Publications by authors named "Thomas M Barber"

85 Publications

Relationship between Maternal Serum Thyroid-Stimulating Hormone and Fertilisation-Conceived Pregnancy Outcomes.

J Hum Reprod Sci 2022 Apr-Jun;15(2):163-170. Epub 2022 Jun 1.

Department of Clinical Nutrition & Dietetics, University of Sharjah, Muwailih, Sharjah, United Arab Emirates.

Background: Thyroid dysfunction impairs female fertility and pregnancy outcome. Optimal preconception and gestational TSH level is still debatable in IVF-conceived pregnancies.

Aims: To explore the relationships of IVF success and pregnancy outcomes with maternal serum levels of TSH (at both preconception and 12-week IVF-conceived pregnancy). Also, to confirm or refute the recommended TSH level ≤2.5μIU/mL.

Study Setting And Design: Retrospective cohort.

Material And Methods: 158 IVF-conceived pregnant women and 117 age-matched controls non-pregnant (≤39years, BMI 18.5-38kg/m2) were recruited. Preconception and 12-week IVF-conceived pregnancy serum samples were analysed for reproductive hormones, fasting glucose, insulin and TSH levels. Data of pregnant women at 28 weeks for GDM screening (75-gram OGTT) and up until delivery were included.

Statistical Analysis: Binary logistic regression used to predict association between preconception TSH levels and IVF success, and pregnancy outcomes. Association of delta change of hormones was determined with linear regression. Significance level ≤0.05 with 95% confidence interval (CI).

Results: Overall, median (IQR) age was 32(6)years, BMI 25.4(6.9)kg/m2, HbA1c 5.2(0.52)% and TSH 1.82(1.4)μIU/mL. There was no significant association between preconception TSH level and IVF success rate. During the first trimester of IVF-conceived pregnancy, delta change in TSH level was associated with that of progesterone (P=0.03). 12-week gestation TSH level did not predict adverse pregnancy outcomes (i.e. onset of GDM, delivery type and premature delivery); but a higher TSH level predicted earlier delivery in weeks. There was a higher risk of delivery by caesarean section when TSH>2.5μIU/mL.

Conclusion: Variation of maternal TSH within normal range (0.4-4.0μIU/mL) at preconception and 12-week gestation has no predictive effect on IVF success and pregnancy outcomes in IVF-pregnancy. Our data provide no support for a recommended preconception TSH level ≤2.5μIU/mL in IVF-conceived pregnancy, but rather promote a preconception TSH level within normal range.
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http://dx.doi.org/10.4103/jhrs.jhrs_168_21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345284PMC
June 2022

Implications of Resveratrol in Obesity and Insulin Resistance: A State-of-the-Art Review.

Nutrients 2022 Jul 13;14(14). Epub 2022 Jul 13.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.

Resveratrol is a polyphenol chemical that naturally occurs in many plant-based dietary products, most notably, red wine. Discovered in 1939, widespread interest in the potential health benefits of resveratrol emerged in the 1970s in response to epidemiological data on the cardioprotective effects of wine. To explore the background of resveratrol (including its origins, stability, and metabolism), the metabolic effects of resveratrol and its mechanisms of action, and a potential future role of dietary resveratrol in the lifestyle management of obesity. We performed a narrative review, based on relevant articles written in English from a Pubmed search, using the following search terms: "resveratrol", "obesity", "Diabetes Mellitus", and "insulin sensitivity". Following its ingestion, resveratrol undergoes extensive metabolism. This includes conjugation (with sulfate and glucuronate) within enterocytes, hydrolyzation and reduction within the gut through the action of the microbiota (with the formation of metabolites such as dihydroresveratrol), and enterohepatic circulation via the bile. Ex vivo studies on adipose tissue reveal that resveratrol inhibits adipogenesis and prevents the accumulation of triglycerides through effects on the expression of Peroxisome Proliferator-activated Receptor γ (PPARγ) and sirtuin 1, respectively. Furthermore, resveratrol induces anti-inflammatory effects, supported by data from animal-based studies. Limited data from human-based studies reveal that resveratrol improves insulin sensitivity and fasting glucose levels in patients with Type 2 Diabetes Mellitus and may improve inflammatory status in human obesity. Although numerous mechanisms may underlie the metabolic benefits of resveratrol, evidence supports a role in its interaction with the gut microbiota and modulation of protein targets, including sirtuins and proteins related to nitric oxide, insulin, and nuclear hormone receptors (such as PPARγ). Despite much interest, there remain important unanswered questions regarding its optimal dosage (and how this may differ between and within individuals), and possible benefits within the general population, including the potential for weight-loss and improved metabolic function. Future studies should properly address these important questions before we can advocate the widespread adoption of dietary resveratrol supplementation.
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http://dx.doi.org/10.3390/nu14142870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320680PMC
July 2022

Helpful or harmful? The impact of the ketogenic diet on eating disorder outcomes in type 1 diabetes mellitus.

Expert Rev Endocrinol Metab 2022 Jul 24;17(4):319-331. Epub 2022 Jun 24.

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.

Introduction: Eating disorders (EDs) are common complications in people with type 1 diabetes (PwT1D), given the rigid focus on food and insulin dose adjustment. Dietary recommendations for T1D match those for the general population, yet many fail to achieve target HbA1c. Evidence suggests that lower carbohydrate meals and thus reduced insulin requirements may decrease inconsistencies in insulin absorption, maintain euglycemia and weight. Dietary restriction is a recognized risk factor for ED development, and Ketogenic Diets (KD) involve restriction of common family-based foods, thus impacting social normality and microbiome diversity. We reviewed the current literature on PwT1D following a KD to understand effects on ED risks.

Areas Covered: Published data from MEDLINE, Embase, and PsycINFO were used. Search terms included: type 1 diabetes mellitus; or insulin dependent diabetes or T1D AND EDs or anorexia or bulimia or disordered eating AND low-carbohydrate diet or carbohydrate restricted diet or low carb diet or ketogenic diet.

Expert Opinion: Research into the effects of KDs on ED outcomes in PwT1D are limited, given the concerns over risks of diabetic ketoacidosis, hypoglycemia, and dyslipidemia. Longer term studies on the participants' experience and motivations of adhering or admonishing the diet are needed.
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http://dx.doi.org/10.1080/17446651.2022.2089112DOI Listing
July 2022

Novel perspectives of sodium handling in type 2 diabetes mellitus.

Expert Rev Endocrinol Metab 2022 Jul 21;17(4):333-341. Epub 2022 Jun 21.

