Dr Martin Whyte


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

Biography

Areas of specialism

Type 2 diabetes mellitus; Obesity; Insulin resistance

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

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.
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AIMS:

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.

METHODS:

Retrospective, observational study of 1000 consecutive patients admitted to an AMU in a large urban hospital.

EXCLUSION CRITERIA:

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.

RESULTS:

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.

CONCLUSIONS:

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
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
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
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
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Purpose 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. Participants 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. Findings to date 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. Future plans 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
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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Background

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. Go to:

Objective

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. Go to:

Methods

Healthy males, aged 25–60 years, of BA (n = 9) and WE (n = 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. Go to:

Results

Fasting TGs were lower in BAs than WEs on the fructose feeding day (p < 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; p = 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; p = 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 vs −4, IQR −10–1 mmol/L/min; p = 0.004) and fructose (48, IQR 15–68 vs 13, IQR −7–38 mmol/L/min; p = 0.04). Greater suppression of postprandial NEFA was evident in WE than BA after glucose feeding (−73, IQR −81– −52 vs −26, IQR −48– −3 nmol/L/min; p = 0.001) but there was no ethnic difference following fructose feeding. Go to:

Conclusions

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
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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Background

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.

Methods

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.

Results

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, p < 0.0001). The NBSR group was older than the HSE group—median 38 (IQR 32–42) vs 36 (IQR 30–41) years (Wilcoxon test p < 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 (t test, p < 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 %.

Conclusions

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
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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Introduction 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. Methods and analysis 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. Ethics and dissemination 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.
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.
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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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AIMS/HYPOTHESIS:

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.

SUBJECTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS/INTERPRETATION:

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
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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CONTEXT:

Declines in GH and testosterone (Te) secretion may contribute to the detrimental aging changes of elderly men.

OBJECTIVE:

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.

DESIGN, SETTINGS, AND PARTICIPANTS:

A 6-month, randomized, double-blind, placebo-controlled trial was performed on 80 healthy, community-dwelling, older men (age, 65-80 yr).

INTERVENTIONS:

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.

RESULTS:

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.

CONCLUSION:

Coadministration of low dose GH with Te resulted in beneficial changes being observed more often than with either GH or Te alone.
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 (P=0.046). Lixisenatide reduced CM [13C]oleate AUC60-480min concentration (P=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 (P=0.0051, P<0.05). Total glucose production rate (Ra) (P=0.015), Rameal (P=0.0098) and acetaminophen AUC0-360min (P=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.
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 Jul 18. doi: 10.1007/s00464-019-06958-w
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.
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 Aug 16. doi: 10.1111/obr.12927. [Epub ahead of print]
Martin B Whyte (2019). Is high-density lipoprotein a modifiable treatment target or just a biomarker for cardiovascular disease?
JRSM Cardiovascular Disease 2019 ePub ahead of print
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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.