Aims/hypothesis Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes. Methods Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks. Results The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/ lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1. Conclusions/interpretation The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.

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One-hour glucose to predict prediabetes (PreDM=155mg/dL) and type 2 diabetes (T2D= 209 mg/dl) could improve detection with a shorter 1-hour OGTT, but thresholds need validation in longitudinal cohorts. We determined the risk of incident diabetes using the proposed thresholds with a 16-year longitudinal Korean data set (N=6381, BMI=24±4.0 kg/m2; Age 51.2±8.6 y). OGTT was conducted every 2 y, and 3 groups were assigned at baseline: low one-hour plasma glucose (1h-PG) with normal glucose tolerance (NGT) (low 1h-PG: FPG<100, 2h-PG<140, 1h-PG<155), high 1h-PG with NGT (high 1h-PG: FPG<100, 2h-PG<140, 1h-PG≥155), and PreDM (100≤FPG<126 or 140≤2h-PG<200). Time to T2D was compared by the group in a subset (N=230). T2D risk was higher in high 1h-PG and PreDM than low 1h-PG group (HR:4.9 [3.5, 6.8] and 8.8 [6.5, 11.8]). With the subset of progressors, a linear mixed effect model showed that times to T2D from low and high 1h-PG were 24.8±18.5 y and 19.5±12.4 y (P<0.05). The 1h-PG threshold for T2D, 209 mg/dl, was reached 7.5±14.5 y earlier than the 2h-PG threshold, 200 mg/dl. Conclusion: NGT with high 1h-PG is an intermediate state between low 1h-PG NGT and PreDM, and the 1h-PG threshold for T2D allows earlier diagnosis than the current 2h-PG threshold. Disclosure M.Im: None. I.Kim: None. S.T.Chung: None. A.Sherman: None. J.Ha: None. S.Kim: None. S.Ryang: None. D.Kim: None. W.Yi: None. J.Kim: None. H.Kang: None. Y.Kim: None. Y.Kim: None. M.Kim: None. Funding Busan Economic Promotion Agency; National Research Foundation of Korea (2022H1D3A2A01063552); Korea Health Industry Development Institute (HI18C2383); dkNET New Investigator Pilot Program in Bioinformatics; National Institute of Diabetes and Digestive and Kidney Diseases

BackgroundSeveral previous studies have reported that patients with axial spondyloarthritis (axSpA) presented with thoracic pain due to costovertebral joint arthritis. However, little is known about the prevalence and clinically relevant factors of costovertebral joint involvement in patients with axSpA.ObjectivesTo evaluate costovertebral joint involvement in patients with axSpA and to assess its association with disease features.MethodsWe included 150 patients from the Incheon Saint Mary’s axSpA observational cohort who underwent whole spine low-dose computed tomography (ldCT). Costovertebral joint abnormalities were scored by two readers on a scale of 0-48 based on the presence or absence of erosion, osteophyte, and ankylosis. The interobserver reliability of costovertebral joint abnormalities was assessed using intraclass correlation coefficients (ICCs). Associations between costovertebral joint abnormality scores and clinical variables were evaluated using a generalized linear model.ResultsTwo independent readers found costovertebral joint abnormalities in 74 (49%) patients and 108 (72%) patients. The ICCs of scores for erosion, osteophyte, ankylosis, and total abnormality were 0.85, 0.77, 0.93, and 0.95, respectively. For both readers, total abnormality score was correlated with age, symptom duration, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS functional index (BASFI), CT syndesmophyte score (CTSS), and number of bridging spines. Multivariate analyses showed age, ASDAS, CTSS to be independently associated with total abnormality scores in both readers. The frequency of ankylosed costovertebral joint was 10.2% (reader 1) and 17.0% (reader 2) in patients without radiographic syndesmophytes (n = 62), and 10.3% (reader 1) and 17.2% (reader 2) in patients without radiographic sacroiliitis (n = 29).ConclusionCostovertebral joint involvement was common in patients with axSpA, even in the absence of radiographic damage. LdCT is recommended for evaluating structural damage in patients with clinically suspected costovertebral joint involvement.References[1]Ellrodt A, Goldberg D, Oberlin F, Huchet B, Cayla J. Erosive arthritis of the costovertebral joint in seronegative spondyloarthropathy. J Rheumatol 1986;13:452-4.[2]Le T, Biundo J, Aprill C, Deiparine E. Costovertebral joint erosion in ankylosing spondylitis. Am J Phys Med Rehabil 2001;80:62-4.[3]Gazitt T, Nassrallah N, Zisman D. Erosive Costovertebral Joint Arthritis-An Uncommon Manifestation of Ankylosing Spondylitis. Arthritis Rheumatol 2021;73:179.[4]Chui ETF, Tsang HHL, Lee KH, Lau CS, Wong CH, Chung HY. MRI inflammation of facet and costovertebral joints is associated with restricted spinal mobility and worsened functional status. Rheumatology (Oxford) 2020;59:2591-602.[5]Diekhoff T, Hermann KGA, Lambert RG. Future of Low-Dose Computed Tomography and Dual-Energy Computed Tomography in Axial Spondyloarthritis. Curr Rheumatol Rep 2022;24:198-205.Acknowledgements:NIL.Disclosure of InterestsNone Declared.