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The growing amount of evidence suggests the existence of a bidirectional relation between coronavirus disease 2019 (COVID-19) and type 2 diabetes mellitus (T2DM), as these two conditions exacerbate each other, causing a significant healthcare and socioeconomic burden. The alterations in innate and adaptive cellular immunity, adipose tissue, alveolar and endothelial dysfunction, hypercoagulation, the propensity to an increased viral load, and chronic diabetic complications are all associated with glucometabolic perturbations of T2DM patients that predispose them to severe forms of COVID-19 and mortality. Severe acute respiratory syndrome coronavirus 2 infection negatively impacts glucose homeostasis due to its effects on insulin sensitivity and β-cell function, further aggravating the preexisting glucometabolic perturbations in individuals with T2DM. Thus, the most effective ways are urgently needed for countering these glucometabolic disturbances occurring during acute COVID-19 illness in T2DM patients. The novel classes of antidiabetic medications (dipeptidyl peptidase 4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are considered candidate drugs for this purpose. This review article summarizes current knowledge regarding glucometabolic disturbances during acute COVID-19 illness in T2DM patients and the potential ways to tackle them using novel antidiabetic medications. Recent observational data suggest that preadmission use of GLP-1 RAs and SGLT-2is are associated with decreased patient mortality, while DPP-4is is associated with increased in-hospital mortality of T2DM patients with COVID-19. Although these results provide further evidence for the widespread use of these two classes of medications in this COVID-19 era, dedicated randomized controlled trials analyzing the effects of in-hospital use of novel antidiabetic agents in T2DM patients with COVID-19 are needed.

Background: Ramadan fasting (RF) is associated with major changes in meal times. This can affect thyroxine absorption and thyroid function (TF) in patients with hypothyroidism. We aimed to examine the short- and long-term impact of RF on TF in patients with primary hypothyroidism on levothyroxine. Methods: TF tests in patients with primary hypothyroidism attending an endocrine center in the United Arab Emirates were retrospectively analyzed. The impact of RF on TF, namely serum thyrotropin (TSH) TSH, free thyroxine (fT4) and free triiodothyronine (fT3), was investigated in 481 patients within 3 months before Ramadan (BR), 1–2 weeks (PR1), and 3–6 months (PR2) post-Ramadan. Controlled TF was defined as TSH between 0.45 and 4.5 μIU/mL. Inadequate control was defined as TSH >4.5 μIU/mL. Loss of control was defined as having controlled TF at BR and inadequate control at PR1. Multivariable regression analyses were used to assess the association of baseline TSH, baseline levothyroxine dose, and medication use with loss of thyroid control in Ramadan. Results: TSH increased significantly from a median of 2.0 (0.8–3.7) μIU/mL at BR to 2.9 (1.4–5.6) μIU/mL at PR1 (p

The genetic architecture of extreme non-syndromic obesity in adults remains to be elucidated. A range of genes are known to cause monogenic obesity but, even when pathogenic mutations are present, there may be variable penetrance. Here, we present a family where initial discovery of a proband with a mutation in SH2B1 could have led to inaccurate genetic counselling. Whole exome sequencing (WES) of the parents revealed an apparently oligogenic mode of inheritance, with rare mutations in POGZ and MBD5 also segregating in this trio. Subsequent reanalysis of WES data from 91 unrelated adults with severe obesity revealed two other patients who carried more than one rare, predicted-deleterious mutation. In all three cases, the genes involved had known autosomal dominant inheritance, with incomplete penetrance. We caution clinicians and researchers to avoid confining their analysis to individual genes and, in particular, not to stop looking when the first potentially-causative mutation is found.

The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new -onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.

Total daily energy expenditure (“total expenditure”, MJ/d) reflects daily energy needs and is a critical variable in human health and physiology, yet it is unclear how daily expenditure changes over the life course. Here, we analyze a large, globally diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 yr. We show that total expenditure is strongly related to fat free mass in a power-law manner and identify four distinct metabolic life stages. Fat free mass-adjusted daily expenditure accelerates rapidly in neonates (0-1yr) to ~46% above adult values at ~1 yr, declines slowly throughout childhood and adolescence (1-20 yr) to adult levels at ~20 yr, remains stable in adulthood (20-60 yr) even during pregnancy, and declines in older adults (60+ yr). These changes in total expenditure shed new light on human development and aging and should help shape nutrition and health strategies across the lifespan.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether humans have evolved sex differences in the degree of interindividual variation in energy expenditure. We found that, even when statistically comparing males and females of the same age, height, and body composition, there is much more variation in total, activity, and basal energy expenditure among males. However, with aging, variation in total energy expenditure decreases, and because this happens more rapidly in males, the magnitude of greater male variation, though still large, is attenuated in older age groups. Considerably greater male variation in both total and activity energy expenditure could be explained by greater male variation in levels of daily activity. The considerably greater male variation in basal energy expenditure is remarkable and may be explained, at least in part, by greater male variation in the size of energy-demanding organs. If energy expenditure is a trait that is of indirect interest to females when choosing a sexual partner, this would suggest that energy expenditure is under sexual selection. However, we present a novel energetics model demonstrating that it is also possible that females have been under stabilizing selection pressure for an intermediate basal energy expenditure to maximize energy available for reproduction. (C) 2022 The Author(s). Published by Elsevier Ltd.

