Type 1 Diabetes Genetic Consortium Asia function in diabetes and insulin 7th International Diabetes Federation, Western Pacific Region …
LIPID DIABETES
RESEARCH GROUP
Christchurch Hospital
ANNUAL REPORT 2008
30 June 2007 - 30 June 2008
Website: wwwcdhbgovtnz/diabetes/researchhtm
Telephone 64 3 364 0449
Facsimile 64 3 364 0457
C O N T E N T S
Page No
Research
Staff
3
1 Collaborative
Associations 5
2 Main Scientific Research Activities for 2007/2008 6
3 Attendances at Scientific Meetings Educational Courses 7
4
Publications
9
5 Group Research Presented at National and International
meetings
11
6 Other Activities - National and International
12
7 Research Grants and other Funding Support 15
8 Reports by Research
Staff 17
9 Summary of Accounts - June 2007 to June 2008 47
1 Research Staff 2007/2008
Claire Chandler Medical Secretary
Chris
Florkowski MD, MRCP UK, FRACP, FRCPA Physician
Victoria Halliday NZRN Research Assistant
Nikki Hurndell RGON, BN Clinical Nurse Specialist
Alison Luckey BM, MFPM Physician
Roberta McEwan RGON Research Nurse
Patrice McGregor RGON Research Nurse
Jeremy McRae BSc Hons PhD Research Fellow
Zarnia Morrison BN, RCPN Research Nurse
Sarah Plot BN Research Nurse
Annette Reinheimer RGON, BSc Hons Research Nurse
Russell Scott MB, ChB, BMedSci, PhD Monash, FRACP Physician
Brett Shand PhD Senior Research Scientist
Meghan Shannon BSc, PG Dip Diet Dist, NZRD Research Dietitian
Lee Stoner PhD Clinical Research Fellow
Peta Taylor RGON, BSc Hons, PGDip Teach Post-graduate Student
Rob Williams Secretary
Jinny Willis BSc Hons, PhD Senior Research Scientist
Jo Young BSc, MSc Research Scientist
STAFF DEPARTURES DURING THE YEAR
Claire Chandler Medical Secretary
Victoria Halliday NZRN Research Assistant
Jeremy McRae BSc Hons PhD Research Fellow
Maree Piebenga Maternity Leave B Cap Sci, PGDip Diet Research
Dietician
Meghan Shannon BSc, PG Dip Diet Dist, NZRD Research Dietitian
Lee Stoner PhD Clinical Research Fellow
STAFF ARRIVALS DURING THE YEAR
Rob Williams Secretary
TRUSTEES
Russell Scott Physician
David Salthouse Business Executive
Dianne Guerrero Accounts Manager
2 Collaborative Associations
Department of Paediatrics Diabetes Projects
Professor B A Darlow
Canterbury District Health Board
Crop and Food
Dr Alison Wallace
Clinical Biochemistry and molecular pathology
Dr Peter George, Dr A Fellowes
NHMRC Clinical Trials Unit
Professor A Keech
Sydney, Australia
Type 1 Diabetes Genetic Consortium - Asia Pacific Network
Assoc Professor Peter Colman, Professor Grant Morahan
Royal Melbourne Hospital and Walter Eliza Hall Institute
Type 1 Diabetes TrialNet - Australasian Network
Professor Len Harrison, Assoc Professor Peter Colman
Royal Melbourne Hospital and Walter Eliza Hall Institute
Geohealth Laboratory, University of Canterbury
Laura Miller, Dr Jamie Pearce, Professor Ross Barnett
Steroid and Immunobiochemistry
Laboratory, Canterbury Health
Laboratories
Dr John Lewis and Dr Peter Elder
3 Main Scientific Research activities for 2007/2008
1 Clinical and genetic aspects of Adiponectin
2 Vascular function in diabetes and insulin resistance
3 The Metabolic Syndrome and Cardiovascular Disease
4 The Diabetes Registry: Health outcomes and
implications of Diabetes
5 Morbidity and Mortality in Diabetes Mellitus
6 Familial Hypercholesterolaemia
7 HDL and atherosclerosis
8 Immunogenetic aspects of Type 1 Diabetes
Trial Net and the Diabetes Genetic Consortium
9 Lipid Clinic database: Plasma lipid fractions, cardiovascular risk
factors and health outcomes
10 Effects of thiazolidinediones on glomerular function
4 Attendances at Scientific Meetings
Educational Courses
Type 1 Diabetes Genetic Consortium Meeting, Phuket, Thailand; July 2007
Attendee: J Willis
ADVANCE Investigator meeting, Vienna; August 2007
Attendee: R McEwen, P McGregor
EASD: Amsterdam the Netherlands, Sept 2007
Attendee: R Scott
Cardiac Society of Australia and NZ
55th Annual Scientific Meeting,
Christchurch; August 2007
Attendee: J Young, C Florkowski
Canterbury Health Research Society Conference, Christchurch; August 2007
Attendee: J Young
Australian Diabetes Society, Australian Diabetes Educators Association and
New Zealand Society for the Study of Diabetes Joint Meeting, Christchurch
September 2007 Attendees: Dr Brett Shand, Dr Jinny Willis, J Young, C
Florkowski
5th Annual World Congress on the Insulin Resistance Syndrome Boston,
USA October 2007 Attendee: Dr Brett Shand
Cardiovascular lecture: Dr S Voros, Atlanta USA Plaques: whats inside?-
imaging and dissecting atherosclerosis, Sept 2007
Attendee and Chairperson: R Scott
International Atherosclerosis Society Course on HDL structure and Function,
Santorini Greece, Oct 2007
Attendee: R Scott
Annual Scientific Meeting of the Australian Atherosclerosis Society,
Fremantle; October 2007
Attendee: J Young
International Coenzyme Q10 Association Meeting, Kobe, Japan; November 2007
Attendee: J Young, C Florkowski
Steering Committee Meeting TrialNet, Miami, Florida, USA; November 2007
Attendee: Dr J Willis
Immunology of Diabetes Society Congress, Miami, Florida, USA;
November
2007
Attendee: Dr J Willis
New Zealand Paediatric Society Conference, Christchurch, New Zealand,
November 2007
Attendee and Invited Speaker: Dr J Willis
Australasian Atherosclerosis Society Familial Hypercholesterolaemia sub
committee meeting January 2008Adelaide
Attendee: N Reid
CRESCENDO Investigator meeting, Sydney; February 2008
Attendee: R McEwen
Investigators meeting for Protocol BI 121817, Queenstown April, 2008
Attendees: R Scott, S Plot
Investigators meeting for Protocol MK-0431-803-01; Auckland April 2008
Attendees: R Scott, S Plot
7th International Diabetes Federation, Western Pacific Region Congress,
Wellington
March - April, 2008
Attendees: R Scott, B Shand, C Florkowski, J Willis
Diabetes Therapeutic Expert Forum: Boston USA, April 2008
Attendee: R Scott
American Diabetes Assn: San Francisco USA, June 2008
Attendee: R Scott
Advances in Medicine 2008, Chinese University of Hong Kong, June 2008
Attendee and Invited Speaker: R Scott
5 Publications
Collective within group; see individual reports for other publications
AJ Wallace, JA Willis, CM Frampton, JA Monro, DI Hedderley, RS Scott
A
pilot study investigating the Minimed Continuous Glucose Monitoring System
for determination of the blood glucose response of foods European Journal
Clinical Nutrition in press
JM Young, CM Florkowski, SL Molyneux, RG McEwan, CM Frampton, PM George, RS
Scott Effect of Coenzyme Q10 Supplementation on Simvastatin-Induced
Myalgia American Journal of Cardiology 100:1400 -1403 2007
Scott R, Wu M, Sanchez M, Stein P Efficacy and tolerability of the
dipeptidyl peptidase-4 inhibitor Sitagliptin as monotherapy over 12 weeks
in patients with type 2 diabetes International Journal of Clinical
Practice 61 1 2007
Dawson SI, Willis JA, Florkowski CM, Scott RS Cause-specific mortality in
insulin-treated diabetic patients: a 20-year follow-up Diabetes Research
and Clinical Practice 80;16-23, 2008
Dawson SI, Florkowski CM, Willis JA, Scott RS All-cause mortality in
insulin-treated diabetic patients: a 20-year follow-up Diabetes Research
and Clinical Practice 801:e6-9 Epub 2008
Lewis JG, Shand BI, Elder PA, Scott RS Lewis JG, Shand BI, Elder PA, Scott
RS Plasma retinol-binding protein is unlikely to be a useful marker of
insulin resistance, Diabetes Research and Clinical Practice
Apr;801:e13-
5 Epub 2008 Jan 14 2008
Plant SD, Shand BI, Elder PA, Scott RS Adiponectin attenuates endothelial
dysfunction induced by oxidised low-density lipoproteins Diab Vasc Dis
Res 5:102-8 2008
Shand B, Elder P, Scott R, Poa N, Frampton CM Comparison of plasma
adiponectin levels in New Zealand M?ori and Caucasian individuals The New
Zealand Medical Journal Vol 120 No1257 2007
Shand B, Scott R, Connolly S, Clarke R, Baker J, Elder P, Frampton C, Yeo
J Comparative study on the efficacy of pioglitazone in Caucasian and
Polynesian patients with poorly controlled type 2 diabetes Diabetes
Obesity and Metabolism 9:540-547 2007
Scott RS, Loeys T, Davies MJ, Engel SS Efficacy and safety of sitagliptin
when added to ongoing metformin therapy in patients with type 2 diabetes
Diabetes, Obesity and Metabolism in press epub Jan 14 2008
Mckinney C, Merriman M, Chapman P, Gow P, Harrison A, Highton J, Jones P,
Mclean L, ODonnell J, Pokorny V, Spellerberg M, Stamp L, Willis J, Steer
S Evidence for an influence of chemokine ligand 3-like 1 CCL3L1 gene
copy number on susceptibility to rheumatoid arthritis Annals of the
Rheumatic Disease 67: 409-413, 2008
Homer V M, Marais AD, Charlton
F, Laurie A D, Hurndell N, Scott RS,
Mangili F, Sullivan D R, Barter P J, Rye K-A, George P M, Lambert G
Identification and characterization of two non-secreted PCSK9 mutants
associated with familial hypercholesterolemia in cohorts from New Zealand
and South Africa Athersosclerosis 196: 659-666 2008
Chan JC, Scott R, Arjona Ferreira JC, Sheng D, Gonzalez E, Davies MJ, Stein
PP, Kaufman KD, Amatruda JM, Williams-Herman D Safety and efficacy of
sitagliptin in patients with type 2 diabetes and chronic renal
insufficiency Diabetes Obes Metab 10: 546-555, 2008
Young JM, Strey CH, George PM, Florkowski CM, Sies CW, Frampton CM, Scott
RS Effect of atorvastatin on plasma levels of asymmetric dimethylarginine
in patients with non-ischaemic heart failure Eur J Heart Fail 10, 463-466
2008
Lewis JG, Shand BI, Frampton CM, Elder PA, Scott RS Plasma retinol-binding
protein is not a marker of insulin resistance in overweight subjects: A
three year longitudinal study
Clin Biochem 2008 Jun 13 [Epub ahead of print]
SL Molyneux, JM Young, CM Florkowski, M Lever, PM George Coenzyme Q10; Is
There a Clinical Role and a Case for Measurement? Clinical Biochemist
Reviews In press, June
2008
6 Group Research Presented at National and
International Meetings
Miller LJ, Pearce J, Barnett R, Willis JA, Scott RS, Darlow BA Population
mixing and the geographical epidemiology of childhood leukaemia and type 1
diabetes in New Zealand 1980-2004 International Medical Geography
Symposium, Bonn, Germany, July 2007
Plant SD, Shand BI, Elder PA, Scott RS Adiponectin protects endothelial
cells against injury induced by oxidised low-density lipoproteins and
glucose by maintaining intracellular glutathione levels Australian
Diabetes Society, Australian Diabetes Educators Association and New Zealand
Society for the Study of Diabetes Joint Meeting, Christchurch, September
2007 Poster presentation
