Publications by authors named "Margot Umpleby"

Aim: To examine the hypothesis that there would be ethnic differences in the relationship between ectopic fat and tissue-specific insulin resistance (IR) across a spectrum of glucose tolerance in Black African (BA) and White European (WE) men.

Materials And Methods: Fifty-three WE men (23/10/20 normal glucose tolerance [NGT]/impaired glucose tolerance [IGT]/type 2 diabetes [T2D]) and 48 BA men (20/10/18, respectively) underwent a two-step hyperinsulinaemic-euglycaemic clamp with infusion of D-[6,6-H]-glucose and [H]-glycerol to assess hepatic, peripheral and adipose tissue IR. Magnetic resonance imaging was used to measure subcutaneous adipose tissue, visceral adipose tissue (VAT) and intrahepatic lipid (IHL).

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Black African-Caribbean (BAC) populations are at greater risk of cardiometabolic disease than White Europeans (WE), despite exhibiting lower fasting triacylglycerol (TAG) concentrations. However, limited data exist regarding postprandial fatty acid metabolism in BAC populations. This study determined the ethnic differences in postprandial fatty acid metabolism between overweight and obese WE and BAC men.

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Article Synopsis
  • Exercise training significantly reduced liver fat levels in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD), even without substantial weight loss.
  • A pooled analysis of three trials showed that those who exercised had about five times higher odds of achieving a ≥30% reduction in liver fat compared to controls.
  • Improvements were also observed in body measurements, body composition, and aerobic fitness, highlighting the benefits of exercise on liver health regardless of changes in body weight.
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Background And Objectives: Very-low calorie diets (VLCD) achieve weight loss and remission of Type 2 diabetes (T2DM), but efficacy and acceptability in non-European populations is less clear. This feasibility study examines the impact of 10% weight loss through VLCD on metabolic and body composition outcomes in a multi-ethnic cohort of Aotearoa New Zealand (AoNZ) men with prediabetes/early T2DM, and VLCD tolerability/cultural acceptability.

Methods And Study Design: Participants followed a VLCD intervention (mean energy 3033kJ/day) until achievement of 10% weight loss.

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Objective: This work aimed to investigate the effect of the SGLT2 inhibitor, dapagliflozin (DAPA), on cardiac function and the metabolic and hormonal response to moderate exercise in people with type 2 diabetes.

Methods: This was a double-blind, placebo-controlled crossover study with a 4-week washout period. Nine participants were randomly assigned to receive either 4 weeks of DAPA or 4 weeks of placebo.

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Objective: To investigate the mechanism for increased ketogenesis following treatment with the SGLT2 inhibitor dapagliflozin in people with type 2 diabetes.

Research Design And Methods: The design was a double-blind, placebo-controlled, crossover study with a 4-week washout period. Participants received dapagliflozin or placebo in random order for 4 weeks.

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Scope: Fructose exacerbates post-prandial hypertriacylglycerolaemia; perhaps partly due to increased enterocyte de novo lipogenesis (DNL). It is unknown whether this is concentration-dependent or if fructose has a greater effect on lipid synthesis than glucose. Dose-dependent effects of fructose and glucose on DNL and de novo triacylglycerol (TAG)-glycerol synthesis are investigated in a Caco-2 cell model.

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Aim: People of Black African ancestry, who are known to be at disproportionately high risk of type 2 diabetes (T2D), typically exhibit lower hepatic insulin clearance compared with White Europeans. However, the mechanisms underlying this metabolic characteristic are poorly understood. We explored whether low insulin clearance in Black African (BA) men could be explained by insulin resistance, subclinical inflammation or adiponectin concentrations.

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Introduction: The newer glucose-lowering therapies for type 2 diabetes (T2D), the glucagon-like peptide-1 receptor agonists (GLP1-RAs) and the sodium-glucose co-transporter 2 inhibitors (SGLT2i), have additional clinical benefits beyond improving glycaemic control; promoting weight loss, addressing associated cardiovascular risk factors and reducing macrovascular and microvascular complications. Considering their independent mechanisms of actions, there is a potential for significant synergy with combination therapy, yet limited data exist. This 32-week randomised, double-blind, placebo-controlled trial will gain mechanistic insight into the effects of coadministration of exenatide QW, a weekly subcutaneous GLP1-RA, with dapagliflozin, a once daily oral SGLT2i, on the dynamic, adaptive changes in energy balance, total, regional and organ-specific fat mass and multiorgan insulin sensitivity.

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Aims: We aimed to assess ethnic differences in inflammatory markers and their relationships with insulin sensitivity and regional adiposity between white European and black African men.

Methods: A total of 53 white European and 53 black African men underwent assessment of inflammatory markers alongside Dixon-magnetic resonance imaging to quantify subcutaneous and visceral adipose tissue and intrahepatic lipid. A hyperinsulinaemic-euglycaemic clamp was used to measure whole-body and adipose tissue insulin sensitivity.

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Introduction: It is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry.

