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Recent epidemiologic research has examined the relationship between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and diabetes mellitus with inconclusive findings. In this cross-sectional study, we aimed to explore the association between serum PFAS concentrations and the prevalence of prediabetes and pre-diagnostic diabetes in the general Korean population as well as the combined effects of exposure to mixed PFAS compounds. We analyzed data from participants aged ≥19 years enrolled in the Korean National Environmental Health Survey Cycle 4 (2018–2020). Individuals diagnosed with diabetes were excluded to minimize potential bias. We identified cases of pre-diagnostic diabetes based on the HbA1c level ≥6.5% and prediabetes as HbA1c levels of 5.7–6.49%. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDeA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were quantified using high-performance liquid chromatography-tandem mass spectrometry. Survey-weighted logistic regression models were used to assess the relationships between PFAS levels and diabetes risk, adjusting for covariates. Additionally, Bayesian kernel machine regression (BKMR) was used to investigate the combined effects of exposure to mixed PFAS compounds. In the study population excluding participants with diagnosed diabetes (n = 2709), the prevalence of pre-diagnostic diabetes and prediabetes was 4.8% and 30.1%, respectively. Significant positive associations were found between serum PFHxS and PFOS quartiles and pre-diagnostic diabetes risk. Likewise, among those without diagnosed or pre-diagnostic diabetes (n = 2579), the highest quartiles of PFDeA, PFHxS, and PFOS and the overall PFAS level were associated with an increased risk of prediabetes compared with the lowest quartiles. BKMR analysis revealed a significant positive association between overall serum PFAS level and prediabetes risk, which was most marked for PFOS. These findings highlight the potential health implications of PFAS exposure and prediabetes risk. Further research is needed to validate these associations and identify potential mechanistic pathways. [ABSTRACT FROM AUTHOR]

Children with diabetes, and particularly those with obesity, have poor glycemic control. They are thus at higher risk of early microvascular complications. Renal tubulointerstitial markers are integral to evaluating diabetic nephropathy. Various biomarkers have been proposed, but their role in the obese pediatric population is uncertain. We investigated renal injury markers in children with diabetes, according to obesity, and determined their role as early predictors of diabetic nephropathy. Fifty-three children and adolescents, diagnosed with either type 1 or 2 diabetes mellitus, and 43 control children, aged 7–18 years, were included. Clinical and laboratory characteristics, including six renal injury markers, were compared among subjects according to body mass index and presence of diabetes mellitus. Urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase (NAG) showed significant difference between controls and diabetic children, whereas urine NAG was the only biomarker that was significantly lower either in non-obese or obese controls as compared to diabetic children. Urine NGAL, KIM-1, and NAG showed significant correlations with both HbA1c and urine ACR, whereas only urine NAG was significantly correlated with HbA1c even when groups were subdivided based on the presence of either obesity or diabetes. After adjusting for age, sex, body mass index, duration of known diabetes, and urine albumin-to-creatinine ratio, HbA1c remained a significant risk factor for elevated urine NAG. Urine NAG could be a useful indicator of tubulointerstitial damage in children with diabetes in the pre-albuminuric state. Tighter glycemic control appears to be crucial for avoiding early progression to diabetic nephropathy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the associations between the urinary levels of polycyclic aromatic hydrocarbons (PAHs) and diabetes mellitus in Korean adults. Materials and Methods: We examined the data of 6478 participants aged ≥ 19 years from the Korean National Environmental Health Survey (KoNEHS) cycle 2 (2012– 2014). The urinary levels of 1-hydroxypyrene (1-OHP), 2-naphthol (2-NAP), 1-hydroxyphenathrene (1-OHPhe), and 2-hydroxyfluorene (2-OHFlu) were measured by gas chromatography-mass spectrometry. Diabetes mellitus was defined as a self-report of physician-diagnosed diabetes mellitus or the use of oral hypoglycemics or insulin. Analyses were adjusted for sex, age, body mass index, household income, alcohol consumption, physical activity, urinary creatinine and cotinine, menopausal status, and quartiles of all other PAHs. Results: The prevalence of diabetes was 6.5% in the study population. In men, the geometric means of the 2-NAP and 2-OHFlu levels were higher in participants with diabetes mellitus than in those without diabetes mellitus [4.11 vs 3.26 μg/L (P < 0.05) and 0.45 vs 0.40 μg/L (P < 0.05), respectively]. In women, the geometric mean of 2-NAP levels was also higher in participants with diabetes mellitus than in those without diabetes mellitus (1.81 vs 0.56 μg/L, P < 0.05), but there were no significant differences in geometric means for other PAHs. A higher odds ratio (OR) of diabetes was found in participants with the highest quartiles of urinary 2-NAP [OR 1.83, 95% confidence interval (CI) 1.29– 2.60] and 2-OHFlu (OR 1.81, 95% CI 1.10– 2.98) than in those with the lowest quartiles. Conclusion: The urinary 2-NAP and 2-OHFlu levels were associated with diabetes mellitus in Korean adults. Further studies are needed to determine a potential causal relationship between PAH exposure and diabetes mellitus and its underlying mechanism. [ABSTRACT FROM AUTHOR]

