Dr Martin Whyte


Clinical Senior Lecturer in Metabolic Medicine
BSc PhD MAcadMedEd FRCP FHEA
+44 (0)1483 688669
21 PG 00
Mon to Wed

Academic and research departments

School of Biosciences and Medicine.

Biography

Areas of specialism

Type 2 diabetes mellitus; Insulin resistance; Cardiovascular disease

University roles and responsibilities

  • Faculty MD co-ordinator
  • Department PGR co-ordinator

My qualifications

1995
BSc Physiology with Basic Medical Sciences
King's College London
1998
MBBS
King's College Hospital School of Medicine & Dentistry
2002
MRCP
Royal College of Physicians
2010
PhD
King's College London
2014
FHEA
Higher Education Academy
2016
FRCP
Royal College of Physicians
'The Metabolic Effects of Intensive Insulin Therapy in Critically Ill Patients'

Research

Research interests

My teaching

My publications

Highlights

Disparities in glycaemic control, monitoring and treatment in type 2 diabetes: a retrospective cohort analysis

Martin Whyte, William Hinton, Andrew McGovern, Jeremy van Vlymen, Filipa Ferreira, Silvio Calderara, Julie Mount, Neil Munro, Simon de Lusignan

PLoS Medicine Oct 2019; 16 (10), e1002942

https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002942

Publications

R.Mahmud, A.Gray, A.Nabeebaccus, M.B.Whyte (2018). Incidence and outcomes of long QTc in acute medical admissions.
Int J Clinical Practice 2018 Nov;72(11):e13250. doi: 10.1111/ijcp.13250.
View abstract View full publication
Prolonged QT interval on electrocardiogram (ECG) increases the risk of ventricular arrhythmia. Patients admitted to acute medical units (AMU) may be at risk of QT prolongation from multiple, recognised risk factors. Few data exist regarding incidence or outcomes of QT prolongation in acute general medical admissions. The aims were to determine the incidence of Bazett's-corrected QT (QTc) prolongation upon admission to AMU; the relationship between QTc and inpatient mortality, length of stay and readmission; proportion with prolonged QTc subsequently administered QT interval-prolonging drugs. Retrospective, observational study of 1000 consecutive patients admitted to an AMU in a large urban hospital. age <18 years, ventricular pacing, poor quality/absent ECG. QTc determined manually from ECG obtained within 4-hours of admission. QTc prolongation considered ≥470 milliseconds (males) and ≥480 milliseconds (females). In both genders, >500 milliseconds was considered severe. Study end-points, (a) incidence of QTc prolongation at admission; (b) inpatient mortality, length of stay and readmission rates; (c) proportion with QTc prolongation subsequently administered QT interval-prolonging drugs. Of 1000 patients, 288 patients were excluded, therefore final sample was n = 712. Patient age (mean ± SD) was 63.1 ± 19.4 years; females 49%. QTc prolongation was present in n = 50 (7%) at admission; 1.7% had QTc interval >500 ms. Of the 50 patients admitted with prolonged QTc, 6 (12%) were subsequently administered QT interval-prolonging drugs. QTc prolongation was not associated with worse inpatient mortality or readmission rate. Length of stay was greater in those with prolonged QTc, 7.2 (IQR 2.4-13.2) days vs 3.3 (IQR 1.3-10.0; P = 0.004), however, in a regression model, presence of QTc did not independently affect length of stay. QTc interval prolongation is frequent among patients admitted to AMU. QT interval-prolonging drugs are commonly prescribed to patients presenting with prolonged QTc but whether this affects clinical outcomes is uncertain

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McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S (2017). Comparison of medication adherence and persistence in type 2 diabetes: A systematic review and meta-analysis
View abstract View full publication
Limited medication adherence and persistence with treatment are barriers to successful management of type 2 diabetes (T2D). We searched MEDLINE, EMBASE, the Cochrane Library, the Register of Controlled Trials, PsychINFO and CINAHL for observational and interventional studies that compared the adherence or persistence associated with 2 or more glucose‐lowering medications in people with T2D. Where 5 or more studies provided the same comparison, a random‐effects meta‐analysis was performed, reporting mean difference (MD) or odds ratio (OR) for adherence or persistence, depending on the pooled study outcomes. We included a total of 48 studies. Compared with metformin, adherence (%) was better for sulphonylureas (5 studies; MD 10.6%, 95% confidence interval [CI] 6.5‐14.7) and thiazolidinediones (TZDs; 6 studies; MD 11.3%, 95% CI 2.7%‐20.0%). Adherence to TZDs was marginally better than adherence to sulphonylureas (5 studies; MD 1.5%, 95% CI 0.1‐2.9). Dipeptidyl peptidase‐4 inhibitors had better adherence than sulphonylureas and TZDs. Glucagon‐like peptide‐1 receptor agonists had higher rates of discontinuation than long‐acting analogue insulins (6 studies; OR 1.95; 95% CI 1.17‐3.27). Long‐acting insulin analogues had better persistence than human insulins (5 studies; MD 43.1 days; 95% CI 22.0‐64.2). The methods used to define adherence and persistence were highly variable.
Chris Woodmansey, Andrew McGovern, Katherine McCullough, Martin Whyte, Neil Munro, Ana Correa, Piers Gatenby, Simon Jones, Simon de Lusignan (2017). Incidence, demographics and clinical characteristics of diabetes following pancreatic disease: a retrospective cohort study. Diabetes Care 2017;40(11):1486-1493. doi: 10.2337/dc17-0542
View abstract View full publication
This study was conducted to describe the incidence of diabetes following pancreatic disease, assess how these patients are classified by clinicians, and compare clinical characteristics with type 1 and type 2 diabetes. Primary care records in England ( = 2,360,631) were searched for incident cases of adult-onset diabetes between 1 January 2005 and 31 March 2016. We examined demographics, diabetes classification, glycemic control, and insulin use in those with and without pancreatic disease (subcategorized into acute pancreatitis or chronic pancreatic disease) before diabetes diagnosis. Regression analysis was used to control for baseline potential risk factors for poor glycemic control (HbA1c ≥7% [53 mmol/mol]) and insulin requirement. We identified 31,789 new diagnoses of adult-onset diabetes. Diabetes following pancreatic disease (2.59 [95% CI 2.38-2.81] per 100,000 person-years) was more common than type 1 diabetes (1.64 [1.47-1.82]; < 0.001). The 559 cases of diabetes following pancreatic disease were mostly classified by clinicians as type 2 diabetes (87.8%) and uncommonly as diabetes of the exocrine pancreas (2.7%). Diabetes following pancreatic disease was diagnosed at a median age of 59 years and BMI of 29.2 kg/m2. Diabetes following pancreatic disease was associated with poor glycemic control (adjusted odds ratio, 1.7 [1.3-2.2]; < 0.001) compared with type 2 diabetes. Insulin use within 5 years was 4.1% (3.8-4.4) with type 2 diabetes, 20.9% (14.6-28.9) with diabetes following acute pancreatitis, and 45.8% (34.2-57.9) with diabetes following chronic pancreatic disease. Diabetes of the exocrine pancreas is frequently labeled type 2 diabetes but has worse glycemic control and a markedly greater requirement for insulin.