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.

Introduction: As a key regulator of body water, sodium homeostasis forms an essential component of human physiology. Type 2 Diabetes Mellitus (T2D)-associated sodium overload stems from chronic renal retention of sodium, contributing toward the development of adverse cardiovascular sequelae.

Areas Covered: Our traditional model of sodium regulation invokes two compartments: extracellular fluid (ECF [plasma and interstitial fluid]) and intracellular fluid (ICF). Data from the Mars program reveal inconsistencies with this two-space model, including mismatches between net body sodium and water. Recent data utilizing Na magnetic resonance imaging (MRI) show a preponderance of bound sodium within human dermis, consistent with a third space repository and providing compelling evidence to support a three-space model in which dermal sodium binding facilitates sodium homeostasis within the ECF and ICF. This buffer is impaired in T2D, with diminishment of dermal bound sodium that may promote deleterious sequelae of sodium overload within the ECF and ICF.

Expert Opinion: Future studies should focus on novel therapeutic opportunities for sodium regulation in T2D and other conditions of sodium dysregulation. The ratio of free:bound dermal sodium (reflecting sodium storage capacity) could be utilized as a clinical biomarker for salt and water balance, to improve diagnostic accuracy and facilitate clinical decision-making.
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http://dx.doi.org/10.1080/17446651.2022.2092094DOI Listing
July 2022

Obesity definition for personalised treatment of type 2 diabetes.

Lancet 2022 06;399(10342):2189

Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Warwick Medical School, University of Warwick, Warwick, UK.

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http://dx.doi.org/10.1016/S0140-6736(22)00886-8DOI Listing
June 2022

Vitamin D Levels as an Important Predictor for Type 2 Diabetes Mellitus and Weight Regain Post-Sleeve Gastrectomy.

Nutrients 2022 May 13;14(10). Epub 2022 May 13.

Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham NG1 8NS, UK.

Weight Loss Surgery (WLS), including sleeve-gastrectomy (SG), results in significant weight loss and improved metabolic health in severe obesity (BMI ≥ 35 kg/m). Previous studies suggest post-operative health benefits are impacted by nutrient deficiencies, such as Vitamin D (25(OH)D) deficiency, while it is currently unknown whether nutrient levels may actually predict post-surgery outcomes. As such, this study investigated whether 25(OH)D levels could predict metabolic improvements in patients who underwent SG. Patients with severe obesity ( = 309; 75% female) undergoing SG participated in this ethics-approved, non-randomized retrospective cohort study. Anthropometry, clinical data, 25(OH)D levels and serum markers were collected at baseline, 6-, 12- and 18-months post-surgery. SG surgery resulted in significant improvements in metabolic health at 6- and 12-months post-surgery compared with baseline, as expected. Patients with higher baseline 25(OH)D had significantly lower HbA1c levels post-surgery ( < 0.01) and better post-surgical T2DM outcomes, including reduced weight regain ( < 0.05). Further analysis revealed that baseline 25(OH)D could predict HbA1c levels, weight regain and T2DM remission one-year post-surgery, accounting for 7.5% of HbA1c divergence ( < 0.01). These data highlight that higher circulating 25(OH)D levels are associated with significant metabolic health improvements post-surgery, notably, that such baseline levels are able to predict those who attain T2DM remission. This highlights the importance of 25(OH)D as a predictive biomarker of post-surgery benefits.
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http://dx.doi.org/10.3390/nu14102052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143791PMC
May 2022

Glucocorticoid-induced hyperglycaemia and diabetes: Call for action.

Diabet Med 2022 Aug 19;39(8):e14843. Epub 2022 Apr 19.

Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

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http://dx.doi.org/10.1111/dme.14843DOI Listing
August 2022

The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review.

Int J Mol Sci 2022 Jan 9;23(2). Epub 2022 Jan 9.

Institute of Precision Diagnostics and Translational Medicine, Pathology, University Hospitals Coventry and Warwickshire (UHCW) NHS Trust, Coventry CV2 2DX, UK.

Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring.
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http://dx.doi.org/10.3390/ijms23020695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776066PMC
January 2022

COVID-19 Outcomes in Minority Ethnic Groups: Do Obesity and Metabolic Risk Play a Role?

Curr Obes Rep 2021 Oct 15. Epub 2021 Oct 15.

Warwick Medical School, University of Warwick, Coventry, UK.

Purpose Of Review: Globally, minority ethnic groups have been at higher risk of COVID-19 mortality and morbidity than majority populations. This review outlines factors that may interact to create these inequalities and explores the hypothesis that differing levels of cardio-metabolic risk, according to ethnic group, play a role.

Recent Findings: Two UK Biobank studies have reported that the body mass index is more strongly associated with an increased risk of COVID-19 infection and mortality in minority ethnic populations than in White populations. A study of UK patients found that the strongest association between obesity and adverse COVID-19 outcomes was in people of Black ethnicity. Differences in the prevalence of obesity and its metabolic sequelae have been shown to partly mediate ethnic inequalities in COVID-19 outcomes, although not always consistently. It is possible that ethnic differences in the consequences of obesity may explain some of the remaining disparity in COVID-19 risk.
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http://dx.doi.org/10.1007/s13679-021-00459-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518892PMC
October 2021

Low Carb Program Health App Within a Hospital-Based Obesity Setting: Observational Service Evaluation.

JMIR Form Res 2021 Sep 23;5(9):e29110. Epub 2021 Sep 23.

Warwick Medical School, University of Warwick, Coventry, United Kingdom.

Background: Obesity underlies much chronic disease. Digitalization of obesity management provides an opportunity to innovate our traditional model of health care delivery within this setting, and to transform its scalability potentially to the population level.

Objective: The objective was to assess the feasibility and effectiveness of the Low Carb Program app for weight loss, applied within our hospital-based (tier 3) obesity service. Due to the disrupting effects of the COVID-19 pandemic on our obesity service, we compared the clinical outcomes from the Low Carb Program app applied in the context of remote patient appointments over the telephone with the prepandemic traditional standard of care.

Methods: We invited patients who attended our hospital-based obesity service to engage with the Low Carb Program smartphone app. We combined this approach with remote delivery (over the telephone) of obesity management from medical and psychology members of our obesity team during the COVID-19 pandemic. Outcome variables included changes in body weight and changes in HbA as a marker of glycemic control. We compared data from the Low Carb Program group with a retrospective control group (n=126) that had received traditional face-to-face obesity management from our team without concomitant use of the Low Carb Program app in the pre-COVID-19 era. T test comparisons were employed, with P<.05 considered significant.