Objective: To estimate the percentage of infants with large birth size attributable to excess gestational weight gain (GWG), independent of prepregnancy body mass index, among mothers with preexisting diabetes mellitus (PDM).Study Design: We analyzed 2004-2008 Florida linked birth certificate and maternal hospital discharge data of live, term (37-41weeks) singleton deliveries (N=641,857). We calculated prevalence of large-for-gestational age (LGA) (birth weight-for-gestational age≥90th percentile) and macrosomia (birth weight>4500g) by GWG categories (inadequate, appropriate, or excess). We used multivariable logistic regression to estimate the relative risk (RR) of large birth size associated with excess compared to appropriate GWG among mothers with PDM. We then estimated the population attributable fraction (PAF) of large birth size due to excess GWG among mothers with PDM (n=4427).Results: Regardless of diabetes status, half of mothers (51.2%) gained weight in excess of recommendations. Large birth size was higher in infants of mothers with PDM than in infants of mothers without diabetes (28.8% versus 9.4% for LGA, 5.8% versus 0.9% for macrosomia). Among women with PDM, the adjusted RR of having an LGA infant was 1.7 (95% CI 1.5, 1.9) for women with excess GWG compared to those with appropriate gain; the PAF was 27.7% (95% CI 22.0, 33.3). For macrosomia, the adjusted RR associated with excess GWG was 2.1 (95% CI 1.5, 2.9) and the PAF was 38.6% (95% CI 24.9, 52.4).Conclusion: Preventing excess GWG may avert over one-third of macrosomic term infants of mothers with PDM. Effective strategies to prevent excess GWG are needed. [ABSTRACT FROM AUTHOR]

This study evaluated the relationship of insulin resistance (IR) and glycemic control status to the presence and severity of coronary artery disease (CAD) according to diabetes. The relationship of IR parameters including homeostatic model assessment of IR (HOMA-IR), triglyceride-glucose (TyG) index, and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL), and hemoglobin A1C (HbA1C) level to CAD and obstructive CAD was evaluated in 5,764 asymptomatic subjects who underwent coronary computed tomographic angiography. Non-diabetics (n = 4768) and diabetics (n = 996) were stratified into four groups based on the quartiles of HOMA-IR and the TyG index and were grouped based on the TG/HDL cut-offs of 3.5, respectively. CAD and obstructive CAD were defined as the presence of any plaques and plaques with ≥50% stenosis, respectively. The prevalence of CAD (59.0% vs. 39.0%) and obstructive CAD (15.0% vs. 6.6%) was higher in diabetic than in non-diabetic patients (p < 0.001, respectively). In non-diabetic patients, the adjusted odds ratio for both CAD and obstructive CAD significantly increased, but only with higher TyG index quartiles. Unlike non-diabetics, the adjusted odds ratio for obstructive CAD significantly increased in diabetic patients with a TG/HDL level ≥ 3.5. The HbA1C, rather than IR parameters, was independently associated with both CAD and obstructive CAD in diabetics. In conclusion, among IR parameters, TyG index was independently associated with the presence of CAD and obstructive CAD in non-diabetic patients. In contrast, the glycemic control status, rather than IR, was importantly related to both CAD and obstructive CAD in established diabetic patients. [ABSTRACT FROM AUTHOR]

Human mesenchymal stem cells (MSCs) are known to have anti-inflammatory and immunomodulatory functions; thus, several MSC products have been applied as cell therapy in clinical trials worldwide. Recent studies have demonstrated that MSC spheroids have superior anti-inflammatory and immunomodulatory functions to a single cell suspension. Current methods to prepare MSC spheroids include hanging drop, concave microwell aggregation, spinner flask, and gravity circulation. However, all these methods have limitations such as low scalability, easy cell clumping, low viability, and irregular size distribution. Here, we present a nano-patterned culture plasticware named PAMcell™ 3D plate to overcome these limitations. Nano-sized silica particles (700 nm) coated with RGD peptide were arrayed into fusiform onto the PLGA film. This uniform array enabled the seeded MSCs to grow only on the silica particles, forming uniform-sized semi-spheroids within 48 h. These MSC spheroids have been shown to have enhanced stemness, anti-inflammatory, and immunomodulatory functions, as revealed by the increased expression of stem cell markers (Oct4, Sox2, and Nanog), anti-inflammatory (IL-10, TSG6, and IDO), and immunomodulatory molecules (HGF, VEGF, CXCR4) both at mRNA and protein expression levels. Furthermore, these MSC spheroids demonstrated an increased palliative effect on glycemic control in a multiple low-dose streptozotocin-induced