comprehension of the interplay between thyroid hormones, thyroid dysfunctions, and CKD. While there is evidence linking thyroid hormone levels to renal diseases, the association between thyroid hormones, specifically within the normal range, and the risk of CKD incidence is still a subject of debate. The Google Scholar, PubMed, Scopus, and Web of Science, were searched using the medical subject heading (MeSH) terms for the relevant keywords up to December 2023. CONCLUSION: Based on the review, the development of CKD is more consistently associated with higher serum TSH and thereafter lower serum free T3 levels; however, its association with free T4 is more controversial. Furthermore, subclinical and overt hypothyroidisms were considerably associated with incident CKD. Hyperthyroidism and Hashimoto thyroiditis might increase the risk of CKD.

The association of body mass index variability with cardiovascular disease and mortality: a mediation analysis of pooled cohorts.

Aim: We aimed to investigate the effect of BMI variability on CVD and mortality and to explore the mediation effects of the main cardiovascular risk factors contributing to this association. Method: Participants aged 40-65 years were pooled from three cohort studies(ARIC [Atherosclerosis Risk in Communities], MESA [Multi-ethnic Study of Atherosclerosis], and TLGS [Tehran Lipid and Glucose Study]. We employed root mean squared error of the fractional mixed model to calculate BMI variability in the measurement period. In the event assessment period, the hazard ratios for CVD and mortality were estimated using Cox proportional hazard regression models. In the next step, the mediation and interaction effects of fasting plasma glucose, total cholesterol, and systolic blood pressure were determined. Results: A total of 19073 participants were included in this pooled analysis. During a median of 20.7 years of follow-up, 3900 (20.44%) CVD and 6480 (33.97%) all-cause mortality events were recorded. After adjusting for potential confounders, BMI variability was linked to the 1.3 (1.2-1.4) and 1.7 (1.6-1.8) increased risk of CVD and mortality, respectively. Fasting plasma glucose mediated approximately 24% and 8% of the effect of BMI variability on CVD and mortality, respectively. However, systolic blood pressure and total cholesterol did not have mediation effects in this association. Conclusion: High BMI variability is independently associated with the development of CVD and mortality. This association is partly mediated through fasting plasma glucose. Modern cardiometabolic therapies that lower fasting glucose may reduce the risk of future CVD and mortality in individuals with high BMI variability.

Trajectory patterns of metabolic syndrome severity score and risk of type 2 diabetes.

BACKGROUND: The available evidence indicates that the severity of metabolic syndrome tends to worsen progressively over time. We assessed the trajectory of age and sex-specific continuous MetS severity score (cMetS-S) and its association with the development of diabetes during an 18-year follow-up. METHODS: In a prospective population-based Tehran Lipid and Glucose Study, 3931 eligible participants free of diabetes, aged 20-60 years, were followed at three-year intervals. We examined the trajectories of cMetS-S over nine years using latent growth mixture modeling (LGMM) and subsequent risks of incident diabetes eight years later. The prospective association of identified trajectories with diabetes was examined using the Cox proportional hazard model adjusting for age, sex, education, and family history of diabetes, physical activity, obesity (BMI ≥ 30 kg/m2), antihypertensive and lipid-lowering medication, and baseline fasting plasma glucose in a stepwise manner. RESULTS: Among 3931 participants, three cMetS-S trajectory groups of low (24.1%), medium (46.8%), and high (29.1%) were identified during the exposure period. Participants in the medium and high cMetS-S trajectory classes had HRs of 2.44 (95% CI: 1.56-3.81) and 6.81 (95% CI: 4.07-10.01) for future diabetes in fully adjusted models, respectively. Normoglycemic individuals within the high cMetS-S class had an over seven-fold increased risk of diabetes (HR: 7.12; 95% CI: 6.05-12.52). CONCLUSION: Although most adults exhibit an unhealthy metabolic score, its severity usually remains stable throughout adulthood over ten years of follow-up. The severity score of metabolic syndrome has the potential to be utilized as a comprehensive and easily measurable indicator of cardiometabolic dysfunction. It can be employed in clinical settings to detect and track individuals at a heightened risk of developing T2DM, even if their glucose levels are normal.