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Boughton CK, Munro N, Whyte M (2017). Targeting beta-cell preservation in the management of type 2 diabetes. British Journal of Diabetes Dec 2017; 17: 134-144
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Type 2 diabetes (T2D) is widely considered a chronic and progressive disease without cure. As beta-cell function progressively declines over time, blood glucose rises. Current management of T2D involves incremental introduction of dietary and drug therapies to achieve normoglycaemia. However, recent studies have demonstrated remission of T2D following bariatric surgery, very low calorie diet or intensive insulin therapy, raising the possibility that the declining beta-cell function in T2D may be arrested or even reversed. The point at which such interventions are introduced in the course of T2D is key for clinical benefit. Future treatment strategies should be revised to target early beta-cell preservation and thus disease remission. This article reviews the pathogenesis of beta-cell dysfunction and evidence for the clinical benefit of preserving beta-cell function in T2D, and discusses the evidence for beta-cell preservation of current glucose-lowering therapies with particular reference to their effect when initiated at the time of diagnosis of T2D.
Olubukola Ajala; Freda Mold; Charlotte Boughton; Debbie Cooke; Martin Whyte (2017). Childhood predictors of cardiovascular disease in adulthood. A systematic review and meta-analysis. Obesity Reviews 2017 May 25th. doi: 10.1111/obr.12561
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Childhood obesity predicts the risk of adult adiposity, which is associated with the earlier onset of cardiovascular disease [adult atherosclerotic cardiovascular disease, ACVD: hypertension, increased carotid intima media thickness (CIMT) stroke, ischemic heart disease (IHD)] and dysglycaemia. Because it is not known whether childhood obesity contributes to these diseases, we conducted a systematic review of studies that examine the ability of measures of obesity in childhood to predict dysglycaemia and ACVD. Data sources were Web of Science, MEDLINE, PubMed, CINAHL, Cochrane, SCOPUS, ProQuest and reference lists. Studies measuring body mass index (BMI), skin fold thickness and waist circumference were selected; of 1,954 studies, 18 met study criteria. Childhood BMI predicted CIMT: odds ratio (OR), 3.39 (95% confidence interval (CI), 2.02 to 5.67, P < 0.001) and risk of impaired glucose tolerance in adulthood, but its ability to predict ACVD events (stroke, IHD; OR, 1.04; 95% CI, 1.02 to 1.07; P < 0.001) and hypertension (OR, 1.17, 95% CI 1.06 to 1.27, P = 0.003) was weak-moderate. Body mass index was not predictive of systolic BP (r -0.57, P = 0.08) and weakly predicted diastolic BP (r 0.21, P = 0.002). Skin fold thickness in childhood weakly predicted CIMT in female adults only (rs 0.09, P < 0.05). Childhood BMI predicts the risk of dysglycaemia and abnormal CIMT in adulthood, but its ability to predict hypertension and ACVD events was weak and moderate, respectively. Skin fold thickness was a weak predictor of CIMT in female adults.
E. Lioudaki, E. Androulakis, M. Whyte, K. Stylianou, E. Daphnis, E. Ganotakis (2017). The renal effects of SGLT-2 inhibitors and other anti-diabetic drugs: Clinical relevance and potential risks. Clinical Pharmacology & Therapeutics 2017 May 8. doi: 10.1002/cpt.731
E. Lioudaki, E. Androulakis, M. Whyte, K. Stylianou, E. Daphnis, E. Ganotakis (2017). The effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiometabolic profile; beyond the hypoglycaemic action. Cardiovascular Drugs and Therapy 2017 April 25th. doi: 10.1007/s10557-017-6724-3.
Martin B. Whyte (2017). An argument against the use of Occam's razor in modern medical education. Medical Teacher 2017 Apr 10:1-2.
Katie Schwab, Ralph Smith, Vanessa Brown, Martin Whyte, Iain Jourdan (2017). Evolution of stereoscopic imaging in surgery and recent advances. World Journal of Gastrointestinal Endoscopy 2017; 9(8): 368-377
Mae Johnson, Martin Whyte, Robert Loveridge, Richard Yorke, Shairana Naleem (2017). A unified form for CPR and Treatment Escalation Plan improves communication and early collaborative decision making for acute hospital admissions. BMJ Quality Improvement Reports 2017;6:u213254.w6626. doi:10.1136/bmjquality. u213254.w6626
McGovern A, Hinton W, Correa A, Munro N, Whyte M, de Lusignan S (2016). Real world evidence studies into treatment adherence, thresholds for intervention, and disparities in treatment, in people with Type 2 Diabetes in the UK. BMJ Open 2016; 6:e012801 doi:10.1136/bmjopen-2016-012801
View abstract View full publication
The University of Surrey-Lilly Real World Evidence (RWE) diabetes cohort has been established to provide insights into the management of type 2 diabetes mellitus (T2DM). There are 3 areas of study due to be conducted to provide insights into T2DM management: exploration of medication adherence, thresholds for changing diabetes therapies, and ethnicity-related or socioeconomic-related disparities in management. This paper describes the identification of a cohort of people with T2DM which will be used for these analyses, through a case finding algorithm, and describes the characteristics of the identified cohort. A cohort of people with T2DM was identified from the Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) data set. This data set comprises electronic patient records collected from a nationally distributed sample of 130 primary care practices across England with scope to increase the number of practices to 200. A cohort (N=58 717) of adults with T2DM was identified from the RCGP RSC population (N=1 260 761), a crude prevalence of diabetes of 5.8% in the adult population. High data quality within the practice network and an ontological approach to classification resulted in a high level of data completeness in the T2DM cohort; ethnicity identification (82.1%), smoking status (99.3%), alcohol use (93.3%), glycated haemoglobin (HbA1c; 97.9%), body mass index (98.0%), blood pressure (99.4%), cholesterol (87.4%) and renal function (97.8%). Data completeness compares favourably to other, similarly large, observational cohorts. The cohort comprises a distribution of ages, socioeconomic and ethnic backgrounds, diabetes complications, and comorbidities, enabling the planned analyses. Regular data uploads from the RCGP RSC practice network will enable this cohort to be followed prospectively. We will investigate medication adherence, explore thresholds and triggers for changing diabetes therapies, and investigate any ethnicity-related or socioeconomic-related disparities in diabetes management
PurposeParticipantsFindings to dateFuture plans
Louise M Goff, Martin B Whyte, Miriam Samuel, Scott Harding (2016). Significantly greater triglyceridemia in Blacks compared to Whites following high fructose and glucose feeding: a randomized crossover trial. Lipids in Health & Disease 2016; 15(1): 145
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Black African (BA) populations are losing the cardio-protective lipid profile they historically exhibited, which may be linked with increasing fructose intakes. The metabolic effects of high fructose diets and how they relate to blood lipids are documented for Caucasians, but have not been described in BA individuals. The principle objective of this pilot study was to assess the independent impacts of high glucose and fructose feeding in men of BA ancestry compared to men of White European (WE) ancestry on circulating triglyceride (TG) concentrations. Healthy males, aged 25–60 years, of BA ( = 9) and WE ( = 11) ethnicity were randomly assigned to 2 feeding days in a crossover design, providing mixed nutrient meals with 20 % total daily caloric requirements from either added glucose or fructose. Circulating TG, non-esterified fatty acids (NEFA), glucose, insulin and C-peptide were measured over two 24-h periods. Fasting TGs were lower in BAs than WEs on the fructose feeding day ( < 0.05). There was a trend for fasting TG concentrations 24 h following fructose feeding to increase in both BA (baseline median fasting: 0.80, IQR 0.6–1.1 vs 24-h median post-fructose: 1.09, 0.8–1.4 mmol/L;  = 0.06) and WE (baseline median fasting 1.10, IQR 0.9–1.5 vs 24-h median post-fructose: 1.16, IQR 0.96–1.73 mmol/L;  = 0.06). Analysis within ethnic group demonstrated that in TG iAUC was significantly higher in BA compared to WE on both glucose (35, IQR 11–56 −4, IQR −10–1 mmol/L/min;  = 0.004) and fructose (48, IQR 15–68 13, IQR −7–38 mmol/L/min;  = 0.04). Greater suppression of postprandial NEFA was evident in WE than BA after glucose feeding (−73, IQR −81– −52 −26, IQR −48– −3 nmol/L/min;  = 0.001) but there was no ethnic difference following fructose feeding. Understanding the metabolic effects of dietary acculturation and Westernisation that occurs in Black communities is important for developing prevention strategies for chronic disease development. These data show postprandial hypertriglyceridemia following acute feeding of high added fructose and glucose in BA men, compared to WE men, may contribute to metabolic changes observed during dietary acculturation and Westernisation