Results: The mean weight of participants (n=105) was 130.2 kg, with 59% (n=62) females and a mean age of 48.8 years. Most participants (90/105, 86%) completed the Low Carb Program app registration process and engaged with the Low Carb Program app program; at follow-up, most participants (88/105, 84%) had actively engaged with the Low Carb Program app within the prior 30 days. The majority of participants (58/105, 55%) self-reported outcomes within the app. Mean duration of clinical follow-up for recruited participants who received the app was 7.4 months. Paired data were available for 48 participants for body weight and 41 participants for HbA. Paired sample t test analysis revealed a statistically significant mean loss of body weight of 2.7 kg (P=.001) and improvement in HbA of 3.3 mmol/mol (P=.01). The mean weight of control group patients (n=126) was 137.1 kg, with 74% (93/126) females and a mean age of 44.4 years. The mean follow-up for this group was 6 months. Data comparisons between the app user group and the pre-COVID-19 retrospective control group revealed equivalence for loss of body weight and change in HbA between the two groups.

Conclusions: We provide evidence to support the feasibility of implementing the Low Carb Program app combined with remote management; this is the first proof of concept for digitalized management within a hospital-based (tier 3) obesity service. We demonstrate the potential clinical efficacy of the approach in terms of improvements in body weight and glycemic control.
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http://dx.doi.org/10.2196/29110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462489PMC
September 2021

Mechanisms of Central Hypogonadism.

Int J Mol Sci 2021 Jul 30;22(15). Epub 2021 Jul 30.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.

Reproductive function depends upon an operational hypothalamo-pituitary-gonadal (HPG) axis. Due to its role in determining survival versus reproductive strategies, the HPG axis is vulnerable to a diverse plethora of signals that ultimately manifest with Central Hypogonadism (CH) in all its many guises. Acquired CH can result from any pituitary or hypothalamic lesion, including its treatment (such as surgical resection and/or radiotherapy). The HPG axis is particularly sensitive to the suppressive effects of hyperprolactinaemia that can occur for many reasons, including prolactinomas, and as a side effect of certain drug therapies. Physiologically, prolactin (combined with the suppressive effects of autonomic neural signals from suckling) plays a key role in suppressing the gonadal axis and establishing temporary CH during lactation. Leptin is a further key endocrine regulator of the HPG axis. During starvation, hypoleptinaemia (from diminished fat stores) results in activation of hypothalamic agouti-related peptide neurons that have a dual purpose to enhance appetite (important for survival) and concomitantly suppresses GnRH neurons via effects on neural kisspeptin release. Obesity is associated with hyperleptinaemia and leptin resistance that may also suppress the HPG axis. The suppressibility of the HPG axis also leaves it vulnerable to the effects of external signals that include morphine, anabolic-androgenic steroids, physical trauma and stress, all of which are relatively common causes of CH. Finally, the HPG axis is susceptible to congenital malformations, with reports of mutations within >50 genes that manifest with congenital CH, including Kallmann Syndrome associated with hyposmia or anosmia (reduction or loss of the sense of smell due to the closely associated migration of GnRH with olfactory neurons during embryogenesis). Analogous to the HPG axis itself, patients with CH are often vulnerable, and their clinical management requires both sensitivity and empathy.
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http://dx.doi.org/10.3390/ijms22158217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348115PMC
July 2021

Exogenous ketosis in patients with type 2 diabetes: Safety, tolerability and effect on glycaemic control.

Endocrinol Diabetes Metab 2021 Jul 20;4(3):e00264. Epub 2021 May 20.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism University of Warwick Coventry UK.

Introduction: Ketogenic diets have shown to improve glycaemic control in patients with type 2 diabetes. This study investigated the safety, tolerability, and effects on glycaemic control in patients with type 2 diabetes of an exogenous ketone monoester (KE) capable of inducing fasting-like elevations in serum β-hydroxybutyrate (βHB) without the need for caloric or carbohydrate restriction.

Methods: Twenty one participants (14 men and 7 women, aged 45 ± 11 years) with insulin-independent type 2 diabetes, and unchanged hypoglycaemic medication for the previous 6 months, were recruited for this non-randomised interventional study. Participants wore intermittent scanning glucose monitors (IS-GM) for a total of 6 weeks and were given 25 ml of KE 3 times daily for 4 weeks. Serum electrolytes, acid-base status, and βHB concentrations were measured weekly and cardiovascular risk markers were measured before and after the intervention. The primary endpoints were safety and tolerability, with the secondary endpoint being glycaemic control.

Results: The 21 participants consumed a total of 1,588 drinks (39.7 litres) of KE over the course of the intervention. Adverse reactions were mild and infrequent, including mild nausea, headache, and gastric discomfort following fewer than 0.5% of the drinks. Serum electrolyte concentrations, acid-base status, and renal function remained normal throughout the study. Compared to baseline, exogenous ketosis induced a significant decrease in all glycaemic control markers, including fructosamine (335 ± 60 μmol/L to 290 ± 49 μmol/L,  < .01), HbA1c (61 ± 10 mmol/mol to 55 ± 9 mmol/mol [7.7 ± 0.9% to 7.2 ± 0.9%],  < .01), mean daily glucose (7.8 ± 1.4 mM to 7.4 ± 1.3 mM [140 ± 23 mg/dl to 133 ± 25 mg/dl],  < .01) and time in range (67 ± 11% to 69 ± 10%,  < .01).

Conclusions: Constant ketone monoester consumption over 1 month was safe, well tolerated, and improved glycaemic control in patients with type 2 diabetes.
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http://dx.doi.org/10.1002/edm2.264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279633PMC
July 2021

How might remote management of diabetes mellitus during the COVID-19 pandemic impact patient care?

Expert Rev Endocrinol Metab 2021 07 30;16(4):155-158. Epub 2021 Jun 30.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Coventry, UK.

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http://dx.doi.org/10.1080/17446651.2021.1947795DOI Listing
July 2021

Early Predictors of Gestational Diabetes Mellitus in IVF-Conceived Pregnancies.

Endocr Pract 2021 Jun 17;27(6):579-585. Epub 2020 Dec 17.

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Clinical Sciences Research Laboratories, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry, CV2 2DX, United Kingdom.

Objective: Gestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcomes. This study aimed to identify early and reliable GDM predictors that would enable implementation of preventive and management measures.

