Background. Few studies have specifically observed the relationship of sarcopenia, visceral obesity, or their joint effects with lean NAFLD in patients with diabetes. We aimed to investigate the associations of lean NAFLD with sarcopenia, visceral obesity, and sarcopenic visceral obesity (SV) in Chinese patients with type 2 diabetes mellitus (T2DM). Methods. Altogether, 1,112 T2DM patients with BMI <25 kg/m² were enrolled, and 33.18% of them were diagnosed with lean NAFLD by abdominal ultrasonography. Body composition markers were measured by bioelectrical impedance (BIA). Skeletal muscle mass index (SMI) was calculated as appendicular skeletal muscle mass (ASM) divided by weight, and sarcopenia was defined as below the sex-specific average for a young reference population. Visceral obesity was defined as visceral fat area . Participants were categorized into one of the four body composition groups: nonsarcopenia/nonvisceral obesity (NN), nonsarcopenia/visceral obesity (NV), sarcopenia/nonvisceral obesity (SN), and SV. Results. Compared to those in the NN group, patients in the NV and SN groups had a higher risk of lean NAFLD after full adjustments (NV: ; 95% CI: 1.09, 2.78; SN: OR =2.07; 95% CI: 1.23, 3.46). Of note, patients in the SV group had the highest odds of lean NAFLD ( ; 95% CI: 2.10, 5.17). There were no significant interaction effects between sarcopenia and metabolic risk factors on prevalent lean NAFLD. Conclusions. The current study demonstrated that SV was more closely associated with higher prevalent lean NAFLD than sarcopenia or visceral obesity alone in Chinese patients with T2DM. Besides, the harmful effect of sarcopenia on lean NAFLD was not influenced by visceral obesity or other metabolic risk factors. We hypothesize that increasing skeletal muscle mass more than just reducing visceral fat might be more optimal for the prevention and management of lean NAFLD, which needs further investigation in future studies.

Emerging evidence shows that chronic inflammation mediated by toll-like receptors (TLRs) contributes to diabetic nephropathy. Myeloid differentiation primary-response protein-88 (MyD88) is an essential adapter protein of all TLRs except TLR3 in innate immunity. It is unclear whether MyD88 could be a therapeutic target for diabetic nephropathy. Here, we used a new small-molecule MyD88 inhibitor, LM8, to examine the pharmacological inhibition of MyD88 in protecting kidneys from inflammatory injury in diabetes. We showed that MyD88 was significantly activated in the kidney of STZ-induced type 1 diabetic mice in tubular epithelial cells as well as in high glucose-treated rat tubular epithelial cells NRK-52E. In cultured tubular epithelial cells, we show that LM8 (2.5−10 μM) or MyD88 siRNA attenuated high-concentration glucose-induced inflammatory and fibrogenic responses through inhibition of MyD88-TLR4 interaction and downstream NF-κB activation. Treatment with LM8 (5, 10 mg/kg, i.g.) significantly reduced renal inflammation and fibrosis and preserved renal function in both type 1 and type 2 diabetic mice. These renoprotective effects were associated with reduced MyD88-TLR4 complex formation, suppressed NF-κB signaling, and prevention of inflammatory factor expression. Collectively, our results show that hyperglycemia activates MyD88 signaling cascade to induce renal inflammation, fibrosis, and dysfunction. Pharmacological inhibition of MyD88 may be a therapeutic approach to mitigate diabetic nephropathy and the inhibitor LM8 could be a potential candidate for such therapy.

