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.

BACKGROUND SARS-Cov-2 (COVID-19) has become a major worldwide health concern since its appearance in China at the end of 2019.OBJECTIVE To evaluate the intrinsic mortality and burden of COVID-19 and seasonal influenza pneumonia in ICUs in the city of Lyon, France.DESIGN A retrospective study.SETTING Six ICUs in a single institution in Lyon, France.PATIENTS Consecutive patients admitted to an ICU with SARS-CoV-2 pneumonia from 27 February to 4 April 2020 (COVID-19 group) and seasonal influenza pneumonia from 1 November 2015 to 30 April 2019 (influenza group). A total of 350 patients were included in the COVID-19 group (18 refused to consent) and 325 in the influenza group (one refused to consent). Diagnosis was confirmed by RT-PCR. Follow-up was completed on 1 April 2021. MAIN OUTCOME(S) AND MEASURE(S)Differences in 90day adjusted-mortality between the COVID-19 and influenza groups were evaluated using a multivariable Cox proportional hazards model.RESULTS COVID-19 patients were younger, mostly men and had a higher median BMI, and comorbidities, including immunosuppressive condition or respiratory history were less frequent. In univariate analysis, no significant differences were observed between the two groups regarding in-ICU mortality, 30, 60 and 90-day mortality. After Cox modelling adjusted on age, sex, BMI, cancer, sepsis-related organ failure assessment (SOFA) score, simplified acute physiology score SAPS II score, chronic obstructive pulmonary disease and myocardial infarction, the probability of death associated with COVID-19 was significantly higher in comparison to seasonal influenza [hazard ratio 1.57, 95% CI (1.14 to 2.17); P ¼ 0.006]. The clinical course and morbidity profile of both groups was markedly different; COVID-19 patients had less severe illness at admission (SAPS II score, 37 [28 to 48] vs. 48 [39 to 61], P < 0.001 and SOFA score, 4 [2 to 8] vs. 8 [5 to 11], P < 0.001), but the disease was more severe considering ICU length of stay, duration of mechanical ventilation, PEEP level and prone positioning requirement.CONCLUSION After ICU admission, COVID-19 was associated with an increased risk of death compared with seasonal influenza. Patient characteristics, clinical course and morbidity profile of these diseases is markedly different.

Aims: Does Diabetic Retinopathy (DR) relate to a previous dramatic reduction of HbA1c in Type 2 Diabetes (T2D)? Methods: In patients hospitalized for T2D, we collected HbA1c values from previous years, and we defined "Rapid declinors" by a more than −3% reduction between two consecutive HbA1c, and "sustained moderate declinors" by HbA1c declining less than −3%. We analyzed the relation between DR and previous HbA1c courses, adjusted for other risk factors. Results: Our 680 patients had a mean HbA1c at 8.7 ± 1.7% at admission and 8.7 ± 1.8 to 9.0 ± 2.2% during previous years (1500 HbA1C values collected), and 24% had a DR. A previous rapid decline of HbA1c occurred in 13.5% of subjects and related to DR (OR = 1.86, 95%CI:1.02-3.40), especially proliferative (OR = 2.64, 95% CI:1.02-6.80), after adjustment for age, gender, body mass index, arterial hypertension and diabetic kidney disease, blood lipids and statin treatment, duration of diabetes and mean previous HbA1c. A previous moderate reduction of HbA1c as occurred in 28.3% other subjects was not related to DR. Conclusions: In subjects hospitalized for T2D, a previous rapid decline of HbA1c was related to proliferative DR, whereas a sustained moderate decline appeared to be safe.

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Visual diseases come in many flavors, with a large variety of affected tissues (eye anterior segment, retina, optic nerve, cortex …), ages of onset, rates of progression and causal factors. In Western countries, if the majority of these diseases are now curable, millions of people are still affected by blindness or low vision, as many retinal diseases (age‐related macular degeneration, retinitis pigmentosa, diabetic retinopathy, glaucoma…) still lack efficient treatments. In a facility devoted to mouse phenotyping, it is thus of major importance to propose an efficient visual phenotyping platform, to pick up visual defects in screened mutants, to assess the beneficial effects of potential treatments or the eventual adverse effects of drugs targeting the CNS – vision screen being mandatory in CNS drug development. While the tests performed in human clinics are transposable to rodents, the small eye size of the mouse hinders a fine assessment of the retinal fundus, especially in the periphery. To maximize our chances to detect even early phenotypes, we are moving toward a recently developed fundus imaging system (Paques et al., IOVS 2007), which allows to acquire high quality digital images of the fundus, up to the ciliary margin, and fluorescein angiography, allowing for a later diagnostic confirmation by ophthalmologists. Together with slit lamp examination and electroretinography, this constitutes a solid first line of visual phenotyping.

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