Methods: The participants were a 28-week prospective cohort of in vitro fertilization (IVF)-conceived pregnant women (≤39 years, body mass index [BMI] 18.5-38 kg/m) without a known history of diabetes mellitus. Fasting blood samples were analyzed at baseline (pre-IVF) and 12 weeks' gestation for reproductive hormones, glucose, serum insulin, lipids, thyroid function, adiponectin, and lipopolysaccharide-binding protein. At 28 weeks, a 75-g oral glucose tolerance test was used to screen for GDM.

Results: For the overall group at baseline, 22% had BMI ≥30 kg/m, 45% had polycystic ovary syndrome, 16% had hemoglobin A1C of 5.7% to 6.1%, and 14% had a past history of GDM. At 28 weeks of gestation (n = 158), 34 women had developed GDM and 124 had not. Significant baseline predictors of GDM onset included greater BMI (29.0 vs 25.8 kg/m), older age (34 vs 32 years), higher levels of follicle-stimulating hormone/luteinizing hormone ratio (1.2 vs 1.0), hemoglobin A1C (5.5 vs 5.2%), insulin (10.6 vs 7.1 μIU/mL), homeostatic model assessment of insulin resistance (2.2 vs 1.7), total cholesterol (199 vs 171 mg/dL), and low-density lipoprotein cholesterol (123 vs 105 mg/dL), and lower triglyceride levels (74 vs 76 mg/dL). Significant 12-week GDM predictors included greater maternal weight gain (delta: 3.4 vs 1.5 kg) and higher levels of insulin (11.3 vs 7.6 μIU/mL), triglycerides (178 vs 120 mg/dL), and homeostatic model assessment of insulin resistance (2.3 vs 1.5). Twelve-week BMI is a predictor of GDM following adjustment for polycystic ovary syndrome status and maternal age.

Conclusion: While preconception maternal BMI, age, and follicle-stimulating hormone/luteinizing hormone ratio are predictors of subsequent development of GDM, early IVF-conceived gestational weight gain is the best predictor of GDM onset.
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http://dx.doi.org/10.1016/j.eprac.2020.10.020DOI Listing
June 2021

Asprosin, a novel pleiotropic adipokine implicated in fasting and obesity-related cardio-metabolic disease: Comprehensive review of preclinical and clinical evidence.

Cytokine Growth Factor Rev 2021 08 28;60:120-132. Epub 2021 May 28.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, United Kingdom; Aston Medical School, College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, United Kingdom; Warwick Medical School, University of Warwick, Coventry, CV4 7AL, United Kingdom. Electronic address:

White adipose tissue is a dynamic endocrine organ that releases an array of adipokines, which play a key role in regulating metabolic homeostasis and multiple other physiological processes. An altered adipokine secretion profile from adipose tissue depots frequently characterizes obesity and related cardio-metabolic diseases. Asprosin is a recently discovered adipokine that is released in response to fasting. Following secretion, asprosin acts - via an olfactory G-protein coupled receptor and potentially via other unknown receptor(s) - on hepatocytes and agouti-related peptide-expressing neurons in the central nervous system to stimulate glucose secretion and promote appetite, respectively. A growing body of both in vitro and in vivo studies have shown asprosin to exert a number of effects on different metabolic tissues. Indeed, asprosin can attenuate insulin signalling and promote insulin resistance in skeletal muscle by increasing inflammation and endoplasmic reticulum stress. Interestingly, asprosin may also play a protective role in cardiomyocytes that are exposed to hypoxic conditions. Moreover, clinical studies have reported elevated circulating asprosin levels in obesity, type 2 diabetes and other obesity-related cardio-metabolic diseases, with significant associations to clinically relevant parameters. Understanding the spectrum of the effects of this novel adipokine is essential in order to determine its physiologic role and its significance as a potential therapeutic target and/or a biomarker of cardio-metabolic disease. The present review offers a comprehensive overview of the published literature on asprosin, including both clinical and preclinical studies, focusing on its role in metabolism and cardio-metabolic disease.
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http://dx.doi.org/10.1016/j.cytogfr.2021.05.002DOI Listing
August 2021

Sodium in the dermis colocates to glycosaminoglycan scaffold, with diminishment in type 2 diabetes mellitus.

JCI Insight 2021 06 22;6(12). Epub 2021 Jun 22.

Warwick Medical School, University of Warwick, Coventry, United Kingdom.

Background: Dietary sodium intake mismatches urinary sodium excretion over prolonged periods. Our aims were to localize and quantify electrostatically bound sodium within human skin using triple-quantum-filtered (TQF) protocols for MRI and magnetic resonance spectroscopy (MRS) and to explore dermal sodium in type 2 diabetes mellitus (T2D).

Methods: We recruited adult participants with T2D (n = 9) and euglycemic participants with no history of diabetes mellitus (n = 8). All had undergone lower limb amputations or abdominal skin reduction surgery for clinical purposes. We used 20 μm in-plane resolution 1H MRI to visualize anatomical skin regions ex vivo from skin biopsies taken intraoperatively, 23Na TQF MRI/MRS to explore distribution and quantification of freely dissolved and bound sodium, and inductively coupled plasma mass spectrometry to quantify sodium in selected skin samples.

Results: Human dermis has a preponderance (>90%) of bound sodium that colocalizes with the glycosaminoglycan (GAG) scaffold. Bound and free sodium have similar anatomical locations. T2D associates with a severely reduced dermal bound sodium capacity.

Conclusion: We provide the first evidence to our knowledge for high levels of bound sodium within human dermis, colocating to the GAG scaffold, consistent with a dermal "third space repository" for sodium. T2D associates with diminished dermal electrostatic binding capacity for sodium.
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http://dx.doi.org/10.1172/jci.insight.145470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262470PMC
June 2021

Ethnicity-specific BMI cutoffs for obesity based on type 2 diabetes risk in England: a population-based cohort study.

Lancet Diabetes Endocrinol 2021 07 11;9(7):419-426. Epub 2021 May 11.

Warwick Medical School, University of Warwick, Coventry, UK.

Background: National and global recommendations for BMI cutoffs to trigger action to prevent obesity-related complications like type 2 diabetes among non-White populations are questionable. We aimed to prospectively identify ethnicity-specific BMI cutoffs for obesity based on the risk of type 2 diabetes that are risk-equivalent to the BMI cutoff for obesity among White populations (≥30 kg/m).

