Semaglutide Treatment in a Patient with Extreme Obesity and Massive Lymphedema: A Case Report.

INTRODUCTION: Extreme obesity (BMI ≥50 kg/m2) is a complex pathology to treat. One of the complications of extreme obesity is massive localized lymphedema (MLL), due to compromised lymphatic drainage. There is a lack of literature guiding the medical management of these conditions. CASE PRESENTATION: We present a 43-year-old male who was admitted to our specialized obesity center for weight management. His initial weight was 255 kg and BMI was 93.7 kg/m2. He suffered from massive multifocal lymphedema of his left leg. He was bedridden due to his condition and malnourished, as shown by multiple vitamin deficiencies. The patient received care from our multidisciplinary team including nurses, dieticians, physical therapists, and psychologists. Treatment with semaglutide was started in hospital and continued at home. The maximal dose used was 1 mg/week but decreased during follow-up to 0.25 mg/week to avoid malnutrition. Protein and nutritional supplements were added. At 28 weeks of therapy, the patient had lost 40 kg or 15.7% of his total body weight. His lymphedema decreased; he had lost at least 16 cm of his left thigh circumference. He was able to walk again and regain autonomy of his daily activities of living. CONCLUSION: Semaglutide can be effective in patients with extreme obesity, with the support of a multidisciplinary team in a specialized obesity center. It can also help decrease MLL. More data are needed to guide medical treatment of patients with extreme obesity and MLL.

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.

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. [...].

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.

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.

Cardiovascular events after a dramatic reduction of HbA1c in hospitalized subjects with type 2 diabetes and high long-term glucose exposure.

OBJECTIVE: 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). RESEARCH DESIGN AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.