Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies.

The treatment of obesity and cardiovascular diseases is one of the most difficult and important challenges nowadays. Weight loss is frequently offered as a therapy and is aimed at improving some of the components of the metabolic syndrome. Among various diets, ketogenic diets, which are very low in carbohydrates and usually high in fats and/or proteins, have gained in popularity. Results regarding the impact of such diets on cardiovascular risk factors are controversial, both in animals and humans, but some improvements notably in obesity and type 2 diabetes have been described. Unfortunately, these effects seem to be limited in time. Moreover, these diets are not totally safe and can be associated with some adverse events. Notably, in rodents, development of nonalcoholic fatty liver disease (NAFLD) and insulin resistance have been described. The aim of this review is to discuss the role of ketogenic diets on different cardiovascular risk factors in both animals and humans based on available evidence

Treatment challenges in type 1 diabetes after roux-en-Y gastric bypass.

Bariatric surgery is an effective treatment of type 2 diabetes in obese patients. The obesity epidemic does not spare patients with type 1 diabetes mellitus (T1DM), but there is no consensus regarding the role of surgery in the management of obese T1DM patients. Published data consistently report significant weight loss after surgery in obese T1DM patients, but long-term glycaemic control remains difficult to achieve. Here we present our experience with a challenging patient and a review of the literature. Our patient successfully underwent a roux-en-Y gastric bypass (RYGB) when she was 28 years old. Five years after surgery, she was diagnosed with latent autoimmune diabetes of adults and insulin therapy was initiated. Insulin therapy proved very difficult to adjust, with frequent episodes of postprandial hyperglycaemia. These difficulties could only be overcome by the initiation of a subcutaneous insulin infusion using a sensor-augmented insulin pump with automated suspension. This change allowed better glycaemic control. Despite considerable weight loss with a concomitant decrease in insulin requirement, glycaemic control remained difficult after surgery. Due to their different impacts on glucose kinetics, the type of surgical operation should be part of the assessment. These patients might benefit from sensor-augmented insulin pump therapy with automated insulin suspension after bariatric surgery. The decision for surgical intervention in these patients should be carefully weighed against the difficulties in achieving adequate glycaemic control

Diabète gestationnel--quelles sont les approches non médicales [Gestational diabetes--what are the non-medical approaches?].

Gestational diabetes is a multifactorial disease that increases the risk for complications for the mother and her child in the short and long term. The perinatal period represents an opportunity not only to assist the mother in improving her own health but also that of the future generation. This article focuses on lifestyle and psychological aspects that form the base for non-medical treatment approaches. Considering different risk factors separately is not sufficient for the improvement of the metabolic and mental health of women with gestational diabetes. With a multimodal interdisciplinary approach that includes physical activity, dietary advice and psychological support, an improvement of the health and well-being of both the mother and her child is expected. Future studies are necessary to confirm this proposed care approach

Low birth weight leads to obesity, diabetes and increased leptin levels in adults: the CoLaus study.

Low birth weight is associated with increased rates of obesity, insulin resistance and type 2 diabetes, but the precise mechanisms for this association remain unclear. We aimed to assess the relationships between birth weight and markers of glucose homeostasis or obesity in adults. Cross-sectional population-based study on 1458 women and 1088 men aged 35-75 years living in Lausanne, Switzerland. Birth weight was self-reported and categorized into ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg. Body composition was assessed by bioimpedance. Leptin and adiponectin levels were measured by ELISA. Women with low birth weight (≤ 2.5 kg) had higher levels of fasting plasma glucose, insulin, HOMA, diabetes and metabolic syndrome; a non significant similar trend was seen in men. In both genders, height increased with birth weight, whereas a U-shaped association was found between birth weight and body mass index, waist circumference and body fat percentage. After adjusting for age, smoking status, physical activity and fat mass, an inverse association was found between leptin and birth weight categories: adjusted mean ± standard error 17.3 ± 0.7, 16.2 ± 0.3, 15.6 ± 0.5 and 14.0 ± 0.8 ng/dL for birth weight categories ≤ 2.5, 2.6-3.5, 3.6-4.0 and >4.0 kg, respectively, in women (p < 0.05) and 9.8 ± 0.8, 9.1 ± 03, 7.8 ± 0.4 and 7.7 ± 0.5 ng/dL in men (p < 0.05). An inverse association was also found between reported birth weight and leptin to fat mass ratio: mean ± standard error 0.77 ± 0.04, 0.73 ± 0.02, 0.69 ± 0.03 and 0.62 ± 0.04 in women (p < 0.05); 0.46 ± 0.05, 0.45 ± 0.02, 0.39 ± 0.02 and 0.38 ± 0.03 in men (p < 0.05). No differences in adiponectin levels were found between birth weight groups. Middle-aged adults born with a low weight present a higher prevalence of diabetes and obesity and also higher leptin levels and leptin to fat mass ratio than adults born with a normal weight. The higher leptin levels and leptin to fat mass ratio among adults born with a low weight might be related to nutritional factors during childhood or to the development of leptin resistance and/or higher leptin production by body fat unit. Subjects born with a low weight should be counselled regarding the risks of developing diabetes and/or cardiovascular disease

Effects of the peroxisome proliferator-activated receptor (PPAR)-γ agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Aims/hypothesis: Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. Methods: In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45mg daily during 6weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. Results: Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals. Conclusions/interpretation: Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones. Trial registration:: ClinicalTrial.gov NCT01090752 Funding:: Hypertension Research Foundation Lausann

Preserving of postnatal leptin signaling in obesity-resistant lou/c rats following a perinatal high-fat diet

Physiological processes at adulthood, such as energy metabolism and insulin sensitivity may originate before or weeks after birth. These underlie the concept of fetal and/or neonatal programming of adult diseases, which is particularly relevant in the case of obesity and type 2 diabetes. The aim of this study was to determine the impact of a perinatal high fat diet on energy metabolism and on leptin as well as insulin sensitivity, early in life and at adulthood in two strains of rats presenting different susceptibilities to diet-induced obesity. The impact of a perinatal high fat diet on glucose tolerance and diet-induced obesity was also assessed. The development of glucose intolerance and of increased fat mass was confirmed in the obesity-prone Wistar rat, even after 28 days of age. By contrast, in obesity-resistant Lou/C rats, an improved early leptin signaling may be responsible for the lack of deleterious effect of the perinatal high fat diet on glucose tolerance and increased adiposity in response to high fat diet at adulthood. Altogether, this study shows that, even if during the perinatal period adaptation to the environment appears to be genetically determined, adaptive mechanisms to nutritional challenges occurring at adulthood can still be observed in rodents

Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-Debridement Antibiotic Treatment for 10 versus 20 days

Background: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot (ST-DFI) remains unknown. Objective: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for ST-DFI results in similar rates of clinical remission and adverse events (AE). Summary Background Data: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. Methods: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of “clinical remission at two-months follow-up”. Results: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat (ITT) population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm (p = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; p = 0.71), and remission in the per-protocol (PP) population (25/32 vs. 18/27; p = 0.32). Overall, eight soft tissue DFIs in the 10-day arm and five cases in the 20-day arm recurred as a new osteomyelitis (8/35 [23%] versus 5/31 [16%]; p = 0.53). Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (ITT population, hazard ratio 0.6, 95%CI 0.3-1.1; PP population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. Conclusions: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way

Langerhans cell histiocytosis of the suprasellar region: diagnosis based on thyroid cytology.

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D), and weight gain. Transcranial biopsy is necessary to define diagnosis and guide treatment decisions, but it is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was made by thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose (FDG) avidity on PET/CT and volume increase during follow-up