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Martin Whyte, Roisin Johnson, Deborah Cooke, Kathryn Hart, Marie McCormack, Jill Shawe (2016). Diagnosing gestational diabetes mellitus in women following bariatric surgery: A national survey of lead diabetes midwives
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Background: Bariatric surgery is becoming more common among women of fertile age to manage obesity. The number of pregnancies following bariatric surgery is, therefore, likely to rise. The standard oral glucose tolerance test (OGTT) may lead to dizziness, sweating and collapse in people after some types of bariatric surgery. Aims: In view of this potential pitfall in the diagnosis of gestational diabetes mellitus (GDM) after bariatric surgery, the authors surveyed midwifery units to establish current practice for the screening and diagnosis of GDM in women who have had bariatric surgery. Methods: Out of 164 English obstetric units, 120 email surveys were sent to a network of lead diabetes midwives in units across England. A reminder email was sent 4 weeks later. Findings: Twenty-seven (22.5%) responses were received. Five respondents (26%) had specific policies in place to manage pregnancies after bariatric surgery. A wide variety of approaches to GDM screening and diagnosis were used in women with a history of bariatric surgery. The OGTT was the most widely used test after bariatric surgery. Conclusions: There is a need for national clinical guidelines to be developed for the diagnosis of GDM after bariatric surgery.
Edison E, Whyte M, van Vlymen J, Jones S, Gatenby P, de Lusignan S, Shawe J (2016). Bariatric surgery in obese women of reproductive age improves conditions that underlie fertility and pregnancy outcomes: retrospective cohort study of UK National Bariatric Surgery Registry (NBSR). Obesity Surgery 2016 Dec;26(12):2837-2842
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The aims of this study are the following: to describe the female population of reproductive age having bariatric surgery in the UK, to assess the age and ethnicity of women accessing surgery, and to assess the effect of bariatric surgery on factors that underlie fertility and pregnancy outcomes. Demographic details, comorbidities, and operative type of women aged 18–45 years were extracted from the National Bariatric Surgery Registry (NBSR). A comparison was made with non-operative cases (aged 18–45 and BMI ≥40 kg/m2) from the Health Survey for England (HSE, 2007–2013). Analyses were performed using “R” software. Data were extracted on 15,222 women from NBSR and 1073 from HSE. Women aged 18–45 comprised 53 % of operations. Non-Caucasians were under-represented in NBSR compared to HSE (10 vs 16 % respectively,  < 0.0001). The NBSR group was older than the HSE group—median 38 (IQR 32–42) vs 36 (IQR 30–41) years (Wilcoxon test  < 0.0001). Almost one third of women in NBSR had menstrual dysfunction at baseline (33.0 %). BMI fell in the first year postoperatively from 48.2 ± 8.3 to 37.4 ± 7.5 kg/m2 ( test,  < 0.001). From NBSR, in the postoperative period, the prevalence of type 2 diabetes fell by 54 %, polycystic ovarian syndrome by 15 %, and any menstrual dysfunction by 12 %. Over half of all bariatric procedures are carried out on women of reproductive age. More work is required to provide prompt and equal access across ethnic groups. At least one in three women suffers from menstrual dysfunction at baseline. Bariatric surgery improves factors that underlie fertility and pregnancy outcomes. A prospective study is required to verify these effects

