Maternal high-fat diet programs white and brown adipose tissue lipidome and transcriptome in offspring in a sex- and tissue-dependent manner in mice

Objective The prevalence of overweight and obesity among children has drastically increased during the last decades and maternal obesity has been demonstrated as one of the ultimate factors. Nutrition-stimulated transgenerational regulation of key metabolic genes is fundamental to the developmental origins of the metabolic syndrome. Fetal nutrition may differently influence female and male offspring. Methods Mice dam were fed either a control diet or a high-fat diet (HFD) for 6-week prior mating and continued their respective diet during gestation and lactation. At weaning, female and male offspring were fed the HFD until sacrifice. White (WAT) and brown (BAT) adipose tissues were investigated in vivo by nuclear magnetic resonance at two different timepoints in life (midterm and endterm) and tissues were collected at endterm for lipidomic analysis and RNA sequencing. We explored the sex-dependent metabolic adaptation and gene programming changes by maternal HFD in visceral AT (VAT), subcutaneous AT (SAT) and BAT of offspring. Results We show that the triglyceride profile varies between adipose depots, sexes and maternal diet. In female offspring, maternal HFD remodels the triglycerides profile in SAT and BAT, and increases thermogenesis and cell differentiation in BAT, which may prevent metabolic complication later in life. Male offspring exhibit whitening of BAT and hyperplasia in VAT when born from high-fat mothers, with impaired metabolic profile. Maternal HFD differentially programs gene expression in WAT and BAT of female and male offspring. Conclusion Maternal HFD modulates metabolic profile in offspring in a sex-dependent manner. A sex- and maternal diet-dependent gene programming exists in VAT, SAT, and BAT which may be key player in the sexual dimorphism in the metabolic adaptation later in life.

First Trimester Potential Biochemical Predictive Tests for Gestational Diabetes Mellitus: A Systematic Review

Objective: Gestational diabetes mellitus (GDM) is the most common metabolic complication during pregnancy. So, a large number of studies have evaluated the usefulness of different screening tests. The aim of this study was focused on the potential of only first-trimester screening used in the prediction of GDM. Materials and Methods: In this systematic review, we searched PubMed, EMBASE, and Scopus (between 2010 and 2020) and also searched the reference lists of the relevant articles manually. After performing a thorough evaluation of the 242 potentially eligible papers, only 60 papers were selected in terms of the inclusion criteria. Search key terms were combining ‘Gestational diabetes’ or ‘GD’ “gestational diabetes mellitus” or” GDM” or pregnancy-induced diabetes’ with at least one of the following terms: “screening test”, “first-trimester”, “prediction”, “marker predictor”, “serum marker”. Results: A total of 161954 pregnant women were evaluated in these reviewed studies. Moreover, many tests were assessed in the first trimester of pregnancy to predict GDM. This review showed that hs-CRP, FPG, TG, and LDL-C along with maternal BMI in the first trimester were related to the increased risk of developing GDM. Other tests were used in only one or two studies. Conclusion: This review showed that hs-CRP, FPG, TG, and LDL-C along with maternal BMI in the first trimester were linked to an increased risk of developing GDM. It is recommended that further well-designed studies by considering the cost-effective advantages of these predictive tests, should be performed.

Epigenetic: New Insight in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is the more frequent metabolic complication of pregnancy with a prevalence that is significantly increased in the last decade accounting for 12–18% of all pregnancies. Recent evidences strongly suggests that epigenetic profile changes could be involved in the onset of GDM and its related maternal and fetal complications. In particular, the unfavorable intrauterine environment related to hyperglycemia, a feature of GDM, has been evidenced to exert a negative impact on the establishment of the epigenome of the offspring. Furthermore the adverse in utero environment could be one of the mechanisms engaged in the development of adult chronic diseases. The purpose of this article is to review a number of published studies to fill the gap in our understanding of how maternal lifestyle and intrauterine environment influence molecular modifications in the offspring, with an emphasis on epigenetic alterations.

