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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.

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.

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.

Background Ketoacidosis is a severe metabolic complication mainly reported in diabetic patients. Therapeutic fasting is a millennial worldwide practice, believed to improve a large panel of health conditions, but its efficiency and safety profile have not yet been established. We report here a case of euglycemic ketoacidosis in a non-diabetic woman. Case description A 51-year-old woman without a history of excessive alcohol use or medical history, except for a depressive disorder, was admitted in the emergency room for altered general status, deep asthenia, muscular weakness, articular pain, nausea, vomiting, and consciousness disorders. She was practicing during the previous 48 h a therapeutic fasting following a progressive restrictive diet for 4 d. She was diagnosed with ketoacidosis and hospitalized in the intensive care unit. Her laboratory test results indicated pH 7.28, bicarbonate 7 mmol/L, significant ketone bodies, glycemia 8.9 mmol/L without glycosuria, and negative blood alcohol assessment. Glycated hemoglobin was 5.5%, and blood glucose never went above 9 mmol/L. Serum concentrations of free fatty acids were high at 1.13 mmol/L (normal range: 0.13–0.45). Plasma insulin and peptide C were in the normal ranges. Comprehensive plasma and urinary biochemistry panels, including energetic substrates, and chromatography of amino acids and organic acids did not indicate any energetic or metabolic deficiency. The ketoacidosis regressed, and the overall outcome was favorable after intravenous glucose infusion for 48 h, without insulin requirement. Conclusions This report is the first case, to our knowledge, of euglycemic ketoacidosis thought to be induced by therapeutic fasting in a non-diabetic patient. Practitioners should be aware of this complication of fasting.

International audience; No abstract available

We were interested in the recent article by Cundy et al. (1), who described a rapid and durable decline of estimated glomerular filtration rate (eGFR) in four subjects with type 2 diabetes after their HbA1c had fallen from 118 mmol/mol (12.9%) to 48 mmol/mol (5.5%). Fifteen years ago, we reported that GFR and its estimations correlated with HbA1c, each +1% (+9 mmol/mol) HbA1c being associated with +5–6 mL/min/1.73 m2 GFR (2). One could then fear a –35 mL/min/1.73 m2 GFR reduction after a rapid –7% reduction of HbA1c. We have recently shown that a dramatic reduction of HbA1c, by more than 27 mmol/mol (–3%), could be detected during the years preceding admission in 13.5% of 680 patients hospitalized …

In type 2 diabetes, Diabetic Retinopathy (DR) can worsen with rapid glucose control in specific circumstances. We sought whether DR can be systematically related to a previous dramatic reduction of HbA1c. In patients hospitalized for uncontrolled or complicated type 2 diabetes, we collected values of HbA1c from the previous years. "Rapid declinors" were defined by a reduction of more than -3% between two consecutive HbA1c values, and "sustained moderate declinors" if the HbA1c always declined without reaching -3%. We compared the prevalences of DR according to the previous HbA1c courses, and adjusted the analysis for risk factors for DR. Our 680 patients were mainly men (56.8%), 62±10 years old, with 14±10 year duration of diabetes. Their BMI was 32.1±6.1 kg/m2. Sixty-seven percent had arterial hypertension, 67.5% were treated by a statin and 44.5% had a Diabetic Kidney Disease. They were poorly controlled: mean HbA1c at 8.7±1.7% at admission. One thousand and five hundred previous HbA1c values were available: 9.0±1.9% during the previous year (n=641, time -4±4 months before), 8.7±1.8% during the year before (n=363, time -16±4 months), 8.7±1.8% during the second year before (n=253, time -30±4 months), and 9.0±2.2% for the most ancient (n=243, time -65±27 months).One hundred and sixty-three subjects (24%) had a DR, associated to a longer duration of diabetes, higher previous HbA1c, arterial hypertension, Diabetic kidney disease, and dyslipidemia. A previous rapid decline of HbA1c was related to DR (OR=1.869, 95% CI:1.028-3.401) after adjustment for age, gender, BMI, arterial hypertension and DKD, blood lipids and statin treatment, duration of diabetes and the mean of previous available HbA1c. The relation between DR and a previous sustained moderate reduction of HbA1c as occurred in 193 other subjects (28.3%) was NS (OR=0.798, 95% CI:0.485-1.313). In subjects with poorly controlled T2D, a history of rapid decline of HbA1c was found to predispose to DR in our population, whereas a sustained moderate decline was safe. Disclosure A. Larroumet: None. J. Korobelnik: Board Member; Self; Novo Nordisk Inc. Consultant; Self; Allergan, Bayer AG, Novartis France, Roche Pharma. N. Foussard: None. L. Blanco: None. K. Mohammedi: None. M. Monlun: None. V. Rigalleau: None.

