E S Kilpatrick

San Diego Zoo, San Diego, California, United States

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Publications (110)

  • [Show abstract] [Hide abstract] ABSTRACT: Menopausal estrogen loss leads to an increased bone loss. Soy isoflavones can act as selective estrogen receptor modulators, their role in bone turnover is unclear. The primary outcome was assessing changes in plasma bone turnover markers. The secondary outcomes were assessing changes in cardiovascular risk markers including insulin resistance, blood pressure and lipid profile. We performed a double blind randomised parallel study where 200 women within 2 years after the onset of their menopause were randomised to 15 g soy protein with 66mg isoflavone (SPI) or 15 g soy protein alone (SP), daily for 6 months. There was a significant reduction in type I collagen crosslinked Beta C-telopeptide (βCTX) (bone-resorption marker) with SPI supplementation (0.40 ± 0.17 vs. 0.15 ± 0.09µg/L; p < 0.01) compared to SP supplementation (0.35 ± 0.12 vs. 0.35 ± 0.13µg/L; p = 0.92) after 6 months. There was also a significant reduction in type I procollagen-N-propeptide (P1NP) (bone-formation marker) with SPI supplementation (50.5 ± 25.0 vs. 34.3 ± 17.6µg/L; p < 0.01), more marked between 3 and 6 month. Following SPI there was a significant reduction in fasting glucose, fasting insulin, insulin resistance and systolic blood pressure whereas no significant changes in these parameters was observed with SP. There were no significant changes in fasting lipid profile and diastolic blood pressure with either preparation. There was a significant increase in TSH and reduction in free thyroxine (p < 0.01) with SPI supplementation though free tri-iodothyronine was unchanged. In conclusion, soy protein with isoflavones may confer a beneficial effect on bone health, analogous to the mode of action of anti-resorptive agents albeit to a less magnitude. There was a significant improvement of cardiovascular risk markers, but a significant increase in TSH and reduction in free thyroxine after SPI supplementation indicating a detrimental effect on thyroid function. This article is protected by copyright. All rights reserved.
    Article · Jul 2016 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research
  • Article · May 2015 · Annals of internal medicine
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    [Show abstract] [Hide abstract] ABSTRACT: Background Obese patients with type two diabetes mellitus (T2DM) may have a better prognosis than patients of normal weight, but reports are limited by study size, duration and confounders. Methods We investigated the relationship between body mass index (BMI) and prognosis in 10,568 patients with T2DM without known CV disease followed for a median of 10.6 (IQR: 7.8–13.4) years. Hospital admissions for acute coronary syndrome (ACS), cerebrovascular accidents (CVA) and heart failure (HF) and all-cause mortality were recorded. Information on comorbidity (cancer, lung diseases and chronic renal failure) was also collected as confounder. Results Median age was 63 ± 19 years, 54% were men and median BMI was 28.8 (IQR: 25.2–32.4 kg.m2). Adjusting for differences in age and other variables, patients in the highest quartile of BMI had the greatest risk of hospitalisation for ACS or HF (HRs with 95% CI for highest versus lowest quartile were 1.39 1.14–1.70; p = 0.001 and 1.36 1.08–1.71; p = 0.01 respectively) but the risk of CVA was similar amongst BMI quartiles. However, patients in higher BMI quartiles had lower mortality rates, with the nadir of risk at BMI 25–30 kg/m2 (adjusted for confounders). Greater BMI was associated with lower mortality especially amongst older patients. Conclusions Patients with T2DM and moderately increased BMI, in the overweight range of 25–30 kg/m2, have a lower mortality than slimmer patients. Amongst older patients, even higher BMI may be associated with lower risk. However, obesity is associated with an increased risk of hospitalisation for cardiovascular events.
