Monday, February 02, 2009

Endodiabology February 2009

ENDODIABOLOGY
Endodiabology.blogspot.com

NORTHEAST
NEWSLETTER
FOR SPRs AND BOSSES TRAPPED
IN THE NORTHERN DEANERY

FEBRUARY 2009
Editors: Shaz Wahid (shahid.wahid@sthct.nhs.uk) and
Petros Perros (petros.perros@ncl.ac.uk) and Arut Vijayaraman (riarut@aol.com )
Associate Editors: Shafie Kamarrudin, Ravi Erukulapati

SpR PLACEMENTS (NTN year of training from 1st October 2008)
• RVI- Shafie Kamarrudin (3), Beas Bhattacharya (5), Asgar Madathil (4), Kathryn Stewart (2), Rohanna Wright (1), Chandima Idampitiya (4), Preeti Rao (2)
• North Tyneside/Wansbeck- Ravi Erukalapati(4), Sudeep Manohar (2)
• South Tyneside- Sukesh Chandran(5)
• Gateshead- Arutchelvan Vijayaraman (5)
• Sunderland- Jeevan Mettayil (3), Sarah Steven (1)
• North Tees/Hartlepool- Khaled Mansur-Dukhan (5), Stuart Little (1)
• Middlesbrough- Anjali Santhakumar (2), Arif Ullah (2), Yahya Maghoub
• Carlisle- Naveen Siddaramaiha (1)
• Bishop Auckland Srikanth Mada(2)
• Durham-
• NGH/QEH- Freda Razvi (5)
• Research with numbers (supervisor)- Eelin Lim(5-Prof Taylor)

MEETINGS / LECTURES / ANNOUNCEMENTS
• 10th February 2009 SfE Clinical Cases meeting, London. Contact www.endocrinology.org .
• 11th-13th March 2009 DUK Annual Professional Conference, Birmingham. Contact www.diabetes.org.uk
• 16th – 19th March 2009 BES 2009, Harrogate. Contact www.endocrinology.org .
• 18th March 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 23rd & 24th April 2009 Middlesbrough insulin pump course. Contact
• 29th April 2009 RCP Acute Medical Emergencies, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 30th April 2009 Novo Nordisk Symposium, Lumley Castle Hotel. Contact & see letters section.
• 7th-8th May 2009 ABCD Spring Meeting, Bristol, www.diabetologists.org.uk
• 11th May 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 5th-9th June 2009 American Diabetes Association 69th Annual Scientific Sessions, New Orleans, USA. Contact meetings@diabetes.org .
• 10th-13th June 2009 ENDO 2009, Washington, USA. Contact endostaff@endo-societ.org or www.endo-society.org/scimeetings .
• 24th June 2009 Northern Endocrine & Diabetes Summer CME, Freeman Hospital. Contact
• 1st July 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 10th September 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 27th September-1st October 2009 45th EASD Annual meeting, Vienna, Austria. Contact www.easd.org
• 12th October 2009 Northern Endocrine & Diabetes Autumn CME, JCUH, Middlesbrough. Contact
• 2nd-4th November 2009 Society for Endocrinology Clinical Update 2009, venue TBC. Contact www.endocrinology.org
• 2nd November 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 3rd November 2009 RCPL Medicine Update, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
• 25th November 2009 Northern Endocrine Region Research and Audit Group annual meeting, Lumley Castle, Durham 2pm-8pm. Contact shahid.wahid@sthct.nhs.uk
• 26th & 27th November 2009 Middlesbrough insulin pump course. Contact Rudy.Bilous@stees.nhs.uk


