Normalization of HbA1c Following an Ad-Libitum, Non-Ketogenic Low Carbohydrate Diet Along With Antidiabetic Agents

Background and Aims: Recent scientific research has found that remission of T2DM can be achieved with substantial weight loss following hypocaloric diet or bariatric surgery. The DiRECT study has shown that after 12 months of dietary management, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. The aim of our study was to investigate the impact of an ad-libitum, low carbohydrate non-ketogenic diet (LCNK) on T2DM control and weight loss of patients reporting to our clinic. Materials and Methods: We reviewed the medical charts of 131 T2DM patients (60% male) who were not receiving insulin; the average number of years with T2DM was 8.4years, mean age was 52.8±1.0 years, mean HbA1c was 8.4±0.1 %, and mean BMI was 32.7±0.6 kg/m2. We instructed patients on an ad-libitum LCNK diet providing 130 - 150g of carbohydrate/day coupled with combination therapy of Metformin and any of the currently available antidiabetic drugs (except those known to induce weight gain). Those on sulfonylurea or glitazones had their doses tapered down and eventually discontinued. Results: All patients came for a first follow up visit within 3 months of being instructed on the diet. Significant weight loss was observed in these patients (91.5±1.7 vs. 85.6±1.5 Kg, p<0.001); equivalent to a 6% decrease in weight. An A1C level below 6.5 % was observed in 60% of our patients who came for a first follow-up visit and it correlated with weight loss. Given that 10% of our population gained weight due to poor adherence to the diet; A1C below 6.5 % was achieved in 50% of our 42 patients who lost between 0-5kg, and in 60% of those who lost between 5-10kg (48 patients), and in 63% of those who lost 10-15kg (19 patients), and in 100% of those who lost more than 15kg (4 patients). We observed in them significant decreases in FBS, cholesterol, LDL, TG, and SGPT. Of the 131 patients, 59 came for a second follow-up visit within 7.5 months and an even more significant weight loss was observed (92.0±2.6 vs. 83.8±2.0 Kg, p<0.001); equivalent to a 9 % decrease. An A1C level below 6.5 % was observed in 63% of patients who came for a second follow-up visit. Given that 14% of the 59 gained weight; A1C below 6.5 % was achieved in 42% of our 12 patients who lost between 0-5kg, and in 61% of those who lost between 5-10kg (19 patients), and in 57% of those who lost 10-15kg (8 patients), and in 90% of those who lost more than 15kg (11 patients). Antidiabetic agents were in general progressively decreased and adjusted to individual needs. At the end 27% were only on metformin. Conclusion: A LCNK diet is easy to prescribe and easily followed by T2D patients (no calorie restriction or counting). We recommend its use especially in the primary care setting because it brings diabetes under immediate control by lowering A1C levels below 6.5% in more than 60% of patients as shown by our results, as well as inducing significant weight loss.

Males deploy multifaceted strategies and hijack longevity pathways to induce premature demise of the opposite sex

Interactions between the sexes negatively impact health in many species, including mammals1–9. In mice, sexual interactions induce weight gain and shorten lifespan in females, independent of fertilization6,9. In Caenorhabditis, males shorten the lifespan of the opposite sex (females or hermaphrodites)1–3,8. However, the mechanisms underlying the negative influence of males on lifespan – and their overlap with known longevity pathways – are still largely unknown. Here, we use transcriptomic profiling and targeted screens to systematically uncover new conserved genes involved in male-induced demise. Interestingly, deficiency of these genes individually, and especially in combination, induces strong protection, highlighting the benefit of combining interventions to extend lifespan. Some genes (e.g. acbp-3, col-43) only extend hermaphrodite lifespan when knocked-down in the presence of males, suggesting specific protective mechanisms against male-induced demise. However, we also uncover two previously unknown longevity genes (sri-40 and delm-2) that, when knocked-down, extend hermaphrodite lifespan both with and without males, which points to new broad mechanisms of resistance. In sharp contrast, many classical long-lived mutants are actually short-lived in the presence of males, suggesting that males hijack and suppress known longevity pathways. This systematic analysis reveals striking differences in longevity in single sex versus mixed sex environments and uncovers the elaborate network of functional regulation elicited by sexual interactions, which could extend to other species.

