S L Atkin

Weill Cornell Medical College in Qatar, Ad Dawḩah, Baladīyat ad Dawḩah, Qatar

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Publications (249)1066.54 Total impact

  • P. Costanzo, D. Lai, S. L. Atkin
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    ABSTRACT: The term “obesity paradox” corresponds to the research observation that overweight or obese patients may counterintuitively have a survival benefit once a disease is established. This appears also true in type 2 diabetes mellitus, where it has been shown that being overweight or obese is associated with better survival. The reasons behind this paradox remain unclear but likely derive from an intricate relationship between insulin resistance, fat storage, and inflammatory responses in type 2 diabetes. In this review, we look at what the potential mechanisms may be underlying this paradox.
    Current Cardiovascular Risk Reports 07/2015; 9(7). DOI:10.1007/s12170-015-0461-6
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    ABSTRACT: Whether obesity is associated with a better prognosis in patients with type 2 diabetes mellitus is controversial. To investigate the association between body weight and prognosis in a large cohort of patients with type 2 diabetes followed for a prolonged period. Prospective cohort. National Health Service, England. Patients with diabetes. The relationship between body mass index (BMI) and prognosis in patients with type 2 diabetes without known cardiovascular disease at baseline was investigated. Information on all-cause mortality and cardiovascular morbidity (such as the acute coronary syndrome, cerebrovascular accidents, and heart failure) was collected. Cox regression survival analysis, corrected for potential modifiers, including cardiovascular risk factors and comorbid conditions (such as cancer, chronic kidney disease, and lung disease), was done. 10 568 patients were followed for a median of 10.6 years (interquartile range, 7.8 to 13.4). Median age was 63 years (interquartile range, 55 to 71), and 54% of patients were men. Overweight or obese patients (BMI >25 kg/m2) had a higher rate of cardiac events (such as the acute coronary syndrome and heart failure) than those of normal weight (BMI, 18.5 to 24.9 kg/m2). However, being overweight (BMI, 25 to 29.9 kg/m2) was associated with a lower mortality risk, whereas obese patients (BMI >30 kg/m2) had a mortality risk similar to that of normal-weight persons. Patients with low body weight had the worst prognosis. Data about cause of death were not available. In this cohort, patients with type 2 diabetes who were overweight or obese were more likely to be hospitalized for cardiovascular reasons. Being overweight was associated with a lower mortality risk, but being obese was not. National Institute for Health Research and University of Hull.
    Annals of internal medicine 05/2015; 162(9):610-618. DOI:10.7326/M14-1551 · 16.10 Impact Factor
  • Diabetologie und Stoffwechsel 04/2015; 10(S 01). DOI:10.1055/s-0035-1549541 · 0.31 Impact Factor
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    ABSTRACT: Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans. ISRCTN Registry ISRCTN39650237.
    PLoS ONE 03/2015; 10(3):e0116212. DOI:10.1371/journal.pone.0116212 · 3.53 Impact Factor
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    ABSTRACT: Polyphenols and other compounds found in cocoa and chocolate have therapeutic potential in the management of diabetes in humans. Polyphenols benefits have been proposed supported by in vitro studies, animal work and clinical trials, which have been conducted mostly in healthy volunteers. The energy dense formulations of many cocoa and chocolate products which can be up to 50% sugar by weight have given the perception that chocolate may be harmful through its contribution to obesity. A review of both clinical trial databases and published literature yielded 15 registered trials and seven published studies. The published data interventions reported are diverse vary widely in quality, including poor selection of control products or inadequate blinding procedures. There are also inconsistencies in reporting of data with limited information on the effect of cocoa and chocolate supplementation on weight and glycemic control despite the potential benefits reported with respect to the cardiovascular risk factors of endothelial function and lipids. More studies are required powered for primary clinical outcomes together with the development of standardized product formulations that optimize the dose of polyphenols within a palatable and energy restricted product.
    Journal of Agricultural and Food Chemistry 03/2015; DOI:10.1021/acs.jafc.5b00776 · 3.11 Impact Factor
  • Diabetes & Metabolism 03/2015; 41:A31. DOI:10.1016/S1262-3636(15)30111-7 · 2.85 Impact Factor
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    ABSTRACT: Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814.