See www.worlddiabetescongress.org for the IDF world diabetes conference.
TRAINING ISSUES
NEW TPD See letters section for an introduction to our new TPD that also includes training advice.
ARCPs/RITAs/PYAs These are planned for Weds 13th May to Friday 15th May 2009. Nicky Leech will be distributing details. For those of you requiring a PYA keep Thurs 14th May 2009 free.
Acute Medicine Level 2 training for SpRs For this year’s ARCPs/RITAs any SpR who has not had their PYA will be expected to have 4 ACAT assessments and 4 Mini-CEXs/CbDs specifically in relation to Acute Medicine in their portfolio for the panel to review.
Acute Medicine Level 2 training for StRs Any trainee appointed after August 2007 will be considered a StR and for their ARCP they will be expected to have 4 ACAT assessments, 4 Mini-CEXs and 4 CbDs specifically in relation to Acute Medicine, a valid ALS qualification, evidence of achievement of all the procedures deemed necessary for Acute Medicine Level 2 training, Evidence of achievement of all emergency presentations to level 2, Evidence of achievement of 2/3rds top 20 presentations to level 2 and Evidence of ½ of other presentations to level 2. It is recommended to use the pages available from the Acute Medicine e-portfolio to collect the later evidence that CMT (ST1-ST2) trainees should already have. If you do not have access to this then contact your Post-Grad Education Centre Manager who should be able to get you access to the e-portfolio for CMTs.
DIABETES & ENDOCRINOLOGY PIMD WEBSITE Our specialty website is available on http://mypimd.ncl.ac.uk/PIMDDev . Click onto the specialty training tab then follow to Diabetes & Endocrinology. This site is essential reading, especially for ARCP preparation.
Registering with PMETB It is essential that all new SpRs/StRs (even LATs) register with the PMETB through the newly created Joint Royal Colleges of Physicians Training Board (formally the JCHMT) on www.jrcptb.org.uk although it is still possible to link with this site using the old www.jchmt.org.uk link. Not doing so means your training is not counted.
Log Book/Portfolio Documentation It is a trainee’s responsibility to make sure their portfolio/log book is prospectively completed and the necessary signatures obtained. Any experience that is not signed off by your educational supervisor at the time cannot be counted towards training.
Assessment tools Please see www.jrcptb.org.uk; it is the trainee’s responsibility to give all the appropriate forms to their Educational or Clinical Supervisor. It is the trainee’s responsibility to make sure that the appropriate assessment summaries are available in their portfolio for ARCP purposes, e.g. MSF Summary Form.
Acute Care Assessment Tool The ACAT is a tool that is commendable. It provides a method of assessing how Trainees managed their on-call period. It is recommended that at least one is available for ARCP purposes. It can be downloaded from the JRCPTB website.
Case Based Discussions (CbD) The pilot form is available from the JRCPTB website. It is a must for trainers to use as a tool to document feedback in clinic. This has always been done informally, but now there is a method to formally document it. I basically use it for when a SpR presents a new case to me in clinic.
Documenting CCU and ITU experience As of now it is essential that trainees document their CCU and ITU experience. This is best done by keeping a summary log of the cases seen on CCU and ITU and linking it with reflection or assessment. This should then be signed off by your Educational Supervisor to be of any use at the Acute Medicine PYAs.
Community Diabetes The curriculum is undergoing some slight revision to reflect the importance that trainees gain “practical” experience in issues around commissioning, service delivery with no “walls”, patient centred care in a district and other “political” issues/changes. That is, it is important to be prepared to utilise management skills around these areas upon attaining a CCT.
Training Committee Chair- Jola Weaver,; Regional Speciality Advisor- Shaz Wahid,; Programme Director- Nicky Leech; Consultant member (SAC rep)- Richard Quinton,; Consultant member-Jean MacLeod,; Consultant member (Research Advisor)-Simon Pearce; Consultant member-Simon Eaton,; SpR representative- Arutchelvan Vijayaraman ; SpR representative- Jeevan Mettayil
NEWS FROM THE NORTHEAST
• Congratulations to Nicky Leech as our new TPD, see her letter below.
• Shaz Wahid will be the new Regional Specialty Advisor (service delivery) with Richard Quinton still the regions rep on the national SAC committee (training matters).
• Richard Quinton attended the Endocrine Society of India annual congress, Cochin, Kerala, Dec 2008 as invited speaker on the Genetics of Idiopathic Hypogonadotrophic Hypogonadism. At the conference he met up with Dr V Suresh, who was Visiting Fellow at the RVI with us a few years back & is now Assistant Professor in Endocrinology at Department of Endocrinology at SVIMS, Tirupati, Andhra Pradesh & Dr Muthu Jayapaul, who has only just returned to India to join a newly-formed Endocrinology consortium in Madras (Chennai).
• Congratulations to Roy Taylor in obtaining a research grant from Diabetes UK. Effect of change in pancreas and liver fat content upon beta cell function and hepatic insulin action during weight loss in type 2 diabetes. £126,000. Taylor R., Mathers J, Hollingsworth K.
• Simon Eaton will Chair the Long Term Conditions Group for the SHA and would be very grateful for people to contact him if they are interested in contributing to the work of implementing the “Our Vision Our Future LTC” report.
• Simon Eaton will be relinquishing the NRDSAG chair and would be interested in hearing from someone who may want to take on this role.
• Sue Roberts was awarded CBE in the New Year Honours, congratulations!
• I am pleased to announce that Arut has agreed to become a Senior Editor on the ENDODIABOLOGY team and will continue this role through Consultant hood.
• Congratulations to Rohanna Wright on obtaining a place on the SPARROWS programme for the ADA. She will be joined by Bernadette Woodward a DSN at JCUH.
• Congratulations to John Parr on being asked by the ABCD to be their regional champion for the North East. See the letters section. Hopefully this may well lead to an ABCD meeting being held in the North East in the near future.
• We have appointed 2 NTNs from run-through, Catherine Napier & Atif Munir. Both of whom were excellent at interview. Interviews for vacancies will be held 3rd March 09 and June 09.