JM Young, SD Plant, CM Florkowski, CM Frampton, RS Scott Detection of pre-
clinical vascular disease in pre-diabetic subjects using pulse wave
analysis Australian Diabetes Society, Australian Diabetes Educators
Association and New Zealand Society for the Study of Diabetes Joint
Meeting, September, 2007 Poster presentation
Plant SD, Shand BI, Elder PA, Scott RS Adiponectin protects
endothelial
cells against injury induced by oxidised low-density lipoproteins and
glucose by maintaining intracellular glutathione levels 5th Annual World
Congress on the Insulin Resistance Syndrome Boston, USA October 2007
Poster presentation
Russell Scott, Michael dEmden, James Best, Paul Drury, Christian Ehnholm,
Antero Kesaniemi, Chris Pardy, Dana Tse, Philip Barter, Marja-Riitta
Taskinen, Samuel Copt, Anthony Keech on behalf of the FIELD Investigators
Features Of Metabolic Syndrome Identify Individuals With Type 2 Diabetes
Mellitus At High Risk For Cardiovascular Events And Greater Absolute
Benefits Of Fenofibrate AHA Annual meeting; Circulation, 116: 838, 2007
Willis JA Type 1 Diabetes in Canterbury Children and Adolescents:
Incidence and Geography New Zealand Paediatric Society Conference,
Christchurch, New Zealand, November 2007 Plenary speaker
JM Young, CM Florkowski, SL Molyneux, HC Potter, RG McEwan, CM Frampton, PM
George, RS Scott Coenyzme Q10, metabolic myopathy, genotypes and statin-
induced myalgia Proceedings of the Fifth Conference of the International
Coenzyme Q10 Association, November, 2007 Poster presentation
B Shand, R Scott, P Elder, J Lewis
Comparison of metabolic syndrome
markers to predict changes in fasting glucose concentration in overweight
non-diabetic subjects 7th WP-IDF Meeting, Diabetes Research and Clinical
Practice 79 supp 1 S16, 2008
R Scott, T Loeys, M Davies, S Engel Efficay and safety of Sitagliptin or
rosiglitazone when added to ongoing metformin therapy in patients with type
2 diabetes 7th WP-IDF Meeting, Diabetes Research and Clinical Practice 79
supp 1 S32, 2008
JA Willis, LJ Miller, RS Scott, BA Darlow, J Pearce, R Barnett Increasing
incidence of Type 1 Diabetes in Canterbury children and adolescents and
spatial-temporal clustering 7th WP-IDF Meeting, Diabetes Research and
Clinical Practice 79 supp 1 S36, 2008
LJ Miller, J Pearce, JA Willis, R Barnett, RS Scott, BA Darlow Population
mixing and Type 1 Diabetes in Canterbury, New Zealand 7th WP-IDF Meeting,
Diabetes Research and Clinical Practice 79 supp 1 S36, 2008
JM Young, CM Florkowski, SL Molyneux, RG McEwan, CM Frampton, PM George, RS
Scott Is there a role for coenzyme Q10 supplementation in statin-induced
myopathy Proceedings of Health Research Society of Canterburys Scientific
Meeting, Christchurch, 2007 New Zealand Medical Journal 121
1271:113-4
April, 2008 Oral presentation
Cuthbertson D, Palmer J, Thompson C, Skyler J, the Type 1 Diabetes Trialnet
Study Group JA Willis, collaborator, the Diabetes Prevention Trial - Type
1 Study Group Comparisons of OGTT Indices between Participants in the
TrialNet Natural History Study and Participants in the Diabetes Prevention
Trial-Type 1 ADA 68th Annual meeting; Diabetes 57 [supp1]: A264, 2008
Poster presentation
J Best, P Drury, Y-A Kesaniemi, P Colman, R Scott, M-K Taskinen on behalf
of the FIELD Investigators Maintenance of Glycemic Control in over 4,000
People with Type 2 Diabetes in 3 Countries for 5 Years with Metformin,
Sulfonylurea and Insulin Therapy ADA 68th Annual meeting; Diabetes 57
supp 1 A114, 2008
7 Other Activities - National and International
Professor Russell Scott
Regional Editor: Diabetes Research and Clinical Practice, Western
Pacific Region
Editorial Board
Diabetes Obesity and Metabolism
Medical Consulting Group
MSD New Zealand
Pfizer New Zealand
Lilly New Zealand
Member Eion Edgar National Diabetes Centre for Diabetes Research
Advisory Board
Referee of Publications
Diabetes Care American Diabetes
Association
Royal Australasian College of Physicians
New Zealand Medical Journal
Diabetes Research and Clinical Practice
Diabetes Obesity and Metabolism
Referee of Research Applications
Health Research Council New Zealand
Heart Foundation of New Zealand
New Zealand Principal Investigator and member of Management Committee
for the FIELD Study - a 3 country study on heart disease prevention in
diabetes mellitus through lipid-modification
Chairperson Scientific organising Committee WPIDF 2008 meeting
Supervision of PHD Fellows
J McRae
P Taylor
J Young
Invited Speaker:
Pre meeting Symposium, EASD, Amsterdam, Sept 2007 The diabetes
challenge: keeping glucose in range
South East Asia Diabetes Forum, Chiang Mai Thailand, Oct 2007 DPP-4
Inhibitor based therapies in the management of type 2 Diabetes
Korean Diabetes Association, Busan Korea, Nov 2007 Januvia-the
first physiological glucose regulator for optimal treatment of type 2
diabetes
Advances in Medicine 2008, Chinese University of Hong Kong, June
2008 What after metformin: Incretin Enhancers and DPP-4
Inhibition
Advances in Medicine 2008, Chinese University of Hong Kong, June
2008 Achieving glycemic control without therapeutic compromise with
Sitagliptin
Dr Chris Florkowski
Chair, New Zealand Branch of the Australasian Association of Clinical
Biochemists AACB
Corresponding Member, Committee of Evidence Based Laboratory Medicine
EBLM of the International Federation of Clinical Chemistry IFCC
Member, Organising Committee for 2008 Chemical Pathology Course CPC
for Australasian Association of Clinical Biochemists / Royal College
of Pathologists Perth
Member, Organising Committee, 2008 Programme for Annual Royal College
of Pathologists of Australasia RCPA Update Meeting
Invited Speaker for Annual Royal College of Pathologists of
Australasia RCPA Update Meeting; Sydney, March 2008 topic: e-GFR,
an update
Examiner, Royal College of Pathologists of Australasia
Member, Editorial Board of Clinical Biochemist Reviews
Member, Expert Panel for Clinical Commenting of the Quality Assurance
Programme of the Royal College of Pathologists of Australasia QAP-
RCPA
Journal Referee: Diabetes Research and Clinical Practice, Clinical
Endocrinology, Clinical Biochemist Reviews, Pathology, Annals of
Clinical Biochemistry
Member, Australasian Creatinine Consensus Working Group 2007-
Member, AACB Working Party on Porphyria 2007- Organiser of
Porphyria Expert Comments Programme, with global membership
Invited talks:
Australasian Association of Clinical Biochemists Current Concepts Tour:
Invited Lecturer 2007: Evidence Based Laboratory Medicine EBLM
a Hamilton, NZ - May 2007
b Melbourne, June 2007
c Brisbane, July 2007
d Perth, August 2007
e Adelaide, August 2007 with video link-up to remote
territories
f Sydney and Hobart through pre-recorded lectures
International Federation of Clinical Chemistry IFCC Worldlab Meeting,
Fortaleza, Brazil September 2008 Two invited talks on Evidence Based
Laboratory Medicine
Invited Speaker 5th International Coenzyme Q10 Association Meeting, Kobe
Japan November 2007 Coenzyme Q10 and prediction of outcomes in cardiac
failure
Royal College of Pathologists of Australasia RCPA Update Meeting;
Sydney,
Australia; March 2008; e-GFR: an update
Invited lecturer to 2008 Chemical Pathology Course CPC for Australasian
Association of Clinical Biochemists / Royal College of Pathologists, Perth
Lead poisoning
Dr Brett Shand
Member, Scientific Organising Committee, 7th International Diabetes
Federation, Western Pacific Region Congress, Wellington, 2008
Referee of Publications -
Diabetes Research and Clinical Practice
Internal Medicine Journal
Dr Jinny Willis
National Co-ordinator New Zealand Data Centre, TrialNet
Referee of Publications
Diabetic Medicine
Diabetes Research Clinical Practice
Invited Speaker:
New Zealand Paediatric Society Conference, Christchurch, New Zealand
November 2007 Type 1 Diabetes in Canterbury Children and Adolescents:
Incidence and Geography New Zealand Paediatric Society Conference,
Christchurch, New Zealand
Referee of Grant Applications
Marsden Fund
Supervision of PhD Fellows
J McRae
P Taylor
K Volkova
8 Research Grants and other Funding Support
New Zealand National Heart Foundation
J Young: Small Project Grant Application
15,000
Health Research Council
J Young: Does Ezetimibe correct vascular dysfunction? 102,122
NZSSD Eli Lilly award:
Dr J Willis: HDL cholesterol function and CVD in Diabetes 30,000
2007 Pfizer New Zealand: 33,000
Dr B Shand: Commissioned project: Use of Lipid Clinic database to
investigate
the effect of changes in lipid-lowering medication on CVD risk
New Zealand National Heart Foundation and the Paykel Trust
Dr B Shand To attend the 5th Annual World Congress
On the Insulin Resistance Syndrome,
Boston, USA October, 2007
Special Grants
Diabetes and Heart Research Trust Salary to J Young 50,000
J Willis: Montgomery Trust
40,000
Australian Atherosclerosis Society Trust Travel Grants J Young
2,900
NZSSD Travel Grant J Young
300
NZSSD Travel Grant J Willlis 450
Other RESEARCH Funding and EDUCATION Support
The George Institute University of Sydney
The Clinical Trials Centre University of Sydney
Merck and Co USA and NZ
Eli Lilly NZ
Novartis Australia
Novo Nordisk New Zealand and
Australia
Pfizer International
Boehringer Ingelheim Australia
Juvenile Diabetes Research Foundation USA
Parexel Australia
Sanofi Aventis
MedPace USA
Trilogie Phytotherapy Australia
FournierPharma Australia and France
Takeda International
GlaxoSmithKline International
Reports by Research Staff
CHRISTOPHER FLORKOWSKI
Clinical Research Physician
Present Positions
Consultant Chemical Pathologist to Canterbury Health Laboratories
Clinical Research Physician, Lipid and Diabetes Research Group
Physician to Diabetes and Lipid Disorders Clinics, Canterbury Health Board
Adjunct Associate Professor in Chemical Pathology,
Christchurch School of Medicine and Health Sciences, University of Otago
Research Projects
Co-Investigator to Clinical Trials programme undertaken by Lipid and
Diabetes Research Group see reports by other staff
Outcomes of Insulin-Treated Diabetes: Twenty year mortality and morbidity
in a population-based cohort of insulin-treated diabetic subjects in
Canterbury, New Zealand, as a follow-up to previously reported mortality
rates at 9 and 15 years Now
published
Co-enzyme Q10 studies
1 Further Bio-availability studies are ongoing using commercial
preparations
2 Studies ongoing of CoQ10 in subjects with Familial
Hypercholesterolaemia
3 Studies have been initiated of the effects of co-enzyme Q10
supplementation in patients with metabolic syndrome