Fasting during Ramadan is one of the five pillars of Islam and is obligatory for all healthy Muslims from the age of puberty. Though individuals with some illness and serious medical conditions, including some people with diabetes, can be exempted from fasting, many will fast anyway. It is of paramount importance that people with diabetes that fast are given the appropriate guidance and receive proper care. The International Diabetes Federation (IDF) and Diabetes and Ramadan (DaR) International Alliance have come together to provide a substantial update to the previous guidelines. This update includes key information on fasting during Ramadan with type 1 diabetes, the management of diabetes in people of elderly ages and pregnant women, the effects of Ramadan on one's mental wellbeing, changes to the risk of macrovascular and microvascular complications, and areas of future research. The IDF-DAR Diabetes and Ramadan Practical Guidelines 2021 seek to improve upon the awareness, knowledge and management of diabetes during Ramadan, and to provide real-world recommendations to health professionals and the people with diabetes who choose to fast.

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

Publisher Copyright: © 2021 The Authors Understanding the impacts of activity on energy balance is crucial. Increasing levels of activity may bring diminishing returns in energy expenditure because of compensatory responses in non-activity energy expenditures.1–3 This suggestion has profound implications for both the evolution of metabolism and human health. It implies that a long-term increase in activity does not directly translate into an increase in total energy expenditure (TEE) because other components of TEE may decrease in response—energy compensation. We used the largest dataset compiled on adult TEE and basal energy expenditure (BEE) (n = 1,754) of people living normal lives to find that energy compensation by a typical human averages 28% due to reduced BEE; this suggests that only 72% of the extra calories we burn from additional activity translates into extra calories burned that day. Moreover, the degree of energy compensation varied considerably between people of different body compositions. This association between compensation and adiposity could be due to among-individual differences in compensation: people who compensate more may be more likely to accumulate body fat. Alternatively, the process might occur within individuals: as we get fatter, our body might compensate more strongly for the calories burned during activity, making losing fat progressively more difficult. Determining the causality of the relationship between energy compensation and adiposity will be key to improving public health strategies regarding obesity.

BackgroundRamadan fasting (RF) is a religious obligation for all healthy adult Muslims. The sick and pre-pubertal children are exempt, but many choose to fast for various reasons. In this “real world” study, glycaemic control has been investigated in the context of RF in children and adolescents with type 1 diabetes mellitus (T1DM) and compared multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) outcomes.MethodsChildren and adolescents with T1DM seen at Imperial College London Diabetes Centre who decided to fast in the ensuing Ramadan were educated with their families about diabetes mellitus management during RF using an adapted CHOICE (Carbohydrate, Insulin, and Collaborative Education) educational programme. Pertinent data including hypoglycaemia episodes and diabetic ketoacidosis (DKA) were obtained through patient/family interviews. Information on weight, glycated hemoglobin (HbA1c), and blood glucose levels from continuous glucose monitoring (CGM)/flash glucose monitoring (FGM) before (1 month prior), during, and after (1 month afterwards) Ramadan were retrieved retrospectively from the electronic database. Data are presented as mean ± SD.ResultsForty-two patients [age 13.5 ± 2.4 years; 27 (64.3%) males; T1DM duration 4.9 ± 3.1 years] were included in the study and were able to fast for 22 ± 9 days during Ramadan. Twenty-three (54.8%) of the patients were on MDI and 19 (45.2%) were on CSII. No statistically significant differences were seen in CGM/FGM generated mean blood glucose level before, during, and after Ramadan [one-way ANOVA (F(2, 80) =1.600, p = 0.21)]. HbA1c and weight after Ramadan did not change significantly compared to baseline (paired t-test; p = 0.02 and p = 0.08, respectively). Between MDI and CSII groups, there was no significant difference in fasting days (p = 0.49), frequency of hypoglycaemia episodes (p = 0.98), DKA frequency (p = 0.37), HbA1c level (p = 0.24), and weight (p = 0.11) after Ramadan.ConclusionData show no significant deterioration in indicators of overall glycaemic control which remained inadequate. RF should be discouraged in children with poorly controlled T1DM.

