Progression of skin autofluorescence of AGEs over 4 years in patients with type 1 diabetes.

BACKGROUND: The deposit of advanced glycation end-products is involved in diabetic complications. It can be evaluated by measuring the skin autofluorescence (sAF). We searched whether sAF progressed over 4 years in type 1 diabetes and analysed its relationship with the development of nephropathy. METHODS: Two measurements of skin autofluorescence (sAF) were completed on 154 patients during years 2009 and 2013. Baseline factors associated with the progression of sAF were analysed by multivariate regression analysis. The relations among sAF progression, microalbuminuria, and impaired estimated glomerular filtration rate (eGFR) were analysed by logistic regression analysis. RESULTS: The patients were 51 ± 16 years old, with duration of diabetes of 23 ± 13 years, HbA1c: 7.7 ± 1.0%, 20.7% were treated by continuous subcutaneous insulin infusion (CSII). The sAF progressed by +18.1% over 4 years. Two interacting (P = .04) variables were associated with the later progression of sAF: mildly impaired eGFR and treatment by CSII. The patients with mildly impaired eGFR had the highest progression of sAF (+11.5% P = .01). Continuous subcutaneous insulin infusion was associated with a reduced progression of sAF in patients without kidney impairment (ß = -7.2%, P = .01). A +10% progression of sAF during the follow-up was associated with more microalbuminuria: OR = 1.45, P = .02, and more mildly impaired eGFR (<90 mL/min/1.73 m2 ): OR 1.22, P = .03 at 4 years of follow-up. CONCLUSIONS: The skin autofluorescence of advanced glycation end-products progresses in patients with type 1 diabetes, more if they have diabetic nephropathy, less if they are treated by continuous subcutaneous insulin infusion. This progression is associated with the development of nephropathy.

Skin autofluorescence predicts cardio-renal outcome in type 1 diabetes: a longitudinal study.

BACKGROUND: We aimed to analyze the relationships between skin autofluorescence (SAF) and incident macrovascular events and renal impairment after 4 years of follow-up in patients with type 1 diabetes (T1D). METHODS: Two hundred and forty-three patients (51.2 ± 16.7 years old) with T1D participated. SAF was measured by AGE-Reader-TM at inclusion. Macrovascular events (MVE), estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER) were recorded then and 4 years later. Multivariate logistic regression was used to analyze the relationships between SAF and incident MVE and renal profile 4 years later. RESULTS: Patients with incident MVE had a higher SAF (p = 0.003). SAF predicted incident MVE after adjustment for age, sex, body mass index, tobacco, diabetes duration, hypertension, HbA1c, AER, eGFR (OR 4.84 [95 % CI 1.31-17.89], p = 0.018). However, this relation was no longer significant after adjustment for history of MVE. An inverse relation was found between SAF and incident eGFR (p = 0.0001). Patients with incident eGFR <60 ml/min/1.73 m(2) had a SAF higher than patients with normal eGFR. After adjustment for the previous criteria, SAF remained associated with the risk of impaired incident eGFR (OR 7.42 [95 % CI 1.59-34.65], p = 0.018). No relation was found between SAF and increased AER 4 years later. CONCLUSIONS: SAF predicts MVE in patients with T1D, adjusted for cardiovascular risk factors but the most powerful predictive factor remains history of MVE. SAF also predicts eGFR impairment, adjusted for initial AER and renal function. SAF could be a useful non-invasive tool for estimating risk of cardiovascular or renal impairment in patients with T1D.

High Risk of Acute Kidney Failure in Kidney Transplant Recipients Early after Bariatric Surgery.

Bariatric surgery is routinely proposed to patients suffering from obesity including kidney transplant recipients. In this specific population, bariatric surgery has a positive impact in long-term outcomes in terms of patient and graft survival. We report here the cases of 4 patients with five post-kidney transplantation bariatric surgeries who experimented acute renal injury early after surgery. Creatinine rising occurred between day 14 and day 20 after surgery. In all cases, it was due to dehydration leading to a pre-renal acute renal failure. The specific care of kidney transplanted patients is discussed: single kidney associated with pre-existing altered kidney function associated with concomitant use of nephrotoxic drugs. Specific education intervention before surgery associated with careful early management of hydration after surgery is mandatory for these patients.

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, 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 (TBW). 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 is needed to guide medical treatment of patients with extreme obesity and MLL.

Long-Term Results After Bariatric Surgery in Super-Super-Obese Patients.

Introduction: Despite addressing to high risk population, we can propose laparoscopic bariatric surgery to super-super-obese (SSO) patients (body mass index [BMI] ≥60 kg/m2). The aim of this study was to report our experience in terms of weight loss and improvement of medical comorbidities after a follow-up of 5 years in the SSO population who underwent different bariatric procedures. Methods: This retrospective study includes all SSO patients who underwent bariatric surgery (sleeve gastrectomy [SG] and/or gastric bypass) between 2006 and 2017. The population was divided in three groups (SG alone; Roux-en-Y gastric bypass [RYGB] alone and SG+RYGB). The rate of complication and the weight-loss results were analyzed. Results: Among 43 patients who underwent surgery, the mean age was 42[31-54]. There were more women (72%) with the mean preoperative BMI of 64.9 kg/m2 [59.6-70.1]. There were 9 SGs, 26 RYGB, and 8 SG revised to gastric bypass (SG+RYGB) after a median delay of 23.5 months [16.5-32]. The perioperative complication rate was 25%, and there was 1 postoperative death. The median follow-up was 69 months [1-128]. The mean percentage of excess weight loss (%EWL) was 39.2% [18.2-60.3] after 5 years. For the SG group, the %EWL was inferior -27.1 [-3.6 to 57.8], but with no significant difference. An improvement of comorbidities' rate was recorded in all groups of patients. Conclusion: Bariatric surgery in SSO patients leads to an improvement of comorbidities even if the weight-loss results, especially in the SG group, are less favorable. The two steps approach should be re-evaluated by shortening the interval between. Other surgical strategies than RYGB are needed to be evaluated to improve long-term weight loss.

A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery.

Mutations in genes encoding proteins located in the leptin/melanocortin pathway have been identified in the rare cases of genetic obesities. Heterozygous variants of MRAP2, encoding a G coupled-protein receptor accessory protein implicated in energy control notably via the melanocortin-4 receptor, have been recently identified. A 24-year-old patient with early-onset severe obesity (body mass index [BMI]: 64 kg/m2) associated with hypertension, respiratory complications, nonalcoholic fatty liver disease, and type 2 diabetes was referred to our department. Sleeve gastrectomy was successful. A new heterozygous variant in MRAP2 (NM_138409.4: c.154G>C/p.G52R) variant was identified in the patient DNA. Functional assessment confirmed that this new variant was pathogenic. We report a new pathogenic loss-of-function mutation in MRAP2 in a patient suffering from a severe multicomplicated obesity. This confirms the metabolic phenotype in patients with this monogenic form of obesity. Longer follow-up will be necessary. Our finding will allow a personalized medicine.

Long-term changes in body image after bariatric surgery: An observational cohort study.

BACKGROUND: While body image improves in the first few months after surgery, data on long-term changes in body image after bariatric surgery are scarce and contradictory. METHODS: We assessed body image through the Stunkard Figure Rating Scale and the Multidimensional Body-Self Relations Questionnaire-Appearance Scale, which measures appearance evaluation and orientation, overweight preoccupation, and self-classified weight. Surveys were conducted before surgery and at regular intervals until 5 years after bariatric surgery. RESULTS: 61 patients were included in the study. No patients were lost to follow-up until 18 months after bariatric surgery. At 5 years, there were 21 patients (34%) lost to follow-up. We detected an overall improvement in body image until 12-18 months post-surgery. Scores declined after 5 years post-surgery but were still higher than preoperative evaluations. Overweight preoccupation did not change throughout the follow-up period. There was a positive correlation between body weight lost and appearance evaluation. There was also a positive correlation between weight loss and the Body Areas Satisfaction Scale. There was a negative correlation between weight loss and overweight preoccupation. Appearance orientation and self-classified weight were not correlated with weight loss. CONCLUSIONS: Body image improved after bariatric surgery but was not maintained for all 5 years after surgery.

Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing's disease in remission.

Context: Impaired cognition and altered quality of life (QoL) may persist despite long-term remission of Cushing's disease (CD). Persistent comorbidities and treatment modalities may account for cognitive impairments. Therefore, the role of hypercortisolism per se on cognitive sequelae remains debatable. Objective: To investigate whether memory and QoL are impaired after long-term remission of CD in patients with no confounding comorbidity. Design and Setting: Cross-sectional case-control study in two tertiary referral centers. Patients: 25 patients (44.5 ± 2.4 years) in remission from CD for 102.7 ± 19.3 Mo and 25 well-matched controls, without comorbidity or treatment liable to impair cognition. Main Outcome Measures: Hippocampus- and prefrontal cortex-dependent memory, including memory flexibility and working memory, were investigated using multiple tests including sensitive locally-developed computerized tasks. Depression and anxiety were evaluated with the MADRS and HADS questionnaires. QoL was evaluated with the SF-36 and CushingQoL questionnaires. The intensity of CD was assessed using mean urinary free cortisol and a score for clinical symptoms. Results: CD patients displayed similar performance to controls in all cognitive tests. In contrast, despite the absence of depression and a minimal residual clinical Cushing score, patients had worse QoL. Most of the SF36 subscales and the CushingQoL score were negatively associated only with the duration of exposure to hypercortisolism (p≤ 0.01 to 0.001). Conclusions: Persistent comorbidities can be a primary cause of long-lasting cognitive impairment and should be actively treated. Persistently altered QoL may reflect irreversible effects of hypercortisolism, highlighting the need to reduce its duration. Clinical Trial Registration number: https://clinicaltrials.gov, identifier NCT02603653.

Oral Hydration, Food Intake, and Nutritional Status Before and After Bariatric Surgery.