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E. Lioudaki, M.B.Whyte (2016). Acute cardiac decompensation in a patient with beta-thalassemia and diabetes mellitus following cessation of chelation therapy. Clinical Case Reports 2016; 4(10): 992-996
McGovern A, Tippu Z, Hinton W, Munro N, Whyte M, de Lusignan S (2016). A systematic review of adherence rates by medication class in type 2 diabetes: Study protocol. BMJ Open 2016; 6:e010469 doi:10.1136/bmjopen-2015-010469
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Treatment options for type 2 diabetes are becoming increasingly complex with people often prescribed multiple medications, and may include both oral and injectable therapies. There is ongoing debate about which drug classes provide the optimum second-line and third-line treatment options. In the real world, patient adherence and persistence determines medication effectiveness. A better understanding of adherence may help inform the choice of second-line and third-line drug classes. This systematic review will compare adherence and persistence rates across the different classes of medication available to people with type 2 diabetes. It will include all identified studies comparing medication adherence or persistence between two or more glucose-lowering medications in people with type 2 diabetes. Research databases (MEDLINE, EMBASE, The Cochrane Library, The Register of Controlled Trials, PsychINFO and CINAHL) will be searched for relevant articles, using a comprehensive search strategy. All identified medication trials and observational studies will be included which compare adherence or persistence across classes of diabetes medication. The characteristics and outcomes of all the included studies will be reported along with a study quality grade, assessed using the Cochrane Risk Assessment Tool. The quality of adjustment for confounders of adherence or persistence will be reported for each study. Where multiple (n ≥3) studies provide compare adherence or persistence across the same 2 medication classes, a meta-analysis will be performed. No ethics approval is required. This review and meta-analysis (where possible) will provide important information on the relative patient adherence and persistence, with the different classes of diabetes therapies. Once complete, the results will be made available by peer-reviewed publication.
IntroductionMethods and analysisEthics and dissemination
M.B.Whyte and R.P. Vincent (2015). How the routine reporting of laboratory measurement uncertainty might affect clinical decision making in Acute & Emergency Medicine. Emergency Medicine Journal 2016;33:278-279 doi:10.1136/emermed-2015-205438
MB Whyte, CA Manu, D Hopkins, S Thomas (2015). Evidence of patient self-testing at clinic review: association with glycaemic control. Br J Diab Vasc Dis 2015;15(2):75-77.
M.B.Whyte, A.Quaglia, D.Hopkins (2015). Insulin detemir may be less efficacious in patients with non-alcoholic fatty liver disease and hypertriglyceridaemia. Clinical Case Reports Dec 2015
MB Whyte, S Pramodh, L Srikugan, JA Gilbert, JP Miell, RA Sherwood, AM McGregor, SJB Aylwin (2015). Importance of cannulated prolactin test in the definition of hyperprolactinaemia. Pituitary 2015;18(3): 319-25
M.B.Whyte, S Velusamy, SJB Aylwin (2014). Disease severity and staging of obesity: A rational approach to patient selection. Current Atherosclerosis Reports 2014; 16:456
I.Karageorgiou, C Chandler, MB Whyte (2014). Silent diabetes mellitus, periodontitis, and a new case of thalamic abscess. BMJ Case Reports 2014; doi:10.1136/bcr-2014-204654
L.Lee, W.I. Sung, M.M. Akhtar, M. Whyte (2012). Diaphoresis and abdominal pain caused by extra-adrenal paraganglionomas. BMJ Case Reports. July 2012
M. Whyte, N. Jackson, F. Shojaee-Moradie, R. Beale, D. Treacher, R.H.Jones, A.M. Umpleby (2010). The Metabolic Effects of Intensive Insulin Therapy in Critically Ill Patients. Am J Physiol 2010; 298(3): E697 - E705.
View abstract View full publication
Our aim was to investigate the effects of glycemic control and insulin concentration on lipolysis, glucose, and protein metabolism in critically ill medical patients. For our methods, the patients were studied twice. In study 1, blood glucose (BG) concentrations were maintained between 7 and 9 mmol/l with intravenous insulin. After study 1, patients entered one of four protocols for 48 h until study 2: low-insulin high-glucose (LIHG; variable insulin, BG of 7-9 mmol/l), low-insulin low-glucose (LILG; variable insulin of BG 4-6 mmol/l), high-insulin high-glucose [HIHG; insulin (2.0 mU . kg(-1).min(-1) plus insulin requirement from study 1), BG of 7-9 mmol/l], or high-insulin low-glucose [HILG; insulin (2.0 mU.kg(-1).min(-1) plus insulin requirement from study 1), BG of 4-6 mmol/l]. Age-matched healthy control subjects received two-step euglycemic hyperinsulinemic clamps achieving insulin levels similar to the LI and HI groups. In our results, whole body proteolysis was higher in patients in study 1 (P < 0.006) compared with control subjects at comparable insulin concentrations and was reduced with LI (P < 0.01) and HI (P = 0.001) in control subjects but not in patients. Endogenous glucose production rate (R(a)), glucose disposal, and lipolysis were not different in all patients in study 1 compared with control subjects at comparable insulin concentrations. Glucose R(a) and lipolysis did not change in any of the study 2 patient groups. HI increased glucose disposal in the patients (HIHG, P = 0.001; HILG, P = 0.07 vs. study 1), but this was less than in controls receiving HI (P < 0.03). In conclusion, low-dose intravenous insulin administered to maintain BG between 7-9 mmol/l is sufficient to limit lipolysis and endogenous glucose R(a) and increase glucose R(d). Neither hyperinsulinemia nor normoglycemia had any protein-sparing effect.
Marwood S, Constantin-Teodosiou D, Casey E, Whyte M, Boobis L, Bowtell J (2010). No Acetyl Group deficit is evident at the onset of exercise at 90% of maximal oxygen uptake in humans. J Sports Sci 2010; Jan 20: 1-13
M.Whyte, C.Down, J.Miell, M.Crook. (2009). Lack of laboratory assessment of severe hyponatraemia is associated with detrimental clinical outcomes in hospitalised patients. Int J Clin Practice 2009; 63(10): 1451 - 1455
Shojaee-Moradie F, Baynes KCR, Pentecost C, Bell JD, Thomas EL, Jackson NC, Stolinski M, Whyte M, Lovell D, Bowes SB, Gibney J, Jones RH, Umpleby AM. (2007). Exercise training reduces fatty acid availability and improves insulin sensitivity of glucose metabolism. Diabetologia 2007; 50(2): 404 - 413.
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It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. We randomised 17 sedentary overweight male subjects (age 50 +/- 2.6 years, BMI 27.6 +/- 0.5 kg/m(2)) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic-euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg(-1) min(-1)]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group. Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise

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Giannoulis MG, Sonksen PH, Umpleby M, Breen L, Pentecost C, Whyte M, McMillan CV, Bradley C, Martin FC. (2006). The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab 2006; 91(2): 477 - 484
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Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men. To assess the effects of near-physiological GH with/without Te administration on lean body mass, total body fat, midthigh muscle cross-section area, muscle strength, aerobic capacity, condition-specific quality of life (Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire), and generic health status (36-Item Short-Form Health Survey) of older men. A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65-80 yr). Participants were randomized to receive 1) placebo GH or placebo Te, 2) recombinant human GH (rhGH) and placebo Te (GH), 3) Te and placebo rhGH (Te), or 4) rhGH and Te (GHTe). GH doses were titrated over 8 wk to produce IGF-I levels in the upper half of the age-specific reference range. A fixed dose of Te (5 mg) was given by transdermal patches. Lean body mass increased with GHTe (P = 0.008) and GH (P = 0.004), compared with placebo. Total body fat decreased with GHTe only (P = 0.02). Midthigh muscle (P = 0.006) and aerobic capacity (P < 0.001) increased only after GHTe. Muscle strength changes were variable; one of six measures significantly increased with GHTe. Significant treatment group by time interactions indicated an improved Age-Related Hormone Deficiency-Dependent Quality of Life questionnaire score (P = 0.007) in the GH and GHTe groups. Bodily pain increased with GH alone, as determined by the Short-Form Health Survey (P = 0.003). There were no major adverse effects. Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.