4 Publication pending on outcomes in heart failure in relation to CoQ10
levels
5 Grant funding pending for an intervention study in Hypertension
Glucose Meter evaluation studies undertaken in Diabetes Services
Fluorescence of skin collagen in diabetes: protocols developed for studies
Meetings Attended
5th International Coenzyme Q10 Association Meeting, Kobe, Japan November
2007 Invited Speaker
Joint ADS, NZSSD Annual Scientific Meeting, Christchurch, September 2007
Cardiac Society, ANZ Christchurch, August 2007
Endocrine Society of Australasia Christchurch, August 2007
Australasian Association of Clinical Biochemists, Annual Scientific
Meeting, Melbourne; October 2007
Royal College of Pathologists of Australasia, Update Meeting; Sydney,
Australia; March 2008 Invited Speaker
Chemical Pathology Course CPC for Australasian Association of
Clinical
Biochemists / Royal College of Pathologists, Perth; February 2008 Invited
Speaker
Abstracts
1 Florkowski CM, Wheeler B, Hunt P, MacKenzie K, Potter HC, George PM
Three Cases of Congenital Adrenal Hypoplasia with Novel Mutations in
the NROB1 DAX-1 gene Ann Clin Biochem 2008; 45 Suppl 1: 28 Short-
listed for Poster Prize
2 Florkowski CM, Molyneux SL, Richards AM, George PM Coenzyme Q10
predicts total mortality in patients with chronic heart failure;
outcomes from the Battlescarred cohort Proceedings of the 5th
International Coenzyme Q10 Association, 2007, p43
3 Florkowski CM, Molyneux SL, Richards AM, George PM Plasma coenzyme
Q10 is an independent predictor of mortality in chronic heart failure
In: Proceedings of the Australasian Association of Clinical Biochemists
45th Annual Scientific Conference, Melbourne, Australia, September 24-
27, 2007 Clin Biochem Rev 2007;28:Suppl i:S15 Best Oral
Presentation Prize
Publications
1 Florkowski CM, Molyneux SL, George PM Rosuvastatin in older patients
with systolic heart failure N Engl J Med 2008 Mar 20; 35812:
1301
2 Livesey J, Elder P, Ellis MJ,
Florkowski C, McKenzie R, Liley B
Response to the letter by Bolland et al on defining vitamin D
deficiency NZ Med J 2007 Nov 9; 1201265: U2815
3 Florkowski CM, Beaven DW Prevalence of new and known diabetes
mellitus, impaired glucose tolerance, and impaired fasting glucose
NZ Med J 2007 Aug 10; 1201259; U2674
4 Wheeler B, George PM, MacKenzie K, Hunt P, Potter HC, Florkowski CM
Three cases of congenital adrenal hypoplasia with novel mutations in
the NROB1DAX-1 gene Annals Clin Biochem 2008 In Press
5 Walmsley TA, Potter HC, George PM, Florkowski CM Pseudo-
hypertriglyceridaemia: a measurement artefact due to glycerol kinase
deficiency Postgrad Med J 2008 In Press
6 Florkowski CM Sensitivity, specificity, Receiver-Operator
Characteristic ROC curves and likelihood ratios: communicating the
performance of diagnostic tests Clin Biochem Revs 2008 In Press
7 Soule S, Florkowski C, Potter H, Pattison D, Swan M, Hunt M, George P
Intermittent severe hyponatraemia due to nephrogenic syndrome of
inappropriate antidiuresis Ann Clin Biochem 2008 In Press
8 Young JM, Strey CH, George PM,
Florkowski CM, Sies CW, Frampton CM,
Scott RS Effect of atorvastatin on plasma levels of asymmetric
dimethylaraginine in patients with non-ischemic heart failure Eur J
Heart Fail 2008; May; 105: 463-6
9 Chew JSC, Saleem M, Florkowski CM, George PM Cystatin C - A paradigm
of evidence based laboratory medicine Clin Biochem Rev 2008; 292:
47-62
10 Molyneux SL, Young JM, Florkowski CM, Lever M, George PM Coenzyme
Q10: Is There a Clinical Role and a Case for Measurement? Clin
Biochem Revs 2008; 292: 71-82
11 Dawson SI, Willis J, Florkowski CM, Scott RS Cause-specific
mortality in insulin-treated diabetic patients: a 20-year follow-up
Diabetes Res Clin Pract 2008 Apr; 801: 16-23
12 Dawson SI, Willis J, Florkowski CM, Scott RS All-cause mortality in
insulin-treated diabetic patients: Diabetes Res Clin Pract 2008 Apr;
901:36-9
Other Activities
Chair, New Zealand Branch of the Australasian Association of Clinical
Biochemists AACB
Corresponding Member, Committee of Evidence Based Laboratory Medicine
EBLM of the International Federation of Clinical Chemistry IFCC
Member, Organising Committee for 2008
Chemical Pathology Course CPC for
Australasian Association of Clinical Biochemists / Royal College of
Pathologists Perth
Member, Organising Committee, 2008 Programme for Annual Royal College of
Pathologists of Australasia RCPA Update Meeting
Invited Speaker for Annual Royal College of Pathologists of Australasia
RCPA Update Meeting; Sydney, March 2008 topic: e-GFR, an update
Examiner, Royal College of Pathologists of Australasia
Member, Editorial Board of Clinical Biochemist Reviews
Member, Expert Panel for Clinical Commenting of the Quality Assurance
Programme of the Royal College of Pathologists of Australasia QAP-RCPA
Journal Referee: Diabetes Research and Clinical Practice, Clinical
Endocrinology, Clinical Biochemist Reviews, Pathology, Annals of Clinical
Biochemistry
Member, Australasian Creatinine Consensus Working Group 2007-
Member, AACB Working Party on Porphyria 2007- Organiser of Porphyria
Expert Comments Programme, with global membership
Invited talks:
Australasian Association of Clinical Biochemists Current Concepts Tour:
Invited Lecturer 2007: Evidence Based Laboratory Medicine EBLM
g Hamilton, NZ - May 2007
h Melbourne, June 2007
i
Brisbane, July 2007
j Perth, August 2007
k Adelaide, August 2007 with video link-up to remote
territories
l Sydney and Hobart through pre-recorded lectures
International Federation of Clinical Chemistry IFCC Worldlab Meeting,
Fortaleza, Brazil September 2008 Two invited talks on Evidence Based
Laboratory Medicine
Invited Speaker 5th International Coenzyme Q10 Association Meeting, Kobe
Japan November 2007 Coenzyme Q10 and prediction of outcomes in cardiac
failure
Royal College of Pathologists of Australasia RCPA Update Meeting; Sydney,
Australia; March 2008; e-GFR: an update
Invited lecturer to 2008 Chemical Pathology Course CPC for Australasian
Association of Clinical Biochemists / Royal College of Pathologists, Perth
Lead poisoning
ALISON LUCKEY
Clinical Research Physician
Provided clinical support to the entire range of clinical studies detailed
in the Groups report
Review of Ethics applications
NIKKI REID
Clinical Nurse Specialist: Lipid Disorders and CVD Prevention
Current Responsibilities
Co-ordination of Lipid Disorders and
CVD Prevention Clinics for the CDHB
Lipid disorders and cardiovascular risk identification, assessment,
diagnosis, treatment and education for cardiovascular prevention of
patients and families referred to the Clinics
Familial Hypercholesterolemia Program in Canterbury
Education of other health professionals in lipid disorders and
cardiovascular prevention
Liaison with staff of the Lipid and Diabetes Research Group
Databases
Collect anthropometric data for Clinic database
Maintain databases of special risk groups
Maintain records and organise genetic screening for relatives of clients
with identified familial cholesterol disorders
Abstracts of Research:
Identification and Characterization of two non- secreted PCSK9 mutants
associated with familial hypercholesterolemia in cohorts from New Zealand
and South Africa Atherosclerosis: 1962008 659-666
Attendances at Scientific meetings:
Australasian Atherosclerosis Society Familial Hypercholesterolaemia sub
committee meeting January 2008Adelaide
Other Activities
Family Screening Programme for identification of Familial
Hypercholesterolemia
Lectures to Practice Nurses, Cardiology
nursing staff, Post Graduate
nursing students, pharmacists and general public on Cardiovascular Risk
Assessment, Lipid Lowering Therapies and Familial Hypercholesterolaemia
ROBERTA BOBBY McEWAN
Research Nurse
Current Research Projects
1 ADVANCE study - A factorial randomised trial of blood pressure
lowering with a fixed low-dose Perindopril-Indapamide combination and
intensive glucose control with a modified-released Gliclazide-based
regimen for the prevention of vascular disease among high-risk
individuals with type 2 diabetes
76 participants were randomised at Christchurch site, a 4-6 year
study Completed and published, site closure due July 2008
2 RECORD study - A long term, open label, randomised study in patients
with type 2 diabetes, comparing the combination of Rosiglitazone and
either Metformin or Sulphonylurea with Metformin plus Sulphonylurea
on cardiovascular endpoints and glycaemia
A worldwide study in 20 countries 4466 participants were
randomised with an average 6-year follow-up Christchurch has
recruited 7
participants Due for completion December 2008
3 CRESCENDO study - Randomized, multinational, multicenter, double-
blind, placebo-controlled, two-arm parallel group trial of Rimonabant
SR141716 20 mg OD for reducing the risk of major cardiovascular
events in abdominally obese patients with clustering risk factors
Lead site - A worldwide study to recruit 17,000 participants 4 year
follow-up Currently recruiting
44 ZOLIP study - A multicentre, double-blind, randomised study to
compare the efficacy and safety of the combination of 145 mg
Fenofibrate and 40 mg Simvastatin with 40 mg Simvastatin monotherapy
in patients with mixed dyslipidaemia at risk of cardiovascular
disease not adequately controlled by 40 mg Simvastatin alone
Lead site - ANZ and European sites Christchurch is the lead site for
New Zealand and has registered 31 participants to date 113
randomised worldwide Recruitment completed
5 DORADO study - DORADO-AC - Optimized Doses of Darusentan as Compared
to an Active Control in Resistant Hypertension
A Phase 3 Randomized, Double-Blind, Placebo- and Active-Controlled,
Multi-centre, Parallel Group Study to Evaluate the Safety and
Efficacy of Darusentan in Subjects with Resistant Hypertension
Receiving Combination Therapy with Three or More Antihypertensive
Drugs, Including a Diuretic, as Compared to Guanfacine or Placebo
Protocol DAR-312
Lead site - Being conducted worldwide, 18 week intensive Blood
Pressure study commenced August 2007 recruitment continues
8 DORADO-AC-EX - A Double-Blind, Active-Controlled, Long-Term Safety
Extension Study to the Phase 3 DORADO-AC Study Protocol DAR-312
of Darusentan in Resistant Hypertension
A Double-Blind, Active-Controlled, Long-Term Safety Extension Study
of Optimized Doses of Darusentan in Subjects with Resistant
Hypertension Despite Receiving Combination Therapy with Three or More
Antihypertensive Drugs, Including a Diuretic, as Compared to
