Ectopic Fat Deposition on Insulin Sensitivity: Correlation of Hepatocellular Lipid Content and M Value

. Purpose. This study aimed to explore the relationship among insulin sensitivity and ectopic fat depots in participants with different glucose status. Methods. Fifty-nine men and women were enrolled in this study: 29 with normal glucose tolerance (NGT), 17 with impaired glucose tolerance (IGT), and 13 with type 2 diabetes mellitus (T2DM). All participants underwent a hyperinsulinemiceuglycemic clamp to assess the insulin sensitivity index ( value) and magnetic resonance imaging to measure the hepatocellular lipid content (HCL), skeletal muscle fat content including intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) of tibialis anterior (ta), and soleus muscle (sol). Results. The value of NGT group was higher than those of IGT and T2DM groups ( = 0.001). Participants with T2DM had the highest HCL and IMCL (ta) compared with those in NGT and IGT groups ( = 0.001). The value had an inverse relationship with HCL ( = −0.789, = 0.001), IMCL (sol) ( = −0.427, = 0.002), and IMCL (ta) ( = −0.419, = 0.002). Stepwise linear regression analysis showed that HCL (standardized = −0.416; = 0.001) had an independent relationship with value. Conclusions. Hepatocellular lipid content deposition happens earlier than skeletal muscle fat deposition. HCL is an independent risk factor for insulin resistance and may be used to evaluate the risk of developing T2DM as a noninvasive marker of insulin sensitivity index

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Thyroid Feedback Quantile-based Index correlates strongly to renal function in euthyroid individuals

AbstractBackground Previous studies have reported a negative relationship between thyroid-stimulating hormone (TSH) and renal function in euthyroid individuals, but others have found that higher free thyroxine (FT4) was associated with an increased risk of chronic kidney disease. This study was designed to analyze the relationship between thyroid and renal function from a new perspective of sensitivity to thyroid hormone.Methods This retrospective study included 2831 euthyroid individuals who underwent a health examination at the First Hospital of China Medical University between January 2017 and December 2018. Parametric Thyroid Feedback Quantile-based Index (PTFQIFT4), TSH index (TSHI), thyrotroph T4 resistance index (TT4RI), free triiodothyronine to FT4 ratio (FT3/FT4), the secretory capacity of the thyroid gland (SPINA-GT) and the sum activity of peripheral deiodinases (SPINA-GD) were calculated. We also innovated the TT3RI and PTFQIFT3 indices based on FT3 and TSH. Renal function was assessed by estimated glomerular filtration rate (eGFR) CKD-EPI and creatinine-cystatin C-KDIGO equations.Results After adjustment of basic characteristics and comorbidities, linear regression showed that eGFR CKD-EPI was positively associated with FT3/FT4 (β = 23.31), and inversely correlated to PTFQI FT4 (β= −2.69) (both p < .001). When comparing the fourth versus the first quartile of PTFQI FT4, the odds ratio (OR) for a reduced renal function was 1.89 (95% CI 1.28–2.80), and the OR was 0.64 (95% CI 0.43–0.95) when comparing quartiles of FT3/FT4 (both p for trend< .05). In addition, for every 1SD increase in PTFQI FT4, the OR for a reduced renal function was 1.27 (95%CI 1.10–1.47). TSHI, TT4RI and TT3RI also showed a negative correlation to renal function. Similar results were obtained in SPINA-GD as in FT3/FT4.Conclusions In euthyroid individuals, decreased sensitivity to thyroid hormone is associated with reduced renal function. The composite PTFQIFT4 index correlates more strongly to renal function than TSH or T4 alone.KEY MESSAGESDecreased sensitivity to thyroid hormone is associated with reduced renal function in the euthyroid population.The recently developed composite index PTFQIFT4 seems to correlate more strongly to renal function than individual TSH or FT4 parameters.Innovative indices TT3RI and PTFQIFT3 based on the interaction between T3 and TSH may also reflect sensitivity to thyroid hormone

Ectopic Fat Deposition on Insulin Sensitivity: Correlation of Hepatocellular Lipid Content and M Value

Purpose. This study aimed to explore the relationship among insulin sensitivity and ectopic fat depots in participants with different glucose status. Methods. Fifty-nine men and women were enrolled in this study: 29 with normal glucose tolerance (NGT), 17 with impaired glucose tolerance (IGT), and 13 with type 2 diabetes mellitus (T2DM). All participants underwent a hyperinsulinemic-euglycemic clamp to assess the insulin sensitivity index (M value) and magnetic resonance imaging to measure the hepatocellular lipid content (HCL), skeletal muscle fat content including intramyocellular lipid (IMCL) and extramyocellular lipid (EMCL) of tibialis anterior (ta), and soleus muscle (sol). Results. The M value of NGT group was higher than those of IGT and T2DM groups (P=0.001). Participants with T2DM had the highest HCL and IMCL (ta) compared with those in NGT and IGT groups (P=0.001). The M value had an inverse relationship with HCL (r=-0.789, P=0.001), IMCL (sol) (r=-0.427, P=0.002), and IMCL (ta) (r=-0.419, P=0.002). Stepwise linear regression analysis showed that HCL (standardized β=-0.416; P=0.001) had an independent relationship with M value. Conclusions. Hepatocellular lipid content deposition happens earlier than skeletal muscle fat deposition. HCL is an independent risk factor for insulin resistance and may be used to evaluate the risk of developing T2DM as a noninvasive marker of insulin sensitivity index

The trans-ancestral genomic architecture of glycemic traits

Abstract Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P &lt; 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution