Semaglutide as a potential treatment for obesity in Smith-Kingsmore syndrome (SKS) patients: A mosaic mutation case report.

We present for the first-time efficacy and tolerability of GLP-1-RA (Semaglutide) in Smith-Kingsmore syndrome (SKS). SKS is a rare genetic disorder characterized by intellectual disability, macrocephaly, seizures and distinctive facial features due to MTOR gene mutation. We present a 22-year-old woman with mosaic SKS and severe obesity (Body Mass Index ≥40 kg/m²), treated with semaglutide. She achieved a 9 kg (7.44%) weight loss over 12 months without adverse effects.This case highlights semaglutide's potential in managing obesity in SKS patients, emphasizing the need for further research in this rare genetic disorder.

Semaglutide 2.4 mg/wk for weight loss in patients with severe obesity and with or without a history of bariatric surgery.

OBJECTIVE: This retrospective cohort study aimed to assess the effectiveness of semaglutide 2.4 mg in patients with severe obesity (BMI ≥ 40 kg/m2 ) who had previously undergone bariatric surgery (BS) but failed to achieve satisfactory weight loss or experienced weight regain compared with patients without a history of BS with similar BMI. METHODS: The authors analyzed data from 129 patients with a BMI ≥ 40 kg/m2 , including 39 with (BS+) and 90 without (BS-) a history of BS. The patients received semaglutide treatment for 24 weeks starting at 0.25 mg/wk and gradually increasing to reach a final dose of 2.4 mg/wk. The treatment outcomes were assessed based on the percentage of weight loss, changes in BMI, and waist circumference. RESULTS: Semaglutide treatment resulted in significant 9.1% weight loss in the BS+ group, with no significant difference in weight loss between the BS+ and BS- groups. CONCLUSIONS: This study is the first, to the authors' knowledge, to compare the effectiveness of semaglutide treatment in patients with versus those without a history of BS, providing valuable evidence of its efficacy. By focusing on individuals with severe obesity (BMI > 40 kg/m2 and associated comorbidities), it fills a gap in the current literature and highlights the potential of semaglutide 2.4 mg as a treatment option for this specific population.

Renal function is highly associated with podiatric risk in diabetic patients.

Background: Chronic kidney disease (CKD) is correlated with the incidence of diabetic foot ulcer (DFU). Furthermore, the International Working Group on the Diabetic Foot (IWGDF) has proposed a classification of the risk factors for DFU. The purpose of this study was to investigate the relationship between the IWGDF risk classification and the glomerular filtration rate level estimated by the CKD Epidemiology Collaboration formula (eGFR). Methods: We conducted a prospective multicentric study. Patients were recruited from either diabetology or nephrology departments. The secondary objectives were to determine this relationship after excluding people on dialysis and to identify the factors associated with podiatric risk. Results: Four hundred and eighty-six patients were included, with a mean age of 64.2 years (±15.7) and a mean diabetes duration of 15.7 years (±12.1). Based on the IWGDF classification, 53.5% of the population were in podiatric stage 0, 11.7% in stage 1 and 34.8% in stage 2 or 3. The mean eGFR level was significantly lower in patients with podiatric risk ≥2 (36.8 ± 33.9 mL/min/1.73 m2 vs 71.9 ± 35.3 mL/min/1.73 m2, P < .0001) and a significant association was found between the eGFR and the podiatric risk. This association remained significant after the exclusion of the hemodialysis patients. After receiver operating characteristic analysis, a cutoff of 45 ± 11 mL/min/1.73 m2 (area under the curve 0.76) was found discriminant to define a group of CKD patients at higher risk for podiatric stage ≥2. Conclusion: eGFR levels are linked to podiatric stages in diabetes mellitus. Patients with eGFR <45 mL/min/1.73 m2 and dialysis patients should be carefully managed in collaboration with diabetic foot specialized centers.

Use of the SINBAD score as a predicting tool for major adverse foot events in patients with diabetic foot ulcer: A French multicentre study.

OBJECTIVE: To assess the relationship between the site, ischaemia, neuropathy, bacterial infection, area, depth (SINBAD) score and major adverse foot events in patients with diabetes and foot ulcers. METHODS: For this retrospective ancillary study, patients (n = 537) followed for a diabetic foot ulcer (DFU) in six French hospitals were included between 1 February 2019 and 17 March 2019, and between 1 February 2020 and 17 March 2020. The SINBAD score was assessed at inclusion. The frequency of a composite outcome consisting of eight major adverse foot events (MAFE) was assessed after 5-6 months of follow-up: hospitalisation for DFU, septic surgery, revascularisation, minor amputation, major amputation, death, secondary infection and ulcer recurrence. A logistical regression explored the link between the SINBAD score and MAFE and each of its component. RESULTS: A low SINBAD score (from 0 to 3) was observed in 61% of patients and a high (from 4 to 6) in 39%. MAFE occurred in, respectively, 24% and 28% of these patients. Multivariate analyses showed a significant relationship between the SINBAD score and MAFE, with the continuous SINBAD score: odds ratio (OR) 1.72 [95% CI (1.51-1.97)] or dichotomic SINBAD score (values: 0-3 and 4-6): OR 3.71 [95% CI (2.54-5.42)]. The SINBAD score (continuous or dichotomic) at inclusion was also significantly associated with six out of the eight components of the MAFE. CONCLUSIONS: The SINBAD score is a useful tool for predicting major adverse foot events.

Medication Errors at Hospital Admission and Discharge: Risk Factors and Impact of Medication Reconciliation Process to Improve Healthcare.

OBJECTIVE: First, the aim of the study was to assess the prevalence, characteristics, and severity of unintended medication discrepancies (UMDs) and medication errors (MEs) at admission and discharge of hospitalization. Second, the aim of the study was to identify clinical and hospitalization factors associated with risk of UMDs as well as characteristics of the medication reconciliation process associated with UMDs detection. METHODS: This prospective observational study included all adult patients admitted from 2013 to 2015 in the Endocrinology-Diabetology-Nutrition Department of Montpellier Hospital, France. Clinical pharmacists conducted medication reconciliation by collecting the best possible medication history from different sources and comparing it with admission and discharge prescriptions to identify discrepancies. Unintended medication discrepancies corrected by the physician were considered as MEs. Risk factors of UMDs were identified with logistic regression. RESULTS: Of 904 patients included, 266 (29.4%) had at least one UMD, at admission or at discharge. In total, 378 (98.2%) of 385 UMDs were considered to be MEs. Most MEs were omissions (59.3%). Medication errors were serious or very serious in 36% of patients and had potentially moderate severity in almost 40% of patients. The risk of UMDs increased constantly with the number of treatments (P < 0.001). Thyroid (adjusted odds ratio [OR] = 1.79, 95% CI = 1.12-2.86) and infectious diseases (adjusted OR = 1.80, 95% CI = 1.17-2.78) were associated with UMDs risk at admission. The best type of source for the detection of UMDs was the general practitioner or nurse (OR = 2.64, 95% CI = 1.51-4.63). CONCLUSIONS: Unintended medication discrepancies are frequent at hospital and depend on intrinsic clinical parameters but also on practice of medication reconciliation process, such as number and type of sources used.

Comparison of a new versus standard removable offloading device in patients with neuropathic diabetic foot ulcers: a French national, multicentre, open-label randomized, controlled trial.

INTRODUCTION: The offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. Orthèse diabète is a new customized removable knee-high offloading device immobilizing foot and ankle joints, with some specific and innovative features that may improve offloading. We aimed to evaluate the efficiency of this device in DFU healing. RESEARCH, DESIGN AND METHODS: The evaluation of Offloading using a new removable ORTHOsis in DIABetic foot study is a French multicenter (13 centers) randomized controlled trial with blinded end points evaluation. Adults with neuropathic DFU were randomly assigned to either Orthèse Diabète (experimental device), or any type of conventional (usually used in France) removable offloading devices (control group). The primary outcome was the 3-month proportion of patients with fully healed DFU. RESULTS: Among 112 randomized patients (men 78%, age 62±10 years), the primary outcome occurred in 19 (33%) participants using conventional device vs 19 (35%) Orthèse Diabète users (p=0.79). Study groups were also comparable in terms of prespecified secondary end points including occurrence of new DFU (25% vs 27% in conventional and experimental groups), ipsilateral lower-limb amputation (4% vs 10%) or infectious complications (14% vs 13%) (p>0.05 for all). Adverse events were comparable between groups, including 4 deaths unrelated to study allocation (1 sudden death, 2 ventricular arrhythmias and 1 pancreatic cancer). Adverse events believed to be related to the device were higher in the Orthèse Diabète group than in the control group (15% vs 4%). Orthèse Diabète was less frequently worn than conventional devices (46% vs 66%, p=0.04). CONCLUSIONS: Orthèse Diabète, a new removable offloading orthosis immobilizing foot and ankle joints did not show superiority compared with conventional removable devices in neuropathic DFU healing and cannot be recommended to heal DFU. TRIAL REGISTRATION NUMBER: NCT01956162.

Intuitive eating is associated with weight loss after bariatric surgery in women.

BACKGROUND: Although the data on eating behavior after bariatric surgery are substantial, data on "intuitive eating" are lacking. OBJECTIVE: The aim of this study was to evaluate the link between intuitive eating and weight loss after bariatric surgery. METHODS: This cross-sectional study used a self-administered questionnaire freely available on social networks and targeted women who had undergone bariatric surgery. Intuitive eating was evaluated with the Intuitive Eating Scale-2 (IES-2). The 3 questionnaire subscores (Eating for Physical Rather than Emotional Reasons, Reliance on Hunger and Satiety Cues, and Unconditional Permission to Eat) were also analyzed. The relation between IES-2 scores and the relative variation in body mass index [BMI (in kg/m2)] was assessed with linear regression models. Adjusted ß (ßAdj) and standardized ß $( {{\rm{\beta }}_{{\rm{Adj}}}^{{\rm{STD}}}} )$ were reported. RESULTS: We analyzed the responses of 401 women with a mean age of 39 ± 11 y, a mean preoperative BMI of 45.5 ± 7.9, and a mean current BMI of 30.5 ± 7. The mean relative BMI loss was 32.7 ± 12.9%, and the mean IES-2 score was 3.3 ± 0.6. The total IES-2 score was associated with the relative BMI loss, with ∼2.6% BMI loss for each 1-point increase in the IES-2 score [PAdj = 0.007; ßAdj = -2.57 (95% CI: -4.44, -0.70); ${\rm{\beta }}_{{\rm{Adj}}}^{{\rm{STD}}}$= -0.12] after adjusting for elapsed time since surgery and type of surgery. Eating for Physical Rather than Emotional Reasons was the subscore most strongly associated with BMI change after adjustment [PAdj = 0.002; ßAdj = -2.08 (95% CI: -3.37, 0.79); ${\rm{\beta }}_{{\rm{Adj}}}^{{\rm{STD}}}$ = -0.14]. CONCLUSIONS: This study highlights a significant association between intuitive eating and BMI decrease after bariatric surgery. Furthermore, eating behaviors changed with increasing time since surgery. An intuitive nutritional approach may be complementary with bariatric surgery in the postoperative phase, which should prompt complementary prospective studies to evaluate the effectiveness of therapeutic education programs centered on intuitive eating in the postoperative period.

Decreased RNF41 expression leads to insulin resistance in skeletal muscle of obese women.

CONTEXT: Toll-like receptor 4 (TLR4) activation contributes to obesity-associated insulin resistance in skeletal muscles (SM). TLR4 signaling involves two pathways: the myeloid differentiation primary response gene 88 (MyD88) leading to inflammatory cytokines production and the toll/interleukin-1 receptor domain-containing adapter-inducing interferon (IFN) I (TRIF)-dependent pathways leading to type 1 interferon (IFNI) and interferon stimulated genes (ISG) expression. The E3 ubiquitin ligase RNF41 allows the preferential activation of the TRIF-IFNI pathway; however, its role in insulin response has not been reported. METHODS: We measured RNF41 level and IFNI pathway activation (ISG expression) in SM biopsies of obese insulin sensitive (OIS) and obese insulin resistant (OIR) women. Then we isolated and differentiated in myotubes, primary human SM cell progenitors from OIS and OIR SM biopsies. We modulated RNF41 and ISG expression in these myotubes and investigated their effects on insulin response. RESULTS: RNF41 expression is down-regulated in vivo in OIR SM and myotubes compared to OIS SM and myotubes. TLR4 activation with palmitate induces TRIF-IFNI pathway and ISG in OIS myotubes but not in OIR myotubes. Inhibition of RNF41 expression with siRNF41 in OIS myotubes treated with palmitate attenuates insulin response, IFNI pathway activation and ISG induction, mimicking OIR phenotype. Further, overexpression of RNF41 in OIR myotubes increases insulin response and ISG expression. Exposure to IFNI or to its inducer polyinosinic-polycytidylic acid, restores ISG expression and insulin sensitivity in OIR myotubes and OIS myotubes transfected with siRNF41. CONCLUSION: Our results identify RNF41 as essential to IFNI pathway activation in order to maintain muscle insulin sensitivity during human obesity.

Patients with diabetes are at high risk of serious medication errors at hospital: Interest of clinical pharmacist intervention to improve healthcare.

BACKGROUND: Medication errors (ME) are major public health issues in hospitals because of their consequences on patients' morbi-mortality. This study aims to evaluate the prevalence of ME at admission and discharge of hospitalization in diabetic and non-diabetic patients, and determine their potential clinical impact. METHOD: This prospective observational study was conducted at the Endocrinology-Diabetology-Nutrition Department. All adult patients admitted were eligible. A total of 904 patients were included, of which 671 (74.2%) with diabetes mellitus. Clinical pharmacists conducted medication reconciliation: they collected the Best Possible Medication History and then compared it with admission and discharge prescriptions to identify medication discrepancies. ME were defined as unintended medication discrepancies if corrected by the physician. RESULTS: Clinical pharmacists allowed correcting ME in 176/904 (19.5%) patients at admission and in 86/865 (9.9%) patients at discharge. More than half of ME were omissions. Diabetic patients were more affected by ME than non-diabetic patients, both at admission (22.1% vs 12.0%, p<0.001) and at discharge (11.4% vs 5.7%, p=0.01). The diabetic group also had more potentially severe and very severe ME. Diabetic patients had on average twice more medications than non-diabetic patients (8.7±4.5 vs 4.4±3.4, p<0.001). The polypharmacy associated with diabetes, but not diabetes mellitus itself, was identified as a risk factor of ME. CONCLUSIONS: The intervention of clinical pharmacists allowed correcting 378 ME in 25.8% of the cohort before they caused harm. Clinicians, pharmacists and other health care providers should therefore work together to improve patients' safety, in particular in high-risk patients such as diabetic patients.

Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women.

CONTEXT: Obesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity. OBJECTIVES: We compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development. METHODS: 30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression. RESULTS: Systemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR. CONCLUSION: Our results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.

Grape polyphenols supplementation reduces muscle atrophy in a mouse model of chronic inflammation.

OBJECTIVES: Polyphenols (PP) have demonstrated beneficial effects on low-grade inflammation and oxidative stress; however, little is known about their effect on highly inflamed muscle. The purposes of this study were (i) to evaluate muscle alteration induced by high-grade inflammation, and (ii) to test the effects of red grape PP supplementation on these alterations. METHODS: We used a transgenic mice model (transforming growth factor [TGF] mice) to develop a high T cell-dependent inflammation and C57 BL/6 control (CTL) mice model. Skeletal muscles of TGF and CTL mice were investigated for inflammation, atrophy and oxidative stress markers. Isolated mitochondria from hindlimb muscles were used for respiration with pyruvate as substrate and oxidative damages were measured by Western blot. TGF mice were supplemented with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk. Data were analyzed by one-way analysis of variance (ANOVA) and post hoc Bonferroni's multiple comparison tests. RESULTS: TGF mice presented skeletal muscle inflammation, oxidative stress, mitochondrial alteration and muscle atrophy. Atrophy was associated with two distinct pathways: (i) one linked to inflammation, NF-κB activation and increased ubiquitin ligase expression, and (ii) one dependent on reactive oxygen species (ROS) production leading to damaged mitochondria accumulation and activation of caspase-9 and 3. Supplementation of TGF mice with a mixture of red grape polyphenols (50 mg/kg/d) for 4 wk improved mitochondrial function and highly decreased caspases activation, which allowed muscle atrophy mitigation. CONCLUSIONS: These observations suggest that nutritional dosages of red grape polyphenols might be beneficial for reducing skeletal muscle atrophy, even in a high-grade inflammation environment.

Systems medicine approaches for the definition of complex phenotypes in chronic diseases and ageing. From concept to implementation and policies.

Chronic diseases are diseases of long duration and slow progression. Major NCDs (cardiovascular diseases, cancer, chronic respiratory diseases, diabetes, rheumatologic diseases and mental health) represent the predominant health problem of the Century. The prevention and control of NCDs are the priority of the World Health Organization 2008 Action Plan, the United Nations 2010 Resolution and the European Union 2010 Council. The novel trend for the management of NCDs is evolving towards integrative, holistic approaches. NCDs are intertwined with ageing. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has prioritised NCDs. To tackle them in their totality in order to reduce their burden and societal impact, it is proposed that NCDs should be considered as a single expression of disease with different risk factors and entities. An innovative integrated health system built around systems medicine and strategic partnerships is proposed to combat NCDs. It includes (i) understanding the social, economic, environmental, genetic determinants, as well as the molecular and cellular mechanisms underlying NCDs; (ii) primary care and practice-based interprofessional collaboration; (iii) carefully phenotyped patients; (iv) development of unbiased and accurate biomarkers for comorbidities, severity and follow up of patients; (v) socio-economic science; (vi) development of guidelines; (vii) training; and (viii) policy decisions. The results could be applicable to all countries and adapted to local needs, economy and health systems. This paper reviews the complexity of NCDs intertwined with ageing. It gives an overview of the problem and proposes two practical examples of systems medicine (MeDALL) applied to allergy and to NCD co-morbidities (MACVIA-LR, Reference Site of the European Innovation Partnership on Active and Healthy Ageing).

Nutrient deficiencies in patients with obesity considering bariatric surgery: a cross-sectional study.

BACKGROUND: Nutritional deficiencies are common after bariatric surgery, but few studies have examined them preoperatively. The objective of this study was to evaluate several vitamins, nutrients, and nutritional markers and their determinants in patients with obesity considering bariatric surgery. METHODS: Preoperative values of fasting plasma glucose, insulin, lipid profile, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone, thyroid-stimulating hormone, calcium, phosphate, albumin, magnesium, total proteins, liver function tests, iron, ferritin, folate, vitamin A, vitamin B12, selenium, and zinc were evaluated in 267 Caucasian outpatients (74.2% women, aged 40.5±12.6 years) who were considering bariatric surgery. The determinants of nutrient variability were analyzed by linear regression for nutrients with a prevalence of deficiency>10%, i.e., serum 25(OH)D, iron, phosphate, magnesium, and vitamin A. RESULTS: Prevalence of inadequate concentrations was high for 25(OH)D (67.9% with values ≤ 20 ng/mL), magnesium (35.4%), phosphate (21.6%), iron (18.8%), and vitamin A (16.9%). Multiple deficiencies were common; 28.5%, 12.1%, and 6.3% of patients had 2, 3, and 4 deficiencies, respectively. In multivariate analyses, metabolic characteristics had an important impact on deficiencies, with lower values of 25(OH)D and vitamin A with increasing body mass index, lower values of 25(OH)D and magnesium with increasing fasting plasma glucose, and a positive correlation between vitamin A and triglycerides. Elevated TSH was associated with low iron concentrations. CONCLUSION: At all ages, micronutrient deficiencies were common, with high prevalence of concentration inadequacies for 25(OH)D, magnesium, phosphate, iron, and vitamin A. High body mass index and high fasting plasma glucose increased the risk of deficiencies, particularly for 25(OH)D. Preoperative screening and correction of deficiencies should be advised.

Grape polyphenols prevent fructose-induced oxidative stress and insulin resistance in first-degree relatives of type 2 diabetic patients.

OBJECTIVE: To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS: Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS: In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid-reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS: A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Homocysteine as a determinant of left ventricular ejection fraction in patients with diabetes.

BACKGROUND: A link between homocysteine (Hcy) and left ventricular ejection fraction (LVEF) emerged from recent studies but was yet not explored specifically in diabetic patients. This study aimed to assess the relationship between LVEF and Hcy in a cohort of adults with diabetes. METHODS: LVEF was determined through the measure of left ventricular end-diastolic/end-systolic volumes in 409 consecutive asymptomatic patients with diabetes who underwent stress myocardial perfusion imaging. Clinical and biological parameters which were determinants of LVEF in univariate analyses with p<0.15 were included in a multivariate analysis. RESULTS: In univariate analyses, factors significantly associated with a LVEF<55% were gender [women vs. men, odds ratio (OR)=0.22 (0.13; 0.38)], peripheral arterial disease [OR=2.49 (1.34; 4.62)], active smoking [OR=1.97 (1.16; 3.33)], silent myocardial ischemia (SMI) [OR=2.19 (1.25; 3.86)], the highest vs. the lowest tertile of creatinine [OR=2.08 (1.17; 3.68)], of albuminuria [OR=2.22 (1.27; 3.90)] and of Hcy [OR=1.83 (1.07; 3.13)]. No relationship was observed between blood pressure and decrease in LVEF. In the multivariate analysis, female gender was confirmed as being protective for having a LVEF<55%. Presence of SMI [OR=2.20 (1.14; 4.23)] and Hcy ≥15 µmol/L [OR=1.81 (1.06; 3.07)] were the two remaining significant factors associated with an increased relative risk of having LVEF<55%. A trend was only observed for the criteria active smokers. CONCLUSIONS: This study highlights an inverse relationship between Hcy and LVEF in patients with diabetes, independent of age, gender, SMI, smoking, blood pressure, renal function, folates, vitamin B12, lipid parameters and hepatic enzymes.