Guanfacine Protocol DAR-312-E
Lead site - A long term extension to DORAD-AC study Duration is
until termination/completion of study or drug comes to market
Meetings Attended
1 ADVANCE Investigator meeting, Vienna; August 2007
2 CRESCENDO Investigator
meeting, Sydney; February 2008
PATRICE MCGREGOR
Research Nurse Coordinator
Current Research Projects
1 Coordinator for ADVANCE study- Action in Diabetes and Vascular Disease
A six year factorial randomised trial of blood-pressure lowering with a
fixed low-dose Perindopril-Indapamide combination and intensive glucose
control with a modified release gliclizide-based regimen for the prevention
of vascular disease among high risk individuals with Type 2 Diabetes
Mellitus
75 participants were randomised to the study which has now been completed
with the blood pressure arm results having been presented at Vienna in
August 2007 and the diabetes arm results presented in San Francisco in June
2008
2 Coordinator for Zolip study-
A study evaluating the effectiveness of using a combination of Fenofibrate
and Simvastatin in people at risk of cardiovascular disease
Twenty one participants completed the 24 week study in Christchurch and the
study will close out in August 2008
3 Coordinator for REASSURE study-
Randomized, multinational, multicentre, double-blind, placebo controlled,
parallel group, fixed dose Rimonabant
SR14171620mg OD study on HbA1c in
overweight or obese subjects with type 2 diabetes not adequately controlled
on two oral antidiabetic agents
Recruitment will be completed in August 2008 for this 52 week study
Christchurch anticipates twenty participants will be randomised to the
study
4 Coordinator for SYR 322 study-
A multi-centre, randomised, doule-blind, placebo controlled study to
determine the efficacy and safety of SYR-322 compared to placebo in
subjects with Type 2 Diabetes Three treatment arms, 26 week treatment
duration study
A new medication being developed to improve blood glucose levels in Type 2
diabetes
12 participants have now completed the initial 26 week study of the
Metformin arm and all 12 have entered the open label extension study which
continues until the end of 2010
5 Coenzyme Q10 bioavailability study
Coenzyme Q10 is increasing used as an adjunctive therapy for cardiovascular
disease However coenzyme Q10 supplements are relatively expensive and are
poorly absorbed Recently, new formulations of CoQ10 have been prepared
with the aim of improving uptake of coenzyme Q10 by the body This study
will compare the coenzyme Q10 levels in the blood following
supplementation
of either a soy bean oil coenzyme Q10 preparation or new formulation of
coenzyme Q10 The study will involve 36 male subjects taking a single dose
of the two preparations two weeks apart, with blood samples being collected
before and during a 10-hour period following ingestion of either
supplement The coenzyme Q10 levels in the blood samples will be measured
to determine if there are any differences in the magnitude of the increase
in coenzyme Q10 levels caused by the two supplements This study is funded
by Trilogie Products Pty Ltd
Meetings Attended
ADVANCE Investigator Meeting Vienna August 2007
JEREMY MCRAE
PhD Student
Research Projects completed 2008 and PhD awarded
1 Investigation of variants of the Adiponectin Receptors
This projects focus is genetic variation in adiponectin and its
cognate receptors We have genetic repositories of several well-
characterised cohorts covering several appropriate disease states:
full type 2 diabetes, individuals with aspects of the metabolic
syndrome and age-matched healthy controls Each of these has over
300
individuals, providing sufficient numbers for fully powered studies
I sequenced the coding regions of the adiponectin receptors,
candidate genes for type 2 diabetes and identified variants also
called Single Nucleotide Polymorphisms or SNPs Several were
established to be novel and these were examined for useful
haplotypes An initial population of 46 individuals were genotyped to
identify haplotype tags and strong linkage disequilibrium between
SNPs
The complete cohorts were then genotyped for the selected SNPs This
provided a set of approximately 15000 genotypes The final stages of
analysis of this data set are being completed
2 Investigation of functional elements of the promoters of the
Adiponectin Receptors
The promoter regions of the receptors contain genetic elements for
controlling expression and hence production of functional receptors
Identification of these elements elucidates when and where the
receptors will be produced The promoters were amplified by PCR and
ligated into cloning vectors A series of nested deletions was
generated by
amplifying successively shorter regions These were
subcloned into a reporter plasmid so that the promoter regions
control expression of a signal The reporter plasmids were
transfected into liver and muscle cell lines to test the response in
different tissue types Variable expression dependent upon promoter
length was observed
ZARNIA MORRISON
Research Nurse
Current Research Projects
1 A multinational randomised double blind placebo controlled forced
titration 2×2 factorial design study of efficacy and safety of long
term administration of nateglinide and valsartan in the prevention of
diabetes and cardiovascular outcomes in subjects with Impaired Glucose
Tolerance IGT Navigator Study
This 6-year study using nateglinide 60mg and valsartan 180mg daily
commenced in June 2002 There are 600 participating centres in 40 countries
throughout the word There are two centres in New Zealand one in
Christchurch and one in Dunedin An amendment to the protocol increased the
number of participants to be recruited from 7500 to
9150 and worldwide
recruitment closed in November 2003, 9,524 patients have been recruited
worldwide Our site recruited 15 patients and the Dunedin site recruited
20 The study is due to finish in January 2010
2 A Phase III, Multicentre, randomised, Double blind clinical trial to
study the safety and efficacy of the addition of sitagliptin MK-0431
to patients with type 2 diabetes mellitus who have inadequate glycemic
control on Insulin therapy alone or in combination with metformin
This is a placebo controlled double blind 24 week study Patients on
insulin alone or in combination with metformin at a dose of at least 1500mg
per day with inadequate glycemic control will be eligible to participate
Patients will continue on their current insulin /- metformin regimen and
be randomized to treatment with sitagliptin 100mg qd or placebo for a 24
week fixed insulin dose double blind treatment period This study commenced
in Feburary 2007 in Christchurch, Hastings and Auckland Christchurch
enrolled 10 patients These 10 patients have all completed the study
requirements however due to slow recruitment worldwide the study
continues
internationally and is due to be completed at the end of 2008
3 A Phase 2b, Randomised, Double-Blind,Parallel-Group, Study of Safety
and Efficacy of 16 weeks of Treatment with DIO-902 or DIO-902 placebo
in addition to Metformin and Atorvastatin or Atorvastatin placebo in
subjects with type 2 diabetes mellitus protocol No DIO-502
All subjects enrolled in this protocol will be on a stable dose of
metformin and will continue on that dose throughout the study Patients
will be randomised to either placebo, DIO-902 150mg, DIO-902 300mg, or DIO-
902 450mg They will also be randomised to atorvastatin 10mg or placebo At
week 8 all participants will go on to open label atorvastatin and continue
on the same dose of DIO-902 Recruitment for this study commenced in
December 2007 however the study was terminated early in May 2008 by the
sponsor as the compound had caused abnormal liver function tests
4 A 76-Week, Worldwide, Multicenter, Double-Blind, Randomized, Placebo-
Controlled Study to Assess the Tolerability and Efficacy of
Anacetrapib When Added to Ongoing Therapy With a Statin in Patients
With
Hypercholesterolemia or Mixed Hyperlipidemia
This is a 92 week, phase III, parallel group study to assess MK-0859
anacetrapib as an add on treatment to statin therapy in participants with
high cholesterol or mixed hyperlipidemia The study will assess the long-
term effectiveness, safety and tolerability of anacetrapib Approximately
1500 males and females will be enrolled world-wide The participants will
already be taking a stable dose of lipid modifying therapy must include a
statin with less than ideal HDL cholesterol levels Participants will
remain on their current lipid modifying therapy for the study duration and
if eligible, they will be randomised to either anacetrapib or placebo at a
1:1 ratio for 76 weeks At each visit bloods will be drawn, vital signs
taken, medication compliance and adverse events monitored A physical
examination and electrocardiogram will be completed before randomisation,
at 24 weeks and the end of the study After stopping the study drug,
participants will be followed up with two phone calls and will attend a
visit 12 weeks post their final dose Recruitment for this study commenced
in June
2007 and continues our site has been allocated ten patients
5/ A multicenter, double-blind, randomized, 12-month, placebo-
controlled study to evaluate the lipid-lowering effect, safety and
tolerability of AVE5530 25 mg/day and 50mg/day when added to ongoing
stable statin therapy HMG-CoA reductase inhibitors in patients with
primary hypercholesterolemia
This study will assess the efficacy and safety of AVE5530 25 mg and 50 mg
when added to statin treatment in comparison with placebo in the
management of patients with primary hypercholesterolemia and LDL-C levels
still equal or greater than 100 mg/dL 259 mmol/L The minimum duration
of treatment will be 12 months but may be extended up to approximately 18
months We are currently waiting on final ethical approval for this study
MAREE PIEBENGA
Research Coordinator 03 FTE
Current Research Projects:
1 Randomised, Double-Blind, Placebo -Controlled Efficacy and Safety
Study of Colesevelam HCL Administered to Paediatric Patients With
Heterozygous Familial Hypercholesterolemia on a Stable Dose
of
Statins or Treatment Naïve to Lipid-Lowering Therapy Protocol WEL-
410
Phase IV
Colesevelam WelChol is a new bile acid sequestrant approved by the
USFDA in January 2000 Welchol has a high specificity for binding
bile acids in the gut resulting in reduction of serum cholesterol,