Methods: In this population-based cohort study, we used electronic health records across primary care (Clinical Practice Research Datalink) linked to secondary care records (Hospital Episodes Statistics) from a network of general practitioner practices in England. Eligible participants were aged 18 years or older, without any past or current diagnosis of type 2 diabetes, had a BMI of 15·0-50·0 kg/m and complete ethnicity data, were registered with a general practitioner practice in England at any point between Sept 1, 1990, and Dec 1, 2018, and had at least 1 year of follow-up data. Patients with type 2 diabetes were identified by use of a CALIBER phenotyping algorithm. Self-reported ethnicity was collapsed into five main categories. Age-adjusted and sex-adjusted negative binomial regression models, with fractional polynomials for BMI, were fitted with incident type 2 diabetes and ethnicity data.

Findings: 1 472 819 people were included in our study, of whom 1 333 816 (90·6%) were White, 75 956 (5·2%) were south Asian, 49 349 (3·4%) were Black, 10 934 (0·7%) were Chinese, and 2764 (0·2%) were Arab. After a median follow-up of 6·5 years (IQR 3·2-11·2), 97 823 (6·6%) of 1 472 819 individuals were diagnosed with type 2 diabetes. For the equivalent age-adjusted and sex-adjusted incidence of type 2 diabetes at a BMI of 30·0 kg/m in White populations, the BMI cutoffs were 23·9 kg/m (95% CI 23·6-24·0) in south Asian populations, 28·1 kg/m (28·0-28·4) in Black populations, 26·9 kg/m (26·7-27·2) in Chinese populations, and 26·6 kg/m (26·5-27·0) in Arab populations.

Interpretation: Revisions of ethnicity-specific BMI cutoffs are needed to ensure that minority ethnic populations are provided with appropriate clinical surveillance to optimise the prevention, early diagnosis, and timely management of type 2 diabetes.

Funding: National Institute for Health Research.
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http://dx.doi.org/10.1016/S2213-8587(21)00088-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208895PMC
July 2021

The Low-Carbohydrate Diet: Short-Term Metabolic Efficacy Versus Longer-Term Limitations.

Nutrients 2021 Apr 3;13(4). Epub 2021 Apr 3.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.

Background: Diets have been a central component of lifestyle modification for decades. The Low-Carbohydrate Diet (LCD), originally conceived as a treatment strategy for intractable epilepsy (due to its association with ketogenesis), became popular in the 1970s and since then has risen to prominence as a weight loss strategy.

Objective: To explore the efficacy, limitations and potential safety concerns of the LCD.

Data Sources: We performed a narrative review, based on relevant articles written in English from a Pubmed search, using the terms 'low carbohydrate diet and metabolic health'.

Results: Evidence supports the efficacy of the LCD in the short-term (up to 6-months) for reduction in fat mass and remission of Type 2 Diabetes Mellitus (T2D). However, the longer-term efficacy of the LCD is disappointing, with diminishment of weight loss potential and metabolic benefits of the LCD beyond 6-months of its adoption. Furthermore, practical limitations of the LCD include the associated restriction of food choices that restrict the acceptability of the LCD for the individual, particularly over the longer term. There are also safety concerns of the LCD that stem from nutritional imbalances (with a relative excess of dietary fat and protein intake with associated dyslipidaemia and increased risk of insulin resistance and T2D development) and ketotic effects. Finally, the LCD often results in a reduction in dietary fibre intake, with potentially serious adverse consequences for overall health and the gut microbiota.

Conclusions: Although widely adopted, the LCD usually has short-lived metabolic benefits, with limited efficacy and practicality over the longer term. Dietary modification needs tailoring to the individual, with careful a priori assessments of food preferences to ensure acceptability and adherence over the longer term, with avoidance of dietary imbalances and optimization of dietary fibre intake (primarily from plant-based fruit and vegetables), and with a posteriori assessments of the highly individual responses to the LCD. Finally, we need to change our view of diets from simply an excipient for weight loss to an essential component of a healthy lifestyle.
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http://dx.doi.org/10.3390/nu13041187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066770PMC
April 2021

Dietary Influences on the Microbiota-Gut-Brain Axis.

Int J Mol Sci 2021 Mar 28;22(7). Epub 2021 Mar 28.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire NHS Trust, Clifford Bridge Road, Coventry CV2 2DX, UK.

Over unimaginable expanses of evolutionary time, our gut microbiota have co-evolved with us, creating a symbiotic relationship in which each is utterly dependent upon the other. Far from confined to the recesses of the alimentary tract, our gut microbiota engage in complex and bi-directional communication with their host, which have far-reaching implications for overall health, wellbeing and normal physiological functioning. Amongst such communication streams, the microbiota-gut-brain axis predominates. Numerous complex mechanisms involve direct effects of the microbiota, or indirect effects through the release and absorption of the metabolic by-products of the gut microbiota. Proposed mechanisms implicate mitochondrial function, the hypothalamus-pituitary-adrenal axis, and autonomic, neuro-humeral, entero-endocrine and immunomodulatory pathways. Furthermore, dietary composition influences the relative abundance of gut microbiota species. Recent human-based data reveal that dietary effects on the gut microbiota can occur rapidly, and that our gut microbiota reflect our diet at any given time, although much inter-individual variation pertains. Although most studies on the effects of dietary macronutrients on the gut microbiota report on associations with relative changes in the abundance of particular species of bacteria, in broad terms, our modern-day animal-based Westernized diets are relatively high in fats and proteins and impoverished in fibres. This creates a perfect storm within the gut in which dysbiosis promotes localized inflammation, enhanced gut wall permeability, increased production of lipopolysaccharides, chronic endotoxemia and a resultant low-grade systemic inflammatory milieu, a harbinger of metabolic dysfunction and many modern-day chronic illnesses. Research should further focus on the colony effects of the gut microbiota on health and wellbeing, and dysbiotic effects on pathogenic pathways. Finally, we should revise our view of the gut microbiota from that of a seething mass of microbes to one of organ-status, on which our health and wellbeing utterly depends. Future guidelines on lifestyle strategies for wellbeing should integrate advice on the optimal establishment and maintenance of a healthy gut microbiota through dietary and other means. Although we are what we eat, perhaps more importantly, we are what our gut microbiota thrive on and they thrive on what we eat.
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http://dx.doi.org/10.3390/ijms22073502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038019PMC
March 2021

Early Metabolic Benefits of Switching Hydrocortisone to Modified Release Hydrocortisone in Adult Adrenal Insufficiency.

Front Endocrinol (Lausanne) 2021 11;12:641247. Epub 2021 Mar 11.