Background: The results of population-based studies show a diverse association between the triglyceride-glucose (TyG) index and hypertension. The present study aimed to investigate this association based on a cross-sectional study on Chinese adults and meta-analysis of epidemiology studies.Methods: The cross-sectional analysis used the baseline data from the on-going REACTION study in China. The TyG index was calculated as Ln [triglyceride(mg/dl)×fasting plasma glucose(mg/dl)/2]. A multivariate-adjusted logistic regression model was used to calculate the odds ratio (OR) with a 95% confidence interval (CIs) for the prevalence of hypertension, with the lowest TyG quartile as a reference.Results: A total of 4,177 participants aged 58.62 ± 8.40 years were included. TyG was significantly associated with higher odds of hypertension (OR:1.273, 95% CI:1.171-1.384), and the association remained pronounced with isolated systolic hypertension (OR:1.161, 95% CI:1.045-1.289) and systolic-diastolic hypertension (OR:1.313, 95% CI:1.163-1.483) but not with isolated diastolic hypertension (OR:1.164, 95% CI:0.929-1.460). In the present meta-analysis, 34 relevant studies were included through systematic searches of PUBMED, Embase, and the Cochrane Library. A positive association between the TyG index and hypertension was revealed in the meta-analysis of cohort studies (HR:1.57, 95% CI:1.25-1.96) and cross-sectional studies (OR:2.01, 95% CI:1.47-2.76).Conclusion: Elevated TyG index levels were significantly associated with a higher risk of clinical hypertension, which may provide new insights into the clinical management of hypertension.

Purpose: Prognostic nutritional index (PNI) is an effective tool to evaluate the nutritional conditions and predict prognosis, but clinical data are limited for the use of PNI in diabetic retinopathy (DR). This study aimed to investigate the relationship of PNI with the prevalence and severity of DR in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: This cross-sectional analysis enrolled 1023 individuals with T2DM hospitalized between 2017– 2020. PNI was calculated as 10 × serum albumin (g/l) + 0.005 × total lymphocyte count (cells/mL). DR severity was categorized as no, nonproliferative, and vision-threatened DR (VTDR) according to the modified Airlie House classification. Multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) for the prevalent DR in the top (Q4) compared with the bottom quartile (Q1) of PNI levels were estimated by using logistic regression analyses. Results: PNI levels were significantly lower in individuals with VTDR than those with no and nonproliferative DR (both P < 0.001), and the proportions of individuals with DR were significantly decreased in the top quartile compared with the bottom quartile of PNI levels (P < 0.001). After adjustments for age, gender, DM duration, obesity-related risk factors and clinical biochemical parameters, the higher levels of PNI were significantly associated with a lower prevalence of DR (Q4 vs Q1: OR = 0.402, 95% CI: 0.250– 0.649, P < 0.001), with a 5.9% reduction in the prevalence of DR for a per-unit increment in the levels of PNI (OR = 0.941, 95% CI: 0.911– 0.972, P < 0.001). The association of PNI and obesity-related indexes (body mass index and waist circumference) with the severity of DR was independent of each other (P< 0.001). Conclusion: PNI was inversely and independently associated with the severity and prevalence of DR, which suggested that PNI could likely be used to predict DR prognosis in clinical practice.

Background: Triglyceride glucose (TyG) index is a good surrogate biomarker to evaluate insulin resistance (IR). The study aimed to investigate whether the TyG index is related to the severity of diabetic foot ulcers (DFUs) in patients with type 2 diabetes mellitus (T2DM).Methods: A total of 1059 T2DM patients were enrolled in this observational, retrospective, single‐center study. TyG index was calculated as ln[fasting triglycerides (mg/dl) × fasting glucose (mg/ dl)/2]. The severity of DFUs was classified into mild‐to‐moderate DFUs (Wagner grade score < 3) and severe DFUs (Wagner grade score ≥ 3) based on Wagner classification. Patients were stratified according to the tertiles of TyG index. Logistic regression models were implemented to explore the association between TyG index and the severity of DFUs. Subgroup analyses were used to verify the reliability of results.Results: Compared with the reference lowest TyG tertile (T1), the highest tertile (T3) was associated with 0.377‐fold increased risk of prevalence of severe DFUs (odds ratio [OR] 1.377, 95% confidence interval [CI] 1.017–1.865) (P = 0.039). After adjusting for potential confounders, the multivariable‐adjusted OR and 95% CI were 1.506 (1.079–2.103) (P = 0.016) in patients with highest tertile. Moreover, subgroup analyses indicated that the association was stronger among men, patients with age ≥ 65 years, duration of diabetes more than 10 years, or without PAD.Conclusions: Elevated TyG index is independently associated with severity of DFUs even after adjusting conventional confounders.