but with a favourable side effect profile Recruitment began for
this study in November 2006 and was completed in April 2007 5
people were screened and randomised into this 32 week study This
study had an 8-week double-blind treatment period, followed by an 18-
week open-label period The study completed in December 2007
SARAH PLOT
Nurse Specialist Study Co-ordinator
1 A Long-Term, Open Label Extension Study to Investigate the Long-Term
Safety of SYR110322 SYR-322 In Subjects with Type 2 Diabetes
Protocol SYR-322-OLE-012 Phase III
SYR-322 is a new medication being developed to improve blood glucose
levels in Type 2 diabetes This study commenced in December 2006 and
has now been extended to four years in duration Participants
who had
successfully completed SYR-322 Phase III, protocols SYR-322-SULF-007,
SYR-322-MET-008, SYR-322-PIO-009, SYR-322-PLC-010 or SYR-322-INS-011
were able enter this study and have been assigned to open label study
medication The study is due to be completed in 20011
2 A Multi-Centre, Randomized, Double-Blind Study to Determine the
Efficacy and Safety of the Addition of SYR-322 25 mg versus Dose
Titration from 30 mg to 45 mg of ACTOS Pioglitazone HCl in Subjects
with Type 2 Diabetes Mellitus Who Have Inadequate Control on a
Combination of Metformin and 30 mg of Pioglitazone HCl Therapy
Protocol 01-06-TL-3222OPI-004 Phase III
SYR-322 is a new medication being developed to improve blood glucose
levels in Type 2 diabetes This study completed recruitment in
February 2008 with 5 participants randomised Participants in this
study are using metformin plus pioglitazone 30mg and are then
assigned to receive either SYR-322 25 mg or placebo or an additional
15 mg of pioglitazone or placebo The study lasts for a maximum of 74
weeks
3 A Multi-Centre,
Randomised, Double-Blind Study to Evaluate
the Safety and Efficacy of the Addition of Sitagliptin Compared With
the Addition of Glimepiride in Patients With Type 2 Diabetes Mellitus
Who Have Inadequate Glycemic Control on Metformin Protocol 803-01
Phase lll
This study is actively recruiting and commenced in June 2008 People
in the study are using high dose Metformin 1500 mg/day and have
inadequate diabetes control ie: HbA1c 65- 90 This study lasts
for 35 weeks The study medication Sitagliptin, has been approved for
use by the FDA as a prescription medicine for Type 2 Diabetes
4 A Randomised, Double-Blind Placebo -Controlled Parallel Group
Efficacy and Safety Study of BI 1356 5mg administered orally once
daily Over 24 Weeks in Type 2 Diabetic Patients With Insufficient
Glycaemic Control Despite Metformin Therapy Protocol BI 121817
Phase III
BI 1356 is a new medication being developed to improve blood glucose
levels in Type 2 diabetes This study is actively recruiting and
commenced in May 2008 People in this study will be using
metformin
alone or in combination with one other oral diabetes medication and
have inadequate diabetes control ie: have an HbA1c between 65-90
or 70-10; depending on their diabetes medications The study
lasts for a maximum of 32 weeks An open label extension to this
study Protocol BI 121840 with a 78 week treatment period is
planned
Completed Research Projects
1 Randomised, Double-Blind, Placebo-Controlled Efficacy and Safety
Study of Colesevelam HCL Administered to Paediatric Patients With
Heterozygous Familial Hypercholesterolemia on a Stable Dose of Statins
or Treatment Naïve to Lipid-Lowering Therapy Protocol WEL-410 Phase
IV
Colesevelam WelChol is a new bile acid sequestrant approved by the
USFDA in January 2000 Welchol has a high specificity for binding
bile acids in the gut resulting in reduction of serum cholesterol,
but with a favourable side effect profile Recruitment began for
this study in November 2006 and was completed in April 2007 Five
people were screened and randomised into this 32 week study
This
study had an 8-week double-blind treatment period, followed by an 18-
week open-label period The study was completed in December 2007
Attendances at Meetings
1 Investigators meeting for Boehringer Ingelheim; Protocol BI 121817,
Queenstown April 2008
2 Investigators meeting for MERCK; ProtocolMK-0431-803-01; Auckland
April 2008
ANNETTE REINHEIMER
Clinical Study Co-ordinator
Current Research Projects
1 A Long Term, Open-Label Extension Study to Investigate the Long-Term
safety of SYR110322 Alogliptin in Subjects with Type 2 Diabetes
Recruitment for this study began in January 2007
2 A Multicenter, Randomized, Double-Blind, Placebo- and Active-
Controlled Study to Assess the Efficacy, and Tolerability of MK-
6213 co-administered with Atorvastatin in Patients with Primary
Hypercholesterolemia Recruitment will begin in August 2008
3 A Phase 11B, Multicenter, Double-Blind, Placebo, Dose-Ranging
Finding Clinical Trial of MK-0941 in Patients with Type 2 Diabetes
Mellitus with Inadequate Glycemic Control on Basal
Insulin
Recruitment for this study will begin in August 2008
4 A Mulitcenter, Double-Blind, Randomised Study to Establish the
Clinical
Benefit and safety of Vytorin verses Simvastatin in patients
presenting with Acute Coronary Syndrome Recruitment is in
progressinitiated by another reseach group
Completed Research Projects
1 A Multi-Center, Randomised, Double-Blind, Placebo-Controlled 36
week- Study to Evaluate the Efficacy and Safety of extended Release
ER Niacin/Laropiprant in Patients with Type 2 Diabetes mellitus
Recruitment closed for this study in December 2007 with the last
patient completing the study July 2008
Attendances at Meetings
1 Investigators Meeting for MERCK MK-6213 Frankfurt Oct 2007
2 Rejuvenation Meeting Improve -it Study Auckland May 2008
3 Investigator meeting for Merck MK-0941 New York June 2008
Further Education
Diabetes Nurses Symposium Wellington 2008
DR BRETT SHAND
Scientist
Current Research Projects
1 Studies comparing the role of markers of insulin resistance to
predict the development of impaired glucose control and
atherosclerosis in overweight subjects
This prospective study in 250 overweight individuals, evaluated the
ability of commonly used and several new markers of insulin
resistance to predict worsening in blood glucose control over a 3-
year period Particular emphasis was given to the insulin sensitising
cytokine, adiponectin and binding proteins involved in steroid and
vitamin metabolism The study was carried out in collaboration with
the Steroid and Immunobiochemistry Laboratory, Canterbury Health
Laboratories with clinical and laboratory data collection being
completed in June 2007 Complete data was obtained on 211 subjects
The main findings of the study were that metabolic markers such as
adiponectin and the triglyceride:HDL cholesterol ratio were more
sensitive markers of incipient glucose intolerance than insulin
derived indices, but that the predictive potential of all these
markers reduced as glucose control became more impaired The results
of the study have been published in several papers with several
more
papers currently in preparation
As part of the main study we also compared plasma adiponectin levels
in Maori and Caucasian people, to determine whether or not Maori have
genetically low levels of adiponectin Low levels of adiponectin
increase the risk of developing type 2 diabetes The study in 111
Maori and New Zealand European matched pairs showed that Maori people
tend to have lower levels of adiponectin in their blood It is
possible these low adiponectin levels may contribute to the higher
prevalence of type 2 diabetes in the Maori population The findings
of this study were published in June 2007 in the New Zealand Medical
Journal
The adiponectin research program also included laboratory
investigations on the beneficial anti-atherosclerotic effects of
adiponectin This work was undertaken by Dr Stuart Plant, funded by a
grant from Diabetes UK The series of experiments showed that
adiponectin protected cultured vascular cells against oxidative
damage caused by high concentrations of oxidised lipoproteins and
glucose These findings were published
Diabetes and Cardiovascular
Research in June 2008
2 An investigation of the mechanism of the anti-proteinuric effects of
pioglitazone
Pioglitazone is a drug with insulin sensitising properties used in
the treatment of type 2 diabetes In addition to its insulin
sensitising effect, pioglitazone also reduces protein loss in the
urine The mechanism of this anti-proteinuric effect is not fully
understood This study, funded by the 2006 Eli Lilly Diabetes
Specialist Research Grant, will investigate the effect of
pioglitazone on the filtration units in the kidney responsible for
removing waste products from the blood The study will involve
measuring the urinary excretion levels of proteins of different size
and electrostatic charge in patients with type 2 diabetes and kidney
disease, before and after a 3-month course of pioglitazone This
data will be used to determine whether pioglitazone causes changes in
the size of the pores in the filter or the level of electrostatic
charge barriers in these filters Ethical approval for the study has
been obtained, appropriate
study medication has been provided by Eli
Lilly NZ and screening and enrollment of patients for the study is
being carried out at present
3 Epidemiological studies using Lipid Clinic database
Since 1997, a clinical database and frozen plasma sample repository
have been collected from new patients attending the Lipid Outpatient
Clinic at Christchurch Hospital To date, 3022 patients are included
in this database that provides a valuable resource for
epidemiological research on lipid disorders and the development of
the metabolic syndrome and type 2 diabetes Over the last year the
database has been updated to include all the Framingham variables
This new database will be used in a collaborative study with Pfizer,
New Zealand and the Departments of Medicine and Epidemiology
Preventative Medicine, Monash University Medical School, Melbourne,
to assess whether changing lipid-lowering medication has adverse
clinical affects in patients with lipid disorders
4 Assessment of a new, non-invasive, skin test for measuring blood
glucose control
The usual way of checking
for high blood glucose levels is by a blood
test that measures the amount of glucose attached to a protein in the
blood called haemoglobin the glycated haemoglobin test However,
several recent studies have shown that similar information can be
obtained by measuring the fluorescence of a protein in the skin,