    Journal of the American Heart Association 12/2014; 3(1):e000706. DOI:10.1161/JAHA.113.000706 · 2.88 Impact Factor
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    ABSTRACT: ORAI and stromal interaction molecule (STIM) are store-operated channel molecules that play essential roles in human physiology through a coupling mechanism of internal Ca(2+) store to Ca(2+) influx. However, the roles of ORAI and STIM in vascular endothelial cells under diabetic conditions remain unknown. Here, we investigated expression and signalling pathways of ORAI and STIM regulated by high glucose or hyperglycaemia using in vitro cell models, in vivo diabetic mice and tissues from patients. We found that ORAI1-3 and STIM1-2 were ubiquitously expressed in human vasculatures. Their expression was upregulated by chronic treatment with high glucose (HG, 25 mM D-glucose), which was accompanied by enhanced store-operated Ca(2+) influx in vascular endothelial cells. The increased expression was also observed in the aortae from genetically modified Akita diabetic mice (C57BL/6-Ins2(Akita)/J) and streptozocin-induced diabetic mice, and aortae from diabetic patients. HG-induced upregulation of ORAI and STIM genes was prevented by the calcineurin inhibitor cyclosporin A and NFATc3 siRNA. Additionally, in vivo treatment with the nuclear factor of activated T cells (NFAT) inhibitor A-285222 prevented the gene upregulation in Akita mice. However, HG had no direct effects on ORAI1-3 currents and the channel activation process through cytosolic STIM1 movement in the cells co-expressing STIM1-EYFP/ORAIs. We concluded that upregulation of STIM/ORAI through Ca(2+)-calcineurin-NFAT pathway is a novel mechanism causing abnormal Ca(2+) homeostasis and endothelial dysfunction under hyperglycaemia. ORAI1-3 and STIM1-2 are ubiquitously expressed in vasculatures and upregulated by high glucose. Increased expression is confirmed in Akita (Ins2(Akita)/J) and STZ diabetic mice and patients. Upregulation mechanism is mediated by Ca(2+)/calcineurin/NFATc3 signalling. High glucose has no direct effects on ORAI1-3 channel activity and channel activation process.
    Journal of Molecular Medicine 12/2014; 93(5). DOI:10.1007/s00109-014-1234-2 · 4.74 Impact Factor
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    Richard Hammersley, Marie Reid, Stephen L Atkin
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    ABSTRACT: Mood is widely assessed in nutrition research, usually with rating scales. A core assumption is that positive mood reinforces ingestion, so it is important to measure mood well. Four relevant theoretical issues are reviewed: (i) the distinction between protracted and transient mood; (ii) the distinction between mood and emotion; (iii) the phenomenology of mood as an unstable tint to consciousness rather than a distinct state of consciousness; (iv) moods can be caused by social and cognitive processes as well as physiological ones. Consequently, mood is difficult to measure and mood rating is easily influenced by non-nutritive aspects of feeding, the psychological, social and physical environment where feeding occurs, and the nature of the rating system employed. Some of the difficulties are illustrated by reviewing experiments looking at the impact of food on mood. The mood-rating systems in common use in nutrition research are then reviewed, the requirements of a better mood-rating system are described, and guidelines are provided for a considered choice of mood-rating system including that assessment should: have two main dimensions; be brief; balance simplicity and comprehensiveness; be easy to use repeatedly. Also mood should be assessed only under conditions where cognitive biases have been considered and controlled.
    Nutrition Research Reviews 12/2014; 27(02):1-11. DOI:10.1017/S0954422414000201 · 3.86 Impact Factor
  • Canadian Journal of Diabetes 10/2014; 38(5). DOI:10.1016/j.jcjd.2014.07.020 · 0.46 Impact Factor
  • 74th Scientific Sessions (2014), San Francisco; 06/2014
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    ABSTRACT: 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.
    Heart (British Cardiac Society) 06/2014; 100(Suppl 3):A66. DOI:10.1136/heartjnl-2014-306118.116 · 6.02 Impact Factor
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    Myint M Aye, Stephen L Atkin
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    ABSTRACT: Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long-term hypoglycemia or reduce diabetes-related complications.
    Drug, Healthcare and Patient Safety 04/2014; 6:55-67. DOI:10.2147/DHPS.S59566
  • Eric S Kilpatrick, Stephen L Atkin
    BMJ (online) 04/2014; 348:g2867. DOI:10.1136/bmj.g2867 · 16.38 Impact Factor
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    ABSTRACT: Background A new formula was recently proposed by Cordovo et al. that was more highly correlated with low-density lipoprotein (LDL) measured directly than the Friedewald LDL formula. We conducted this prospective study to establish whether the new formula allows true variations in LDL within the same individual to be tracked more closely than that of the Friedewald formula.