Warwickshire Institute for the Study of Diabetes Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry, United Kingdom.

Purpose: To compare metabolic effects of modified release hydrocortisone (MR-HC) with standard hydrocortisone (HC) therapies in adults with Adrenal Insufficiency (AI).

Methods: Adult patients (n = 12) with AI, established on HC therapy, were recruited from Endocrinology clinics at University Hospitals Coventry and Warwickshire (UHCW), UK. Baseline (HC) metabolic assessments included fasting serum HbA1C, lipid and thyroid profiles, accurate measures of body composition (BodPod), and 24-h continuous measures of energy expenditure including Sleeping Metabolic Rate (SMR) using indirect calorimetry within the Human Metabolism Research Unit, UHCW. All participants then switched HC to MR-HC with repeat (MR-HC) metabolic assessments at 3 months. Paired-sample t-tests were used for data comparisons between HC and MR-HC assessments: P-value <0.05 was considered significant.

Results: Following exclusion of 2 participants, analyses were based on 10 participants. Compared with baseline HC data, following 3 months of MR-HC therapy mean fat mass reduced significantly by -3.2 kg (95% CI: -6.0 to -0.4). Mean (SD) baseline HC fat mass vs repeat MR-HC fat mass: 31.9 kg (15.2) vs 28.7 kg (12.8) respectively, P = 0.03. Mean SMR increased significantly by +77 kcal/24 h (95% CI: 10-146). Mean (SD) baseline HC SMR vs repeat MR-HC SMR: 1,517 kcal/24 h (301) vs 1,594 kcal/24 h (344) respectively, P = 0.03. Mean body fat percentage reduced significantly by -3.4% (95% CI: -6.5 to -0.2). Other measures of body composition, energy expenditure, and biochemical analytes were equivalent between HC and MR-HC assessments.

Conclusions: In adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR.
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http://dx.doi.org/10.3389/fendo.2021.641247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992002PMC
December 2021

Relationship Between Maternal Bone Biomarkers and Fetal Adiposity Through Normal Pregnancy.

J Clin Endocrinol Metab 2021 06;106(7):e2647-e2655

Unit of Endocrinology, Diabetes Mellitus and Metabolism, Aretaieion University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Purpose: To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy.

Methods: One hundred pregnant women (aged 30.4 ± 5.6 years, mean ± SD) with prepregnancy body mass index = 24.1 ± 4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement.

Results: In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter.

Conclusions: Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight.
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http://dx.doi.org/10.1210/clinem/dgab152DOI Listing
June 2021

Obesity and polycystic ovary syndrome.

Clin Endocrinol (Oxf) 2021 10 31;95(4):531-541. Epub 2021 Jan 31.

Institute of Reproductive & Developmental Biology, Department of Metabolism, Digestion & Reproduction, Imperial College London, London, UK.

The increased global prevalence of obesity over the last 40-years has driven a rise in prevalence of obesity-related co-morbidities, including polycystic ovary syndrome (PCOS). On a background of genetic susceptibility, PCOS often becomes clinically manifest following weight gain, commonly during adolescence. A common endocrinopathy affecting between 6%-10% of reproductive-age women, PCOS presents with the cardinal features of hyperandrogenism, reproductive and metabolic dysfunction. PCOS associates with insulin resistance, independently of (but amplified by) obesity. Insulin resistance in PCOS is characterized by abnormal post-receptor signalling within the phosphatidylinositol-kinase (PI3-K) pathway. Multiple factors (including most notably, weight gain) contribute towards the severity of insulin resistance in PCOS. Compensatory hyperinsulinaemia ensues, resulting in over-stimulation of the (intact) post-receptor mitogen-activated protein kinase (MAP-K) insulin pathway, with consequent implications for steroidogenesis and ovarian function. In this concise review, we explore the effects of weight gain and obesity on the pathogenesis of PCOS from the perspective of its three cardinal features of hyperandrogenism, reproductive and metabolic dysfunction, with a focus on the central mediating role of the insulin pathway. We also consider key lifestyle strategies for the effective management of obese and overweight women with PCOS.
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http://dx.doi.org/10.1111/cen.14421DOI Listing
October 2021

Mechanisms of Insulin Resistance at the Crossroad of Obesity with Associated Metabolic Abnormalities and Cognitive Dysfunction.

Int J Mol Sci 2021 Jan 7;22(2). Epub 2021 Jan 7.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.

Obesity mediates most of its direct medical sequelae through the development of insulin resistance (IR). The cellular effects of insulin occur through two main postreceptor pathways that are the phosphatidylinositol 3-kinase (PI3-K) and the mitogen-activated protein kinase (MAP-K) pathways. Obesity-related IR implicates the PI3-K pathway that confers the metabolic effects of insulin. Numerous and complex pathogenic pathways link obesity with the development of IR, including chronic inflammation, mitochondrial dysfunction (with the associated production of reactive oxygen species and endoplasmic reticulum stress), gut microbiota dysbiosis and adipose extracellular matrix remodelling. IR itself plays a key role in the development of metabolic dysfunction, including hypertension, dyslipidaemia and dysglycaemia. Furthermore, IR promotes weight gain related to secondary hyperinsulinaemia, with a resulting vicious cycle of worsening IR and its metabolic sequelae. Ultimately, IR underlies obesity-related conditions such as type 2 diabetes mellitus (T2D) and polycystic ovary syndrome (PCOS). IR also underlies many obesity-related malignancies, through the effects of compensatory hyperinsulinaemia on the relatively intact MAP-K insulin pathway, which controls cellular growth processes and mitoses. Furthermore, the emergent data over recent decades support an important role of obesity- and T2D-related central IR in the development of cognitive dysfunction, including effects on hippocampal synaptic plasticity. Importantly, IR is largely reversible through the optimisation of lifestyle factors that include regular engagement in physical activity with the avoidance of sedentariness, improved diet including increased fibre intake and sleep sufficiency. IR lies at the key crossroad between obesity and both metabolic and cognitive dysfunction. Given the importance of IR in the pathogenesis of many 21st century chronic diseases and its eminent reversibility, it is important that we all embrace and facilitate optimised lifestyles to improve the future health and wellbeing of the populace.
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http://dx.doi.org/10.3390/ijms22020546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827338PMC
January 2021

Impact of the COVID-19 pandemic on neuroendocrine tumour services in England.

Endocrine 2021 01 5;71(1):14-19. Epub 2021 Jan 5.

