Introduction. Des études antérieures ont rapporté un lien entre la rétinopathie diabétique (RD) et l'artériopathie oblitérante des membres inférieurs (AOMI), mais le rôle des facteurs de risque traditionnels susceptibles de médier cette association reste incertain. Nous avons étudié l'association entre la RD et le risque de développer une AOMI majeure, et l'influence des facteurs de risque cardiovasculaire sur cette association dans la cohorte prospective SURDIAGENE (SURvie, DIAbète de type 2 et GENEtique) de sujets diabétiques de type 2. Méthodes. Un modèle de Cox multi-ajusté a été utilisé pour évaluer le risque d'AOMI majeure (amputation ou revascularisation) pendant le suivi en fonction des stades de RD (absente, non-proliférante, proliférante) à l'inclusion. Résultats. Parmi 1320 participants, 94 personnes (7,1%) développaient une AOMI majeure pendant 7,1 (4,4-10,7) années de suivi, avec un taux d'incidence de 9,6 pour 1000 personnes-années. L'incidence cumulée augmentait avec la sévérité de la RD (p<0,0001; test log-rank). Le risque d'AOMI était significativement plus élevé en cas de RD non-proliférante (HR ajusté 2,31 IC 95% (1,43-3,81); p=0,0006) et de RD proliférante (3,14 (1,15); p=0,007) versus absence de RD. Aucune hétérogénéité n'était observée dans différents sous-groupes. La RD améliorait l'index statistiques-C (+0,023 IC 95% (0,003-0,044) ; p=0,02), et les tests de reclassification pour le risque d'AOMI majeur à 5 ans : IDI (+0,209 (0,130-0,321) ; p<0,001) et NRI (+0,562 (0,382-0,799); p<0,001). Conclusion.Le risque d'AOMI majeure augmente proportionnellement à la gravité de la RD, indépendamment des facteurs de risque cardiovasculaire. La RD a une valeur pronostique significative dans la prédiction de l'AOMI.Mots clés : artériopathie oblitérante des membres inférieurs, rétinopathie diabétique, diabète de type 2, microvasculaire. Introduction.Previous studies reported an association between diabetic retinopathy (DR) and lowerextremity arterial disease (LEAD), but the role of traditional risk factors that may mediate this association remains uncertain. We evaluated the association between DR stages and LEAD, its prognostic value, and the influence of potential contributors to this relationship in a prospective cohort of patients with type 2 diabetes, SURDIAGENE (SURvival, type 2 DIAbetes and GENEtics). Methods. DR was staged at baseline as absent, non-proliferative, or proliferative. A Cox regression model was fitted in order to compute the hazard ratio (95% CI) for major LEAD (lower-limb amputation or revascularization) during follow-up by baseline retinopathy stages. Results. Among 1320 participants without a history of LEAD at baseline, 94 persons (7.1%) developed a major LEAD during a 7.1 (4.4-10.7) year median follow-up (incidence rate 9.6 per 1000 person-years). The LEAD incidence rate (per 1000 person-years) increased as retinopathy worsened (p<0.0001; log-rank test). The risk of LEAD was significantly higher for non-proliferative DR (adjusted HR 2.31 95% CI (1.43-3.81); p=0.0006) and prolif...

IntroductionSubjects with type 2 diabetes have an excess risk of cancer. The potential role of advanced glycation end products (AGEs) accumulated during long-term hyperglycemia in cancer development has been suggested by biological studies but clinical data are missing. AGEs can be estimated by measuring the skin autofluorescence. We searched whether the skin autofluorescence could predict new cancers in persons with type 2 diabetes.Research design and methodsFrom 2009 to 2015, we measured the skin autofluorescence of 413 subjects hospitalized for uncontrolled or complicated type 2 diabetes, without any history of cancer. The participants were followed for at least 1 year and the occurrences of new cancers were compared according to their initial skin autofluorescences.ResultsThe participants were mainly men (57.9%), with poorly controlled (HbA1c 72±14 mmol/mol or 8.7%±1.8%) and/or complicated type 2 diabetes. Their median skin autofluorescence was 2.6 (2.2–3.0) arbitrary units. Forty-five new cancer cases (10.9%) were registered during 4.8±2.3 years of follow-up: 75.6% of these subjects had skin autofluorescence higher than the median (χ2: p=0.001). By Cox regression analysis adjusted for age, gender, body mass index, history of smoking and renal parameters, skin autofluorescence >2.6 predicted a 2.57-fold higher risk of cancer (95% CI 1.28 to 5.19, p=0.008). This association remained significant after excluding the eight cancers that occurred in the 4 years after inclusion (OR 2.95, 95% CI 1.36 to 6.38, p=0.006). As a continuous variable, skin autofluorescence was also related to new cancers (OR 1.05, 95% CI 1.01 to 1.10, p=0.045).ConclusionsSkin autofluorescence, a potential marker of glycemic memory, predicts the occurrence of cancer in subjects with type 2 diabetes. This relation provides a new clinical argument for the role of AGEs in cancer. Their estimation by measuring the skin autofluorescence may help select subjects with diabetes in cancer screening programs.

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BACKGROUND: Lower-limb peripheral artery disease is one of the major complications of diabetes. Peripheral artery disease is associated with poor limb and cardiovascular prognoses, along with a dramatic decrease in life expectancy. Despite major medical advances in the treatment of diabetes, a substantial therapeutic gap remains in the peripheral artery disease population. Praliciguat is an orally available sGC (soluble guanylate cyclase) stimulator that has been reported both preclinically and in early stage clinical trials to have favorable effects in metabolic and hemodynamic outcomes, suggesting that it may have a potential beneficial effect in peripheral artery disease. OBJECTIVE: We evaluated the effect of praliciguat on hind limb ischemia recovery in a mouse model of type 2 diabetes. METHODS: HLI was induced in leptin receptor-deficient (Lepr db/db ) mice by ligation and excision of the left femoral artery. Praliciguat (10 mg/kg/day) was administered in the diet starting 3 days before surgery. RESULTS: Twenty-eight days after surgery, ischemic foot perfusion and function parameters were better in praliciguat-treated mice than in vehicle controls. Improved ischemic foot perfusion was not associated with either improved traditional cardiovascular risk factors (ie, weight, glycemia) or increased angiogenesis. However, treatment with praliciguat significantly increased arteriole diameter, decreased ICAM1 (intercellular adhesion molecule 1) expression, and prevented the accumulation of oxidative proangiogenic and proinflammatory muscle fibers. While investigating the mechanism underlying the beneficial effects of praliciguat therapy, we found that praliciguat significantly downregulated Myh2 and Cxcl12 mRNA expression in cultured myoblasts and that conditioned medium form praliciguat-treated myoblast decreased ICAM1 mRNA expression in endothelial cells. These results suggest that praliciguat therapy may decrease ICAM1 expression in endothelial cells by downregulating Cxcl12 in myocytes. CONCLUSIONS: Our results demonstrated that praliciguat promotes blood flow recovery in the ischemic muscle of mice with type 2 diabetes, at least in part by increasing arteriole diameter and by downregulating ICAM1 expression.