Background: Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications. Methods: Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group. Results: The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs. Conclusion: Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications.

Aims/Introduction The Metabolic Score for Insulin Resistance (METS-IR) is a novel non-insulin-based metabolic index used as a substitution marker of insulin resistance. However, whether METS-IR is associated with the urinary albumin-to-creatinine ratio (UACR) is not well known. Therefore, we explored the associations between METS-IR and UACR, and compared the discriminative ability of METS-IR and its components for elevated UACR. Materials and Methods This study included 37,290 participants. METS-IR was calculated as follows: (Ln[2 x fasting blood glucose + fasting triglyceride level] x body mass index) / (Ln [high-density lipoprotein cholesterol]). Participants were divided into four groups on the basis of METS-IR: = 75%. Logistic regression analyses were carried out to determine the associations between METS-IR versus its components (fasting blood glucose, triglyceride level, body mass index and high-density lipoprotein cholesterol) with UACR. Results Participants with the highest quartile METS-IR presented a more significant trend toward elevated UACR than toward its components (odds ratio 1.260, 95% confidence interval 1.152-1.378, P < 0.001 in all participants; odds ratio 1.321, 95% confidence interval 1.104-1.579, P = 0.002 in men; odds ratio 1.201, 95% confidence interval 1.083-1.330, P < 0.001 in women). There were significant associations between METS-IR and UACR in younger participants (aged = 5.6 or postprandial blood glucose >= 7.8 mmol/L and systolic blood pressure >= 120 or diastolic blood pressure >= 80 mmHg. The relationships were significant in women with diabetes and hypertension. Conclusions Increased METS-IR was significantly associated with elevated UACR, its discriminative power for elevated UACR was superior to that of its components.

Purpose: The hypertriglyceridemic waist (HTGW) phenotype can predict cardiovascular disease (CVD) risk. Additionally, strong evidence indicates that elevated urinary albumin–creatinine ratio (UACR) is associated with increased prevalence of CVD. However, few studies have explored the association between the HTGW phenotype and UACR. Patients and Methods: In this cross-sectional descriptive study, a total of 40,674 subjects (28,562 women and 12,112 men older than 40 years) were recruited from seven different geographic regional centres. The HTGW phenotype was defined as increased triglyceride levels (triglyceride ≥ 1.5 mmol/L for female and ≥ 2.0 mmol/L for male) and waist circumference (WC; WC ≥ 85 for female and WC ≥ 90 cm for male). Logistic regression analyses were performed to assess the relationship between UACR and the HTGW phenotype. Results: Subjects with the HTGW phenotype showed a more significant trend towards increased excretion of UACR [among all subjects, odds ratio (OR) = 1.303, 95% CI: 1.132– 1.499, P < 0.001; among men, OR = 1.406, 95% CI: 1.057– 1.870, P = 0.019; among women, OR = 1.268, 95% CI: 1.074– 1.496, P = 0.005]. Furthermore, the stratified analysis showed that the OR for high-risk significantly increased in individuals in the HTGW group aged below 65 years, with 5.6 ≤ fasting blood glucose < 7.0 or 7.8 ≤ post-load blood glucose < 11.1 mmol/L, 120 ≤ systolic blood pressure < 140 or 80 ≤ diastolic blood pressure < 90, 24 ≤ body mass index < 28 kg/m², and estimated globular filtration rate > 90 mL/min per 1.73 m². Conclusion: This study has advanced the understanding of visceral obesity and our results supported the fact that the HTGW phenotype is associated with elevated UACR excretion among general Chinese adults.

Background. Physical activity is effective in preventing chronic diseases. However, the impact of different durations of exercise on human health is unknown, especially among people with diabetes or prediabetes. Objective. To explore the relationship between high MET hours per week and the change in glomerular filtration rate (eGFR) in the total population and different subgroups. Methods. A total of 43767 individuals from eight provinces, in China, were recruited. Logistic analysis was used to investigate the association. Participants were divided into 3 groups based on MET hours per week. The primary outcome was an eGFR≤90mL/min/1.73m2. Results. The average eGFR was 100.10 (92.43-106.43) mL/min/1.73². Logistic regression analysis revealed that more than 7.5 MET hours per week (equivalent to more than 150 minutes of moderate-intensity of exercise) was associated with the higher risk of the decreased eGFR even after adjusting for confounding factors (7.5 to <21: OR=1.18, 95% CI [1.09, 1.29]; ≥21: OR=1.12, 95% CI [1.05, 1.19], p for trend: 0.0047). After adjusting for confounding factors, in stratified analyses, there still existed a significant relationship among participants aged from 55 to less than 65 years, but not among participants younger than 55 or older than 65 years. Similarly, there existed a positive association between high MET hours per week and the decreased eGFR in participants without diabetes and prediabetes, but not in participants with diabetes or prediabetes, and the interactions of age and diabetic states were found. However, there was no significant difference in women or men. Conclusions. More than 7.5 MET hours per week (equivalent to more than 150 minutes per week or 60 minutes per day of moderate-intensity exercise) was associated with decreased eGFR among participants aged from 55 to less than 65 years and participants without diabetes and prediabetes, but not among participants aged younger than 55 years and older than 65 years and participants with diabetes or prediabetes. The importance of planning individualized physical activities is highlighted.