The ARDEN NET Centre, ENETS Centre of Excellence, University Hospitals Coventry & Warwickshire NHS Trust, Clifford Bridge Road, Coventry, CV2 DX, UK.

Purpose: During the COVID-19 pandemic, there have been particular concerns regarding the related impact on specialist tumour services. Neuroendocrine tumour (NET) services are delivered in a highly specialised setting, typically delivered in a small number of centres that fulfil specific criteria as defined by the European Neuroendocrine Tumour Society (ENETS). We aimed to address the COVID-19-related impact on specialist NET tumour services in England and other countries.

Methods: Electronic survey addressing patient access and delivery of care distributed to all ENETS Centres of Excellence (CoE) in England and matching number of ENETS CoE elsewhere. Semi-quantitative and qualitative analyses of survey responses were performed.

Results: Survey response of ENETS CoE in England was 55% (6/11). Responses from six non-UK ENETS CoE elsewhere were received and analysed in a similar manner. Relevant disruption of various NET services was noted across all responding Centres, which included delayed patient appointments and investigations, reduced availability of treatment modalities including delayed surgical treatment and a major negative impact on research activities. The comparison between English and non-UK ENETS CoE suggested that the former had significantly greater concerns related to future research funding (p = 0.014), whilst having less disruption to multidisciplinary meetings (p = 0.01). A trend was also noted towards virtual patient appointments in ENETS CoE in England vs. elsewhere (p = 0.092).

Conclusions: Restoration of highly specialised NET services following COVID-19 and planning for future service delivery and research funding must take account of the severe challenges encountered during the pandemic.
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http://dx.doi.org/10.1007/s12020-020-02564-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782563PMC
January 2021

Regulatory microRNAs in Brown, Brite and White Adipose Tissue.

Cells 2020 11 16;9(11). Epub 2020 Nov 16.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK.

MicroRNAs (miRNAs) constitute a class of short noncoding RNAs which regulate gene expression by targeting messenger RNA, inducing translational repression and messenger RNA degradation. This regulation of gene expression by miRNAs in adipose tissue (AT) can impact on the regulation of metabolism and energy homeostasis, particularly considering the different types of adipocytes which exist in mammals, i.e., white adipocytes (white AT; WAT), brown adipocytes (brown AT; BAT), and inducible brown adipocytes in WAT (beige or brite or brown-in-white adipocytes). Indeed, an increasing number of miRNAs has been identified to regulate key signaling pathways of adipogenesis in BAT, brite AT, and WAT by acting on transcription factors that promote or inhibit adipocyte differentiation. For example, MiR-328, MiR-378, MiR-30b/c, MiR-455, MiR-32, and MiR-193b-365 activate brown adipogenesis, whereas MiR-34a, MiR-133, MiR-155, and MiR-27b are brown adipogenesis inhibitors. Given that WAT mainly stores energy as lipids, whilst BAT mainly dissipates energy as heat, clarifying the effects of miRNAs in different types of AT has recently attracted significant research interest, aiming to also develop novel miRNA-based therapies against obesity, diabetes, and other obesity-related diseases. Therefore, this review presents an up-to-date comprehensive overview of the role of key regulatory miRNAs in BAT, brite AT, and WAT.
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http://dx.doi.org/10.3390/cells9112489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696849PMC
November 2020

The expanding role of SGLT2 inhibitors beyond glucose-lowering to cardiorenal protection.

Ann Med 2021 12;53(1):2072-2089

Department of Metabolic and Cardiovascular Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

The kidney plays a major physiological role in glucose homeostasis but also contributes to the pathophysiology of type 2 diabetes (T2D), mediated by renal sodium glucose cotransporters (SGLTs). This recognition led to the development of SGLT2 inhibitors that inhibit proximal renal tubular renal glucose and sodium reabsorption. The glucoretic and natriuretic effect of SGLT2 inhibitors is associated with reductions in HbA levels, body weight, systolic blood pressure and triglycerides. Major vascular complications of T2D include cardiovascular disease and chronic kidney disease (CKD). Results from several cardiovascular outcome trials (CVOTs) with these drugs have highlighted benefits in reducing major adverse cardiovascular events by 11%, reducing the risk of cardiovascular death or hospitalization for heart failure (HF) by 23% and reducing the risk of progression of renal disease by 45%. Their cardiorenal benefits are apparent across a range of eGFRs (within CKD1-3 groups) and the presence or absence of ischaemic heart disease, HF or T2D. In patients with HF with reduced ejection fraction (HFrEF), similar risk reductions in cardiovascular death and HF events are also seen; results from studies in patients with HF with preserved ejection fraction (HFpEF) are awaited. Cardiorenal benefits have been recently reported in patients with CKD, regardless of the presence or absence of T2D. Indications for use of SGLT2 inhibitors have extended beyond glucose-lowering to a central role in cardiorenal protection. This review will first explore the mechanisms by which glycaemic control, weight loss and cardiovascular risk factors are modulated therapeutically with SGLT2 inhibitors. Subsequently, we outline putative mechanisms underpinning the cardiorenal benefits seen, including in HF and CKD, in the context of completed and ongoing clinical studies. Treatment strategies with SGLT2 inhibitors in individuals with CKD or HF, with and/or without T2D are increasingly appealing. Combination therapy with complementary therapeutic agents is also explored.
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http://dx.doi.org/10.1080/07853890.2020.1841281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592607PMC
December 2021

The Health Benefits of Dietary Fibre.

Nutrients 2020 Oct 21;12(10). Epub 2020 Oct 21.

Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.

Background: Dietary fibre consists of non-digestible forms of carbohydrate, usually as polysaccharides that originate from plant-based foods. Over recent decades, our diet within Westernised societies has changed radically from that of our hominid ancestors, with implications for our co-evolved gut microbiota. This includes increased ingestion of ultra-processed foods that are typically impoverished of dietary fibre, and associated reduction in the intake of fibre-replete plant-based foods. Over recent decades, there has been a transformation in our understanding of the health benefits of dietary fibre.

Objective: To explore the current medical literature on the health benefits of dietary fibre, with a focus on overall metabolic health.

Data Sources: We performed a narrative review, based on relevant articles written in English from a PubMed search, using the terms 'dietary fibre and metabolic health'.

Results: In the Western world, our diets are impoverished of fibre. Dietary fibre intake associates with overall metabolic health (through key pathways that include insulin sensitivity) and a variety of other pathologies that include cardiovascular disease, colonic health, gut motility and risk for colorectal carcinoma. Dietary fibre intake also correlates with mortality. The gut microflora functions as an important mediator of the beneficial effects of dietary fibre, including the regulation of appetite, metabolic processes and chronic inflammatory pathways.

