Increased risk of renal events in people with diabetic foot disease: A longitudinal observational study.

OBJECTIVE: Diabetic kidney disease favors diabetic foot ulcers, however we do not know whether the reverse relation exists. We investigated whether diabetic foot disease (DFD) related to an increased risk of developing renal events. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis of a cohort of patients hospitalized for type 2 diabetes mellitus (T2DM) between 2009 and 2017, stratified for the risk of diabetic foot ulcer grades 0 (no risk), 1 and 2 (at risk), and 3 (DFD) according to the International Work Group on Diabetic Foot (IWGDF) classification. We highlighted new renal events (end-stage renal disease or a doubling of serum creatinine) in their medical records until December 2020. The relationship between DFD and later renal events was analyzed by multivariable Cox regression model. RESULTS: Among 519 patients, 142 (27 %) had a DFD at baseline, and 159 (30 %) were classified as Grades 1 or 2. Thirty-six renal events occurred during the 54 ± 27 months of follow-up: 19 subjects started dialysis, 1 had a renal transplantation, and 16 had a doubling of serum creatinine: 15 each in subjects with DFD and subjects at risk, versus 6 in subjects with Grade 0 DFD (logrank: P = 0.001). Adjusted for i) age and sex; ii) hyperglycemic exposure; iii) conventional cardiovascular risk factors; iv) renal parameters: and v) new diabetic foot ulcers during follow-up, DFD (HR 2.7 to 5.9) and being at risk of DFD Grades 1-2 (HR 2.8 to 5.1) were significantly related to new renal events. CONCLUSION: The risk of renal events was increased in people with T2DM and DFD.

More new cancers in type 2 diabetes with diabetic foot disease: A longitudinal observational study.

OBJECTIVE: Cancer has been proposed as the primary cause of death in type 2 diabetes (T2D). The life expectancy is reduced after a diabetic foot ulcer. We investigated whether Diabetic Foot Disease related to an increased risk of developing a new cancer. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis on a cohort of patients hospitalized for T2D between 2009 and 2017, stratified for the risk of diabetic foot ulcer (International Working Group on Diabetic Foot classification). We highlighted new cancers in their medical records until December 2020. The relationship between Diabetic Foot Disease and later cancers was analyzed by multivariable Cox regression and survival curves were compared. RESULTS: Among 519 patients, 27% had a Diabetic Foot Disease, and 159 were classified as grades 1 or 2 (at risk). As compared to the 218 patients graded 0 according to the IWGDF, they were more men, older, with a longer duration of diabetes, more vascular complications, a greater incidence of insulin use, and a higher skin autofluorescence. During the 54 months of follow-up, 63 (12.1%) new cancers were diagnosed. Baseline Diabetic Foot Disease was significantly associated with a higher risk of cancer (multivariable adjusted Hazard ratio: 2.08, 95%CI: 1.02-4.25), whereas the relation was not significant for subjects at risk of DFU (HR: 1.65, 95%CI:0.81-3.35) CONCLUSION: The risk of cancer was increased twofold in T2D with Diabetic Foot Disease.

The skin autofluorescence of advanced glycation end-products relates to the development of foot ulcers in type 2 diabetes: A longitudinal observational study.

OBJECTIVES: The long-term glycemic memory contributes to vascular complications in type 2 diabetes, including those patients with Diabetic Foot Ulcers (DFU). We investigated whether the skin autofluorescence (SAF) of Advanced Glycation End-products related to later DFUs. RESEARCH DESIGN & METHODS: SAF was measured with an AGE-Reader in a retrospective cohort of patients hospitalized from 2009 to 2017 for Type 2 Diabetes. New DFUs were registered until the year 2020 and survival analyses were performed. RESULTS: The 517 patients (men: 58.0 %), were 62 ± 9 years old at baseline, with a duration of diabetes of 14 ± 10 years, HbA1c: 8.7 ± 1.8 %, complications included 33.8 % macroangiopathies, 44.9 % diabetic kidney diseases and 26.7 % retinopathies. According to the IWGDF classification, the grades of risk for DFU were 0 for 43.2 %, 1 for 23.9 %, 2 for 7.2 %, and 3 for 25.7 %. During the 53 months of follow-up, 58 new DFUs occurred, mostly in patients with SAF higher than its median value (2.65 AU). Adjusted for age and sex, conventional risk factors (duration and control of diabetes, arterial hypertension, dyslipidemia, smoking), and other complications (macroangiopathy, diabetic kidney disease, retinopathy), SAF related to later DFUs. Adjusted for the IWGDF classification, SAF related to new DFUs (HR: 1.81, 95%CI:1.25-2.62). This relationship was significant for the 403 subjects without previous history of DFU (HR: 2.32, 95%CI: 1.36-3.95). SAF did not predict recurrence for patients with a previous history of DFUs. CONCLUSION: SAF, a simple non-invasive marker of glycemic memory, independently predicts the occurrence of a first foot ulcer in patients with Type 2 Diabetes.