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Martin B Whyte, Fariba Shojaee-Moradie, Sharaf E Sharaf, Nicola C Jackson, Barbara Fielding, Roman Hovorka, Jeewaka Mendis, David Russell-Jones, Margot Umpleby (2018). Lixisenatide reduces chylomicron triacylglycerol due to increased clearance. Journal of Clinical Endocrinology & Metabolism. 11 September 2018
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Context GLP-1 agonists control postprandial glucose and lipid excursion in type 2 diabetes; however the mechanism(s) are unclear. Objective To determine the mechanism(s) of postprandial lipid and glucose control with lixisenatide (GLP-1 analogue) in type 2 diabetes. Design Randomised, double-blind, cross-over study. Setting Centre for Diabetes, Endocrinology, and Research, Royal Surrey County Hospital, Guildford, UK Patients Eight obese men with type 2 diabetes (57.3±1.9yrs; BMI 30.3±1.0kg/m2, HbA1C 66.5±2.6mmol/mol, [8.2±0.3%]). Interventions Two metabolic studies, four-weeks after lixisenatide or placebo; with cross-over and repetition of studies. Main outcome measures Study one: very-low density lipoprotein (VLDL) and chylomicron (CM) triacylglycerol (TAG) kinetics were measured with iv bolus of [2H5]glycerol in a 12h study, with hourly feeding. Oral [13C]triolein, in a single meal, labelled enterally-derived TAG. Study two: glucose kinetics were measured with [U-13C]glucose in a mixed-meal (plus acetaminophen to measure gastric emptying) and variable iv [6,6-2H2]glucose infusion. Results Study one: CM-TAG (but not VLDL-TAG) pool-size, was lower with lixisenatide (=0.046). Lixisenatide reduced CM [13C]oleate AUC60-480min concentration (=0.048) and increased CM-TAG clearance; with no effect on CM-TAG production rate. Study two: postprandial glucose and insulin AUC0-240min were reduced with lixisenatide (=0.0051, <0.05). Total glucose production rate (Ra) (=0.015), Rameal (=0.0098) and acetaminophen AUC0-360min (=0.006) were lower with lixisenatide than placebo. Conclusions Lixisenatide reduced [13C]oleate concentration, derived from a single meal in CM-TAG, as well as glucose Rameal, through delayed gastric emptying. However day-long CM production, measured with repeated meal-feeding, was not reduced by lixisenatide and decreased CM-TAG concentration was due to increased CM-TAG clearance.
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Philip Kelly, Martin Whyte (2018). The normal range: it’s not normal and it’s not a range.
Postgraduate Medical Journal Nov 2018 November 2018. doi: 10.1136/postgradmedj-2018-135983
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The NHS ‘Choose Wisely’ campaign places greater emphasis on the clinician-patient dialogue. Patients are often in receipt of their laboratory data and want to know whether they are normal. But what is meant by normal? Comparator data, to a measured value, are colloquially known as the ‘normal range’. It is often assumed that a result outside this limit signals disease and a result within health. However, this range is correctly termed the ‘reference interval’. The clinical risk from a measured value is continuous, not binary. The reference interval provides a point of reference against which to interpret an individual’s results—rather than defining normality itself. This article discusses the theory of normality—and describes that it is relative and situational. The concept of normality being not an absolute state influenced the development of the reference interval. We conclude with suggestions to optimise the use and interpretation of the reference interval, thereby facilitating greater patient understanding
Martin B Whyte, Neil Munro (2019). Changing the care pathway for Type 2 diabetes at the time of diagnosis: the role of the multidisciplinary team.
Diabetic Medicine 2019 May;36(5):653-654
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Conventionally, specialists become involved in the later stages of Type 2 diabetes mellitus, whereas evidence supports the role of time‐limited specialist input at the start of treatment journey. The diagnosis of Type 2 diabetes should be seen as a key opportunity for multidisciplinary teams to intensify therapy aimed at quickly correcting underlying metabolic dysfunction.
Abbas N; ElHassan M; Kelly, P; Yorke R; Mustafa O.G; Whyte M.B (2019). Greater illness severity characterises Steroid Diabetes following acute hospitalisation.
Clinical Medicine 2019; Jan;19(1):86-87.
Martin B Whyte, Philip Kelly (2019). Laboratory tests seldom give certainty.
BMJ 2019 365: l1719
Mustafa OG, Whyte MB (2019). The use of GLP-1 receptor agonists in hospitalised patients: an untapped potential
Diabetes/Metabolism Research & Reviews. 2019 May 29:e3191. doi: 10.1002/dmrr.3191. [Epub ahead of print]
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In the outpatient setting, Glucagon‐like peptide‐1 (GLP‐1) receptor agonists have proved to be highly efficacious drugs that provide glycaemic control with a low risk of hypoglycaemia. These characteristics make GLP‐1 receptor agonists attractive agents to treat dysglycaemia in perioperative or high‐dependency hospital settings; where glycaemic variability and hyperglycaemia are associated with poor prognosis. GLP‐1 also has a direct action on the myocardium and vasculature ‐ which may be advantageous in the immediate aftermath of a vascular insult. This is a narrative review of the work in this area.   The aim was to determine the populations of hospitalised patients being evaluated and the clinical and mechanistic end‐points tested, with the institution of GLP‐1 therapy in hospital. We searched the PubMed, Embase, and Google scholar databases, combining the term ‘glucagon‐like peptide 1’ OR ‘GLP‐1’ OR ‘incretin’ OR ‘liraglutide’ OR ‘exenatide’ OR ‘lixisenatide’ OR ‘dulaglutide’ OR ‘albiglutide’ AND ‘inpatient’ OR ‘hospital’ OR ‘perioperative’ OR ‘postoperative’ OR ‘surgery’ OR ‘myocardial infarction’ OR ‘stroke’ OR ‘cerebrovascular disease’ OR ‘transient ischaemic attack’ OR ‘ICU’ OR ‘critical care’ OR ‘critical illness’ OR ‘CCU’ OR ‘coronary care unit’.   Pilot studies were reported in the fields of acute stroke, cardiac resuscitation, coronary care and perioperative care that showed advantages for GLP‐1 therapy; with normalisation of glucose, lower glucose variability and lower risk of hypoglycaemia. Animal and human studies have reported improvements in myocardial performance when given acutely after vascular insult or surgery, but these have yet to be translated into randomised clinical trials.
Surendran A, Dixon D, Whyte MB (2019). Diabetes in Pregnancy - A Practical Guide
Br J Midwifery 2019; 27(7): 413-419
Simon de Lusignan, William Hinton, Emmanouela Konstantara, Neil Munro, Martin Whyte, Julie Mount, Michael Feher (2019). Intensification to injectable therapy in type 2 diabetes: mixed methods study (protocol).
BMC Health Services Research 2019; 19:284
Stuart J Sullivan, Martin B Whyte (2019). ‘Working diagnosis’ as a means to reduce cognitive bias.
Journal Royal College Physicians Edinburgh 2019; 49(2): 172-173
M Dunstan, R Smith, KE Schwab, A Scala, P Gatenby, MB Whyte, TA Rockall, IC Jourdan (2019). Is 3D faster and safer than 4K laparoscopic cholecystectomy? A randomised-controlled trial
Surgical Endoscopy 2019; Apr;34(4):1729-1735 doi: 10.1007/s00464-019-06958-w.
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Laparoscopic surgery has well-established benefits for patients; however, laparoscopic procedures have a long and difficult learning curve, in large part due to the lack of stereoscopic depth perception. Developments in high-definition and stereoscopic imaging have attempted to overcome this. Three-dimensional high-definition (3D HD) systems are thought to improve operating times compared to two-dimensional high-definition systems. However their performance against new, ultra-high-definition ('4K') systems is not known. Patients undergoing laparoscopic cholecystectomy were randomised to 3D HD or 4K laparoscopy. Operative videos were recorded, and the time from gallbladder exposure to separation from the liver (minus on table cholangiogram) was calculated. Blinded video assessment was performed to calculate intraoperative error scores. One hundred and twenty patients were randomised, of which 109 were analysed (3D HD n = 54; 4K n = 55). No reduction in operative time was detected with 3D HD compared to 4K laparoscopy (median [IQR]; 23.41 min [17.00-37.98] vs 20.90 min [17.67-33.03]; p = 0.91); nor was there any decrease observed in error scores (60 [56-62] vs 58 [56-60]; p = 0.27), complications or reattendance. Stone spillage occurred more frequently with 3D HD, but there were no other differences in individual error rates. Gallbladder grade and operating surgeon had significant effects on time to complete the operation. Gallbladder grade also had a significant effect on the error score. A 3D HD laparoscopic system did not reduce operative time or error scores during laparoscopic cholecystectomy compared with a new 4K imaging system.
Background: Methods: Results: Conclusions:
Schwab KE, Curtis NJ, Whyte MB, Smith R, Rockall TA, Ballard K, Jourdan IC (2019). 3D laparoscopy does not reduce operative duration or errors in day case laparoscopic cholecystectomy: A randomised controlled trial.
Surgical Endoscopy 2019 Jul 16. doi: 10.1007/s00464-019-06961-1.
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Contemporary 3D platforms have overcome past deficiencies. Available trainee and laboratory studies suggest stereoscopic imaging improves performance but there is little clinical data or studies assessing specialists. We aimed to determine whether stereoscopic (3D) laparoscopic systems reduce operative time and number of intraoperative errors during specialist-performed laparoscopic cholecystectomy (LC). A parallel arm (1:1) randomised controlled trial comparing 2D and 3D passive-polarised laparoscopic systems in day-case LC using was performed. Eleven consultant surgeons that had each performed > 200 LC (including > 10 3D LC) participated. Cases were video recorded and a four-point difficulty grade applied. The primary outcome was overall operative time. Subtask time and the number of intraoperative consequential errors as identified by two blinded assessors using a hierarchical task analysis and the observational clinical human reliability analysis technique formed secondary endpoints. 112 patients were randomised. There was no difference in operative time between 2D and 3D LC (23:14 min (± 10:52) vs. 20:17 (± 9:10), absolute difference − 14.6%,  = 0.148) although 3D surgery was significantly quicker in difficulty grade 3 and 4 cases (30:23 min (± 9:24), vs. 18:02 (± 7:56),  < 0.001). No differences in overall error count was seen (total 47, median 1, range 0–4 vs. 45, 1, 0–3,  = 0.62) although there were significantly fewer 3D gallbladder perforations (15 vs. 6,  = 0.034). 3D laparoscopy did not reduce overall operative time or error frequency in laparoscopic cholecystectomies performed by specialist surgeons. 3D reduced Calot’s dissection time and operative time in complex cases as well as the incidence of iatrogenic gallbladder perforation (NCT01930344).