Independent association between age- and sex-specific metabolic syndrome severity score and cardiovascular disease and mortality.

Traditional metabolic syndrome (MetS) criteria have several limitations, which hinder its use in clinical practice. To overcome the limitations, we investigated the association between age- and sex-specific continuous MetS severity score (cMetS-S) and cardiovascular disease (CVD) and mortality beyond MetS components in the framework of the Tehran Lipid and Glucose Study. Participants aged 20-60 years at baseline were included in the study. We excluded participants with CVD, cancer, use of corticosteroids, estimated glomerular filtration rate < 30 ml/min/1.73 m2, and those who were pregnant. We evaluated the association between cMetS-S with CVD and mortality over 18 years of follow-up among 8500 participants with continuous and quantile approaches using the Cox proportional hazard regression model. In addition, the model performance of cMetS-S for predicting CVD events was compared to the conventional MetS criteria. Participants with higher cMetS-S had a significantly increased risk for CVD, coronary (CHD) and non-coronary heart disease (non-CHD), and all-cause, cardiovascular, and sudden cardiac death. Independent of the confounders and MetS components, the cMetS-S had the HRs of 1.67 (95% CI 1.47-1.89), 1.60 (95% CI 1.37-1.86), and 1.88 (95% CI 1.50, 2.35) for CVD, CHD, and non-CHD events upon 1-SD increment, respectively. The risk of mortality was increased for 1-SD of cMetS-S (all-cause mortality, HR 1.24; 95% CI 1.09-1.41; CVD mortality, HR 1.72; 95% CI 1.20-2.45; sudden cardiac death, HR 1.60; 95% CI 1.03-2.49). The model fitness of cMetS-S was superior to the conventional MetS criteria in predicting CVD and mortality. The cMetS-S provided an additional risk for CVD and mortality beyond the individual MetS components. Standardized cMetS-S could be a potential universal measure to define MetS severity while considering the weighted contribution of MetS components and their variations by age, sex, and ethnicity.

Development and validation of a continuous metabolic syndrome severity score in the Tehran Lipid and Glucose Study.

Metabolic syndrome (MetS), defined as the coexistence of interrelated cardiometabolic risk factors, is limited by ignoring the severity of the disease and individuals with a pre-metabolic state. We aimed to develop the first age- and sex-specific continuous MetS severity score in the adult population using confirmatory factor analysis (CFA) based on the MetS components in the Middle East. Using data from the population-based Tehran Lipid and Glucose Study (TLGS) I and II datasets, we conducted CFA of the single factor MetS on 8933 adults (20-60 years old) totally, and in age and sex subgroups. We allowed for different factor loadings across the subgroups to formulate age- and sex-specific continuous MetS severity score equations. Thereafter, we validated these equations in the dataset of TLGS III participants. Triglyceride had the highest factor loading across age and sex subgroups, indicating the most correlation with MetS. Except for women aged 40-60 years, waist circumference was the second most significant factor contributing to MetS. Systolic blood pressure was more closely related to MetS in women than in men. Systolic blood pressure and fasting plasma glucose had the weakest correlation with MetS among the 40-60 age group. Moreover, as women age, the contribution of fasting plasma glucose to MetS tended to decline, while it remained relatively constant in men. The resulting MetS severity score was correlated with age and homeostasis model assessment of insulin resistance. Furthermore, the continuous MetS severity score well predicted the traditional MetS according to receiver operating characteristic analysis in the validation dataset. The age- and sex-specific continuous MetS severity score for the West Asian adult population provides a tangible quantitative measure of MetS enabling clinicians to screen and monitor the individuals at risk and assess their metabolic trends.

Sex-specific Trajectories of Insulin Resistance Markers and Reduced Renal Function During 18 Years of Follow-up: TLGS.