We were interested in the recent article from Pantalone et al. (1), who reported that 23.7% of 6,973 subjects with poorly controlled type 2 diabetes (HbA1c >9%) attained HbA1c below 8% within 1 year, based on the electronic health record at Cleveland Clinic. Although the 6,973 participants represented only 6.7% of the 103,969 encountered patients in the database, their fate is a matter of concern, as high rates of vascular and infectious complications have been related to HbA1c above 9%. The follow-up of HbA1c trajectories has shown that high HbA1c usually remains stable or ascending for years, and long-term frank reductions are uncommon, only occurring for 3–4% of the patients (2). Real improvement of …

International audience; Dialysis patients exhibit an inverse, L- or U-shaped association between blood pressure and mortality risk, in contrast to the linear association in the general population. We prospectively studied 9333 hemodialysis patients in France, aiming to analyze associations between predialysis systolic, diastolic, and pulse pressure with all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular endpoints for a median follow-up of 548 days. Blood pressure components were tested against outcomes in time-varying covariate linear and fractional polynomial Cox models. Changes throughout follow-up were analyzed with a joint model including both the time-varying covariate of sequential blood pressure and its slope over time. A U-shaped association of systolic blood pressure was found with all-cause mortality and of both systolic and diastolic blood pressure with cardiovascular mortality. There was an L-shaped association of diastolic blood pressure with all-cause mortality. The lowest hazard ratio of all-cause mortality was observed for a systolic blood pressure of 165 mm Hg, and of cardiovascular mortality for systolic/diastolic pressures of 157/90 mm Hg, substantially higher than currently recommended values for the general population. The 95% lower confidence interval was approximately 135/70 mm Hg. We found no significant correlation for either systolic, diastolic, or pulse pressure with myocardial infarction or nontraumatic amputations, but there were significant positive associations between systolic and pulse pressure with stroke (per 10-mm Hg increase: hazard ratios 1.15, 95% confidence interval 1.07 and 1.23; and 1.20, 1.11 and 1.31, respectively). Thus, whereas high pre-dialysis blood pressure is associated with stroke risk, low pre-dialysis blood pressure may be both harmful and a proxy for comorbid conditions leading to premature death.

Resume La prevalence de la denutrition est elevee en dialyse. Aux facteurs de denutrition lies a l'insuffisance renale, se surajoutent ceux associes a la technique. Une quantite de dialyse inadequate aggrave l'anorexie et la denutrition. En dehors des complications liees a la maladie, les facteurs hypercataboliques associent acidose, deperdition en nutriments et en proteines, facteurs inflammatoires secondaires a l'interaction sangmembrane en hemodialyse ou a la presence de liquide de dialyse peritoneale. Les apports en calories et en proteines doivent etre augmentes par rapport aux apports prescrits chez les patients non dialyses. Les index de dialyse adequate et de denutrition doivent etre mesures regulierement, et adaptes a la technique utilisee. Le type de dialyse, la quantite et la qualite doivent etre adaptes a l'etat clinique du patient.