called collagen This skin test has the advantage of being non-
invasive, with the results being available within two minutes, unlike
the glycated haemoglobin test, which involves a blood test and the
sample being sent to a laboratory for analysis As the fluorescent
apparatus is small and portable the skin test also has the potential
to be used for diabetes screening of a large number of people in a
community setting This screening method would therefore be
considerably cheaper than the cost of blood testing and analysis
We are currently in the planning phase of a project that will assess
the feasibility of using skin fluorescence testing in diabetes care
using apparatus developed recently in the University of Canterbury
The
project will firstly involve validation and calibration of the
fluorescent measuring device, and then clinical evaluation of the test
on patients attending diabetes out-patient clinics or having an oral
glucose tolerance test at a local laboratory for the diagnosis of
diabetes We also plan to investigate whether the skin fluorescent
measurements are related to diabetic complications such as eye, kidney
and nerve diseases Funding applications for the study are currently
being prepared
Publications in referred journals
Shand B, Scott R, Connolly S, Clarke R, Baker J, Elder P, Frampton C, Yeo
J Comparative study on the efficacy of pioglitazone in Caucasian and
Polynesian patients with poorly controlled type 2 diabetes Diabetes
Obesity and Metabolism 9:540-547 2007
Shand BI, Elder PG, Scott RS, Poa N Comparison of plasma adiponectin
levels in New Zealand Maori and Caucasian subjects New Zealand Medical
Journal 120: No 1257 2007
Plant SD, Shand BI, Elder PA, Scott RS Adiponectin acts in conjunction
with glutathione to protect against human endothelium dysfunction induced
by
oxidised low-density lipoproteins and hyperglycaemia Diabetes and
Vascular Disease Research 5:102-108 2008
Lewis JG, Shand BI, Frampton CM Elder PA An ELISA for plasma retinol-
binding protein using monoclonal and polyclonal antibodies: plasma
variation in normal and insulin resistant subjects In Press Clinical
Biochemistry April 2007
Lewis JG, Shand BI, Elder PA, Scott RS Plasma retinol-binding protein is
likely not a useful marker of insulin resistance In Press Diabetes
Research and Clinical Practice June 2008
Lewis JG, Shand BI, Elder PA, Scott RS Plasma retinol-binding protein is
not a marker of insulin resistance in overweight subjects: a three year
longitudinal study In press Clinical Biochemistry June 2008
Lewis JG, Shand BI, Frampton CM, Elder PA, Scott RS Sex hormone-binding
globulin, corticosteroid binding globulin and cortisol are not markers of
insulin resistance in overweight subjects who develop impaired fasting
glucose: a three year longitudinal study Submitted Hormone and Metabolic
Research Biochemistry June 2008
Elmslie JL, Porter RJ, Joyce PR, Hunt PJ, Shand BI, Scott RS Comparison
of
Insulin Resistance, the Metabolic Syndrome and Adiponectin in Overweight
Bipolar Patients taking Sodium Valproate and controls
Submitted Australian and New Zealand Journal of Psychiatry June 2008
Shand BI, Scott RS, Elder PA, Frampton CM, Lewis JG Comparison of commonly
used markers of insulin resistance to predict changes in blood glucose
control in overweight subjects: a three year prospective study Submitted
Obesity July 2008
Published abstracts of conference proceedings
Plant SD, Shand BI, Elder PA, Scott RS Adiponectin protects endothelial
cells against injury induced by oxidised low-density lipoproteins and
glucose by maintaining intracellular glutathione levels Australian
Diabetes Society, Australian Diabetes Educators Association and New Zealand
Society for the Study of Diabetes Joint Meeting, Christchurch, September
2007 and 5th Annual World Congress on the Insulin Resistance Syndrome
Boston, USA October 2007 Poster presentations
Shand B, Scott R, Elder P, Lewis J, Frampton C Comparison of metabolic
syndrome markers to predict changes in fasting glucose concentration in
overweight, non-diabetic subjects International Diabetes Federation,
Western Pacific
Region Congress, Wellington, March-April 2008 Oral
presentation
Research Grants and other Support
2006 Eli Lilly Diabetes Specialist Research Grant
30000 for study titled, Investigation of the mechanism of the anti-
proteinuric effects of pioglitazone
2007 Pfizer New Zealand
33000 for study utilising updated Lipid Clinic database to investigate the
effect of changes in lipid-lowering medication in patients with lipid
disorders
Attendances at Scientific Meetings
Australian Diabetes Society, Australian Diabetes Educators Association and
New Zealand Society for the Study of Diabetes Joint Meeting, Christchurch
September 2007
5th Annual World Congress on the Insulin Resistance Syndrome Boston,
USA October 2007 Funded by travel grants by Paykel Trust and Heart
Foundation of New Zealand
7th International Diabetes Federation, Western Pacific Region Congress,
Wellington March-April, 2008
Other Activities
Member, Scientific Organising Committee, 7th International Diabetes
Federation, Western Pacific Region Congress, Wellington, 2008
Sole editor of Congress Proceedings published in Diabetes Research and
Clinical Practice 79 Suppl 1 March 2008
Preparation of
grant applications for a clinical study titled, The effect
of smoking on factors involved in the development of type 2 diabetes in
pregnant women and their newborn infants Applications made to Heart
Foundation of New Zealand, Canterbury Medical Research Foundation, and
Lottery Health Research Grants- no funding obtained
Preparation of grant application to study the efficacy of DPP4 inhibitors
to optimise natriuretic peptide activity and attenuate fluid retention in
patients with type 2 diabetes and heart failure
Review of medical records and classification of cardiovascular risk in
patients with type 2 diabetes with normal and abnormal levels of urinary
betaine excretion [Study in Collaboration with Betaine and Homocysteine
Research Group, Christchurch Hospital]
Review of papers for Diabetes and Clinical Research, Diabetes Obesity and
Metabolism and American Journal of Cardiology
PETA TAYLOR
Post-graduate Student
Current Research Activities
Peta joined the Lipid and Diabetes Research Group as a PhD student in 2007
after completing an honours degree at the University of Canterbury Peta
is investigating HDL
function in participants with very high levels of HDL
in the presence and absence of cardiovascular disease
MEG SHANNON
Research Dietitian
Meg transfereed her studies over to others in the group following
resignation in 2008
Research Projects:
1 A 50-Week Extension to: A Multicentre, Randomised, Double-Blind
Factorial Study of the Co-Administration of MK-0431 and Metformin in
Patients With Type 2 Diabetes Mellitus who have Inadequate Glycemic
Control
2 A Multi-Centre, Double-Blind, Randomised, Placebo and Active
Comparator Controlled Dose-Range Finding Study of MK-0893 in Patients
With Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control
3 A Multi-Centre, Randomised, Double-Blind, Crossover Design
Study to Evaluate the Lipid-Altering Efficacy and Safety of MK-0524B
Combination Tablet Compared to MK-0524A Simvastatin Co
administration in Patients With Primary Hypercholesterolemia and
Mixed Dyslipidemia
4 Comparative Study of CoQ10 Bioavailability of Nano-Nature vs Generic
Soybean Capsule CoQ10
PETA TAYLOR
Post-graduate Student
Current Research Activities
Peta joined the Lipid and Diabetes Research Group as a PhD student in 2007
after completing an honours degree at the University of Canterbury Peta
is investigating HDL function in participants with very high levels of HDL
in the presence and absence of cardiovascular disease
DR JINNY WILLIS
Scientist
Current Research Projects
1 Epidemiology of Diabetes in Canterbury Children and Adolescents
Type 1 diabetes is an autoimmune disorder thought to be precipitated by
environmental factors in individuals with permissive genotypes Increased
rates of presentation with Type 1 diabetes have been reported in many
populations While the precise aetiology has not yet been defined, it has
been suggested that improved hygiene, leading to reduced exposure of the
developing immune system to infections, may explain increasing attack rates
of Type 1 diabetes
Prospective ascertainment of all incident cases commenced in this region in
1982 Prior to 1982 incident cases were ascertained retrospectively from
hospital
records Clinical and demographic data, including address, were
collected at diagnosis Age and sex specific annual incidence rates were
determined from five-yearly census population denominators This
research investigated geographical factors, including population mixing
parameters, and incidence of Type 1 diabetes in individuals aged 0-14
years diagnosed between 1980-2004 in collaboration with researchers at the
GeoHealth Laboratory, University of Canterbury Address at diagnosis for
each case was geo-coded to census area unit CAU and cluster analysis was
undertaken using the spatial scan statistic to test for spatial-temporal
clustering
For the years 1980-2004, there were 337 new Type 1 diabetes cases aged 0-14
years 164 males, 173 females and the mean SEM age at diagnosis was 879
023 years The incidence ranged from 495 cases to 3245 cases/100 000
person years Mean SEM incidence rates for the age groups 0-4 years, 5-9
years, 10-14 years were 1282 177, 1641 190, 2463 256 cases/100
000 person years respectively The significant increase in incidence rate
over 25 years was 088 cases/100 000 per year, or 5 per annum derived from
Poisson Regression Significant clustering of cases at CAU
was not detected
for the entire 25 year- cohort nor for subsets grouped according to age at
presentation However, distinct spatial clusters were detected when male
and female cases were analysed separately Poisson regression analyses
revealed a significant relationship between Type 1 diabetes incidence and
area level deprivation score p 001, with increased risk found in the
most affluent areas Significantly raised incidence was also shown in
satellite urban communities p0001 and rural areas with a high urban
influence p 005, when compared to the main urban areas of the region
The rate of presentation of Type 1 diabetes in Canterbury children and
adolescents is rapidly increasing Social and geographical characteristics
of the home environment affect the risk for Type 1 diabetes Investigating