Reversible supraventricular tachycardia complicating diabetic ketoacidosis in an adult patient: A case report

Diabetic ketoacidosis (DKA) is a commonly encountered serious acute metabolic complication of diabetes mellitus (DM) in adolescents and young adults. It is traditionally associated with poorly treated or newly diagnosed type 1 DM, however, in the setting of type 2 DM, inadequate insulin treatment, non-compliance to treatment, newly diagnosed DM, acute illnesses, drugs, and extreme stress can precipitate DKA. We report the case of a 42-year-old known diabetic of 7 years duration with a family history of DM who presented with a two-week history of difficulty in breathing, polyuria, and vomiting. On further examination, pulse rate was 220 beats per minute, respiratory rate 40 cycles per minute, temperature 38.4’C. Random blood sugar was 18.1mmol/l with ketonuria ++. Severe acidosis and mild hypokalemia were noted with her electrocardiogram (ECG) showing supraventricular tachycardia. She was managed and discharged in stable condition with a normal ECG after 20 days on admission to continue basal and pre-meal insulin at home. Adequate diabetic education was conducted and follow-up with endocrinology and cardiology units was advised.

Patient-reported outcomes (PROs) in randomised controlled trials in diabetes and pregnancy: protocol for a systematic review

IntroductionDiabetes mellitus is the most common metabolic complication of pregnancy and its prevalence worldwide is rising. The number of randomised controlled trials (RCTs) being conducted in people with diabetes is also increasing. Many studies preferentially publish findings on clinical endpoints and do not report patient-reported outcomes (PROs). In studies that do include PROs, PRO reporting is often of poor quality.MethodsWe will conduct this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using a combination of medical subject headings and keywords (combined using Boolean operators), we will search web-based databases (PubMed, Cochrane and EMBASE) for RCTs published in English between 2013 and 2021. Two reviewers will review titles and abstracts. We will review the full texts of any relevant abstracts and extract the following data: date of publication or recruitment period, journal of publication, country of study, multicentre or single centre, population and number of participants, type of intervention, frequency of PRO assessment and type of PRO (or PRO measurement) used. We will also record if the PRO was a primary, secondary or exploratory outcome. We will exclude reviews, observational studies, unpublished data for example, conference abstracts and trial protocols. Any published RCT that includes data on a PRO as a primary or secondary outcome will then be compared against the Consolidated Standards of Reporting Trials—Patient-Reported Outcome extension checklist, a structured and approved framework for the publication of results of PROs.Ethics and disseminationEthical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 24 March 2021 (CA 2592). We aim to publish our findings in a peer-reviewed journal and present our findings at national and international conferences.Systematic review registrationThis systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42021234917.

Effects of a single 10mg dose of empagliflozin on postprandial insulin kinetics in patients with postbariatric hypoglycaemia

Introduction: Postbariatric hypoglycaemia (PBH) is an increasingly recognized late metabolic complication of Roux-en-Y gastric bypass (GB) surgery. PBH typically manifests with a fact occurring post-meal hyperglycaemic peak, followed by a disproportionately exaggerated insulin response leading to low glucose levels. On this basis, we evaluated the effect of a single dose of empagliflozin 10mg vs. placebo on parameters of insulin kinetics. Materials and methods: Insulin secretion, hepatic insulin extraction and total insulin clearance were evaluated after a single of empagliflozin 10mg vs. placebo followed by a standardized liquid mixed meal were evaluated in 11 subjects with confirmed PBH after GB over 3h. Parameters of interest were calculated using established mathematical models. Indices were compared between the groups using the Wilcoxon signed-rank test. Results Total beta-cell responsiveness tends to be lower with empagliflozin vs. placebo (24.83±11.00 vs. 27.15±9.68 [10-9 min-1], p=0.150). Total first-pass hepatic insulin extraction increased after empagliflozin compared to placebo (49.6±14.2 vs. 39.7±12.1 %, p=0.006), while no significant effect of empaglizflozin on basal first-pass hepatic insulin extraction was observed (79.7±7.1 vs. 81.1±6.6 %, p=0.521). Total insulin clearance resulted to be significantly lower after empagliflozin compared to placebo (3.91±1.58 vs. 3.00±1.27 l/min, p=0.002). Conclusion The present analysis suggests that the hypoglycaemia-attenuating effect of SGLT2-inhibition in patients with PBH is mainly mediated by an increment in insulin clearance, with also a tendency to a reduction in insulin secretion.