    Full-text Article · Jun 2014 · Heart (British Cardiac Society)
  • Article · Mar 2014 · Diabetic Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Obesity is a key trigger for insulin resistance leading to type-2 diabetes mellitus (T2DM). However, recent evidence suggests that obese patients with T2DM may have lower morbidity and mortality compared to patients of normal weight. These reports are limited by statistical power and confounders. We investigated the relationship between Body Mass Index (BMI), mortality and cardiovascular (CV) morbidity in a long-term large cohort of patients with T2DM. Methods: Between 1995 and 2011, weight (BMI), blood pressure, dyslipidemia, smoking and comorbidities was collected in patients with T2DM without known CV disease. Patients were followed prospectively. Total mortality and hospital admissions for acute coronary syndrome (ACS), cerebrovascular accidents (CVA) and heart failure (HF) were gathered. Subjects were divided according to BMI quartiles and in age tertiles. ANOVA was used to compare covariates amongst the BMI groups, Chi square and multivariate Cox-Regression analysis were used to assess the prognostic impact of BMI and confounders on the above-defined events. Sensitivity analysis was performed accounting for cancer, BMI<18.5 and gender. Results: Of 12025 patients (54% men, mean age 60+15 years), followed for a mean of 10+4 years), 4125 (34%)died. In the first age tertile (42+10 years), there was a U-shaped relationship between BMI and outcome; those with BMI 25-28 had the lowest mortality (X2 15.2 P<0.01). In the second age tertile (62+6 years), there was a similar mortality across BMI quartiles (X2 5.1 P=0.14). In the oldest age tertile (75+5 years), mortality was inversely related to BMI; those with BMI 27-30 had the lowest mortality X2 33.0 P<0.0001. Excluding patients with cancer, BMI <18.5 or adjusting for sex did not significantly affect these results. In a multi-variable Cox Regression model, including age, sex, smoking, blood pressure, cancer and diabetes duration, higher BMI was still associated with a lower mortality. However, patients in higher BMI quartiles had a higher incidence of ACS and HF in all age tertiles (all X2 P<0.05) and CVA showed a similar trend. In multi-variable Cox regression models, the association between higher BMI and CV morbidity remained after adjusting for other variables. Conclusion: In this analysis, although being overweight was associated with an increased risk of CV events in patients with T2DM, higher BMIs were associated with a survival benefit in older patients. Slim patients with T2DM may have a more severe metabolic disorder than patients in whom insulin resistance is primarily due to obesity.
    Article · Aug 2013 · European Heart Journal
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    J Konya · J M Ng · H Cox · [...] · E S Kilpatrick
    [Show abstract] [Hide abstract] ABSTRACT: AimsHbA(1c) values are unreliable in patients with diabetes who have chronic kidney disease who receive iron and/or erythropoiesis stimulating agents. The study aimed to evaluate the utility of the complementary glycaemic markers glycated albumin, fructosamine and 1,5 anhydroglucitol in this group of patients. MethodsA prospective study of patients with Type2 diabetes and chronic kidney disease stageIIIB/IV undergoing intravenous iron or erythropoiesis-stimulating agent therapy. Glycaemic control was monitored using HbA(1c), seven-point daily glucose thrice weekly, continuous glucose monitoring, glycated albumin, fructosamine and 1,5 anhydroglucitol. ResultsFifteen patients [9 men; median age 72years (interquartile range 68-74), follow-up period (16.43.7weeks)] received parenteral iron; 15 patients [11 men; 70years (interquartile range 62-75), (17.33.3weeks)] received erythropoiesis-stimulating agent. HbA(1c) fell following treatment with both iron [57mmol/mol (7.4%) to 53mmol/mol (7.0%), P<0.001] and erythropoiesis-stimulating agent [56mmol/mol (7.3%) to 49mmol/mol (6.6%), P=0.01] despite mean blood glucose remaining unchanged (iron: 9.55 to 9.71mmol/l, P=0.07; erythropoiesis-stimulating agent: 8.72 to 8.78mmol/l, P=0.89). Unlike HbA(1c), the glycated albumin, fructosamine and 1,5 anhydroglucitol levels did not change following iron [glycated albumin (16.8 to 16.3%, P=0.10); fructosamine (259.5 to 256mol/l, P=0.89); 1,5 anhydroglucitol (54.2 to 50.9mol/l, P=0.89)] or erythropoiesis-stimulating agent [glycated albumin (17.9 to 17.5%, P=0.29), fructosamine (324.3 to 306.0mol/l, P=0.52), 1,5 anhydroglucitol (58.2 to 46.7mol/l, P=0.35)]. Despite this, HbA(1c) was consistently the marker most closely related to mean blood glucose before and after each treatment (R range 0.7-0.88). Conclusions These data indicate that HbA(1c) was statistically most closely related to mean blood glucose, but clinical trends in glycaemia in patients undergoing iron or erythropoiesis-stimulating agent therapy are likely best assessed by including one of these additional glycaemic markers.
    Full-text Article · Jun 2013 · Diabetic Medicine
  • Article · May 2013 · European Journal of Heart Failure
  • A J Dawson · T Sathyapalan · S L Atkin · E S Kilpatrick
    [Show abstract] [Hide abstract] ABSTRACT: Biological variation refers to the natural fluctuations found when repeated measurements are made in a biological system. Generally, biological variation remains within narrow boundaries in health, but may differ in pathological states, with implications for the diagnosis and monitoring of disease processes. In disease, biological variation may alter such that any subsequent measurement may need to have a greater difference compared with a healthy control to be biologically relevant. Treatments such as insulin or anti-hypertensive therapy have been shown to reduce biological variability closer to normal levels and theoretically this may help prevent complication development or progression in conditions such as diabetes. This article reviews how biological variation can influence our identification and assessment of vascular risk factors in a person with diabetes. The role of biological variation in the diagnosis of diabetes (glucose and HbA(1c) ) is then examined. Finally, the influence that common treatments in diabetes have in modifying biological variation is described. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.