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Shawe J, Ceulemans D, Akhter Z, Neff K, Hart K, Heslehurst N, Stotl I, Agrawal S, Steegers R, Taheri S, Greenslade B, Rankin J , Huda B, Douek I, Ogden J, Galjaard S, Blumenfeld O, Robinson A, Whyte M, Murphy E, Wood C, Devlieger R. (2019). Pregnancy after bariatric surgery: consensus recommendations for periconception, antenatal and postnatal care.
Obesity Reviews 2019 Nov; 20(11): 1507-1522
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The objective of the study is to provide evidence‐based guidance on nutritional management and optimal care for pregnancy after bariatric surgery. A consensus meeting of international and multidisciplinary experts was held to identify relevant research questions in relation to pregnancy after bariatric surgery. A systematic search of available literature was performed, and the ADAPTE protocol for guideline development followed. All available evidence was graded and further discussed during group meetings to formulate recommendations. Where evidence of sufficient quality was lacking, the group made consensus recommendations based on expert clinical experience. The main outcome measures are timing of pregnancy, contraceptive choice, nutritional advice and supplementation, clinical follow‐up of pregnancy, and breastfeeding. We provide recommendations for periconception, antenatal, and postnatal care for women following surgery. These recommendations are summarized in a table and print‐friendly format. Women of reproductive age with a history of bariatric surgery should receive specialized care regarding their reproductive health. Many recommendations are not supported by high‐quality evidence and warrant further research. These areas are highlighted in the paper.
Martin B Whyte (2019). Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?
JRSM Cardiovascular Disease 2019 Aug 12. doi: 10.1177/2048004019869736
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Epidemiological data strongly support the inverse association between high-density lipoprotein cholesterol concentration and cardiovascular risk. Over the last three decades, pharmaceutical strategies have been partially successful in raising high-density lipoprotein cholesterol concentration, but clinical outcomes have been disappointing. A recent therapeutic class is the cholesteryl ester transfer protein inhibitor. These drugs can increase circulating high-density lipoprotein cholesterol levels by inhibiting the exchange of cholesteryl ester from high-density lipoprotein for triacylglycerol in larger lipoproteins, such as very low-density lipoprotein and low-density lipoprotein. Recent trials of these agents have not shown clinical benefit. This article will review the evidence for cardiovascular risk associated with high-density lipoprotein cholesterol and discuss the implications of the trial data for cholesteryl ester transfer protein inhibitors.
Martin Whyte, William Hinton, Andrew McGovern, Jeremy van Vlymen, Filipa Ferreira, Silvio Calderara, Julie Mount, Neil Munro, Simon de Lusignan (2019). Disparities in glycaemic control, monitoring and treatment in type 2 diabetes: a retrospective cohort analysis
PLoS Medicine 2019; https://doi.org/10.1371/journal.pmed.1002942
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Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D. A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate [eGFR]), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population ( 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio [OR] 0.86, 95% CI 0.79–0.95; 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58–0.79; 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31–0.44; 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39–0.65; 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35–0.57; 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79–0.99; 0.04) and retinopathy (OR 0.82, 95% CI 0.70–0.96; 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01–1.20; 0.023) and eGFR (OR 1.09, 95% CI 1.00–1.19; 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79–0.97; 0.01) and neuropathy (OR 0.88, 95% CI 0.80–0.97; 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation. Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups

Background

Methods and findings

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M.B.Whyte, D.Cooke (2019). Standing up for effective communication: why we should sit
BMJ 2019; Nov 23rd; 367: 316-317 (print edition)
Roberts LN, Whyte MB, Arya R (2020). Pulmonary embolism mortality trends in the European region-too good to be true?
Lancet Respir Med. 2020 Jan;8(1):e2. doi: 10.1016/S2213-2600(19)30448-5
M.B.Whyte, F. Shojaee-Moradie, S.E. Sharaf, D.J. Cuthbertson, G. J. Kemp, M. Barrett, N. C. Jackson, R. A. Herring, J. Wright, E.L. Thomas, J. Bell, B. Fielding, and A. M. Umpleby (2020). HDL-apoA-I kinetics in response to 16 weeks exercise training in men with non-alcoholic fatty liver disease (NAFLD)
American Journal of Physiology 2020. Apr 14. doi: 10.1152/ajpendo.00019.2020. [Epub ahead of print]
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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 (VLDL1). However, the effect of exercise on TAG and HDL-C metabolism is unknown. We randomized male participants to 16 wk of supervised, moderate-intensity aerobic exercise ( = 15), or conventional lifestyle advice ( = 12). Apolipoprotein A-I (apoA-I) and VLDL-TAG and apolipoprotein B (apoB) kinetics were investigated using stable isotopes (1-[13C]-leucine and 1,1,2,3,3-2H5 glycerol) pre- and postintervention. Participants underwent MRI/spectroscopy to assess changes in visceral fat. Results are means ± SD. At baseline, there were no differences between exercise and control groups for age (52.4 ± 7.5 vs. 52.8 ± 10.3 yr), body mass index (BMI: 31.6 ± 3.2 vs. 31.7 ± 3.6 kg/m2), and waist circumference (109.3 ± 7.5 vs. 110.0 ± 13.6 cm). Percentage of liver fat was 23.8 (interquartile range 9.8-32.5%). Exercise reduced body weight (101.3 ± 10.2 to 97.9 ± 12.2 kg; < 0.001) and hepatic fat content [from 19.6%, interquartile range (IQR) 14.6-36.1% to 8.9% (4.4-17.8%); = 0.001] and increased the fraction HDL-C concentration (measured following ultracentrifugation) and apoA-I pool size with no change in the control group. However, plasma and VLDL1-TAG concentrations and HDL-apoA-I fractional catabolic rate (FCR) and production rate (PR) did not change significantly with exercise. Both at baseline (all participants) and after exercise there was an inverse correlation between apoA-I pool size and VLDL-TAG and -apoB pool size. The modest effect of exercise on HDL metabolism may be explained by the lack of effect on plasma and VLDL1-TAG.
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Benedict McDonaugh, Martin B Whyte (2020). The evolution and future direction of cardiac biomarkers.
Eur Med J 2020 May. In Press
Martin B. Whyte, Prashanth Vas, Christian Heiss, Michael D. Feher (2020). The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19
Diabetes Research and Clinical Practice 2020 Jun; 164: 108217. doi: 10.1016/j.diabres.2020.108217
M Stedman, M Whyte, M Lunt, M Albanese, M Livingston, R Gadsby, S Anderson, A Heald (2020). The treatment rate of erectile dysfunction (ED) in younger men with Type 2 Diabetes is up to 4 times higher than the equivalent non-diabetes population.
Int J Clin Practice 19th May 2020 doi.org/10.1111/ijcp.13538
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Erectile Dysfunction (ED) is common in older age and in diabetes (DM). Phosphodiesterase type 5‐inhibitors (PDE5‐is) are the first‐line for ED. We investigated how type of diabetes and age of males affects the PDE5‐i use in the primary care setting. 2018‐19 general practice level quantity of all PDE5‐i agents were taken from the GP Prescribing Data set in England. The variation in outcomes across practices was examined across one year, and for the same practice against the previous year. We included 5,761 larger practices supporting 25.8million men of whom 4.2million≥65 years old. Of these, 1.4million had T2DM, with 0.8million of these>65. 137,000 people had T1DM. 28.8million tablets of PDE5‐i were prescribed within the 12 months (2018‐19) period in 3.7million prescriptions (7.7 tablets/prescription), at total costs of £15.8million (£0.55/tablet). The NHS ED limit of 1 tablet/user/week suggests that 540,000 males are being prescribed a PDE5‐i at a cost of £29/year each. With approximately 30,000 GPs practising, this is equivalent to one GP providing 2.5 prescriptions/week to overall 18 males. There was a 3x variation between the highest decile of practices (2.6 tablets/male/year) and lowest decile (0.96 tablets/male/year). The statistical model captured 14% of this variation and showed T1DM males were the largest users, while men age<65 with T2DM were being prescribed 4 times as much as non‐DM. Those T2DM>65 were prescribed 80% of the non‐DM amount. There is wide variation in use of PDE5‐is. With only 14% variance capture, other factors including wide variation in patient awareness, prescribing rules of local health providers, and recognition of the importance of male sexual health by GP prescribers might have significant impact.
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Martin B Whyte (2020). Adult height as a contributor to cardiometabolic risk.
Postgraduate Medical Journal 2020 June 11th doi: 10.1136/postgradmedj-2020-138164. online ahead of print
P.R.J. Vas, M. B. Whyte, N. Papanas (2020). Association between glycaemic control and diabetic foot outcomes: dark side of the moon?
Journal of Diabetes and its Complications 2020; 8th June. doi 10.1016/j.jdiacomp.2020.107650
Simon Steenson, Fariba Shojaee-Moradie, Martin B. Whyte, Kim G. Jackson, Julie L. Lovegrove, Barbara A. Fielding, A.Margot Umpleby (2020). The effect of fructose feeding on intestinal triacylglycerol production and de novo fatty acid synthesis in humans
Nutrients 2020, 12(6), 1781; https://doi.org/10.3390/nu12061781