    Annals of Clinical Biochemistry 04/2014; 52(1). DOI:10.1177/0004563214533515 · 2.08 Impact Factor
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    ABSTRACT: Pollen grain and spore shells are natural microcapsules designed to protect the genetic material of the plant from external damage. The shell is made up of two layers, the inner layer (intine), made largely of cellulose, and the outer layer (exine), composed mainly of sporopollenin. The relative proportion of each varies according to the plant species. The structure of sporopollenin has not been fully characterised but different studies suggest the presence of conjugated phenols, which provide antioxidant properties to the microcapsule and UV (ultraviolet) protection to the material inside it. These microcapsule shells have many advantageous properties, such as homogeneity in size, resilience to both alkalis and acids, and the ability to withstand temperatures up to 250 °C. These hollow microcapsules have the ability to encapsulate and release actives in a controlled manner. Their mucoadhesion to intestinal tissues may contribute to the extended contact of the sporopollenin with the intestinal mucosa leading to an increased efficiency of delivery of nutraceuticals and drugs. The hollow microcapsules can be filled with a solution of the active or active in a liquid form by simply mixing both together, and in some cases operating a vacuum. The active payload can be released in the human body depending on pressure on the microcapsule, solubility and/or pH factors. Active release can be controlled by adding a coating on the shell, or co-encapsulation with the active inside the shell.
    Pharmaceutics 03/2014; 6(1):80-96. DOI:10.3390/pharmaceutics6010080
  • 03/2014; DOI:10.1530/endoabs.34.P233
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is associated with obesity and increased cardiovascular (CV) risk markers. In this study our aim was to assess the effects of six months treatment with liraglutide 1.8 mg od on obesity, and CV risk markers, particularly platelet function, in young obese women with PCOS compared to controls of similar age and weight. Carotid intima-media wall thickness (cIMT) was measured by B-mode ultrasonography, platelet function by flow cytometry, clot structure/lysis by turbidimetric assays and endothelial function by ELISA and post-ischaemic reactive hyperemia (RHI). Data presented as mean change (6-month - baseline) ± standard deviation. Nineteen obese women with PCOS and 17 controls, of similar age and weight, were recruited; baseline atherothrombotic risk markers did not differ between the two groups. Twenty five (69.4%) participants completed the study (13 PCOS, 12 controls). At six months, weight was significantly reduced by 3.0 ± 4.2 and 3.8 ± 3.4 kg in the PCOS and control groups, respectively; with no significant difference between the two groups, P = 0.56. Similarly, HOMA-IR, triglyceride, hsCRP, urinary isoprostanes, serum endothelial adhesion markers (sP-selectin, sICAM and sVCAM), and clot lysis area were equally significantly reduced in both groups compared to baseline. Basal platelet P-selectin expression was significantly reduced at six months in controls -0.17 ± 0.26 but not PCOS -0.12 ± 0.28; between groups difference, 95% confidence interval = -0.14 - 0.26, P = 0.41. No significant changes were noted in cIMT or RHI. Six months treatment with liraglutide (1.8 mg od) equally affected young obese women with PCOS and controls. In both groups, liraglutide treatment was associated with 3-4% weight loss and significant reduction in atherothrombosis markers including inflammation, endothelial function and clotting. Our data support the use of liraglutide as weight loss medication in simple obesity and suggest a potential beneficial effect on platelet function and atherothrombotic risk at 6 months of treatment. Clinical trial reg. no. ISRCTN48560305 . Date of registration 22/05/2012.
    03/2014; 15(1). DOI:10.1530/endoabs.34.P229
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    ABSTRACT: Sporopollenin exine capsules (SECs) derived from plant spores and pollen grains have been proposed as adsorption, remediation and drug delivery agents. Despite many studies there is scant structural data available. This X-ray absorption investigation represents the first direct structural data on the interaction of metals with SECs and allows elucidation of their structure-property relationships. Fe K-edge XANES and EXAFS data have shown that the iron local environment in SECs (derived from Lycopodium clavatum) reacted with aqueous ferric chloride solutions is similar to that of ferrihydrite (FeOOH) and by implication ferritin. Fe K a XRF micro-focus experiments show that there is a poor correlation between the iron distribution and the underlying SEC structure indicating that the SEC is coated in the FeOOH material. In contrast, the Fe K a XRF micro-focus experiments on SECs reacted with aqueous ferrous chloride solutions show that there is a very high correlation between the iron distribution and the SEC structure, indicating a much more specific form of interaction of the iron with the SEC surface functional groups. Fe K-edge XANES and EXAFS data show that the Fe(II) can be easily oxidised to give a structure similar to, but not identical to that in the Fe(III) case, and that even if anaerobic conditions are used there is still partial oxidation to Fe(III).
