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BackgroundGlucose variability is one of components of the dysglycemia in diabetes and may play an important role in development of diabetic vascular complications. The objective of this study was to assess the relationship between glycemic variability determined by a continuous glucose monitoring (CGM) system and the presence and severity of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM).MethodsIn 344 T2DM patients with chest pain, coronary angiography revealed CAD (coronary stenosis ≥ 50% luminal diameter narrowing) in 252 patients and 92 patients without CAD. Gensini score was used to assess the severity of CAD. All participants' CGM parameters and biochemical characteristics were measured at baseline.ResultsDiabetic patients with CAD were older, and more were male and cigarette smokers compared with the controls. Levels of the mean amplitude of glycemic excursions (MAGE) (3.7 ± 1.4 mmol/L vs. 3.2 ± 1.2 mmol/L, p < 0.001), postprandial glucose excursion (PPGE) (3.9 ± 1.6 mmol/L vs. 3.6 ± 1.4 mmol/L, p = 0.036), serum high-sensitive C-reactive protein (hs-CRP) (10.7 ± 12.4 mg/L vs. 5.8 ± 6.7 mg/L, p < 0.001) and creatinine (Cr) (87 ± 23 mmol/L vs. 77 ± 14 mmol/L, p < 0.001) were significantly higher in patients with CAD than in patients without CAD. Gensini score closely correlated with age, MAGE, PPGE, hemoglobin A1c (HbA1c), hs-CRP and total cholesterol (TC). Multivariate analysis indicated that age (p < 0.001), MAGE (p < 0.001), serum levels of HbA1c (p = 0.022) and hs-CRP (p = 0.005) were independent determinants for Gensini score. Logistic regression analysis revealed that MAGE ≥ 3.4 mmol/L was an independent predictor for CAD. The area under the receiver-operating characteristic curve for MAGE (0.618, p = 0.001) was superior to that for HbA1c (0.554, p = 0.129).ConclusionsThe intraday glycemic variability is associated with the presence and severity of CAD in patients with T2DM. Effects of glycemic excursions on vascular complications should not be neglected in diabetes.

SUMMARYPlant roots respond to environmental stresses or the exogenous plant hormone abscisic acid (ABA) by undergoing marked physiological and morphological changes. We show here that PERK4, a gene that encodes a member of the Arabidopsis thaliana proline-rich extensin-like receptor kinase family, plays an important role in ABA responses. Mutation of PERK4 by T-DNA insertion decreased sensitivity to ABA with respect to seed germination, seedling growth and primary root tip growth. The effect on root growth was due to enhanced cell elongation rather than cell division. The cytosolic free calcium concentration and Ca 2+ channel currents were lower in perk4 root cells than in wild-type cells in the presence of ABA. Root growth was similar in wild-type and perk4 plants after the application of a Ca 2+ channel blocker. PERK4 localised to the plasma membrane, and was shown to be an ABA-and Ca 2+ -activated protein kinase. Our data suggest that the receptor-like kinase encoded by PERK4 functions at an early stage of ABA signalling to inhibit root cell elongation by perturbing Ca 2+ homeostasis.

Most land plants have evolved a mutualistic symbiosis with arbuscular mycorrhiza (AM) fungi that improve nutrient acquisition from the soil. In return, up to 20% of host plant photosynthate is transferred to the mycorrhizal fungus in the form of lipids and sugar. Nutrient exchange must be regulated by both partners in order to maintain a reliable symbiotic relationship. However, the mechanisms underlying the regulation of lipid transfer from the plant to the AM fungus remain elusive. Here, we show that the Medicago truncatula AP2/EREBP transcription factor WRI5a, and likely its two homologs WRI5b/Erf1 and WRI5c, are master regulators of AM symbiosis controlling lipid transfer and periarbuscular membrane formation. We found that WRI5a binds AW-box cis-regulatory elements in the promoters of M. truncatula STR, which encodes a periarbuscular membrane-localized ABC transporter required for lipid transfer from the plant to the AM fungus, and MtPT4, which encodes a phosphate transporter required for phosphate transfer from the AM fungus to the plant. The hairy roots of the M. truncatula wri5a mutant and RNAi composite plants displayed impaired arbuscule formation, whereas overexpression of WRI5a resulted in enhanced expression of STR and MtPT4, suggesting that WRI5a regulates bidirectional symbiotic nutrient exchange. Moreover, we found that WRI5a and RAM1 (Required for Arbuscular Mycorrhization symbiosis 1), which encodes a GRASdomain transcription factor, regulate each other at the transcriptional level, forming a positive feedback loop for regulating AM symbiosis. Collectively, our data suggest a role for WRI5a in controlling bidirectional nutrient exchange and periarbuscular membrane formation via the regulation of genes involved in the biosynthesis of fatty acids and phosphate uptake in arbuscule-containing cells.