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We investigated whether Diabetic Retinopathy (DR) is related to Diabetic Foot Ulcers (DFU) development, adjusted for the stratification of the International Work Group on Diabetic Foot (IWGDF) guidance. DR and IWGDF stratification were registered retrospectively in patients hospitalized from 2009 to 2017 for uncontrolled and/or complicated type 2 diabetes. New DFUs were registered until 2020. Survival analyses categorized the subjects for DR, and multivariate Cox regression adjusted for confounders. The 522 patients (57.9% male) were 62±9 years old, with a diabetes duration of 14±10 years, HbA1c of 8.7±1.8%, 33.9% macroangiopathies and 44.8% diabetic kidney diseases. Their grades of DFU risk were 0 for 43.3%, 1 for 23.9%, 2 for 7.1%, and 3 for 25.6%. During the 52 months follow-up (IQR: 32-71), 58 new DFUs and 18 lower-limb amputations occurred, mostly in patients with DR present in 140 (26.8%) patients. Adjusted for age, sex and conventional risk factors (duration and control of diabetes, arterial hypertension, dyslipidemia), and other complications (macroangiopathy, diabetic kidney disease), DR associated with a greater incidence of DFUs. Adjusted for the IWGDF classification, DR was related to new DFUs (HR: 2.51, 95%CI: 1.48-4.26) and amputations (HR: 3.56, 95%CI: 1.26-10.07). This relationship persisted in ascending IWGDF grades, with incidences of DFUs from 2/1000 (grade 0, no DR) to 121/1000 patient-years (grade 3 and DR), and amputations from 0 (grade 0, no DR) to 38/1000 patient-years (grade 3 and DR). Diabetic retinopathy independently relates to the incidence of foot ulcers and amputations in patients hospitalized for type 2 diabetes. This article is protected by copyright. All rights reserved.

Resume La glycation est un processus physiologique accru par l’hyperglycemie chronique. En cas de diabete, la glycation et l’oxydation induisent la formation de produits de la glycation avancee (Advanced Glycation End-products, AGEs), deleteres pour les tissus. Du fait de leurs proprietes optiques, il est possible de mesurer l’autofluorescence cutanee (AF), correlee aux concentrations tissulaires des AGEs. Cette mesure est de realisation facile, et non invasive. L’AF est un marqueur de la memoire metabolique, associe aux valeurs anciennes de l’HbA1c. Cependant, l’âge, la fonction renale et l’heredite influencent les valeurs d’AF. Elle est associee aux complications micro- et macroangiopathiques du diabete quel que soit leur type. En definitive, l’AF pourrait etre utilisee comme marqueur predictif precoce des complications du diabete. Meme si son interpretation reste delicate, l’utilisation de l’AF en pratique courante serait possible afin d’optimiser la prise en charge du patient vers une medecine personnalisee.

In long-lasting diabetes, a dramatic reduction of HbA1c can precede adverse events such as worsening retinopathies or painful neuropathies. We have now analyzed its possible link with later cardiovascular events in subjects with type 2 diabetes, according to their long-term glucose exposure evaluated by skin autofluorescence (SAF) measured with an AGE-READER (Diagnoptics, Groningen, The Netherland).We studied retrospectively a cohort of patients hospitalized for uncontrolled and/or complicated type 2 diabetes from 2009 to 2017. A previous dramatic reduction of HbA1c was defined by more than -1.5 %/4 months, and later cardiovascular events as myocardial infarction, stroke, revascularization procedures, and cardiovascular-related death. Survival analyses were performed before and after categorizing the subjects for their SAF.The 386 subjects were 57.5 % men, 62 ± 9 years old, with a 14 ± 9 years duration of diabetes, most were treated by insulin (63.7 %). The dramatic HbA1c reducers (-3.0 ± 1.5 %) represented 16.5 % of the population. During the 51 months (IQR: 30-71) of follow-up, 53 cardiovascular events occurred and were related to the SAF (2.70 ± 0.64 AUs). Linkage was established between the SAF, the reduction of HbA1c and the cardiovascular events (p = 0.017). With a SAF higher than the median (2.65 AUs), the dramatic reduction of HbA1c was related to later cardiovascular events (HR: 3.84, 95%CI: 1.68-8.76).A dramatic decline of HbA1c leads to a higher risk of cardiovascular events in hospitalized subjects with type 2 diabetes and a high long-term glucose exposure.

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.

Aims As diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to ‘glucose memory’ by evaluating patients’ HbA1c over previous years and their skin autofluorescence (SAF). Methods In 334 patients with T2D and HbA1c levels ≤ 8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment]. Results Our patients were mostly men (58.4%) aged 63 ± 10 years, with a duration of diabetes of 13 ± 10 years and HbA1c = 7.1 ± 0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods −4 ± 3 months (n = 255), −16 ± 4 months (n = 152), −30 ± 4 months (n = 93) and −62 ± 26 months (n = 105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR = 6.75, 95% CI: 1.90–23.90. Moreover, SAF values were higher in those with DR [2.95 ± 0.67 arbitrary units (AU)] vs 2.65 ± 0.65 AU with no DR (P Conclusion Our study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5 years prior to study admission and their SAF values, a marker of glucose memory.

Highlights • The accumulation of Advanced Glycation End-products in the tissues studied as a marker of metabolic memory. • Skin autofluorescence as a marker of glycemic memory in type 2 diabetes. • Skin autofluorescence was independently related to their most ancient HbA1c. • Skin autofluorescence was higher in subjects with microangiopathic complications.

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.

We were interested in the article by Andersen et al. (1), who showed that diabetic polyneuropathy (DPN) was related to baseline HbA1c and its increase in 452 participants with type 2 diabetes in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) (1). If HbA1c trajectories influence DPN, it could be improved by treatment. In the Kumamoto trial, the vibration perception thresholds (VPT) stabilized in patients on intensive glucose control, whereas they increased from 22 to 37 V in those on conventional treatment (2). Andersen et al. (1) cautiously mentioned that their results may not apply to people with type 2 diabetes clinically diagnosed later in the disease course, with higher HbA1c that changed …