1.
Assessment of causal association between thyroid function and lipid metabolism: a Mendelian randomization study.
Wang, JJ, Zhuang, ZH, Shao, CL, Yu, CQ, Wang, WY, Zhang, K, Meng, XB, Gao, J, Tian, J, Zheng, JL, et al
Chinese medical journal. 2021;134(9):1064-1069
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Obesity, dyslipidaemia, and metabolic syndrome are major risk factors for cardiovascular disease, however, effect of thyroid dysfunction on dyslipidaemia and cardiovascular disease is largely unknown. This study used mendelian randomisation (MR), where a genetic variant is used as an instrumental variable to detect the causal effects of exposure to disease. This study used two sample MR analyses to find out whether clinical thyroid function measures show a causal relationship with the changes in lipid levels. The results showed a significant association between the elevated thyrotropin (TSH) level and increased total cholesterol. Also, there was a significant correlation between the free triiodothyronine (FT3): free thyroxine (FT4) ratio and total cholesterol and low-density lipoprotein (LDL). Further robust studies are required to confirm the results and investigate the causal effect of thyroid hormone dysregulation and cardiometabolic diseases due to the limitations of this study. However, healthcare professionals can use the results of this study to understand the importance of the pituitary-thyroid-cardiac axis in lipid metabolism and its impact on cardiometabolic health.
Abstract
BACKGROUND Thyroid dysfunction is associated with cardiovascular diseases. However, the role of thyroid function in lipid metabolism remains partly unknown. The present study aimed to investigate the causal association between thyroid function and serum lipid metabolism via a genetic analysis termed Mendelian randomization (MR). METHODS The MR approach uses a genetic variant as the instrumental variable in epidemiological studies to mimic a randomized controlled trial. A two-sample MR was performed to assess the causal association, using summary statistics from the Atrial Fibrillation Genetics Consortium (n = 537,409) and the Global Lipids Genetics Consortium (n = 188,577). The clinical measures of thyroid function include thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels, FT3:FT4 ratio and concentration of thyroid peroxidase antibodies (TPOAb). The serum lipid metabolism traits include total cholesterol (TC) and triglycerides, high-density lipoprotein, and low-density lipoprotein (LDL) levels. The MR estimate and MR inverse variance-weighted method were used to assess the association between thyroid function and serum lipid metabolism. RESULTS The results demonstrated that increased TSH levels were significantly associated with higher TC (β = 0.052, P = 0.002) and LDL (β = 0.041, P = 0.018) levels. In addition, the FT3:FT4 ratio was significantly associated with TC (β = 0.240, P = 0.033) and LDL (β = 0.025, P = 0.027) levels. However, no significant differences were observed between genetically predicted FT4 and TPOAb and serum lipids. CONCLUSION Taken together, the results of the present study suggest an association between thyroid function and serum lipid metabolism, highlighting the importance of the pituitary-thyroid-cardiac axis in dyslipidemia susceptibility.
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Testosterone Deficiency, Weakness, and Multimorbidity in Men.
Peterson, MD, Belakovskiy, A, McGrath, R, Yarrow, JF
Scientific reports. 2018;8(1):5897
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With age, the occurrence of total testosterone (TT) deficiency in men also increases. Such deficiency can have a detrimental impact on the musculoskeletal system leading to bone and muscle loss, increasing the risk of cardiovascular disease and all-cause mortality. Hence muscle weakness is a known a predicitve factor for chronic disease. Whereby reference ranges have been set for testosterone levels in young healthy men, uncertainty exists about optimal levels throughout different age ranges, ethnicities and in concurrence with diseases. This observational study evaluated how TT deficiency and muscle weakness assessed via grip strength, relates to chronic health conditions in men. The study included 2399 young, middle-aged, and older men in the US, with a diverse ethnic backgrounds, who presented with and without testosterone deficiency. The findings indicated that TT levels were highest amongst young men, yet no particular difference was seen in levels between middle-aged and older men. Grip strength decreased in the higher age categories. Chronic health conditions were more common in young and older men who displayed testosterone deficiencies, whilst low testosterone and reduced grip strength were linked to the presence of chronic disease in all age groups. Overall the study confirmed previous research, that in men with testosterone deficiency chronic disease was much more prevalent, even after accounting for other variables. The study also observed a much lower average of TT levels in young men compared to previous research, in mostly white males. Thus testosterone deficiency appears much more common in men of all ages when including a variety of ethnic groups. As low testosterone may play an early, causal role in the chronic disease process, continuous monitoring of testosterone levels through the life span may aid the early identification of chronic disease development or disease progression. Further research is needed on the independent and joint effects of low TT and muscular weakness. From a clinical perspective, this study affirms that low testosterone in men is a presenting risk factor for chronic disease and that chronic disease is commonly accompanied by low testosterone. It also highlights some unsettled aspects around reference ranges of testosterone
Abstract
The purposes of this study were to evaluate the association between total testosterone (TT) deficiency and weakness on multimorbidity in men. Analyses were performed to examine the prevalence of multimobidity among young, middle-aged, and older men, with and without testosterone deficiency. Multivariate logistic models were also used to determine the association between age-specific TT tertiles and multimorbidity, adjusting for key sociodemographic variables, as well as a secondary analysis adjusted for grip strength. Multimorbidity was more prevalent among men with testosterone deficiency, compared to normal TT in the entire group (36.6% vs 55.2%; p < 0.001); however, differences were only seen within young (testosterone deficiency: 36.4%; normal TT: 13.5%; p < 0.001) and older men (testosterone deficiency: 75.0%; normal TT: 61.5%; p < 0.001). Robust associations were found between the age-specific low-TT (OR: 2.87; 95%CI: 2.14-3.83) and moderate-TT (OR: 1.67; 95%CI: 1.27-2.20) tertiles (reference high-TT) and multimorbidity. Secondary analysis demonstrated that both low TT (OR: 1.82; 95%CI: 1.29-2.55) and moderate-TT (OR: 1.31; 95%CI: 1.01-1.69) were associated with multimorbidity, even after adjusting for obesity (OR: 1.75; 95%CI: 1.07-2.87) and NGS (OR: 1.21 per 0.05 unit lower NGS). Low TT and weakness in men were independently associated with multimorbidity at all ages; however, multimorbidity was more prevalent among young and older men with testosterone deficiency.