CONTEXT: The evidence suggest that insulin resistance (IR) complicates chronic kidney disease (CKD); however, the longitudinal association of IR with development of CKD is unknown. OBJECTIVE: This work aimed to investigate the association between the dynamic course of insulin resistance and CKD. METHODS: In the longitudinal, population-based Tehran Lipid and Glucose Study, 3071 eligible participants aged 20 years or older were followed for 18 years at 3-year intervals. Homeostatic model assessment of insulin resistance (HOMA-IR) and clinical surrogate markers of IR, including triglyceride-glucose index (TyG), visceral adiposity index (VAI), and lipid accumulation product (LAP), were calculated. Using latent variable mixture modeling, sex-specific trajectories were plotted for each IR marker. Trajectory group association of the IR markers with CKD was determined using the multivariable Cox proportional-hazards regression model. RESULTS: For HOMA-IR, 2 distinct trajectory patterns (stable and increasing), and for TyG, VAI, and LAP, 3 trajectories (low, moderate, and high) were identified. The participants with an increasing HOMA-IR trajectory had a significantly increased risk of CKD in men (hazard ratio [HR]: 1.72; 95% CI, 1.06-2.79) and women (HR: 1.37; 95% CI, 1.00-1.89) after adjusting for confounding variables. The high TyG and VAI trajectory classes were associated with a higher risk of CKD than the low TyG and VAI trajectory classes both in men (TyG: HR: 1.97; 95% CI, 1.12-3.46; VAI: HR:1.66; 95% CI, 1.06-2.62) and women (TyG: HR: 1.50; 95% CI, 1.06-2.12; VAI: HR:1.66; 95% CI, 1.20-2.31). In contrast, the high LAP (HR: 3.38; 95% CI, 2.08-5.48) trajectory was associated with incident CKD only in women. CONCLUSION: An increasing trend of HOMA-IR is associated with a higher risk of CKD in men and women. Among clinical IR surrogate markers, abnormal trajectory patterns of LAP in women and TyG and VAI in both sexes are associated with a higher risk of CKD.

BMI variability and incident diabetes mellitus, Tehran Lipid and Glucose Study (TLGS).

Previous epidemiologic studies debated the association of body mass index (BMI) trends with cardiovascular disease and mortality. This study aimed to evaluate the association of BMI variability and slope with the incidence of Type 2 diabetes mellitus (T2DM) in a sex-stratified 15.8-year follow-up in the population-based Tehran Lipid and Glucose Study (TLGS). Of 10,911 individuals aged 20-60 years, 4981 subjects were included and followed for 15.8-years. The slope coefficient of BMI in the linear regression model represented individuals' BMI trends up to the incidence of DM. The root mean squared error (RMSE) of the BMI linear trend was selected to reflect BMI variability through six follow-ups. Cox proportional hazards regression was used to investigate the association of the baseline BMI, BMI slope and RMSE with the incidence of T2DM among men and women. Multivariable-adjusted HRs of T2DM for each SD increment in BMI slope was 1.18 (95% CI: 0.94-1.48, p = 0.161) in normal weight men and 1.26 (95% CI: 1.10-1.44, p = 0.001) in overweight and obese men. However, in women, each SD increment in BMI slope increased the risk of T2DM with a HR of 1.19 (95% CI: 1.01-1.40, p = 0.039) in normal weight, and 1.14 (95% CI: 1.08-1.19, p < 0.001) in women with BMI ≥ 25 kg/m2. In men with a baseline BMI ≥ 25 kg/m2, BMI-RMSE was associated with a decreased risk of T2DM (HR: 0.71, 95% CI: 0.53-0.93, p = 0.015). Baseline BMI was not associated with the risk of diabetes in men and women. Positive BMI slope is associated with the development of diabetes in both sexes. The association of BMI variability with incident T2DM differs according to sex and baseline BMI. BMI variability is associated with a lower risk of T2DM in overweight and obese men. BMI variability in women and baseline BMI in both gender are not related to the risk of T2DM.

Aggressive prolactinomas responsive to temozolomide treatment: Report of two cases.

Refractory aggressive prolactinomas are detected after the unresponsiveness to conventional therapies. We report two cases that underwent temozolomide treatment and have been in near-complete remission ever since. We suggest the pathology techniques for earlier detection and, subsequently, treatment with temozolomide to reduce morbidities and better respond to therapy.