LETTERS
“United we stand, divided we fall”-Shaz Wahid
I remember reading about Mike Besser’s lecture at the ABCD several years ago with the above title, where he extolled the virtues of maintaining practice in both Diabetes & Endocrinology without bowing to external pressures and splitting the specialty. I could not agree more at the time and still remember whilst training as an SpR feeling rather puzzled when it was voiced that training in Diabetes & Endocrinology should be split by folk in the higher echelons of the then JCHMT and the DoH. Thankfully, matters have remained quiet in relation to the latter until recently when the PMETB have talked about issues such as credentialing and indeed there has been a comparison between our training curriculum and the Cardiology training curriculum with the intention to demonstrate that we should model training similar to Cardiology. That is, train in the basics (apparently mainly in primary care settings) but be able to choose time limited periods in more specialist areas (e.g. insulin pumps, reproductive endocrinology, obesity, etc) towards the senior years of training. Hence, rather like Cardiologists producing trainees specialised in such areas as electrophysiology we would produce trainees with a CCT in Diabetes & Endocrinology but credentialed in insulin pumps or gynea-fertility-endocrinology. This fills me with dread. Admittedly, when coming out at the other end I had an interest in renal diabetes but I did have enough of a grounding in the specialty and more importantly developed self-management and leadership skills to set up a diabetic foot service, further develop a transitional diabetes service and rubbed shoulders with the community via a number of initiatives without giving away the crown jewels! I remember sitting next to RT shortly after obtaining Consultant hood when he asked “Shaz did we prepare you”, “not for all eventualities, but I have had enough training to have developed the skills to manage all scenarios”, an answer RT was pleased with. It is not surprising Endocrinologists make good Acute Medicine Physicians as we are well versed in looking at disparate issues of patient care and bringing them together across a Trust or a community with the aim of delivering quality patient care. The current processes of care in the NHS do not lend themselves to remodelling training in Diabetes & Endocrinology along the lines of Cardiology so that we always produce “super specialists”. There are mechanisms within the specialty that already allow one to become a “super specialist” without having to reduce exposure to the basic groundings in the speciality that allow development of our unique specialist skills. In summary, going down the line of either splitting the sugar from hormones or compartmentalising the specialty to produce “super specialists” will only be to the detriment of delivering high quality patient care. Thankfully, our SAC thinks along similar lines as me……………………………………………………..

Thoughts of a New Trainee Programme Director. Life after 9/1/09. Dr Nicky Leech Diabetologists and Endocrinologists may be quiet and discerning but they whisper well. As a consequence I think you all know that I have now been officially appointed after a tough competitive interview!! As the only candidate I failed to convince the panel that I was wholly unsuitable as the Northern Deanery Training Programme Director for our specialty.
Why did we all take six paces backwards when Shaz declared his wish to step down? He has been exceptional and perhaps no one had the courage to follow such an act. Our thanks go to Shaz for steering us through the minefield of MMC and run-through training. He has kept engaged with a challenging system and pioneered the robust implementation of annual portfolio based assessment using the breadth of work-place based assessment tools. His excellent leadership is obvious. Look around you at the health of your diabetes and endocrinology training programme compared to equivalent specialities in the region.
Reflecting on the thoughts of a Guru, I will strive for private and public victory but don’t worry I wont forget to sharpen my sword! On a more personal note, thank you Shaz for your continued support and guidance as I try to take hold of the tiller and learn the ropes.
So what is looming on our horizon? I sense the excitement about the prospect of having another professional exam! This will need to have been achieved by PYA for all those entering speciality training after 2007. What about the rest of you? I would want to be “as qualified as the rest of them” wouldn’t you? When should you sit the exam? That is obviously your decision although it makes far more sense to me to sit very early in training. It will equip you with a wealth of knowledge which can then be applied, releases time for more personalised learning and if you fail (not that any of you will!) ensures you have time to resit without jeopardizing your career progression.
Some of you will have been surprised by the suggestion that they have inadequate evidence of GIM, ITU and cardiology at PYA. All trainees are doing enough but it is the documented evidence that counts. I refer you back to this and previous editions of Endodiabology. In summary; log your cases and ensure you have 4 ACATs, 4 Min-CEXs and 4 CbDs in General medicine including documented evidence of exposure in ITU and cardiology.
Now October and Christmas has passed all trainees should ensure they have sat with their supervisors and agreed their personal development plan (PDP) based on the training needs identified in the previous ARCP.
An old Chinese proverb says “if you don’t scale the mountain you cannot view the plain” so keep climbing as we work through the scree slope of change and if it is any comfort to you “today my mountain feels as steep as yours!”



Do you care for a person with diabetes who has problematic / unusual hypoglycaemia?
Would you like to discuss the case with world experts in hypoglycaemia?
You have the opportunity at this year’s NovoNordisk Symposium on Thursday 30 April 2009
To present, please submit an abstract of no more than 200 words, describing the clinical scenario, and indicating what you hope to achieve from the case discussion.
Submit to: Sally Marshall By 1 April 2009.
Northern Region NovoNordisk Symposium- Hypoglycaemia
Thursday 30 April 2009 Lumley Castle Hotel

Programme
1400 - 1430 Registration and Coffee
Chair Sally Marshall
1430 - 1515 Professor Stephanie Amiel, London
Hypoglycaemia and the Brain
1515 - 1600 Professor Brian Frier, Edinburgh
Hypoglycaemia and Life Issues
1600 – 1615 Tea
1615 - 1730 Dr James Shaw, Newcastle, Local Case Presenters and Expert Panel Discussion
Loss of awareness of hypoglycaemia: practical aspects
1730-1815 Dr Lotte Bjerre Knudsen
The Birth of a Molecule: from Conception to Delivery
1830 Close

ABCD-The best CPD in Diabetes? John Parr ABCD (The Association of British Clinical Diabetologists) is now 10 years old. I was sent by the NRDSAG to its inaugural meeting at Windsor to find out “what it was about”, particularly at the time there was great opposition to a potential rival organization from Diabetes UK. I actually found it an extremely beneficial, refreshing and vibrant meeting and have continued to attend meetings ever since.
For me it’s the best Diabetes CPD in town. Why? Firstly it provides twice-yearly specialist, up to date, timely and comprehensive programmes (see enclosed programmes) by expert speakers, directed to Specialist/Consultant Diabetologists, with enough time to question and debate the issues from the floor. Audience participation is one of its strengths and even the great and the good get questioned rigorously.
Secondly the programme addresses issues and challenges that we consultants face in daily practice, and in such a convivial setting talking to and supporting each other is the best psychotherapy around.
Thirdly its practical side; through country-wide collaboration, audits on triple oral therapy and glargine use in pregnancy have been undertaken and by achieving substantial numbers have made the results meaningful (current audits are on Charcot’s, Exubera, Osteomyelitis Management and Outcome); the Survey of Inpatient Services and through collaboration with Diabetes UK the UK Specialist Services Survey, have all been important. It submits to NICE and contributes to RCP groups. The organization represents consultants in diabetes and many are members.
Fourthly it encourages SpR membership, attendance and participation, through meetings (another venue for posters) and the audit programmes/awards. Indeed a meeting for SpRs follows on from the main meeting – making 2 days of good diabetes education and by taking in the splendid preceding British Thyroid Association meeting in November, extending to 3 days. Is it a meeting just for “old farts”? Not necessarily! It’s also for “young farts” (after all they eventually become “old-farts”) and specialists of all description. Further information is available from http://www.diabetologists-abcd.org.uk/ .

RECENT PUBLICATIONS FROM THE NORTHEAST
1. Langham S, Maggi M, Schulman C, Quinton R, Uhl-Hochgräber K. 2008 health-related quality of life instruments in studies of adult men with testosterone deficiency syndrome: a critical assessment. Journal of Sexual Medicine. 5: 2842-2852.
2. Nicol MR, Papacleovoulou G, Evans DB, Penning TM, Strachan MW, Advani A, Johnson SJ, Quinton R, Mason JI. Estrogen biosynthesis in human H295 adrenocortical carcinoma cells. Mol Cell Endocrinol. 2008 Nov 5. [Epub ahead of print].
3. Igreja S, Chahal HS, Akker SA, Gueorguiev M, Popovic V, Damjanovic S, Burman P, Wass JA, Quinton R, Grossman AB, Korbonits M. Assessment of p27 (cyclin-dependent kinase inhibitor 1B) and AIP (aryl hydrocarbon receptor-interacting protein) genes in MEN1 syndrome patients without any detectable MEN1 gene mutations. Clin Endocrinol (Oxf). 2008 Aug 15. [Epub ahead of print].
4. Ravikumar, B, Gerrard J, Dalla Man C, Firbank MJ, Lane A, English PT, Cobelli C, Taylor R. Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content. Diabetes 57: 2288-95, 2008.
5. Belch JJ, Macuish A, Campbell I, Cobbe S, Taylor R, Prescott R, Lee R, Bancroft J, MacEwan S, Shepherd J, Macfarlane P, Morris A, Jung R, Kelly C, Connacher A, Peden N, Jamieson A, Mathews D, Leese G, McKnight J, O’Brian I, Semple C, Petrie J , Gordon D, Pringle S, MacWalter R. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD): a study of aspirin and antioxidants in patients with Diabetes and asymptomatic peripheral arterial disease. Brit Med J 337:a1840, 2008.
6. Arun CS, Al-Bermani A, Stannard KS, Taylor R. Long term impact of retinal screening upon significant diabetes related visual impairment in the working age population. Diabetic Medicine 2008 in press
7. Jovanovic A, Leverton E, Solanky B, Snaar JEM, Morris PEG, Taylor R. The second meal phenomenon is associated with enhanced muscle glycogen storage. Clin Sci 2008 in press
8. Al-Ozairi E, Waugh JJS, Taylor R. Termination is not the treatment of choice for severe hyperemesis gravidarum: Successful management using prednisolone. Obstetric Medicine 2008 in press
9. Chaturvedi N,Porta M, Klein R,Orchard T,Fuller J,Parving HH,Bilous R,Sjolie AK Effect of candesartan on prevention (DIRECT- Prevent1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes : randomised ,placebo controlled trials. Lancet 2008 372 1394 – 1402.
10. Sjolie AK, Klein R,Porta M, Klein R,Orchard T,Fuller J,Parving HH,Bilous R, Chaturvedi N Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2) : a randomised placebo controlled trial. Lancet 2008 372 1385 – 93.

RECENT PUBLICATIONS IN DIABETES & ENDOCRINOLOGY THAT HIT THE NEWS OR THAT MAY HAVE A SIGNIFICANT IMPACT ON MANAGEMENT
Rennekampff H-O, et al. Chronic wound care. Lancet 2008;372:1860-1862. An excellent editorial, well worth a read and provides useful references.

Spurling G and Walsh M. Aspirin type 2 diabetes: is there any evidence base? BMJ 2008;337:1163-1165. A wonderful summary of the evidence that I feel gives a resounding NO, do you agree? It also links in nicely with the POPADAD study below.

Lecky B and Sathasivam S. Statin induced myopathy. BMJ 2008;337:1159-1162. An essential read that provides practical advice.

Stevens P et al. Early identification and management of chronic kidney disease: summary of NICE guidelines. BMJ 2008;337:812-815. AND Haynes RJ & Landray MJ. Commentary: controversies in NICE guidance on chronic kidney disease. BMJ 2008;337:815-816. An excellent summary very pertinent to those involved in leading the diabetic renal service.

Miller jc et al. Definitive characterisation of adrenal lesions. BMJ 2009;338:233-236. An essential read providing a pragmatic update on adrenal imaging.