BACKGROUND AND AIMS: Bariatric surgery is considered to be the most effective treatment of morbid obesity. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are the most popular procedures. We evaluated nutritional status, micro- and macronutrient intake, and oral hydration in patients before and regularly during 1 year after RYGBP and SG. METHODS: All patients that had been through bariatric surgery with at least 1-year post-surgery were retrospectively included in the study. All participants were evaluated once during the 2 months before the surgery and at 1, 3, 6, and 12 months after surgery. Clinical and biological evaluations as well as dietary investigations were performed. RESULTS: Fifty-seven patients were included in this study (28 RYGBP and 29 SG). Patients in the RYGBP group had significantly higher body weight (132.3 ± 22 versus 122.2 ± 22.2 kg, p = 0.039) than patients in the SG group. Before surgery, total energy intake, oral hydration, and vitamin and mineral intakes were not different between the two groups. RYGBP and SG induced significant similar excess weight loss 1 year after surgery, 48.6 29.8% and 57.6 27.6% of body weight respectively. Energy intake significantly decreased 1 month after surgery and slightly increased from 1 to 12 months without reaching baseline intake levels. Macronutrient repartition did not change during follow-up. Oral hydration significantly decreased after RYGBP (- 58%) and showed a trend to be decreased after SG (- 49%). Sixty-five percent of patients still had vitamin D deficiency 1 year after surgery. Whatever the type of surgery, more than 20% had some vitamin deficiency 1 month after surgery. CONCLUSIONS: Calories intake decreases after bariatric surgery, whatever the type of procedure. In addition, the prevalence of vitamin deficiency is high after bariatric surgery. Lastly, oral hydration is importantly decreased after bariatric surgery, especially after RYGBP.

Lifestyle intervention program in deprived obese adult patients and their non-deprived counterparts.

INTRODUCTION: Although it is known that the prevalence of obesity is high in deprived patients, the link between deprivation and obesity, and the impact of deprivation on compliance and efficacy of a lifestyle intervention program are not known. MATERIALS AND METHODS: Deprivation was assessed in 40 patients (23 Females, mean±SD age: 49±17 years) from the diabetology department and 140 patients (101 Females, age: 50±15 years) from the nutrition department of Bordeaux University hospital. Eighty-seven patients suffering from obesity were evaluated before and after a tailored, multidisciplinary lifestyle intervention. Deprivation was assessed using EPICES scores. Deprivation was defined with an EPICES score > 30. RESULTS: Deprived patients suffering from obesity had significantly higher current (43.8 ±8.4 versus 40.9 ± 5.5 kg/m2, p = 0,02) and maximal BMI (46.1± 8.6 versus 42.3± 5.2 kg/m2, p = 0.002) compared to non-deprived obese. Percentage of body weight loss was not different according to deprivation (4.74 ± 0.75 versus 4.65 ± 1.04%, p = 0.9). EPICES scores were not different according to adherence to lifestyle intervention program (20.5 ± 8.5 versus 29.9 ± 3.9 versus 29.0 ±2.5, no follow up versus partial follow up versus total follow up, p = 0,58). CONCLUSION: Deprived patients suffering from obesity have a more serious disease than non-deprived patients. However, neither compliance to the lifestyle intervention program nor body weight loss differed between deprived patients with obesity and non-deprived ones. Deprivation should not be a limitation when enrolling patients with obesity in lifestyle intervention programs.

Skin autofluorescence, renal insufficiency and retinopathy in patients with type 2 diabetes.

OBJECTIVES: Advanced glycation end-products (AGEs) are involved in diabetic retinopathy (DR). Their accumulation in tissues can be analyzed by measuring the skin autofluorescence (sAF). We hypothesized that renal insufficiency, another cause of high sAF, may disturb the relation between sAF and DR. RESEARCH DESIGN AND METHODS: We measured sAF with an AGE-Reader in 444 patients with type 2 diabetes (T2D), and we analyzed their retinal status. The associations of sAF with DR, and interaction with renal insufficiency were estimated by multivariate logistic regression analysis. RESULTS: Mean age was 62years (standard deviation (SD) 10years), diabetes duration 13 (9) years and mean HbA1C 8.9% (1.8). The prevalence of DR was 21.4% and increased with age, diabetes duration, arterial hypertension, renal parameters (serum creatinine and albumin excretion rates), and sAF. The prevalence of macular edema (ME) was 8.6% and increased with the duration of diabetes, but not with sAF (p=0.11). There was a significant interaction between renal insufficiency and sAF for the relation with DR or ME (p=0.02). For the 83% patients without renal insufficiency (estimated GFR>60mL/min/1.73m2), sAF was related to DR or ME after multivariate adjustment: OR 1.87 (1.09-3.19). The 17% patients with renal insufficiency had the highest rates of DR or ME (38.6%) and the highest sAF, unrelated to each other. CONCLUSIONS: In T2D patients with renal insufficiency, the high sAF does not relate to retinopathy, which should be systematically searched due to its high frequency. For other patients, a high sAF argues for DR screening.