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.

Trial of Lixisenatide in Early Parkinson's Disease.

BACKGROUND: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in persons with Parkinson's disease. Participants in whom Parkinson's disease was diagnosed less than 3 years earlier, who were receiving a stable dose of medications to treat symptoms, and who did not have motor complications were randomly assigned in a 1:1 ratio to daily subcutaneous lixisenatide or placebo for 12 months, followed by a 2-month washout period. The primary end point was the change from baseline in scores on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (range, 0 to 132, with higher scores indicating greater motor disability), which was assessed in patients in the on-medication state at 12 months. Secondary end points included other MDS-UPDRS subscores at 6, 12, and 14 months and doses of levodopa equivalent. RESULTS: A total of 156 persons were enrolled, with 78 assigned to each group. MDS-UPDRS part III scores at baseline were approximately 15 in both groups. At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P = 0.007). At 14 months, after a 2-month washout period, the mean MDS-UPDRS motor scores in the off-medication state were 17.7 (95% CI, 15.7 to 19.7) with lixisenatide and 20.6 (95% CI, 18.5 to 22.8) with placebo. Other results relative to the secondary end points did not differ substantially between the groups. Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%. CONCLUSIONS: In participants with early Parkinson's disease, lixisenatide therapy resulted in less progression of motor disability than placebo at 12 months in a phase 2 trial but was associated with gastrointestinal side effects. Longer and larger trials are needed to determine the effects and safety of lixisenatide in persons with Parkinson's disease. (Funded by the French Ministry of Health and others; LIXIPARK ClinicalTrials.gov number, NCT03439943.).

Skin autofluorescence of advanced glycation end-products relates to new cardiovascular events in type 2 diabetes: A longitudinal observational study.

BACKGROUND: Cardiovascular disease is frequent in type 2 diabetes mellitus (T2DM). We investigated the relationship between skin autofluorescence (SAF) of advanced glycation end-products and later cardiovascular events (CVEs) in patients with T2DM. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis of 504 patients hospitalized for uncontrolled and/or complicated T2DM between 2009 and 2017. SAF was measured using an AGE-Reader. Participants were followed up from admission to December 2020, for the onset of a CVE (myocardial infarction, stroke, revascularization procedures or cardiovascular death). The relationship between SAF and CVE was analyzed by multivariable Cox regression. Log-rank curves were used to compare CVE-free survival in patients whose SAF at admission was above versus below the whole-population median. The analysis was repeated in subjects without/with macroangiopathy (defined as myocardial infarction, stroke, peripheral revascularization) at baseline. FINDINGS: During 54 months of follow-up, 69 (13.7%) patients had a CVE. Baseline SAF was significantly higher in patients with T2DM who later experienced a CVE (2.89 ± 0.70 arbitrary units versus 2.64 ± 0.62 in others, P = 0.002). This relationship was significant after adjusting for age, sex, conventional risk factors (diabetes duration, HbA1c, arterial hypertension, dyslipidemia, smoking, body mass index), vascular complications, C-reactive protein, and treatments for diabetes. The CVE-free survival curves differed between subjects whose SAF was above the whole-population median (log-rank: P = 0.002) and those whose SAF was above the macroangiopathy-free sub-population median (log-rank: P = 0.016). CONCLUSION: SAF of advanced glycation end-products was related to a higher incidence of later CVE in patients with T2DM.

The skin autofluorescence may help to select patients with Type 2 diabetes candidates for screening to revascularization procedures.

Chen et al. recently related the skin autofluorescence (SAF) of Advanced Glycation End-products to subclinical cardiovascular disease in the 3001 participants from the general population (Rotterdam study), with a particularly close relationship for the 413 subjects with diabetes. Because conventional vascular risk factors do not capture the risk in diabetes very well, this relationship may help to select high-risk individuals for the screening of silent myocardial ischemia, which has yet to prove its benefit in randomized controlled trials. Among 477 patients with uncontrolled and/or complicated Type 2 Diabetes, we measured the SAF ten years ago, and we registered new revascularizations during a 54-months follow-up. The patients with SAF > 2.6 Arbitrary units (AUs), the median population value, experienced more revascularizations of the coronary (17/24) and lower-limb arteries (13/17) than patients with a lower SAF, adjusted for age, sex, diabetes duration, vascular complications, and smoking habits: HR 2.17 (95% CI: 1.05-4.48), p = 0.035. The SAF has already been reported to predict cardiovascular events in three cohorts of people with diabetes. We suggest that its measurement may help to improve the performance of the screening before vascular explorations and revascularizations.

Comment on Peker, T.; Boyraz, B. The Relationship between Resistant Hypertension and Advanced Glycation End-Product Levels Measured Using the Skin Autofluorescence Method: A Case-Control Study. J. Clin. Med. 2023, 12, 6606.

We read with interest the recent article by Peker et al. [...].