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Background: The diabetes-cancer link may be mediated by inflammation due to infection such as Human Papilloma Virus (HPV). Exendin 4, a Glucagon-like-peptide 1 agonist, has anti-hyperglycemic and anti- inflammatory effect and can attenuate certain cancer growth. Methods: We used RNA microarray analysis to detect the gene expression after Exendin 4 treatment in the db/db mouse tumor, which was established by inoculation of mouse PV cancer cells (CUP-1). The latter originates from the kidney of baby C57BL/6J mice expressing HPV-16 E7 oncogene. We examined the effect of Exendin 4 on cell proliferation, apoptosis and gene expression along the inflammatory pathway in CUP-1 under different glucose environment. We developed CUP-1 cells with or without target gene overexpression (OE) or downregulation (DR) for inoculation into the db/db mouse. We compared RNA expression of the target gene in cervical cancer specimen from patients with or without diabetes. Results: RNA expression of proteasome 20s (psma) was decreased after Exendin 4 treatment in the db/db mouse tumor. High glucose environment increased cell proliferation in CUP-1 cells, which was enhanced after OE of psma but attenuated after DR of psma. Exendin 4 suppressed NFκB P65 and IκB activation in CUP-1 cells under high glucose medium. After inoculation of CUP-1 cells with DR and OE of psma, the tumor size was decreased and increased in db/db mice respectively. Exendin 4 decreased the tumor volume in the db/db mice of psma OE group. In human cervical cancer specimen, RNA expression of psma was increased in patients with diabetes versus those without diabetes. Conclusion: High glucose increased expression of psma, which activated NFκB inflammation pathway and promoted carcinogenesis. Exendin 4 suppressed the NFκB pathway activation and decreased tumor volume with corroborative evidence from human samples, suggesting that the anti-cancer effect of Exendin 4 might be mediated by the psma-NFκB pathway. Disclosure D. Mao: None. J.C. Chan: None.

OBJECTIVE Multifaceted care has been shown to reduce mortality and complications in type 2 diabetes. We hypothesized that structured care would reduce renal complications in type 2 diabetes. RESEARCH DESIGN AND METHODS A total of 205 Chinese type 2 diabetic patients from nine public hospitals who had plasma creatinine levels of 150–350 μmol/l were randomly assigned to receive structured care (n = 104) or usual care (n = 101) for 2 years. The structured care group was managed according to a prespecified protocol with the following treatment goals: blood pressure 500 μmol/l or dialysis). RESULTS Of these 205 patients (mean ± SD age 65 ± 7.2 years; disease duration 14 ± 7.9 years), the structured care group achieved better control than the usual care group (diastolic blood pressure 68 ± 12 vs. 71 ± 12 mmHg, respectively, P = 0.02; A1C 7.3 ± 1.3 vs. 8.0 ± 1.6%, P < 0.01). After adjustment for age, sex, and study sites, the structured care (23.1%, n = 24) and usual care (23.8%, n = 24; NS) groups had similar end points, but more patients in the structured care group attained ≥3 treatment goals (61%, n = 63, vs. 28%, n = 28; P < 0.001). Patients who attained ≥3 treatment targets (n = 91) had reduced risk of the primary end point (14 vs. 34; relative risk 0.43 [95% CI 0.21–0.86] compared with that of those who attained ≤2 targets (n = 114). CONCLUSIONS Attainment of multiple treatment targets reduced the renal end point and death in type 2 diabetes. In addition to protocol, audits and feedback are needed to improve outcomes.