    Article · Feb 2013 · Diabetic Medicine
  • E S Kilpatrick · A S Rigby · R E Warren · S L Atkin
    [Show abstract] [Hide abstract] ABSTRACT: Aims: Recurrent severe hypoglycaemia in a patient with diabetes is strongly associated with a crash risk while driving. To help ensure road safety, recent changes were made to European Union driving regulations for patients with diabetes. These included the recommendation that more than one episode of severe hypoglycaemia within 12 months would lead to the loss of a driving licence. This study has assessed the impact of this regulation if applied to patients who participated in the Diabetes Control and Complications Trial. Methods: All patients in the Diabetes Control and Complications Trial were assumed to be drivers. Repeated hypoglycaemic episodes within a year were determined during the mean 6.5 years of the study. Results: Of the 1441 patients in the Diabetes Control and Complications Trial, 439 (30%) had more than one severe hypoglycaemic episode during a 12-month period of their study participation. Amongst the study groups, 312/711 (44%) of intensively treated and 127/730 (17%) of conventionally treated patients would have lost their licence at some point during the trial. The risk of licence loss increased with lower mean HbA1c , longer duration of diabetes and younger age (all P < 0.001). Conclusions: More than one episode of severe hypoglycaemia within a year was a frequent event in subjects in the Diabetes Control and Complications Trial, especially in intensively treated patients. If applied to current practice, improving road safety through these changes to European Union regulations could have a substantial impact on drivers who have Type 1 diabetes. This emphasizes the need to take into account the potential effects of severe hypoglycaemia in those who rely on a driving licence.
    Article · Dec 2012 · Diabetic Medicine
  • [Show abstract] [Hide abstract] ABSTRACT: AimsTo investigate the effects of high-polyphenol chocolate upon endothelial function and oxidative stress in Type 2 diabetes mellitus during acute transient hyperglycaemia induced following a 75-g oral glucose challenge.Methods Ten subjects with Type 2 diabetes underwent a double-blinded randomized controlled crossover study. A 75-g oral glucose load was used to induce hyperglycaemia, which was administered to participants 60 min after they had ingested either low (control) or high-polyphenol chocolate. Participants undertook testing at weekly intervals, following an initial cocoa-free period. Endothelial function was assessed by both functional [reactive hyperaemia peripheral artery tonometry (EndoPAT-2000) and serum markers (including intercellular adhesion molecule 1, P-selectin and P-selectin glycoprotein ligand 1]. Urinary 15-F2t-isoprostane adjusted for creatinine was used as an oxidative stress marker. Measurements were made at baseline and 2 h post-ingestion of the glucose load.ResultsPrior consumption of high-polyphenol chocolate before a glucose load improved endothelial function (1.7 ± 0.1 vs. 2.3 ± 0.1%, P = 0.01), whereas prior consumption of control chocolate resulted in a significant increase in intercellular adhesion molecule 1 (321.1 ± 7.6 vs. 373.6 ± 10.5 ng/ml, P = 0.04) and 15-F2t-isoprostane (116.8 ± 5.7 vs. 207.1 ± 5.7 mg/mol, P = 0.02). Analysis of percentage changes from baseline comparing control and high-polyphenol chocolate showed a significant improvement for high-polyphenol chocolate in both measures of endothelial function (P < 0.05) and for urinary 15-F2t-isoprostane (P = 0.04).Conclusion High-polyphenol chocolate protected against acute hyperglycaemia-induced endothelial dysfunction and oxidative stress in individuals with Type 2 diabetes mellitus.
    Article · Oct 2012 · Diabetic Medicine
  • E S Kilpatrick
    [Show abstract] [Hide abstract] ABSTRACT: It is still unclear whether short-term, within-day, variability in glycaemic control is contributory to the development of diabetes micro- or macrovascular complications. However, consistent and compelling data are emerging that longer term fluctuations in glucose, as evidenced by increases in HbA(1c) variability, do indeed add to the mean HbA(1c) value in predicting the risk of microvascular disease. Until now, studies have found this to be the case mainly in type 1 diabetes, but in this issue of Diabetologia (DOI: 10.1007/s00125-012-2572-7 ) an analysis of the Tsukuba Kawai Diabetes Registry in Japan has found that HbA(1c) variability also predicts the risk of nephropathy in type 2 diabetic patients. These observations raise the possibility that reducing rises and falls in HbA(1c) may help avoid hyperglycaemia-related vascular disease without running the same risk of hypoglycaemia that a strategy focusing purely on lower HbA(1c) might incur.