spatial-temporal clusters in presentation may help to define the factors
contributing to the rapidly increasing rate of presentation of Type 1
diabetes in the Canterbury population
2 WHO DiaMond Study
The WHO DiaMond Study is a multinational project determining the incidence
of type 1 diabetes in children under 15 years of age Canterbury incidence
data has been contributed to the study since
commencement of the study in
1990 Local collaborators include all the Christchurch Diabetes Physicians
and the Diabetes Paediatric Physician Prof B Darlow Data is available
from 106 centres in 55 countries, representing about 4 of the worlds
children Data collected in the first 10 years of the study, 1990-1999,
revealed a total of 36,316 cases were diagnosed in the study population of
78 million children The age-adjusted incidence of type 1 diabetes among
106 centres 108 populations varied from 01/100,000/year in China and
Venezuela to 409 per 100,000/year in Finland The average annual increase
in incidence calculated over 96 centres was 28 95 CI 24-32
During 1990-1994, the increase was 24 95 CI 13-34 and during the
second study period 1995-1999 it was slightly higher 30 95 CI 19-
42 The trend estimated by continents showed a statistically
significant increase all over the world except in Central America and West
Indies where the trend was a decrease Canterbury is ranked internationally
in the highest 10 of the incidence distribution for risk of childhood
diabetes, defining a high-risk population with respect to type 1 diabetes
3 TrialNet ANZ
TrialNet is a network of
clinical centres, experts in diabetes and
immunology and specialized laboratories dedicated to testing new
approaches to understanding and preventing type 1 diabetes The network
has developed from the infrastructure of the Diabetes Prevention Trial
DPT-1 conducted in the United States The network is sponsored by a
number of groups within the NIH eg NIDDK, NIAID, NHCHD, the American
Diabetes Association and the Juvenile Diabetes Research Foundation
TrialNet ANZ is a collaboration of Australian and New Zealand centres co-
ordinated from the Alberti Diabetes Centre Royal Melbourne Hospital and
Walter Eliza Hall Institute of Medical Research This Australasian
collaboration is one of four international Trial Net Centres funded to
undertake studies aimed at prevention of type 1 diabetes The New Zealand
Data Centre operates from Christchurch Dr Jinny Willis Recruitment of
first degree relatives in New Zealand commenced in January 2006 To date
there are in excess of 1100 individuals who are enrolled in the study in
New Zealand Individuals participating in this study, who are positive
for autoantibodies against beta cell antigens have been invited to
participate in phase 2 of the
study in which -cell function is assessed
From this year these individuals will have the opportunity to
participate in intervention studies, testing novel approaches to
preventing type 1 diabetes The first two studies are antigen based
therapies and involve either intranasal or oral administration of
insulin
4 Type 1 Diabetes Genetic Consortium Asia and Pacific Network
The aim of this international consortium is to establish a combined
resource of 4300 families to carry out an appropriately powered search
for type 1 diabetes susceptibility genes The consortium is funded by the
Juvenile Diabetes Research Foundation USA When recruitment concluded
in 2007 the New Zealand arm of the study had recruited 43 multiplex
families 174 individuals All affected individuals will be
characterised with respect to HLA, INS, and CTLA-4 genes and
autoantibodies in core laboratories EBV cell lines have been produced
from fresh heparin blood samples to produce a long-term DNA repository
5 The safety and efficacy of BHT-3021, a plasmid vector containing the
human proinsulin gene, in subjects with type 1 diabetes
A plasmid vector, BHT-3021, produced by Bayhill Therapeutics, containing
the
genetic material which codes for human insulin is being investigated in
individuals with type 1 diabetes The research aims to assess the safety of
BHT-3021 and to determine if therapy with BHT-3021 affects the immune cells
that may be responsible for causing damage to the insulin-producing cells
in people with type 1 diabetes BHT-3021 is designed to decrease this
abnormal immunity to insulin and decrease damage to the insulin-producing
cells in the pancreas The research is underway in Auckland, Hamilton,
Wellington and Christchurch There are also study sites in Australia and
the USA The company have successfully completed a study using a similar
agent, BHT-3009, in individuals with relapsing remitting multiple sclerosis
n289
Studies of this type have not been undertaken in New Zealand to date
There is a real need for these studies in new onset type 1 diabetes, where
there is still some remaining beta-cell function to be preserved Further,
individuals newly-diagnosed with type 1 diabetes are very keen to
participate in studies that could potentially improve the outcome of their
disease process
6 Genetic Aspects of Type 2 Diabetes
Type 2 diabetes represents approximately 90 of
all diabetes presentations
While more likely to present in adulthood, the disorder is becoming
increasing prevalent in children and adolescents In New Zealand, the
prevalence of known diabetes is 19 in Europeans, 52 among Maori, and
around 4 in Pacific Island peoples and other ethnic groups About 1 in 27
adults have been diagnosed with diabetes, and as many again may have the
disorder without being aware of it
A novel adipose-specific protein, adiponectin, has been implicated in the
pathogenesis of obesity and type 2 diabetes Our research investigated
polymorphisms or variations in the genes for the adiponectin receptors,
AdipoR1 and AdipoR2, to determine whether any of these variations were
associated with obesity and type 2 diabetes Individuals meeting the
criteria for obesity and type 2 diabetes were recruited locally, and
Healthy Volunteers recruited by the Cardioendocrine Research Group were
also studied as part of this research The prevalence of ten polymorphisms
in the two receptor genes was determined in n932 individuals by Jeremy
McRae, a PhD student in the Lipid and Diabetes Research Group Selected
polymorphisms are also being characterised in individuals recruited by
the
Cardioendocrine Research Group who have had a myocardial infarct This work
was completed by B Chandrakanth a visitor to our laboratory from the
University of Skovde Deciphering the role of these genetic loci should
contribute to the extent to which the natural history of type 2 diabetes
may be manipulated and, through this process lead to recommendations for
preventing or minimising the effect of the disease The research may lead
to the development of new therapies, such as variant adiponectin molecules
capable of binding to the different receptor isoforms, or receptor
agonists
Glycaemic Glucose Equivalents
The Glycaemic Glucose Equivalents GGEs system measures how blood glucose
changes after consumption of a serving of a food This system classifies
whether a food has a high GGE, that is, it causes a large increase in blood
glucose after it is eaten or a low GGE; that is, the response of blood
glucose is lower and more sustained Blood glucose control is especially
important for people with diabetes as high levels of circulating glucose
can cause cellular damage and increase their risk of coronary heart disease
as well as increase their chance of having complications
of diabetes such
as blindness, kidney failure and gangrene Low GGE foods will produce a
smaller, more sustained increase in blood glucose and will improve blood
glucose control in people with diabetes In addition, low GGE foods will
help increase satiety This research is being undertaken in collaboration
with Dr Alison Wallace, Sarah Eady and Dr John Munro of the NZ Crop and
Food Research Institute
7 Functional Studies in HDL
High density lipoprotein cholesterol HDL is thought to protect against
CVD by promoting cholesterol efflux from macrophages There is a well
established inverse relationship between the concentration of high density
lipoprotein cholesterol HDL and cardiovascular disease Increasing plasma
levels of HDL is a major goal of treating dyslipidaemia, in addition to
lowering levels of LDL
Individuals with very high HDL levels do present with cardiovascular
disease, suggesting that in these individuals the high HDL does not afford
protection It is possible that while the amount of HDL is substantial,
the composition or functional behaviour of the HDL is different in these
individuals This research which forms the basis for PhD research being
undertaken by Peta
Taylor will investigate the functional and biochemical
characteristics of HDL isolated from individuals with high HDL without
cardiovascular disease and individuals with high HDL who have manifest
cardiovascular disease
Publications
TORN C, MUELLER PW, SCHLOSSER, BONIFACIO E, BINGLEY PJ and Participating
Laboratories WILLIS JA - Participant Diabetes Antibody Standardisation
Program: evaluation of assays for autoantibodies to glutamic acid
decarboxlase and islet antigen-2 Diabetologia submitted
WALLACE AJ, EADY S, WILLIS JA, FRAMPTON CM , SCOTT RS Considerable
temporal variability in glucose reference curves in humans over a year
period Nutrition Research In press, May 2008
MCKINNEY C, MERRIMAN M, CHAPMAN P, GOW P, HARRISON A, HIGHTON J, JONES P,
MCLEAN L, ODONNELL J, POKORNY V, SPELLERBERG M, STAMP L, WILLIS J, STEER
S Evidence for an influence of chemokine ligand 3-like 1 CCL3L1 gene
copy number on susceptibility to rheumatoid arthritis Annals of the
Rheumatic Disease 67: 409-413, 2008
DAWSON SI, WILLIS JA, FLORKOWSKI CM, SCOTT RS Cause-specific mortality in
insulin-treated diabetic patients: a 20-year follow-up Diabetes Research
and Clinical Practice 80: 16-23,
2008
DAWSON SI, FLORKOWSKI CM, WILLIS JA, SCOTT RS All-cause mortality in
insulin-treated diabetic patients: a 20-year follow-up Diabetes Research
and Clinical Practice 80: e6-e9, 2008
Research Presented at National and International Meetings
Willis JA Type 1 Diabetes in Canterbury Children and Adolescents:
Incidence and Geography New Zealand Paediatric Society Conference,
Christchurch, New Zealand, November 2007 Plenary speaker
Sosenko J, Rafkin-Mervis L, Mahon J, Lachin J, Krause-Steinrauf H, Krischer
J, Cuthbertson D, Palmer J, Thompson C, Skyler J, the Type 1 Diabetes