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Randomized placebo control study of insulin sensitizers (Metformin and Pioglitazone) in psoriasis patients with metabolic syndrome (Topical Treatment Cohort).
Singh, S, Bhansali, A
BMC dermatology. 2016;16(1):12
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As an immune-mediated chronic inflammatory skin condition, psoriasis is associated with obesity, metabolic syndrome, diabetes, and cardiovascular disease. Medications capable of sensitising insulin, such as Metformin and Pioglitazone, have also shown benefits in improving factors associated with metabolic syndrome and psoriasis. This single-centre, parallel-group, randomised, open-label with blinded endpoint evaluated the effects of Metformin with Pioglitazone and placebo in psoriatic patients. Patients with mild-to-moderate psoriasis were randomised to a topical treatment cohort to take 1000 mg metformin daily or 30 mg pioglitazone or placebo groups for 12 weeks. Each participant received a topical ointment containing 5% coal tar during the treatment period. The Metformin and Pioglitazone groups showed significant improvements in psoriasis and metabolic syndrome parameters, such as fasting plasma glucose, total cholesterol, and triglyceride levels, after 12 weeks of treatment. The treatment with metformin resulted in significant improvements in weight, BMI, waist circumference, FPG, triglycerides, and total cholesterol, while the treatment with pioglitazone resulted in significant improvements in FPG, triglycerides, systolic and diastolic blood pressure, cholesterol levels, and LDL cholesterol levels. There was no significant improvement in inflammatory cytokine levels in any group. For further evaluation of the beneficial effects of insulin-sensitising drugs in patients suffering from psoriasis and metabolic syndrome, more robust studies are needed. The study results can be used by healthcare professionals to better understand how insulin-sensitising drugs may decrease the risk of diabetes, cardiovascular disease, and psoriasis in psoriasis patients with metabolic syndrome.
Abstract
BACKGROUND Increased prevalence of metabolic syndrome (MS) is observed in psoriasis. Metformin has shown improvement in cardiovascular risk factors while pioglitazone demonstrated anti proliferative, anti-inflammatory and anti angiogenic effects. Study objective is to evaluate the efficacy and safety of Insulin sensitizers (metformin and pioglitazone) in psoriasis patients with metabolic syndrome (MS). METHODS Single centre, parallel group, randomized, study of metformin, pioglitazone and placebo in psoriasis patients with MS. RESULTS Statistically significant improvement was observed in Psoriasis Area and Severity Index (PASI), Erythema, Scaling and Induration (ESI) and Physician global assessment (PGA) scores in pioglitazone (p values - PASI = 0.001, ESI = 0.002, PGA = 0.008) and metformin groups (p values - PASI = 0.001, ESI = 0.016, PGA = 0.012) as compared to placebo. There was statistically significant difference in percentage of patients achieving 75 % reduction in PASI and ESI scores in metformin (p value - PASI = 0.001, ESI = 0.001) and pioglitazone groups (p vaue - PASI = 0.001, ESI = 0.001). Significant improvement was observed in fasting plasma glucose (FPG) and triglycerides levels in metformin and pioglitazone arms. Significant improvement was noted in weight, BMI, waist circumference, FPG, triglycerides and total cholesterol after 12 weeks of treatment with metformin while pioglitazone showed improvement in FPG, triglyceride levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol and LDL cholesterol levels. There was no difference in pattern of adverse drug reaction in three groups. CONCLUSION Insulin sensitizers have shown improvement in the parameters of MS as well as disease severity in psoriasis patients. TRIAL REGISTRATION CTRI Registration Number: CTRI/2011/12/002252 . Registered on 19/12/2011.