Albuminuric diabetic kidney disease predicts foot ulcers in type 2 diabetes.

Diabetic Foot Ulcers (DFU) are feared among individuals with diabetic kidney disease (DKD), but it is unclear whether they are more frequent, especially in normoalbuminuric DKD. Five hundred and twenty patients admitted in our diabetology ward from 2007 to 2017 were followed up during 54 ±â€¯26 months. New DFUs were registered, and their relationship with the initial renal status was analyzed by LogRank and multivariate Cox regression analysis. The 520 subjects were mainly men (57.9 %), 62 ±â€¯9 years old, with a duration of diabetes of 14 ±â€¯10 years, HbA1c: 8.7 ±â€¯1.8 % (72 ±â€¯19 mmol/mol), and complications: 33.7 % macroangiopathies, 22.1 % previous foot ulcers, 44.8 % DKD, 26.9 % retinopathies. Fifty-seven new DFU occurred, mainly in subjects with DKD. DKD was related to later DFU (HR: 1.79; 95%CI: 1.05-3.07), this relationship stayed significant adjusted for age, gender, and a history of previous DFU (HR: 3.61; 95%CI: 2.11-6.18), and further adjusted for the duration of diabetes, HbA1c, BMI, arterial hypertension, and dyslipidemia. Among the 233 subjects with DKD, 129 (55.3 %) had an isolated AER > 30 mg/24H, 41 (17.6 %) had an isolated eGFR<60 mL/min/1.73 m2, and 63 (27.0 %) cumulated both abnormalities. By Cox regression analysis adjusted for age and gender, albuminuric DKDs were related to later DFU: with eGFR≥60: HR: 1.91; 95%CI: 1.02-3.59, with eGFR<60: HR: 2.53; 95%CI: 1.25-5.10, whereas normoalbuminuric DKD was not: HR: 1.04; 95%CI: 0.35-3.07, despite similar rates of neuropathies, peripheral arterial diseases, and retinopathies. In people with type 2 diabetes, albuminuric DKD was associated with two to three folds increased risk of DFUs, whereas normoalbuminuric DKD was not.

Diabetic retinopathy relates to the incidence of foot ulcers and amputations in type 2 diabetes.

AIMS: We investigated whether Diabetic Retinopathy (DR) is related to Diabetic Foot Ulcer (DFU) development, adjusted for the stratification of the International Work Group on Diabetic Foot (IWGDF) guidance. MATERIALS AND METHODS: DR and IWGDF stratification was registered retrospectively in patients hospitalised from 2009 to 2017 for uncontrolled and/or complicated type 2 diabetes. New DFUs were registered until 2020. Survival analyses categorised the subjects for DR, and multivariate Cox regression adjusted for confounders. RESULTS: 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 (Inter Quartile Range: 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, and dyslipidemia), and other complications (macroangiopathy and diabetic kidney disease), DR was associated with a greater incidence of DFUs. Adjusted for the IWGDF classification, DR was related to new DFUs (HR: 2.51, 95%Confidence Interval [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). CONCLUSIONS: Diabetic retinopathy independently relates to the incidence of foot ulcers and amputations in patients hospitalised for type 2 diabetes.

For diabetic type 1 patients, the skin autofluorescence predicts ulcers and amputations.

We searched whether the accumulation of Advanced Glycation End-products (AGEs), reflected by the skin autofluorescence (SAF), could predict diabetic foot ulcers (DFUs) during the long-term follow-up of people with type 1 diabetes. During year 2009, we measured the SAF with an AGE-Reader in 206 subjects with type 1 diabetes. DFU and amputations were registered during the 10 following years. The relation between the SAF and later DFU was analyzed by Cox model regression, adjusted for vascular risk factors. The 206 participants were mainly men (55.8%), 51 ±â€¯15 years old, with a 22 ±â€¯13 years diabetes duration. Twelve subjects presented a DFU. Their SAF were higher: 2.61 ±â€¯0.89 AU vs 2.11 ±â€¯0.53 for the others (p = 0.003), related to the risk of DFU (OR:3.69; 95% CI: 1.06-12.79) after adjustment for age, gender, diabetes duration, initial HbA1c, arterial hypertension, history of smoking, blood lipids and use of a statin. Five subjects were amputated, also related to the initial SAF: OR: 11.28 (95% CI: 1.76-79.97) after adjustment for age, gender, duration of diabetes, and HbA1c. The SAF has already been related to diabetic neuropathy and peripheral arterial disease. It predicts DFU in type 1 diabetes, which suggests that AGEs play a role in this highly specific and feared complication.