Early Enteral Feeding Improves Tolerance of Parenteral Nutrition in Preterm Newborns

(1) Background: The tolerance of preterm newborns for the high nutritional intakes given by parenteral nutrition (PN) is still debated because of the risk of metabolic complications. Despite enteral nutrition (EN) being the preferred route of nutrition, an exclusive enteral feeding is not always possible, as in preterm newborns, the gut is immature and less tolerant of EN. We aimed to study the impact of a minimal enteral feeding (MEF) on the possible early metabolic complications of PN in a cohort of preterms with gestational age at birth GA ≤ 29 + 6/7 weeks of postmenstrual age. (2) Methods: We divided the study sample in two cohorts: 1) Late-Feeding (cohort 1), newborns who received MEF starting from the 8th day of age, and (2) Early-Feeding (cohort 2), newborns who received MEF, consisting of the administration of at least 4–5 mL/kg/day by the enteral route, in the first 7 days of age. The primary outcome of the study was the rate of at least one metabolic complication, including hyperglycemia, hypertriglyceridemia, or metabolic acidosis. (3) Results: We enrolled 80 newborns (Late-Feeding cohort 51 vs. Early-Feeding cohort 29). The rate of all metabolic complications was statistically higher in the Late-Feeding cohort compared to the Early-Feeding cohort. Binary logistic regression analysis showed that late administration of MEF negatively influenced the rate of all metabolic complications. (4) Conclusions: Early minimal administration of EN is associated with less frequent PN-related metabolic side effects and a higher rate of survival in critically ill newborns.

Impact of Diabetes Mellitus on Renal transplant outcome

Diabetes Mellitus (DM) is a potent risk factor for post-transplant cardiovascular complications and infections. Management of diabetes and its complications in renal transplant recipients is a challenging task. This is a frequently encountered predicament in transplant setups. An erratic glycemic control during dialysis is a predictor of poor graft and patient outcomes after kidney transplantation. Literature review reveals majority studies explaining post-transplant diabetes and its role in graft and patient survival. However, a wide range of opinion exists about the impact of pre-transplant DM on transplant outcomes. Measurement of HbA1c levels is a significant tool for assessment of glycemic control. A target HbA1c level of <7% is recommended for diabetic patients irrespective of presence or absence of Chronic Kidney Disease (CKD). However, diabetic patients with CKD are at risk of hypoglycemia owing to decreased insulin metabolism so it is safe to keep HbA1c levels between 7-8% in this population. Immunosuppressive medications have a strong contributory role in deterioration of glycemic control. So, it is imperative to achieve strict pre-transplant diabetes control in order to avoid post-transplant complications. Post-transplant diabetes mellitus (PTDM) has been a subject of a large number of trials and is not only considered a serious metabolic complication but also a predisposing factor of diabetic nephropathy in transplanted kidney.

Frequency of Hypoglycemia in Severe Acute Malnutrition

Malnutrition is a major health problem throughout the world and contributes to at least one third of all children deaths worldwide. Hypoglycemia is a basic metabolic complication in pediatric patients which can be easily prevented by proper care and management. Objective of this study was to determine the frequency of hypoglycemia in sever acute Malnurished children (SAM). The study was conducted in nutritional division of Nangarhar University Teaching Hospital pediatric department. For 8 months, all the patients were subjected for measurement of blood glucose level by glucose oxidase method .Hypoglycemia was labeled according to value mentioned in operational definition. The study included a total of 252 patients with SAM. 137 (54.4%) were Males and 115 (45.6%) females with no significant difference in the number of gender and with an average age of (Mean± SD) 16.20±11.74 (6 months to 60 months). Out of 252 patients 54.80% (138) were hypoglycemic, and 85.70% (216) suffering from Marasmus. 38.9% of children’s caregivers were illiterate and 86.5% poor and middle-level of socioeconomic status. 12.7%( 32) of the SAM children with hypoglycemia were dying, most of the patient from Nangarhar province. Sever acute malnutrition (SAM) constitutes a significant health problem and important cause of mortality and morbidity in children, in marasmus patients the hypoglycemia is more common than kwashiorkor children; early diagnosis and treatment can prevent and decrease the morbidity and mortality of Sever acute malnutrition (SAM) in children significantly, education, socioecnomic status of caregivers are important in prevention of sever acute malnutrition (SAM) and their complications.

Epigenetic Alterations Related to Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.