    Journal of Materials Chemistry B 02/2014; 2(8):945-959. DOI:10.1039/c3tb21523g · 4.73 Impact Factor
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    ABSTRACT: Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance (IR), dyslipidaemia and subsequent risk of diabetes and cardiovascular (CV) disease. Lowering triglycerides by atorvastatin in PCOS was associated with improved IR and CV risk. This study investigated the effect of long-term niacin/laropiprant therapy on CV risk and IR in obese women with PCOS. In this double-blind randomized placebo-controlled trial, 13 and 12 PCOS women completed a 12 week course of niacin/laropiprant or placebo respectively. Fasted subjects had an endothelial function test (EndoPat2000) and then consumed a mixed meal with blood sampled postprandially for 6 hour before and after intervention. Changes in High density lipoprotein cholesterol (HDL-c), triglycerides, Reactive hyperaemic index (RHI), high sensitivity c reactive protein (hsCRP) and insulin sensitivity were measured. By 12 weeks, niacin/laropiprant lowered low density lipoprotein-cholesterol (13%) and increased HDL-c (17%). Despite a reduction in fasting triglycerides (21%), the drug had no effect on their postprandial rise (2.69 ±1.44 vs. 2.49 ± 1.14 mmol/L, p = 0.72). However, following the mixed meal, plasma glucose area under the curve increased from 13.1 ± 2.9 to 14.0 ±mmol/L, p = 0.05, as a consequence of both increased insulin resistance (HOMA-IR: 2.2 (1.2, 4.2) vs. 3.8(1.3, 5.5), p = 0.02) and a reduced acute insulin response to glucose (424 (211,975) vs. 257(122,418) pmol/mmoL, p = 0.04). Niacin/laropiprant did not improve RHI (1.97 ± 0.40 vs. 2.05 ± 0.58, p = 0.33) or hsCRP. In PCOS, Niacin/laropiprant had a significant negative impact on postprandial glucose and no improvement in postprandial hypertriglyceridaemia, with at least the former mediated through increased insulin resistance and reduced beta cell function. This data may help explain why the improvement in fasting lipids has not translated into improved cardiovascular risk markers in PCOS. Clinical trial registration Number (www.clinicaltrials.gov): NCT01118598.
    Diabetes Obesity and Metabolism 01/2014; 16(6). DOI:10.1111/dom.12255 · 5.46 Impact Factor

Publication Stats

3k Citations
1,066.54 Total Impact Points


  • 2014–2015
    • Weill Cornell Medical College in Qatar
      Ad Dawḩah, Baladīyat ad Dawḩah, Qatar
  • 2006–2014
    • Hull York Medical School
      York, England, United Kingdom
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1994–2014
    • University of Hull
      • • Hull York Medical School (HYMS)
      • • Diabetes and Endocrinology
      Kingston upon Hull, England, United Kingdom
    • University of Nottingham
      Nottigham, England, United Kingdom
    • Liverpool Hospital
      Liverpool, New South Wales, Australia
  • 2012
    • San Diego Zoo
      San Diego, California, United States
    • The University of York
      • Hull York Medical School
      York, England, United Kingdom
  • 2010
    • Centre For Diabetes And Endocrinology
      Johannesburg, Gauteng, South Africa
  • 2008–2010
    • Hull and East Yorkshire Hospitals NHS Trust
      Kingston upon Hull, England, United Kingdom
  • 2009
    • University of Glasgow
      Glasgow, Scotland, United Kingdom
  • 2004–2005
    • The Australian Society of Otolaryngology Head & Neck Surgery
      Evans Head, New South Wales, Australia
  • 1996–1997
    • Kingston Hospital
      Kingston Seymour, England, United Kingdom
  • 1994–1995
    • Kingston General Hospital
      Kingston, Ontario, Canada
  • 1993–1995
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      • Department of Endocrinology
      Liverpool, England, United Kingdom