diabetes model compared with the same number of MSC single cell suspensions. Taken together, this study presents a new method to produce uniform-sized MSC spheroids with enhanced anti-inflammatory and immunomodulatory functions in vitro and in vivo. • Mesenchymal stem cells have anti-inflammatory and immunomodulatory functions. • 3D MSC spheroids have superior anti-inflammatory and immunomodulatory functions to 2D monolayer cells. • MSC spheroids formed on a new culture device named PAMcell™ have enhanced functions in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background There are limited data regarding the influence of glycemic status on the risk of subclinical coronary atherosclerosis on coronary computed tomographic angiography (CCTA) in asymptomatic individuals. Methods We analyzed 6434 asymptomatic individuals who underwent CCTA. The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥ 50% diameter stenosis was defined as significant. Of study participants, 2197 (34.1%), 3122 (48.5%), and 1115 (17.3%) were categorized as normal, prediabetic and diabetic individuals, respectively. Results Compared with normal individuals, there were no statistically differences in the adjusted odds ratios of prediabetic individuals for significant coronary artery stenosis (0.98, 95% confidence interval [CI] 0.80–1.22, p = 0.888), any plaque (0.96, 95% CI 0.86–1.07, p = 0.483), calcified plaque (0.90, 95% CI 0.79–1.01, p = 0.080), non-calcified plaque (1.02, 95% CI 0.88–1.17, p = 0.803), and mixed plaque (1.00, 95% CI 0.82–1.22, p = 0.983). However, adjusted odds ratios for significant coronary artery stenosis (1.71, 95% CI 1.34–2.19, p < 0.001), any plaque (1.45, 95% CI 1.26–1.68, p < 0.001), calcified plaque (1.35, 95% CI 1.15–1.57, p < 0.001), non-calcified plaque (1.33, 95% CI 1.11–1.59, p = 0.002), and mixed plaque (1.64, 95% CI 1.30–2.07, p < 0.001) of diabetic individuals were significantly higher than those of the normal individuals. Conclusion In asymptomatic individuals, diabetic individuals had a higher risk for subclinical coronary atherosclerosis, but prediabetic individuals were not associated with an increased risk of subclinical coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Purpose: Suboptimal frequency of glycosylated hemoglobin (HbA1c) monitoring is associated with poor diabetes control. We aimed to analyze compliance to HbA1c testing guidelines and explore associated individual and area-level determinants, focusing on regional variation.Methods: This cross-sectional study between the period of 2012-2013 was conducted by using the Korean National Health Insurance Research Database, and included 45,634 patients diagnosed with diabetes mellitus, who were prescribed any anti-diabetic medications, including insulin. We calculated the proportion of each HbA1c testing frequency (≥1, ≥2, or ≥4 times per year) stratified by 17 administrative regions. Multilevel and multivariate logistic analyses were performed with regional (proportion of farmer population) and individual characteristics (age, sex, income level, duration of diabetes, and most visited medical institution).Results: Overall, 67.3% of the patients received≥1 HbA1c test per year; 37.8% and 6.1% received ≥2 and ≥4 tests per year, respectively. Those managed in secondary-level hospitals or clinics and those living in rural areas were less likely to receive HbA1c testing. Even after adjusting for individual and regional level characteristics, significant area level variation was observed (variance participant coefficients were 7.91%, 9.58%, and 14.43% for testing frequencies of ≥1, ≥2, and ≥4 times a year, respectively).Conclusions: The frequency of HbA1c monitoring is suboptimal in Korea, especially in rural areas. Moreover, significant regional variation was observed, implying a contextual effect. This suggests the need for developing policy actions to improve HbA1c monitoring. In particular, access to HbA1c testing in rural primary care clinics must be improved. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To estimate the prevalence of gestational diabetes mellitus (GDM) prevalence estimates for subgroups of US Asian and Pacific Islander (API) women by using data from 2005 and 2006 birth certificates. Methods: Using 2005–2006 natality files from states that implemented the revised 2003 US birth certificate, which differentiates between GDM and preexisting diabetes (2005: 12 states; 2006: 19 states), we calculated age-adjusted GDM prevalence estimates for API mothers who delivered singleton infants. Results: Among 3,108,877 births, US APIs had a substantially higher age-adjusted prevalence of GDM (6.3%) than whites (3.8%), blacks (3.5%), or Hispanics (3.6%). Among API subgroups, age-adjusted GDM prevalence varied significantly, from 3.7% among women of Japanese descent to 8.6% among women of Asian Indian descent. Foreign-born APIs had significantly higher GDM rates than US-born APIs except among women of Japanese and Korean ancestry. Conclusion: Overall, US API women have the highest risk for GDM among all US racial/ethnic groups. However, APIs are a heterogeneous group by genetic background, culture, and diet and other lifestyle behaviors. Our findings imply that, whenever possible, API subgroups should be evaluated separately in health research. [Copyright &y& Elsevier]