Esophageal involvement is a common situation found in 50 to 80% of patients with scleroderma, but Boerhaave's syndrome is rare in this context. The authors report the first case of spontaneous esophageal rupture occurring in a chronic renal failure patient treated by continuous ambulatory peritoneal dialysis. In this observation, sclerodermal esophageal dyskinesia, chronic renal failure which is a classical cause of vomiting and the peritoneal dialysis which play an increasing role in the intraabdominal pressure are potential contributing factors to Boerhave's syndrome. In such patients presenting risk factors, even if they are asymptomatic, it seems reasonable to propose esophageal explorations with manometry or/and endoscopy looking for dyskinesia or other complications of gastro-esophageal reflux.

Cardiovascular morbidity and mortality in hemodialyzed patients are increased due to the frequently abnormal lipid metabolism. It has been reported that this abnormal lipid metabolism could be partially corrected by some highly permeable membranes, such as polysulfone or cellulose triacetate. We investigated the influence of 4 months of dialysis with a polyamide membrane upon the course of lipid parameters in 6 patients presenting a hypertriglyceridemia2 mmol/l while on bicarbonate dialysis with a cellulose membrane. Lipid parameters improved after 4 months of hemodialysis with a polyamide membrane. Serum triglyceride and cholesterol levels decreased, while HDL cholesterol and HDL levels rose significantly (p0.05). Apolipoprotein B decreased significantly (p0.05). Following heparin administration, lipoprotein lipase activity improved (p0.02), associated with a decrease apolipoprotein C3 (p0.05). The fractional clearance rate of triglycerides rose significantly (p0.01). The use of highly permeable polyamide membranes results in a significant improvement in lipid disturbances of dialysis patients due to an increased lipoprotein lipase activity, induced perhaps by the removal of circulating inhibitors such as apolipoprotein C3.

In eight patients remaining acidotic after more than 1 year of bicarbonate haemodialysis, we studied the effect of correcting the chronic metabolic acidosis using acetate-free biofiltration for 4 months on the course of secondary hyperparathyroidism. An AN69 capillary membrane was employed with a bicarbonate infusion rate initially set at 1.8 l/h in all patients and then adjusted in each one to obtain a predialysis bicarbonate of ≥23 mmol/l. Standard blood chemistry parameters were determined every 2 weeks. Measurements of PTH, calcifediol and calcitriol, as well as calcium-PTH curves were determined at the beginning and end of the study. While acetate-free biofiltration appears to be an adequate technique for the correction of chronic metabolic acidosis when bicarbonate dialysis fails, this study indicates that it does not influence secondary hyperparathyroidism in haemodialysed patients. The level of intact PTH did not vary significantly and the calcium-PTH curves at 0 and 4 months were superimposable with no significant differences in the set point and the slope of the curves.

A significant percentage of dialysed patients have inadequate protein intake. One strategy for treating the protein malnutrition in peritoneal dialysis patients is to replace glucose in the dialysis solution by amino acids. A new peritoneal dialysis solution containing 1.1% amino acids in a formulation optimized for renal patients and with a lactate concentration of 40 mmol/l has been evaluated. Fifteen CAPD patients completed a non-randomized prospective 3-month study. Each patient received 2 litres of the optimised 1.1% amino acid solution for the second exchange of the day with a dwell time of 5-6 h. Indicators of efficacy were serum albumin and transferrin. After 3 months of intraperitoneal amino acids, serum albumin levels significantly increased from 32.7 +/- 2.3 to 35.1 +/- 2.2 g/l (mean +/- SD; P < 0.01). This occurred in parallel with a significant increase in transferrin levels from 2.21 +/- 0.26 to 2.39 +/- 0.27 g/l (P < 0.05). As expected, urea rose from 23.7 +/- 6.8 to 29.9 +/- 9.4 mmol/l. Interestingly bicarbonate did not change (25.5 +/- 4.2 versus 25.2 +/- 3.3 mmol/l). These results suggest that the optimized formulation is effective in improving nutritional parameters in CAPD patients while avoiding unwanted side-effects such as acidosis.