    Article · Jun 2012 · Diabetologia
  • A Wakil · KA Smith · S L Atkin · E S Kilpatrick
    [Show abstract] [Hide abstract] ABSTRACT: It is unknown whether glycaemic variability adds to the risk of microvascular complications of diabetes over and above the mean glucose value for a patient. We examined the effect of purposefully induced short-term glycaemic variability on oxidative stress markers. Eleven healthy subjects underwent three sequential glycaemic states; sustained hyperglycaemia, sustained euglycaemia and variable glycaemia, using glycaemic clamps for 3 h. Twenty-four hours urinary 8-isoprostane-PGF2α was measured before and after each glycaemic state to assess oxidative stress. The median and interquartile range of the urinary 8-iso-PGF2α in ng/24 h were (1373, 513), (996, 298) and (1227, 472) for the euglycaemic, hyperglycaemic and variable states, respectively. There was no significant difference in urinary isoprostanes between the three different states; mean ranks 20.9, 11.9 and 18.2 for the euglycaemic state, hyperglycaemic state and glycaemic variability state, respectively, p = 0.083. In conclusion, we did not see a significant increase in the urinary isoprostanes when glycaemic variability was induced under controlled conditions in healthy individuals.
    Article · May 2012 · Diabetes Obesity and Metabolism
  • E S Kilpatrick · A S Rigby · S L Atkin · B M Frier
    [Show abstract] [Hide abstract] ABSTRACT: Severe hypoglycaemia may have a role in aggravating micro- and macrovascular disease in diabetes. Data from the Diabetes Control and Complication Trial have been reanalysed to ascertain whether the frequency of severe hypoglycaemia exerted an influence on the development and progression of retinopathy or nephropathy in people with Type 1 diabetes. Using binary longitudinal multiple logistic regression, HbA(1c) at study baseline, mean HbA(1c) throughout the study and the number of severe hypoglycaemic episodes during the trial were compared to examine the risk of development/progression of retinopathy and nephropathy. Average HbA(1c) during the study and/or HbA(1c) at baseline were independently predictive of retinopathy and nephropathy both in the intensively and the conventionally treated patients (all P ≤ 0.001). However, the number of hypoglycaemic episodes did not add to HbA(1c) in predicting retinopathy [odds ratio (95% CI) 0.99 (0.96-1.01), P = 0.51 in intensively treated patients, 0.94 (0.89-1.00), P = 0.05, conventional] or nephropathy [odds ratio (95% CI) 0.98 (0.95-1.01), P = 0.48 intensive, 1.03 (0.98-1.10), P = 0.17 conventional]. The frequency of exposure to severe hypoglycaemia did not predict a different risk of developing retinopathy or nephropathy in either treatment group of the Diabetes Control and Complications Trial at any given HbA(1c) .
    Article · Feb 2012 · Diabetic Medicine
  • D Mellor · ES Kilpatrick · T Sathyapalan · [...] · SL Atkin
    Conference Paper · Jan 2012
  • Waqas Shafiq · Ewan Masson · Eric Kilpatrick · [...] · Stephen Lindow
    Article · Jun 2011 · Practical Diabetes International
  • J.M. Ng · S L Atkin · A S Rigby · [...] · E S Kilpatrick
    [Show abstract] [Hide abstract] ABSTRACT: To examine the impact of extensive flooding in a UK city in 2007 on the glycaemic control of patients with diabetes mellitus. This was a longitudinal study in patients with diabetes mellitus 12 months before and after the floods in Hull and East Yorkshire, UK. All patients registered with diabetes mellitus were sent questionnaires about their experiences during and after the floods. Glycaemic control for patients directly affected by the floods was compared against those unaffected. Of 1743 respondents, 296 patients had been affected by the floods (110 insulin treated, 186 lifestyle and oral agents) and 1447 unaffected (482 insulin treated, 965 lifestyle and oral agents). There was a rise in mean HbA(1c) of affected individuals comparing 12 months before the floods with 12 months after [mean (95% confidence interval), 7.6% (7.5-7.7) vs. 7.9% (7.7-8.0), P = 0.002], but not those unaffected [7.5% (7.4-7.6) vs. 7.5% (7.4-7.6), P = 0.46]. The difference was mainly in insulin-treated patients [8.6% (8.3, 8.9) affected vs. 8.2% (8.1, 8.3) unaffected, (P = 0.002)]. Glycaemic control deteriorated in diabetes patients following the floods but was almost exclusively confined to patients taking insulin and was worst at 6-9 months following the event. Insulin-treated patients may need specific targeting in the event of a natural disaster.