Introduction: Evidence indicates cardiovascular risk may start early in life. Data on specific risk factors including lipids in childhood and adolescence are scant. We investigate lipid profiles in overweight/obese patients. Methods: Data on pediatric ICLDC patients (N=11,116) with complete lipid profile (2009-2019) were extracted. Overweight/obese category (BMI ≥ 85th percentile) was divided into: prediabetes (Pre-Dia), type1 (T1DM), type 2 (T2DM) and normoglycemic (NGT) groups. Lipid percentiles were calculated for all lipids; distribution curves were plotted on R and statistical analyses performed on SPSS24. Results: Patients (n=4659) included: Pre-Dia (24%), diabetes (T1DM 6%, T2DM 2%) and NGT (68%). Total cholesterol (TC), LDL and non-HDL were significantly increased (p≤0.001) and HDL was significantly decreased (p≤0.001) in diabetes groups compared to NGT; except TC in NGT vs. Pre-Dia. Different trends arose in between diabetes groups whereby TC, LDL and non-HDL were significantly increased (p≤0.001) while HDL was significantly decreased (p≤0.001); except for LDL, non-HDL and TC in T1DM vs. T2DM, non-HDL in Pre-Dia vs. T1DM and TC in Pre-Dia vs. T2DM. Conclusion: Even at an early age, significant increases in TC, LDL and non-HDL, accompanied by decreases in HDL, were observed in patients with type 1, type 2 diabetes and prediabetes groups. Early intervention may need to be considered. Disclosure T. Ali: None. S. Radha: None. R. Helal: None. E. Fojas: None. S. I. El-refer: None. H. M. Sabbour: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Novo Nordisk. N. Lessan: None.

Flash glucose monitoring (FGM)-derived markers of glucose control and variability and laboratory measured HbA1c among patients with diabetes on insulin in context of Ramadan fasting (RF) were examined and compared.FGM data on insulin-treated patients (n = 20, age 42.3 ± 11.4 years; 18 male, 2 female; 13 with type 1 and 7 with type 2 diabetes) who fasted during Ramadan were used to calculate Q-score as an indicator of glycaemia before, during and after RF. Post-hoc analysis in a group of patients (n = 12) who had HbA1c available and appropriate for these periods was performed. Other relevant data were extracted from patient records.Mean glucose (9.6 ± 1.32 v 10.78 ± 1.64 mmol/l; P 0.0001) and Q-score increased significantly with Ramadan fasting and reduced after Ramadan. Post-hoc subgroup analysis showed a significant rise in eA1c (7.2 ± 0.4%; 55.0 ± 4.4 mmol/mol v 7.7 ± 0.5%; 61.0 ± 5.5 mmol/mol) but not in laboratory HbA1c with Ramadan fasting; eA1c reduced after Ramadan (P = 0.018).Ramadan fasting was associated with a deterioration in overall glucose control and time in hyperglycaemia in insulin-treated patients. FGM-derived markers are useful and a preferable alternative to HbA1c in Ramadan studies.

In this study we prospectively collected data on the use of liraglutide 3 mg in obese Arab patients. As part of routine care, 2092 patients were dispensed liraglutide 3 mg. Median age was 38 years and 77% were women. Median baseline weight was 95 kg and body mass index was 36.6 kg/m2 . Of the patients, 188 (9%) had previous bariatric surgery. Seven hundred and eighty-seven patients were treated for ≥16 weeks and their median (interquartile range) weight loss was 6.0 (2.4-9.4) kg, equivalent to 6.4% (2.6%-9.7%) of baseline weight (P 5% of baseline weight while 182 (23%) achieved >10% weight loss. There was no difference in percentage weight loss between postbariatric surgery (n = 76) and non-surgical patients (n = 711). As a result of adverse events, mainly gastrointestinal symptoms, 140 (6.7%) of the patients stopped treatment. One patient developed acute pancreatitis in the context of gallstone disease but made an uneventful recovery. Liraglutide 3 mg was well tolerated and resulted in weight loss in routine clinical care similar to that seen in randomized controlled trials.

