Low-Normal Free Thyroxine Levels in Euthyroid Male Are Associated with Prediabetes

Abnormal thyroid function is associated with impaired glucose homeostasis. This study aimed to determine whether free thyroxine (FT4) influences the prevalence of prediabetes in euthyroid subjects using a cross-sectional survey derived from the Korea National Health and Nutrition Examination Survey, conducted between 2013 and 2015. We studied 2,399 male participants of >20 years of age who were euthyroid and non-diabetic. Prediabetic participants had lower FT4 concentrations than those without prediabetes, but their thyrotropin concentrations were similar. We stratified the population into tertiles according to FT4 concentration. After adjusting for multiple confounding factors, glycosylated hemoglobin (HbA1c) levels significantly decreased with increasing FT4 tertile, whereas fasting plasma glucose (FPG) levels were not associated with FT4 tertiles (HbA1c, P<0.01 in T3 vs. T1; FPG, P=0.489 in T3 vs. T1). The prevalence of prediabetes was significantly higher in T1 (odds ratio, 1.426; 95% confidence interval, 1.126 to 1.806; P<0.01) than in T3. In conclusion, subjects with low-normal serum FT4 had high HbA1c and were more likely to have prediabetes. These results suggest that low FT4 concentration is a risk factor for prediabetes in male, even when thyroid function is within the normal range.

Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome

BACKGROUND: The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.METHODS: We examined the effects of gemigliptin on renal tubulointerstitial fibrosis induced in mice by unilateral ureteral obstruction (UUO). Using immunohistochemical and Western blot analysis, we quantitated components of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment, and in vitro in human kidney tubular epithelial human renal proximal tubule cells (HK-2) cells, we further analyzed the effect of gemigliptin on transforming growth factor-β (TGF-β)-stimulated production of profibrotic proteins.RESULTS: Immunohistological examination revealed that gemigliptin ameliorated UUO-induced tubular atrophy and renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1β, which had all been markedly increased by UUO. In line with thein vivoresults, TGF-β markedly increased NLRP3 inflammasome markers, which were attenuated by gemigliptin treatment. Furthermore, gemigliptin treatment attenuated phosphorylated nuclear factor-κB levels, which had been increased in the UUO kidney as well as in TGF-β-treated cultured renal cells.CONCLUSION: The present study shows that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis and the renoprotective effect of gemigliptin is associated with attenuation of NLRP3 inflammasome activation.

Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown. METHODS: From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated. RESULTS: Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores. CONCLUSION: Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

Relationship between Circulating FGF21 Concentrations and the Severity of Coronary Artery Damage in Subjects with Cardiovascular Disease

OBJECTIVE: Fibroblast growth factor (FGF) 21 is a recently established therapeutic target for treating metabolic syndromes, which include potential precursors to cardiovascular disease, suggesting a link between FGF21 and atherosclerosis. However, the association between serum FGF21 concentrations and coronary artery disease remain controversial. The aim of this study is to evaluate the association between circulating FGF21 concentrations and coronary artery lesions and clinical severity. METHODS: We enrolled 137 subjects who underwent coronary angiography, due to suspected acute coronary syndrome (ACS), from December 2009 to July 2012. Serum FGF21 levels were measured. Coronary artery lesions and clinical severities of the subjects were evaluated using the SYNergy between percutaneous coronary intervention with (paclitaxel-eluting) TAXus stent and cardiac surgery (SYNTAX) and Global Registry of Acute Coronary Events (GRACE) scoring system, respectively. RESULTS: After adjusting for established cardiovascular disease risk factors, including age, body mass index, total cholesterol, and low-density lipoprotein cholesterol, patients with coronary artery lesions (n=112 men) had significantly higher levels of FGF21 than individuals without such lesions (n=25; men) (377.1±20.1 pg/mL vs. 267.1±43.5 pg/mL; p=0.026). However, no correlations were found between serum levels of FGF21 and either the calculated STNTAX score (r=0.117; p=0.176) or GRACE risk score, which is a risk prediction tool applicable for ACS subjects (r=0.113; p=0.193). CONCLUSION: Although serum levels of FGF21 were higher in individuals with coronary lesions than in those without such lesions, FGF21 levels were not associated with angiographic severity.

Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice

BACKGROUND: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice. METHODS: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. RESULTS: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. CONCLUSION: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.

Association between household size, residential area, and osteoporosis: analysis of 2008 to 2011 Korea National Health and Nutrition Examination Survey

BACKGROUND/AIMS: The prevalence of single-person households has rapidly increased in Korea. Individuals living alone and in rural areas may have a higher risk of various metabolic diseases due to differences in lifestyle. However, few studies have investigated the association of household size and residential area with health-related problems. This study aimed to evaluate the association of household size and residential area with risk of osteoporosis in postmenopausal women. METHODS: This cross-sectional study enrolled 3,058 postmenopausal women from the 2008 to 2011 Korea National Health and Nutrition Examination Survey (KNHANES). We examined the association between bone mineral density (BMD) and household size and residential area. RESULTS: Individuals living in rural areas had significantly lower BMD of the lumbar spine than those living in an urban area. Subsequently, we divided the participants into four groups according to household size and residential areas. Lumbar spine BMD was significantly lower in individuals living in rural single-person households than those in urban households with two or more individuals, even after adjustment for multiple confounding factors. In addition, individuals in rural single-person households had significantly greater odds of osteoporosis in the lumbar spine than those in urban households with two or more residents. CONCLUSIONS: Individuals in rural single-person households had significantly lower BMD and greater odds of osteoporosis in lumbar spine than urban households with two or more individuals. The results of this study suggest that individuals living in rural single-person households may benefit from more careful screening for osteoporosis.