Trialnet Study Group JA Willis, collaborator, the Diabetes Prevention
Trial - Type 1 Study Group Comparisons of OGTT Indices between
Participants in the TrialNet Natural History Study and Participants in the
Diabetes Prevention Trial-Type 1 Diabetes 57 [suppl1]: 914-P, 2008 poster
presentation
Willis JA, Miller LJ, Scott RS, Darlow BA, Pearce J, Barnett R Increasing
Incidence of Type 1 Diabetes in Canterbury Children and Adolescents and
Spatial-Temporal Clustering Diabetes Research and Clinical Practice 79
2008: S36 Oral presentation
Miller LJ, Pearce J, Willis JA, Barnett R, Scott RS, Darlow BA
Population
Mixing and Type 1 diabetes in Canterbury, New Zealand Diabetes Research
and Clinical Practice 79 2008: S36
Attendances at Scientific Meetings Educational Courses
Type 1 Diabetes Genetic Consortium Meeting, Phuket, Thailand; July 2007
Steering Committee Meeting TrialNet, Miami, Florida, USA; November 2007
Immunology of Diabetes Society Congress, Miami, Florida, USA; November
2007
New Zealand Paediatric Society Annual Scientific Meeting, Christchurch, NZ,
November 2007
7th International Diabetes Federation, Western Pacific Region Congress,
Wellington, NZ, April 2008
Other Activities - National and International
National Co-ordinator New Zealand Data Centre, TrialNet
Referee of Publications
Diabetic Medicine
Diabetes Research Clinical Practice
Referee of Grant Applications
Marsden Fund
Supervision of PhD Fellows
J McRae
P Taylor
K Volkova
Research Grants and other Funding Support
NZSSD:
2007 Eli Lilly Diabetes Specialist Research Grant
HDL-Cholesterol Function and Cardiovascular Disease in Diabetes
2 years, 30 000
2008 Travel grant, 450
Diabetes Heart Research Trust:
Montgomery Trust support for
Type 1 Diabetes Research Projects
2 years, 80 000
JO YOUNG
Research Scientist
Current Research Projects
1 Cardiovascular health and coenzyme Q10
People with high cholesterol levels, either inherited familial
hypercholesterolemia or not inherited, have an increased risk of
heart disease and are often prescribed statins Statins lower
cholesterol levels by up regulating the liver receptors for
cholesterol uptake Coenzyme Q10 is an essential compound for the
production of energy in muscles and is also an antioxidant Coenzyme
Q10 is made by the same pathway that makes cholesterol As a result
of the shared pathway, statins also lower coenzyme Q10 in the body
The study will examine plasma coenzyme Q10 levels in patients with
the genetic conditions of FH Familial Hypercholesterolemia - when
cholesterol levels are very high in the untreated state compared to
patients without FH on statin therapy Healthy volunteers will serve
as controls It is possible that reductions in coenzyme Q10 levels
may be limiting the
maximum beneficial effect of statin therapy This
study will also examine whether statin-treated people with more
impaired vascular function have lower coenzyme Q10 levels, and thus
may benefit from coenzyme Q10 supplementation to further reduce
cardiovascular risk To date, 70 out of a total of 90 participants
have completed for this study
2 Mechanisms of susceptibility to statin-induced muscle aches
People with high cholesterol levels are often prescribed drugs called
statins, which lower cholesterol levels by stopping their body making
cholesterol Some people cannot take statins to lower their
cholesterol levels, because they experience severe muscle pain
myalgia and fatigue as side effects Approximately 140,000 New
Zealanders currently taking this medicine are affected by these side
effects of statins This study is designed to explore potential
mechanisms for increased susceptibility to statin-induced myalgia
muscle aches It is possible inherited genetic variation
associated with muscle aches may increase a persons susceptibility
to statin induced muscle aches
Therefore we compared mutations
associated with three inherited metabolic myopathies in patients who
have previously stopped taking statin medication due to this side
effect with patients who do not experience myalgia with statin
therapy For one of the mutations, Q12X in the AMPD1 gene, we found
37 of statin intolerant patients with this mutation compared with
26 of statin tolerant patients, p010 We are now collaborating
with another research group in order to increase the number of
patients in this study If it is found that these genetic variations
increase susceptibility to statin-induced myalgia, this may help us
to predict those people who are more likely to develop muscle aches
when given statin medication This study is funded by a grant from
the National Heart Foundation
3 Coenzyme Q10 supplementation to improve cardiovascular risk in statin-
treated patients with the metabolic syndrome
Coenzyme Q10 is an increasingly used complementary medicine for
prevention of cardiovascular disease Although simultaneous coenzyme
Q10 therapy in patients receiving statin
therapy can prevent plasma
coenzyme Q10 depletion, it remains unknown if prophylactic coenzyme
Q10 replacement in statin treated patients would translate into
clinical benefits We have previously shown that that reductions in
coenzyme Q10 levels due to statin therapy were associated with
improvements in vascular function It is possible that these
reductions in coenzyme Q10 levels may be limiting the maximum
beneficial effect of statin therapy There is preliminary evidence
that coenzyme Q10 supplementation with and without fibrates can
improve endothelial function This study is designed to investigate
whether supplementing with coenzyme Q10 in statin-treated patients
with the metabolic syndrome further improves vascular function,
thereby giving additional benefit to cardiovascular disease
reduction This study is funded by a grant from the National Heart
Foundation
4 Does ezetimibe correct vascular dysfunction?
Hypercholesterolemia contributes to plaque formation in the arterial
wall and impairs the ability of cells lining the arteries
endothelium to govern
vessel-relaxation and so regulate blood flow
Statins improve vascular function and reduce cardiovascular events
through both LDL- lowering and LDL-independent effects, but the
effect of ezetimibe on vascular function is unknown Combination
therapy for hypercholesterolemia with ezetimibe plus low-dose statin
will achieve identical reductions in LDL-cholesterol levels as
compared with high-dose statin This 12-week study will investigate
whether LDL-lowering with ezetimibe plus low-dose statin corrects
vascular dysfunction to the same extent as high dose statin in
subjects with the metabolic syndrome Comparable improvements in
vascular function would indicate that subjects using this safe low-
dose combination therapy would receive similar benefits in reducing
cardiovascular disease as more risky high-dose statin therapy This
study is funded by a grant from the Health Research Council of NZ
5 Coenzyme Q10 bioavailability study
Coenzyme Q10 is increasing used as an adjunctive therapy for
cardiovascular disease However coenzyme Q10 supplements are
relatively expensive and
are poorly absorbed Recently, new
formulations of CoQ10 have been prepared with the aim of improving
uptake of coenzyme Q10 by the body This study will compare the
coenzyme Q10 levels in the blood following supplementation of either
a soy bean oil coenzyme Q10 preparation or new formulation of
coenzyme Q10 The study will involve 36 male subjects taking a single
dose of the two preparations two weeks apart, with blood samples
being collected before and during a 10-hour period following
ingestion of either supplement The coenzyme Q10 levels in the blood
samples will be measured to determine if there are any differences in
the magnitude of the increase in coenzyme Q10 levels caused by the
two supplements This study is funded by Trilogie Products Pty Ltd
Abstracts of Research
JM Young, CM Florkowski, SL Molyneux, HC Potter, RG McEwan, CM Frampton, PM
George, RS Scott Coenyzme Q10, metabolic myopathy, genotypes and statin-
induced myalgia Proceedings of the Fifth Conference of the International
Coenzyme Q10 Association, November, 2007 Poster presentation
JM Young, SD Plant, CM Florkowski, CM Frampton,
RS Scott Detection of pre-
clinical vascular disease in pre-diabetic subjects using pulse wave
analysis Proceedings of the New Zealand Society for the Study of Diabetes,
140, September, 2007 Poster presentation
JM Young, CM Florkowski, SL Molyneux, RG McEwan, CM Frampton, PM George, RS
Scott Is there a role for coenzyme Q10 supplementation in statin-induced
myopathy Proceedings of Health Research Society of Canterburys Scientific
Meeting, Christchurch, 2007 New Zealand Medical Journal 121 1271:113-4
April, 2008 Oral presentation
Publications
SL Molyneux, JM Young, CM Florkowski, M Lever, PM George Coenzyme Q10; Is
There a Clinical Role and a Case for Measurement? Clinical Biochemist
Reviews In press, June 2008
JM Young, CH Strey, CM Florkowski, CM Frampton, RS Scott, PM George Effect
of Atorvastatin on Plasma Levels of Asymmetric Dimethylarginine in Patients
with Non-Ischaemic Heart Failure European Journal of Heart Failure 10: 463-
466 2008
JM Young, CM Florkowski, SL Molyneux, RG McEwan, CM Frampton, PM George, RS
Scott Effect of Coenzyme Q10 Supplementation on Simvastatin-Induced
Myalgia American Journal of Cardiology 100: 1400-1403 2007
Research Grants
and other Support
Diabetes and Heart Research Trust
Research Funding for 2008 50,000
National Heart Foundation Small Project Grant Application 15,000
Australian Atherosclerosis Society Trust Travel Grant 1,700
Australian Atherosclerosis Society Travel Grant 1,200
NZSSD Travel Grant 300
Attendances at Scientific Meetings
1 International Coenzyme Q10 Association Meeting, Kobe, Japan; November
2007
2 Annual Scientific Meeting of the Australian Atherosclerosis Society,
Fremantle; October 2007
3 NZSSD, ADS and ADEA Annual Scientific Meeting, Christchurch;
September 2007
4 Canterbury Health Research Society Conference, Christchurch; August
2007
5 Cardiac Society of Australia and NZ 55th Annual Scientific Meeting,
Christchurch; August 2007
Other Research Activities
PhD Student - Department of Medicine, University of Otago, Christchurch
10 Summary of Accounts
Accounts
CDHB treasury manages accounts
The information provided is for 12 months of the financial year
2007 costs
2008
costs
Diabetes Account 776 138,181 91,165
Vascular-Lipid Account 747 693,910 640,626
Total 832,091
731,791
Source:cdhb.govt.nz