Interactions of antidepressants, mood-stabilisers and antipsychotics with food

Aim: The aim of the paper was to review and analyse the literature addressing interactions between food and antidepressants, mood stabilisers and antipsychotics. Literature review: The observed food and drug interactions are mutual and might lead to a decrease of the therapeutic effect, an increase of the drug toxicity or changes in the nutritional status. Drug and food interactions can modify the pharmacokinetic (e.g. absorption, metabolism) and/or pharmacodynamic properties of drugs. The food intake alters the absorption of trazodone XR, sulpiride, ziprasidone, lurasidone and quetiapine XR. Coffee, tea and possibly turmeric influence CYP1A2 in a dose-dependent manner. Fruit juices (grapefruit, Seville orange, blueberry), curcumin and piperine inhibit CYP3A4. In human studies, significant interactions between food and sertraline, clomipramine, clozapine and carbamazepine were found. Food containing tyramine was shown to interact with MAO inhibitors altering their pharmacodynamic properties. Both malnutrition and obesity may have an impact on the pharmacokinetic properties of some mood stabilisers and antipsychotics. On other hand, the majority of antipsychotics, mood stabilisers and some antidepressants induce weight gain. Changes in taste perception can occur during pharmacotherapy with some antidepressants (tricyclics, selective serotonin reuptake inhibitors), antipsychotics (risperidone) and mood-stabilisers (lithium, valproate). Conclusions: Appropriate care and consideration must be taken when attempting to extrapolate results of in vitro or animal studies to humans. To evaluate the clinical significance of a specific food and drug interaction, it might be necessary to measure the concentration of the pharmaceutical compound and its metabolites in blood serum.

Switching to Aripiprazole as a Strategy for Weight Reduction: A Meta-Analysis in Patients Suffering from Schizophrenia

Weight gain is one of the major drawbacks associated with the pharmacological treatment of schizophrenia. Existing strategies for the prevention and treatment of obesity amongst these patients are disappointing. Switching the current antipsychotic to another that may favorably affect weight is not yet fully established in the psychiatric literature. This meta-analysis focused on switching to aripiprazole as it has a pharmacological and clinical profile that may result in an improved weight control. Nine publications from seven countries worldwide were analyzed. These encompassed 784 schizophrenia and schizoaffective patients, 473 (60%) men and 311 (40%) women, mean age years. The major significant finding was a mean weight reduction by kgs following the switch to aripiprazole (). Switching to an antipsychotic with a lower propensity to induce weight gain needs be explored as a strategy. Our analysis suggests aripiprazole as a candidate for such a treatment strategy.

A high-fat diet as a model of fatty liver disease in rats

PURPOSE: The objective of the present study was to analyze the physiological and metabolic changes occurring in rats subjected to high-fat diet for one month. METHODS: The animals received a modified AIN-93 diet with increased lipid content and decreased carbohydrate content, while the control group received the normal AIN-93 diet. RESULTS: It was observed that the high-fat diet did not induce weight gain but led to greater gain of hepatic fat compared to control. Biochemcal parameters, glycemia, total cholesterol and serum protein did not differ between groups. In parallel, rats receiving the high-fat diet consumed less feed. CONCLUSION: The development of obesity through high-fat diet is associated with increased energy intake and time of exposure to the diet, while the metabolic syndrome is more associated with the combination of a diet rich in fat and carbohydrates.

Nature Against Nurture: Calcification in the Right Thalamus in a Young Man with Anorexia Nervosa and Obsessive-Compulsive Personality Disorder

ABSTRACTThis report describes the case of a young man with a large calcification in the right thalamus that was first diagnosed at 9 years of age. Case history reveals specific eating rituals and other obsessive-compulsive personality traits during the patient's childhood and adolescence, fulfilling diagnostic criteria of obsessive-compulsive personality disorder. After a critical life event the patient develops anorexia nervosa. We suggest that our case and further literature provide evidence for an involvement of specific thalamic structures, such as the dorsomedial nucleus, in the development of anorexia nervosa. Furthermore, the treatment of the patient by a combined psychotherapeutic and pharmacotherapeutic approach is described. We focus on the beneficial effect of the atypical antipsychotic olanzapine, which can induce weight gain by an increase of leptin levels.