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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. They consumed hourly mixed-nutrient drinks that were high-fructose (30% energy) or low-fructose (<2% energy) for 11 h. Oral 2H2O was administered to measure fasting and postprandial DNL. Postprandial chylomicron (CM)-TAG and very low-density lipoprotein (VLDL)-TAG kinetics were measured with an intravenous bolus of [2H5]-glycerol. CM and VLDL were separated by their apolipoprotein B content using antibodies. Plasma TAG ( < 0.005) and VLDL-TAG ( = 0.003) were greater, and CM-TAG production rate (PR, = 0.046) and CM-TAG fractional catabolic rate (FCR, = 0.073) lower when high-fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower ( = 0.005) and apoB48 ( = 0.039), apoB100 ( = 0.013) and non-esterified fatty acids (NEFA) ( = 0.013) were higher after high-fructose. Postprandial hepatic fractional DNL was higher than intestinal fractional DNL with high-fructose ( = 0.043) and low-fructose ( = 0.043). Fructose consumption had no effect on the rate of intestinal or hepatic DNL. We provide the first measurement of the rate of intestinal DNL in humans. Lower CM-TAG PR and CM-TAG FCR with high-fructose consumption suggests lower clearance of CM, rather than elevated production, may contribute to elevated plasma TAG, possibly due to lower insulin-mediated stimulation of lipoprotein lipase
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PRJ Vas, D Hopkins, MD Feher, F Rubino, MB Whyte (2020). Diabetes, Obesity and COVID-19: A Complex Interplay
Diabetes, Obesity and Metabolism 2020 In Press
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With the accumulation of observational data showing an association of metabolic co‐morbidities with adverse outcomes from COVID‐19, there is a need to disentangle the contributions of pre‐existing macro‐ and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID‐19, the clinical and research questions which arise from this relationship, and the types of studies needed to answer those questions. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience of or interest in the management of COVID‐19.
Martin B. Whyte, Philip A. Kelly, Elisa Gonzalez, Roopen Arya, Lara N. Roberts (2020). Pulmonary Embolism in hospitalised patients with COVID-19
Thrombosis Research 195 (2020): 95-99
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Background: Coronavirus disease 2019 (COVID-19) is characterised by dyspnoea and abnormal coagulation parameters, including raised D-dimer. Data suggests a high incidence of pulmonary embolism (PE) in ventilated patients with COVID-19. Objectives: To determine the incidence of PE in hospitalised patients with COVID-19 and the diagnostic yield of Computer Tomography Pulmonary Angiography (CTPA) for PE. We also examined the utility of D-dimer and conventional pre-test probability for diagnosis of PE in COVID-19. Patients/methods: Retrospective review of single-centre data of all CTPA studies in patients with suspected or confirmed COVID-19 identified from Electronic Patient Records (EPR). Results: There were 1477 patients admitted with COVID-19 and 214 CTPA scans performed, of which n = 180 (84%) were requested outside of critical care. The diagnostic yield for PE was 37%. The overall proportion of PE in patients with COVID-19 was 5.4%. The proportions with Wells score of ≥4 (‘PE likely’) was 33/134 (25%) without PE vs 20/80 (25%) with PE (P = 0.951). The median National Early Warning-2 (NEWS2) score (illness severity) was 5 (interquartile range [IQR] 3–9) in PE group vs 4 (IQR 2–7) in those without PE (P = 0.133). D-dimer was higher in PE (median 8000 ng/mL; IQR 4665–8000 ng/mL) than non-PE (2060 ng/mL, IQR 1210–4410 ng/mL, P < 0.001). In the ‘low probability’ group, D-dimer was higher (P < 0.001) in those with PE but had a limited role in excluding PE. Conclusions: Even outside of the critical care environment, PE in hospitalised patients with COVID-19 is common. Of note, approaching half of PE events were diagnosed on hospital admission. More data are needed to identify an optimal diagnostic pathway in patients with COVID-19. Randomised controlled trials of intensified thromboprophylaxis are urgently needed.
Zixing Tan, Mike Stedman, Martin Whyte, Simon Anderson, George Thomson, Adrian Heald (2020). Personal protective equipment (PPE) and infection among healthcare workers – what is the evidence?
International Journal of Clinical Practice 2020. Online ahead of print https://doi.org/10.1111/ijcp.13617
Lara Roberts, Martin Whyte, Loizos Georgiou, Gerard Giron, Julia Czuprynska, Catherine Rea, Bipin Vadher, Raj Patel, Emma Gee, Roopen Arya (2020). Post-discharge venous thromboembolism following hospital admission with COVID-19
Blood 2020. In press
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The association of severe COVID-19 with an increased risk of VTE has resulted in specific guidelines for its prevention and management. The VTE risk appears highest in those with critical care admission. The need for post discharge thromboprophylaxis remains controversial and this is reflected in the conflicting recommendations of expert guidelines. Our local protocol provides thromboprophylaxis to COVID-19 patients during admission only. We report post-discharge VTE data from an ongoing quality improvement programme incorporating root cause analysis of hospital-associated VTE (HA-VTE). Following 1,877 hospital discharges associated with COVID-19, there were 9 episodes of HA-VTE diagnosed within 42 days, to give a post-discharge rate of 4.8 per 1000 discharges. Over 2019, following 18,159 discharges associated with a medical admission; there were 56 episodes of HA-VTE within 42 days (3.1 per 1000 discharges). The odds ratio for post-discharge HA-VTE associated with COVID-19 compared to 2019 was 1.6 (95% CI 0.77-3.1). Hospitalisation with COVID-19 does not appear to increase the risk of post-discharge HA-VTE compared to hospitalisation with other acute medical illness. Given the risk-benefit ratio of post discharge thromboprophylaxis remains uncertain, randomised controlled trials to evaluate the role of continuing thromboprophylaxis in patients with COVID-19 following hospital discharge are required.