Conclusions: Multiple factors contribute to our fibre-impoverished modern diet. Given the plethora of scientific evidence that corroborate the multiple and varied health benefits of dietary fibre, and the risks associated with a diet that lacks fibre, the optimization of fibre within our diets represents an important public health strategy to improve both metabolic and overall health. If implemented successfully, this strategy would likely result in substantial future health benefits for the population.
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http://dx.doi.org/10.3390/nu12103209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589116PMC
October 2020

Older age does not influence the success of weight loss through the implementation of lifestyle modification.

Clin Endocrinol (Oxf) 2021 02 6;94(2):204-209. Epub 2020 Nov 6.

Division of Biomedical Sciences, Warwick Medical School, Clinical Sciences Research Laboratories, University Hospitals Coventry and Warwickshire, Coventry, UK.

Objective: Age is sometimes a barrier for acceptance of patients into a hospital-based obesity service. Our aim was to explore the effect of age on the ability to lose weight through lifestyle interventions, implemented within a hospital-based obesity service.

Design: Retrospective study.

Patients: We included a cohort of randomly selected patients with morbid obesity (n = 242), who attended our hospital-based obesity service during 2005-2016 and received only lifestyle weight loss interventions.

Measurements: Primary outcome measures were percentage weight loss (%WL) and percentage reduction in body mass index (%rBMI) following implemented lifestyle interventions. Data were stratified according to patient age at referral: group 1 (age < 60 years, n = 167) and group 2 (age ≥ 60 years, n = 75). Weight loss was compared between groups, and correlations with age at referral were explored.

Results: The duration of hospital-based weight loss interventions ranged between 1 and 143 months (mean: 38.9 months; SD: 32.3). Baseline BMI at referral differed significantly between groups 1 and 2 (49.7 kgm [SD: 8.7] vs 46.9 kgm [SD: 6.1], respectively; P < .05). Following implemented lifestyle interventions, between groups 1 and 2 there were no differences in %WL (6.9% [SD: 16.7] vs 7.3% [SD: 11.60], respectively; P = NS) or %rBMI (8.1% [SD: 14.9] vs 7.8% [SD: 11.7], respectively; p = NS). Overall, there was no significant correlation between patient age at referral and %WL (r = -.13, p = NS).

Conclusions: Older age does not influence the success of weight loss through the implementation of lifestyle modification within a hospital-based obesity service. Therefore, age per se should not influence clinical decisions regarding acceptance of patients to hospital-based obesity services.
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http://dx.doi.org/10.1111/cen.14354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821294PMC
February 2021

Modification of fecal microbiota as a mediator of effective weight loss and metabolic benefits following bariatric surgery.

Expert Rev Endocrinol Metab 2020 09 25;15(5):363-373. Epub 2020 Aug 25.

Division of Biomedical Sciences, Warwick Medical School, University of Warwick , Coventry, UK.

Introduction: Bariatric surgery (primarily Laparoscopic Sleeve Gastrectomy [LSG] and Roux-en-Y Gastric Bypass [RYGB]) is an efficacious and durable therapeutic option for weight loss in obesity. The mechanisms that mediate weight loss following bariatric surgery remain incompletely understood.

Areas Covered: Pubmed search of published data on fecal microbiota, metabolic health, LSG, and RYGB. The fecal microbiome plays a key role in the establishment and maintenance of metabolic wellbeing, and may also contribute (through fecal dysbiosis) to metabolic dysfunction. LSG and RYGB both result in characteristic, procedure-specific changes to the fecal microbiota that may mediate at least some of the resultant weight-loss and metabolically beneficial effects, when applied to the management of obesity.

Expert Opinion: The human fecal microbiome, containing around 100 trillion microbes, evolved over millions of years and interacts symbiotically with its human host. Rodent-based studies have provided insights into the complexities of the gut-microbiome-brain axis. This includes the important role of the gut microbiome in the mediation of normal immunological development, inflammatory pathways, metabolic functioning, hypothalamic appetite regulation, and the absorption of essential nutrients as by-products of bacterial metabolism. Fecal transformation is likely to provide an important therapeutic target for future prevention and management of obesity and metabolic dysfunction.
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http://dx.doi.org/10.1080/17446651.2020.1801412DOI Listing
September 2020

Psoriatic disease and body composition: A systematic review and narrative synthesis.

PLoS One 2020 13;15(8):e0237598. Epub 2020 Aug 13.

Warwick Medical School, University of Warwick, Coventry, United Kingdom.

Background: Obesity is a leading comorbidity in psoriatic disease, including both psoriasis (PsO) and psoriatic arthritis (PsA), and is associated with adverse metabolic and cardiovascular (CV) outcomes. Anthropometric parameters, such as weight, body mass index (BMI) and waist-to-hip ratio, have been extensively reported in psoriatic disease. However, the associations of body composition and fat distribution with psoriasis have not yet been fully defined.

Objectives: To identify whether patients with psoriatic disease, including psoriatic arthritis, have altered body composition compared with the general population, and to review existing modalities for the assessment of body composition.

Methods: Electronic searches of the literature were conducted in PubMed, Medline (Ovid®), Embase (Ovid®), Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar. Titles and abstracts were reviewed by two authors independently against a set of prespecified inclusion/exclusion criteria. The research question was answered with a systematic literature review and results were summarized narratively.

Results: Twenty-five full text articles met the inclusion criteria and were included in the final narrative analysis. The studies were of heterogeneous design and used a range of objective measures to assess body composition, including simple anthropometric measures, bioimpedance analysis (BIA), dual energy X-ray absorptiometry (DXA) and computed tomography (CT). Few studies met all the quality assessment criteria. Clinical heterogeneity prevented meta-analysis.

Conclusions: Patients with psoriatic disease reveal defined body composition changes that are independent of obesity and the customary metabolic syndrome, including higher overall body fat, visceral fat and sarcopenia. These findings emphasize that patients with psoriatic disease should be screened for abnormal adipose effects beyond their weight and body mass index (BMI). Our findings show that the last decade has seen an exciting expansion of research interest in the development and validation of new modalities for the assessment of body composition. There is no consensus on the optimal assessment method of body composition for this diverse group; hence there is a need for validation of existing modalities and standardization of assessment tools.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237598PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425946PMC
October 2020
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