AIM To evaluate the effectiveness and safety of bariatric surgery in patients with coexisting type 1 diabetes and obesity who choose to undergo bariatric surgery for weight management. MATERIALS AND METHODS We conducted a retrospective, longitudinal review of the clinical data of patients with type 1 diabetes, followed up at our centre after bariatric surgery had been performed elsewhere. RESULTS Sixty-one patients were included, of whom 51% were women, and 57 (93%) were Emirati Arab, three (5%) were other Arab, and one (2%) was White in ethnic origin. The mean age at surgery was 31 years. A total of 42 patients (69%) underwent sleeve gastrectomy, 17 (28%) gastric bypass, and two (3%) gastric banding. In 48 patients with complete follow-up data, improvements were observed at 12 months in the median (interquartile range [IQR]) values for body mass index (BMI; 38.5 [34.9-40.9] to 26.1 [24.2-29.6] kg/m2 , P

Summary The doubly labeled water (DLW) method measures total energy expenditure (TEE) in free-living subjects. Several equations are used to convert isotopic data into TEE. Using the International Atomic Energy Agency (IAEA) DLW database (5,756 measurements of adults and children), we show considerable variability is introduced by different equations. The estimated rCO2 is sensitive to the dilution space ratio (DSR) of the two isotopes. Based on performance in validation studies, we propose a new equation based on a new estimate of the mean DSR. The DSR is lower at low body masses (, Graphical Abstract, Highlights 5,756 doubly labeled water (DLW) measures highlight variation from calculation equation We derive here new equations for calculating CO2 production when using DLW These equations outperform previous equations in validation studies We recommend these equations should be adopted in future studies using DLW in humans, Speakman et al. use a large database of doubly labeled water measurements to show the choice of equation for the calculation of energy expenditure introduces significant variation into the final estimate. They then derive new equations that outperform previous equations in validation studies against chamber calorimetry.

Copyright © 2021 The Author(s). Type 2 diabetes rates vary significantly across geographic regions. These differences are sometimes assumed to be entirely driven by differential distribution of environmental triggers, including obesity and insufficient physical activity (IPA). In this review, we discuss data which conflicts with this supposition. We carried out a secondary analysis of publicly available data to unravel the relative contribution of obesity and IPA towards diabetes risk across different populations. We used sex-specific, age-standardized estimates from Non-Communicable Disease Risk Factor Collaboration (NCD-RisC) on diabetes (1980–2014) and obesity (1975–2016) rates, in 200 countries, and from WHO on IPA rates in 168 countries in the year 2016. NCD-RisC and WHO organized countries into nine super-regions. All analyses were region- and sex-specific. Although obesity has been increasing since 1975 in every part of the world, this was not reflected in a proportional increase in diabetes rates in several regions, including Central and Eastern Europe, and High-income western countries region. Similarly, the association of physical inactivity with diabetes is not homogeneous across regions. Countries from different regions across the world could have very similar rates of diabetes, despite falling on opposite ends of IPA rate spectrum. The combined effect of obesity and IPA on diabetes risk was analyzed at the worldwide and country level. The overall findings highlighted the larger impact of obesity on disease risk; low IPA rates do not seem to be protective of diabetes, when obesity rates are high. Despite that, some countries deviate from this overall observation. Sex differences were observed across all our analyses. Overall, data presented in this review indicate that different populations, while experiencing similar environmental shifts, are apparently differentially subject to diabetes risk. Sex-related differences observed suggest that males and females are either subject to different risk factor exposures or have different responses to them. The work presented in this paper is part of a PhD project by the first author (Budour Alkaf); internal funding by Imperial College London Diabetes Centre is gratefully acknowledged. The authors are also grateful for The Medical Research Council, UK (grant numbers: MR/M013138/1, MRC/BBSRC MR/S03658X/1 (JPI HDHL H2020)) for their financial support during the authors time when conducting this piece of work and writing this paper.

Ramadan fasting (RF) can represent various challenges to glycaemic control especially in insulin-treated patients with diabetes. We aimed to assess the effect of RF on several glucose metrics using flash glucose monitoring (FGM).Complete FGM data for 29-30 days before, during and after Ramadan were available for 40 patients with type 1 (n = 13) and type 2 diabetes (n = 27) on insulin (with or without oral hypoglycaemic) treatment. Indicators of mean glucose, glucose variability (GV) and time in different glycaemic ranges were analysed.RF was associated with increase in time in hyperglycaemia (38.5 ± 18.2 vs 48.7 ± 20.7%; P 0.001) and decrease in time in hypoglycaemia (3.2 ± 2.8 vs 2.1 ± 2.1%; P = 0.003), and time in target range (56.3 ± 17.2 vs 47.9 ± 19.7%, P 0.001). There were no significant differences in markers of GV with RF; however, RF was associated with a significant reduction in GV during the day but not night time with an increase in the ensuing non-fasting period.In insulin-treated patients, RF is associated with an increase in time in hyperglycaemia, a reduced time in target range and nocturnal increase in GV, indicating a need for more refined management algorithms.