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Article Synopsis
  • The study aimed to analyze the relationship between the FTO allele (rs9939609) and insulin sensitivity (IS) and glucose tolerance in people with obesity, using various tests to measure these factors in 97 individuals with a BMI ≥35.
  • There were significant differences in insulin sensitivity between male genotype groups, with A/A showing lower glucose disappearance, metabolic clearance, and overall insulin sensitivity compared to T/T genotype, while no differences were found among females.
  • The results indicated that females generally had better insulin sensitivity and glucose tolerance than males, while the FTO risk-allele effect was only observed in males, highlighting the need for further research in this area.
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It has been proposed that a high sugar intake was associated with cardiovascular disease (CVD) risk and metabolic syndrome depending on the amount of carbohydrate (CHO), other nutrients in foods, and underlying metabolic disturbances. This study aimed to investigate the effects of high (HS) and low sugar (LS) diets on metabolic profiles in 25 middle-aged men at increased CVD risk in a 12-week randomised cross-over intervention study. An isocaloric dietary exchanged model consisted of HS (24% energy from sugar) and LS (6% energy from sugar) with comparable total CHO, fat and fibre composition in normal foods was used.

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In this study, we aimed to assess ethnic differences in visceral (VAT), deep subcutaneous (dSAT), and superficial subcutaneous (sSAT) adipose tissue and their relationships with inflammatory markers between white European (WE) and black West African (BWA) men with normal glucose tolerance (NGT) and type 2 diabetes (T2D). Forty-two WE (23 NGT/19 T2D) and 43 BWA (23 NGT/20 T2D) men underwent assessment of plasma inflammatory markers using immunoassays alongside Dixon magnetic resonance imaging to quantify L4-5 VAT, dSAT and sSAT. Despite no ethnic differences in sSAT and dSAT, BWA men exhibited lower VAT ( = 0.

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Objective: To determine the effect of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on glucose flux, lipolysis, and ketone body concentrations during insulin withdrawal in people with type 1 diabetes.

Research Design And Methods: A double-blind, placebo-controlled crossover study with a 4-week washout period was performed in 12 people with type 1 diabetes using insulin pump therapy. Participants received dapagliflozin or placebo in random order for 7 days.

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A high fructose intake exacerbates postprandial plasma triacylglycerol (TAG) concentration, an independent risk factor for cardiovascular disease, although it is unclear whether this is due to increased production or impaired clearance of triacylglycerol (TAG)-rich lipoproteins. We determined the in vivo acute effect of fructose on postprandial intestinal and hepatic lipoprotein TAG kinetics and de novo lipogenesis (DNL). Five overweight men were studied twice, 4 weeks apart.

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A Nutrition Society member-led meeting was held on 9 January 2020 at The University of Surrey, UK. Sixty people registered for the event, and all were invited to participate, either through chairing a session, presenting a '3 min lightning talk' or by presenting a poster. The meeting consisted of an introduction to the topic by Dr Barbara Fielding, with presentations from eight invited speakers.

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Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL). However, the effect of exercise on TAG and HDL-C metabolism is unknown.

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Objectives: In men of black west African (BAM) and white European (WEM) ethnicity, we aimed to (1) compare adipose tissue, peripheral and hepatic insulin sensitivity and (2) investigate associations between ectopic fat and insulin sensitivity by ethnicity.

Design And Methods: In overweight BAM (n = 21) and WEM (n = 23) with normal glucose tolerance, we performed a two-step hyperinsulinaemic-euglycaemic clamp with infusion of [6,6 2H2]-glucose and [2H5]-glycerol to measure whole body, peripheral, hepatic and adipose tissue insulin sensitivity (lipolysis). Visceral adipose tissue (VAT), intrahepatic lipids (IHL) and intramyocellular (IMCL) lipids were measured using MRI and spectroscopy.

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Aims: We aimed to assess ethnic differences in visceral adipose tissue (VAT), intrahepatic (IHL), intrapancreatic (IPL) and intramyocellular lipids (IMCL) between healthy white European (WE) and black west African (BWA) men.

Methods: 23 WE and 20 BWA men underwent Dixon-magnetic resonance imaging to quantify VAT, IHL and IPL; and proton-magnetic resonance spectroscopy to quantify IMCL. Insulin sensitivity and beta-cell function were determined using homeostasis model assessment (HOMA-2).

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Background: Anthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations.

Objective: In the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome.

Methods: A double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.

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Aims/hypothesis: Type 2 diabetes is more prevalent in black African than white European populations although, paradoxically, black African individuals present with lower levels of visceral fat, which has a known association with insulin resistance. Insulin resistance occurs at a tissue-specific level; however, no study has simultaneously compared whole body, skeletal muscle, hepatic and adipose tissue insulin sensitivity between black and white men. We hypothesised that, in those with early type 2 diabetes, black (West) African men (BAM) have greater hepatic and adipose tissue insulin sensitivity, compared with white European men (WEM), because of their reduced visceral fat.

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Context: Intrapancreatic lipid (IPL) has been linked to β-cell dysfunction. Black populations disproportionately develop type 2 diabetes (T2D) and show distinctions in β-cell function compared with white populations.

Objective: We quantified IPL in white European (WE) and black West African (BWA) men with early T2D and investigated the relationships between IPL and β-cell insulin secretory function (ISF).

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