    Article · May 2011 · Diabetic Medicine
  • K.A. Smith · J Shepherd · A Wakil · E S Kilpatrick
    [Show abstract] [Hide abstract] ABSTRACT: Oxidative stress describes the cellular damage caused by excess reactive oxygen species not adequately inactivated by antioxidants. Oxidative stress has been implicated in playing a role in many disorders. Lipid peroxidation end-products are employed as markers of oxidative stress, of which the isoprostane, 8-iso-PGF(2α), is widely used. 8-iso-PGF(2α) is measured in plasma or urine by gas chromatography-mass spectrometry (GC/MS), liquid chromatography-mass spectrometry (LC/MS), tandem-mass spectrometry or enzyme-linked immunosorbent assay (ELISA). However, discrepancies between the specificity of these methods means correlation is poor. A tandem-mass spectrometric (LC/MS/MS) method, using immunoaffinity purification, for urinary 8-iso-PGF(2α) was developed and compared with two commercial ELISAs (A--Cayman Chemicals, B--Oxford Biomedical Research) in urine samples (n = 156). An LC/MS/MS method coupled to immunoaffinity purification was developed with satisfactory performance and comparison to ELISAs A and B. Spearman rank correlation demonstrated significant correlation between all methods (P = <0.0001); however, r² values ranged from 0.68 to 0.72. Bland-Altman plots revealed a proportional positive bias of ELISA B when compared with ELISA A and LC/MS/MS. Furthermore, the agreement between ELISA A and LC/MS/MS was poor. The poor agreement between methods for measurement of 8-iso-PGF(2α) highlights differences in selectivity. 8-iso-PGF(2α) is an isoprostane, a family of isomeric end-products of arachidonic acid peroxidation, which are produced by peroxidation or enzymatically. This makes avoiding cross-reactivity between 8-iso-PGF(2α) and related isomers challenging. When assessing oxidative stress studies, the selectivity of the methods used should be taken into account, particularly when comparing studies.
    Article · Feb 2011 · Annals of Clinical Biochemistry
  • L W Cho · E S Kilpatrick · B G Keevil · [...] · S L Atkin
    [Show abstract] [Hide abstract] ABSTRACT: Women with polycystic ovary syndrome (PCOS) were found to have a higher biological variability in insulin resistance (IR) compared to controls, but it is unknown whether this variability in IR differs between PCOS who are anovulatory compared to those who have an ovulatory cycle. The primary aim of this study was to compare and contrast the variability of IR in women with ovulatory and anovulatory PCOS, in comparison to normal subjects. 53 Caucasian women with PCOS and 22 normal ovulating women were recruited. Fasting blood was collected each day on 10 consecutive occasions at 3-4 day intervals for analysis of insulin, glucose, progesterone, and testosterone. Analysis of progesterone levels showed 22 of 53 women with PCOS to have had an ovulatory cycle. Insulin resistance was calculated by HOMA method. Women with anovulatory PCOS had higher mean and variability of IR compared to those having an ovulatory cycle, and both were significantly higher than controls (mean ± SEM; HOMA-IR 4.14 ± 0.14 vs. 3.65 ± 0.15 vs. 2.21 ± 0.16, respectively) after adjustment or BMI. The mean BMI for individual PCOS patients correlated with mean HOMA-IR (p=0.009). Insulin resistance in women with anovulatory PCOS is both higher and more variable than in ovulatory PCOS. Since anovulatory PCOS therefore mimics the IR features of type 2 diabetes more closely, anovulation may be particularly associated with a higher cardiovascular risk compared to PCOS patients who ovulate.
    Article · Feb 2011 · Hormone and Metabolic Research
  • L Wilkinson · DD Mellor · EA Masson · [...] · ES Kilpatrick
    Article · Jan 2011 · Diabetic Medicine
  • DD Mellor · ES Kilpatrick · SL Atkin
    Article · Jan 2011 · Diabetic Medicine

Publication Stats

2k Citations


  • 2012
    • San Diego Zoo
      San Diego, California, United States
  • 2011
    • Hull and East Yorkshire Hospitals NHS Trust
      Kingston upon Hull, England, United Kingdom
  • 2009
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 2007
    • University of Hull
      • Academic Cardiology
      Kingston upon Hull, England, United Kingdom