Hepatic insulin resistance affects the efficacy of metformin in patients with newly diagnosed type 2 diabetes: A Sub-Analysis of the MARCH trial.

AIM: Our study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients. METHODS: We chose 291 participants who were allocated to a 48-week metformin treatment in the "Metformin and Acarbose in Chinese as initial Hypoglycemic treatment" (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment. RESULTS: Multiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of ß cell function (HOMA-ß), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI. CONCLUSIONS: Patients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-ß, IR, and lower Matsuda index were indicators of better hepatic IR improvement.

Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity.

Background: Impaired sensitivity to thyroid hormones (TH) was associated with metabolic syndrome. The study aimed to explore the association between central TH sensitivity indices and insulin resistance (IR) in euthyroid adults with obesity. Methods: This cross-sectional study enrolled 293 euthyroid outpatients with obesity in Beijing Chao-Yang Hospital. We used the thyroid feedback quantile-based index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotrophic T4 resistance index (TT4RI) to indicate central TH sensitivity. IR was assessed by homeostasis model assessment of insulin resistance (HOMA-IR), hepatic insulin resistance index (hepatic-IR), the Matsuda index, and the adipose tissue insulin resistance index (Adipo-IR). Participants were categorized according to tertiles of TH sensitivity indices. We used multiple linear regressions to explore the associations. Results: There was a significant stepwise increase in HOMA-IR and Adipo-IR from the lowest to the highest tertiles of TH sensitivity indices (all P<0.05). After adjustment for age, sex, body mass index, hypertension, hyperlipidemia, and diabetes, only Adipo-IR was significantly associated with TH sensitivity indices. On average, each unit increased in TFQI, TSHI, and TT4RI was associated with 1.19 (P=0.053), 1.16 (P=0.04), and 1.01 (P=0.03) units increased in Adipo-IR, respectively. There was no significant association between TH sensitivity indices and HOMA-IR, hepatic-IR, and the Matsuda index after adjustment for other risk factors. Conclusions: Reduced central TH sensitivity was associated with increased adipose tissue insulin resistance in euthyroid adults with obesity. The results further confirmed the importance of TH sensitivity on metabolic diseases.

Associations of Insomnia With Insulin Resistance Traits: A Cross-sectional and Mendelian Randomization Study.

CONTEXT: Insomnia is associated with insulin resistance (IR) in observational studies; however, whether insomnia is causally associated with IR remains unestablished. OBJECTIVE: This study aims to estimate the causal associations of insomnia with IR and its related traits. METHODS: In primary analyses, multivariable regression (MVR) and 1-sample Mendelian randomization (1SMR) analyses were performed to estimate the associations of insomnia with IR (triglyceride-glucose index and triglyceride to high-density lipoprotein cholesterol [TG/HDL-C] ratio) and its related traits (glucose level, TG, and HDL-C) in the UK Biobank. Thereafter, 2-sample MR (2SMR) analyses were used to validate the findings from primary analyses. Finally, the potential mediating effects of IR on the pathway of insomnia giving rise to type 2 diabetes (T2D) were examined using a 2-step MR design. RESULTS: Across the MVR, 1SMR, and their sensitivity analyses, we found consistent evidence suggesting that more frequent insomnia symptoms were significantly associated with higher values of triglyceride-glucose index (MVR, ß = 0.024, P < 2.00E-16; 1SMR, ß = 0.343, P < 2.00E-16), TG/HDL-C ratio (MVR, ß = 0.016, P = 1.75E-13; 1SMR, ß = 0.445, P < 2.00E-16), and TG level (MVR, ß = 0.019 log mg/dL, P < 2.00E-16, 1SMR: ß = 0.289 log mg/dL, P < 2.00E-16) after Bonferroni adjustment. Similar evidence was obtained by using 2SMR, and mediation analysis suggested that about one-quarter (25.21%) of the association between insomnia symptoms and T2D was mediated by IR. CONCLUSIONS: This study provides robust evidence supporting that more frequent insomnia symptoms are associated with IR and its related traits across different angles. These findings indicate that insomnia symptoms can be served as a promising target to improve IR and prevent subsequent T2D.