TIR assessed by CGM is associated with DR in type 2 diabetes.

Aims/Introduction The relationship between glycemic variability ( GV ) and diabetic complications has gained much interest and remains under debate. Furthermore, the association of GV with diabetic complications has not been examined in latent autoimmune diabetes of the adult ( LADA ). Therefore, we evaluated the relationships among several metrics of GV with diabetic retinopathy ( DR ) in patients with LADA and type 2 diabetes mellitus. Materials and Methods A total of 192 patients with LADA and 2,927 patients with type 2 diabetes mellitus were enrolled. After continuous glucose monitoring for 72 h, three metrics of GV including standard deviation, coefficient of variation and mean amplitude of glycemic excursions were calculated. DR was assessed by fundus photography performed with a digital non‐mydriatic camera. Results The prevalence of DR was 20.3 and 26.4% in LADA and type 2 diabetes mellitus patients ( P < 0.001), respectively. Generally, LADA patients had fewer cardiometabolic risk factors than type 2 diabetes mellitus patients, and all GV metrics were significantly higher in LADA than in type 2 diabetes mellitus. In the multivariate logistic regression analysis, no metrics for GV were identified as independent risk factors of DR (standard deviation: P = 0.175; coefficient of variation: P = 0.769; mean amplitude of glycemic excursions: P = 0.388) in LADA . However, the standard deviation was significantly associated with DR ( OR 1.15, P = 0.017) in patients with type 2 diabetes mellitus after adjusting for confounders. The independent relationships of coefficient of variation and mean amplitude of glycemic excursions with DR ( P = 0.194 and P = 0.251, respectively) did not reach statistical significance in type 2 diabetes mellitus. Conclusions GV is more strongly associated with DR in type 2 diabetes than in LADA , suggesting that different glucose‐lowering strategies should be used for these two types of diabetes.

Unlike glucose, 1,5-AG is hard to be metabolized in vivo, and its transport is influenced by an acute glucose load in hepatocytes.

Background The regulation of vascular smooth muscle cell (VSMC) phenotype plays an important role in intracranial aneurysm (IA) formation and progression. However, the underlying mechanism remains unclear. Metformin is a 5′ AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature. The present study investigated whether metformin modulates VSMC phenotype switching via the AMPK/acetyl-CoA carboxylase (ACC) pathway during IA pathogenesis. Methods Adult male Sprague-Dawley rats (n = 80) were used to establish an elastase-induced IA model. The effects of metformin on AMPK activation and VSMC phenotype modulation were examined. We also established a platelet-derived growth factor (PDGF)-BB-induced VSMC model and analyzed changes in phenotype including proliferation, migration, and apoptosis as well as AMPK/ACC axis activation under different doses of metformin, AMPK antagonist, ACC antagonist, and their combinations. Results Metformin decreased the incidence and rupture rate of IA in the rat model and induced a switch in VSMC phenotype from contractile to synthetic through activation of the AMPK/ACC pathway, as evidenced by upregulation of VSMC-specific genes and decreased levels of pro-inflammatory cytokines. AMPK/ACC axis activation inhibited the proliferation, migration, and apoptosis of VSMCs, in which phenotypic switching was induced by PDGF-BB. Conclusions Metformin protects against IA formation and rupture by inhibiting VSMC phenotype switching and proliferation, migration, and apoptosis. Thus, metformin has therapeutic potential for the prevention of IA.

