Background: Fibrosis is the most important prognostic factor for nonalcoholic fatty liver disease (NAFLD). Insulin resistance plays a key role of fibrosis progression. We evaluated the association between changes in homeostasis model assessment of insulin resistance (HOMA-IR) values and changes in fibrosis status in NAFLD.Methods: We analyzed the data of 15,728 participants with NAFLD (86% men, mean age 40.5 years) who had no diabetes at baseline and visited our centers for health check-ups both in 2012 and 2016. The participants were classified into four groups according to the degree of change in HOMA-IR values from baseline to the end of follow-up: G1 (1.00). NAFLD was assessed by ultrasonography, and fibrosis status was evaluated by the NAFLD fibrosis score (NFS) and the aspartate aminotransferase to platelet ratio index (APRI).Results: After the 4-year follow-up, the multivariable-adjusted odds ratio (OR) for progression of fibrosis probability increased with increasing HOMA-IR values (OR, 2.25; 95% confidence interval [CI], 1.87 to 2.71 for NFS; and OR, 2.55; 95% CI, 2.05 to 3.18 for APRI, G4). This tendency remained consistent throughout the subgroup analyses, except in those for female sex and a body mass index <25 kg/m2. The OR for regression of fibrosis probability decreased with increasing HOMA-IR values (OR, 0.33; 95% CI, 0.25 to 0.43 for NFS, G4).Conclusion: Changes in HOMA-IR values were associated with changes in fibrosis status in patients with NAFLD without diabetes, which underscores the role of insulin resistance in liver fibrosis.

This study evaluated whether glomerular hyperfiltration (GHF) could predict nonalcoholic fatty liver disease (NAFLD) and fibrosis. A longitudinal cohort study including 147,479 participants aged 20–65 years without NAFLD and kidney disease at baseline was performed. GHF cutoff values were defined as age- and sex-specific estimated glomerular filtration rate (eGFRs) above the 95th percentile, and eGFR values between the 50th and 65th percentiles were used as reference groups. NAFLD was diagnosed via abdominal ultrasonography, and the fibrosis status was evaluated using the NAFLD fibrosis score and Fibrosis-4. During 598,745 person years of follow-up (median, 4.6 years), subjects with GHF at baseline had the highest hazard ratio (HR) for the development of NAFLD (HR 1.21; 95% CI 1.14–1.29) and fibrosis progression (HR 1.42; 95% CI 1.11–1.82) after adjusting for confounding factors. A higher baseline eGFR percentile maintained a higher risk of NAFLD and fibrosis probability. The persistent GHF group during follow-up had the highest HR for NAFLD compared to the persistent non-GHF group (HR 1.31; 95% CI 1.14–1.51). These results were consistent in all subgroups and statistically more prominent in participants without diabetes. GHF was positively associated with increased risk of NAFLD and probability of liver fibrosis in healthy adults.

Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: The prevalence of type 1 diabetes (T1D) is increasing globally, and it is true that adult patients make up a much larger proportion. However, due to the nature of the disease, events of hypoglycemia and hyperglycemia occur frequently in T1D patients, making stable target blood glucose management difficult. Therefore, the development of systematic education programs that reflect the diverse characteristics of patients is being demanded both clinically and from a policy perspective. Objective: After periodic implementation of structured education for patients with T1D through the Home and Self-care Program (HELP), supported by the Korean government, we evaluated the program’s effects on glycemic control. Methods: We analyzed 119 T1D subjects older than 15 years. Nursing and nutrition education were provided separately to the subjects up to four times a year, with a physician consultation at each visit, and remote support using smartphones and a digital application was provided between sessions. Patients were followed at average intervals of 2 to 4 months for up to 24 months. The primary endpoint was the mean difference in glycated hemoglobin A1c (HbA1c) at each follow-up visit from baseline. Continuous glucose monitoring (CGM) metrics including time in target range (TIR), time below range (TBR), and coefficient of variation (CV) were also evaluated. Results: The mean HbA1c of study subjects was 8.62% at baseline (mean duration 10.0 years). Patients who received at least one educational session had a significant reduction in HbA1c: from 1.63 ± 2.03 (P < 0.001, after adjustment 1.69, 95% confidence interval (CI) 1.24 - 2.13) at the 1st visit to 1.23 ± 1.31 (p = 0.01, 1.28, 0.78 - 1.79) at the 8th visit. Among CGM users, the mean TIR of 70 - 180 mg/dL was at least 55.0% for 24 months. The mean TBR (70 and 54) also gradually improved to the recommended range (≤ 4% and ≤ 1%) in patients who received at least one educational session: from 6.82 ± 8.11 (after adjustment 6.85, 95% CI 4.72 - 8.98) at the 1st visit to 3.43 ± 4.37 (3.16, 1.68 - 4.64) at the 8th visit for TBR 70 (P for trend = 0.003), from 1.76 ± 3.48 (1.77, 0.78 - 2.77) at the 1st visit to 0.44 ± 0.89 (0.36, 0.04 – 0.69) at the 8th visit for TBR 54 (P for trend = 0.001). Conclusions: The HELP protocol for glycemic control in patients with T1D is effective, producing significant improvement immediately and long-term maintenance effects, including CGM indices.

Nonalcoholic fatty liver disease (NAFLD), which has recently undergone a change in its definition and acronym to “metabolic dysfunction associated fatty liver disease (MAFLD),” is clinically significant as an increasingly prevalent independent risk factor for cardiovascular diseases. Insulin resistance is considered to be a key mechanism in the development and progression of NAFLD/MAFLD, and fatty liver disease itself may exacerbate insulin resistance. In this review, we describe the mechanisms underlying the interaction between insulin resistance and fatty liver, and we summarize the therapeutic attempts based on those mechanisms.

Background: Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.Methods: We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.Results: The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.Conclusion: CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.

The interplay between glomerular hyperfiltration (GHF) and downstream renal dysfunction and hepatic fibrosis in metabolic dysfunction–associated stea