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Recent studies have shown that circulating fibroblast growth factor (FGF) 23 and vitamin D levels are closely correlated with insulin resistance. The aim of this study was to investigate the relationship among serum FGF 23 levels, serum 25-hydroxyvitamin D [25(OH)D] levels, and non-alcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This study enrolled 331 hospitalized T2DM patients (209 patients with NAFLD and 122 patients without NAFLD). Serum FGF23 levels were measured using a sandwich enzyme-linked immunosorbent assay. Serum 25(OH)D levels were determined by an electrochemiluminescence immunoassay. NAFLD was diagnosed by hepatic ultrasound, and the fatty liver index (FLI) was calculated to quantify hepatic steatosis. Results showed that T2DM patients with NAFLD had significantly higher serum FGF23 levels (44.17 [37.92-51.30] pg/mL vs 40.21 [34.07-48.33] pg/mL, P = .002), but lower serum 25(OH)D levels (16.43 [12.70-21.37] ng/mL vs 19.59 [13.78-26.26] ng/mL, P = .002) than those without NAFLD. Moreover, the incidence rate of NAFLD increased with increasing serum FGF23 levels and decreased with increasing 25(OH)D levels (both P < .05). Logistic regression analysis showed that both serum FGF23 and 25(OH)D levels were independent factors for NAFLD (both P < .05). Furthermore, a multiple stepwise regression analysis also revealed that both serum FGF23 and 25(OH)D levels were independently correlated with FLI (both P < .01). In conclusion, both high FGF23 and low vitamin D levels showed an independent relationship with NAFLD in Chinese T2DM patients, indicating that FGF23 and vitamin D function via different regulatory pathways in the liver.

Serum 1,5-anhydroglucitol (1,5-AG) levels can not only accurately reflect the mean blood glucose over the previous 1–2 weeks in diabetic patients but also offers the advantage of representing postprandial glucose. To evaluate the clinical significance of 1,5-AG in diabetes detection, especially when used in combination with fasting plasma glucose (FPG), a total of 3098 participants at high risk for diabetes (1467 men, 1631 women) were enrolled. A total of 1471 (47.5%) participants were diagnosed with diabetes, and the mean 1,5-AG level in the diabetic group was significantly lower than that in non-diabetic group [12.5 (7.8–17.5) μg/mL vs. 20.5 (15.3–26.4) μg/mL, P < 0.001]. The optimal cut-off point was 15.9 μg/mL, for which the sensitivity, specificity, and area under the curve (AUC) were 69.2%, 72.3%, and 0.781, respectively. For the combination of FPG and 1,5-AG, the sensitivity, specificity, and AUC improved to 82.5%, 83.5%, and 0.912, respectively. This method helped 75.8% of the participants avoid an oral glucose tolerance test (OGTT), reducing the need to carry out the OGTT by 43.9% compared to the use of the FPG criterion only. In conclusion, the addition of FPG to serum 1,5-AG improves the efficiency of diabetes screening in the Chinese population.

BackgroundRecently, basic and clinical studies have provided evidence supporting the relationship between circulating levels of fibroblast growth factor (FGF) 23 and the development of atherosclerosis. Given that diabetes is an established risk factor for lower extremity atherosclerotic disease (LEAD), the goal of the present study was to explore the relationship between serum FGF23 levels and LEAD, as well as the related factors, in Chinese patients with type 2 diabetes mellitus (T2DM).MethodsA total of 401 hospitalized T2DM patients (201 subjects with LEAD and 200 subjects without LEAD) were enrolled in this study. Serum FGF23 levels were determined by a sandwich enzyme-linked immunosorbent assay. Femoral intima-media thickness (F-IMT) and lower limb atherosclerotic plaque were assessed through color Doppler ultrasound.ResultsThe median (interquartile range) serum FGF23 levels in the entire study population was 42.08 (35.59–49.17) pg/mL. Subjects with LEAD had significantly higher serum FGF23 levels compared with those without LEAD (44.00 [37.54–51.30] pg/mL versus 40.42 [32.61–48.23] pg/mL, P < 0.001). Logistic regression showed that serum FGF23 levels were independently and positively correlated with the presence of LEAD (odds ratio 1.039, 95% confidence interval 1.012–1.067, P = 0.004). In addition, multiple liner regression analysis revealed that serum FGF23 levels were positively associated with F-IMT (standardized β = 0.175, P < 0.001). Furthermore, this relationship remained significant after additional adjustment for gender and factors potentially affecting serum FGF23 levels (serum calcium, serum phosphorus, and glomerular filtration rate), respectively (both P < 0.01).ConclusionsIn Chinese patients with T2DM, serum FGF23 levels were independently and positively correlated with the presence of LEAD.