Belch j, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008;337:1030-1034. This multicentre, randomised, double blind, 2x2 factorial, placebo controlled trial recruited 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318) were the different therapy arms in the trial. The end-points measured were: primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke. 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% vs 18.3%): hazard ratio 0.98 (95% CI 0.76-1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% vs 5.5%): 1.23 (0.79-1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89). A profound NO for the use of aspirin as primary prevention is provided by this trial, admittedly in this group of patients studied. However, adding the other 7 trials with similar results in relation to primary prevention of cardiovascular disease with aspirin into the mix has certainly resulted in a change in my practice. Do you agree…………..

Astrup A, et al. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-1913. This phase II, randomised, double-blind, placebo-controlled trial in five Danish obesity management centres assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline, dopamine, and serotonin-in patients with obesity (originally it was developed as anti-parkinson’s drug). After a 2 week run-in phase, 203 obese patients (BMI 30<
=40 kg/m2) were prescribed an energy restricted diet and randomly to treatment with tesofensine 0.25 mg (n=52), 0.5 mg (n=50), or 1.0 mg (n=49), or placebo (n=52) once daily for 24 weeks. The primary outcome was percentage change in bodyweight. Analysis was by modified intention to treat (all randomised patients with measurement after at least one dose of study drug or placebo). 161 (79%) participants completed the study. After 24 weeks, the mean weight loss produced by diet and placebo was 2.0% (SE 0.60). Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5% (0.87), 9.2% (0.91), and 10.6% (0.84), respectively, greater than diet and placebo (p<0.0001). The most common adverse events caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia. After 24 weeks, tesofensine 0.25 mg and 0.5 mg showed no significant increases in systolic or diastolic blood pressure compared with placebo, whereas heart rate was increased by 7.4 bpm in the tesofensine 0.5 mg group (p=0.0001). This trial suggests that tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved drugs. However, further trials are awaited.

Drucker DJ, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008;372:1240-1250. In this 30-week, randomised, non-inferiority study the authors compared a long-acting release formulation of exenatide 2 mg administered once weekly to 10 mcg exenatide administered twice a day, in 295 patients with type 2 diabetes (HbA1c 8.3% [SD 1.0], mean fasting plasma glucose 9 [SD 2] mmol/L, weight 102 [SD 20] kg, diabetes duration 6.7 [SD 5.0] years). The patients were naive to drug therapy, or on one or more oral antidiabetic agents. The primary endpoint was the change in HbA1c at 30 weeks. At 30 weeks, the patients given exenatide once a week had significantly greater changes in HbA1c than those given exenatide twice a day (-1.9 [SE 0.1%] vs -1.5 [0.1%], 95% CI -0.54% to -0.12%; p=0.0023). A significantly greater proportion of patients receiving treatment once a week versus twice a day achieved target HbA1c levels of 7.0% or less (77%vs 61% of evaluable patients, p=0.0039). Hence, exenatide once weekly resulted in significantly greater improvements in glycaemic control than exenatide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight. Very interesting times in managing Type 2 diabetes with a plethora of new therapies that require careful evaluation and integration in care, obviously led by “specialists”.
Holman, RR, et al. Long-term follow-up after tight control of blood pressure in Type 2 diabetes. NEJM 2008;359:1565-1576. 1148 UKPDS patients with newly diagnosed type 2 DM and hypertension were randomly assigned, over a 4-year period beginning in 1987, to tight or less-tight blood-pressure control regimens. The 884 patients who underwent post-trial monitoring were asked to attend annual UKPDS clinics for the first 5 years, but no attempt was made to maintain their previously assigned therapies. Annual questionnaires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5, and questionnaires were used for all patients in years 6 to 10. Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis, according to the previous randomization categories. Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial. Significant relative risk reductions found during the trial for any diabetes-related end point, diabetes-related death, microvascular disease, and stroke in the group receiving tight, as compared with less tight, blood-pressure control were not sustained during the post-trial follow-up. No risk reductions were seen during or after the trial for myocardial infarction or death from any cause, but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant (P=0.02). This follow-up study has shown that the benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost. A seminal study that answers a question my patients often ask “Doc can I stop my BP tablets now that it is controlled?” “NO-and here is why UKPDS”.
Holman RR, et al. 10-Year follow-up of intensive glucose control in Type 2 diabetes. NEJM 2008;359:1577-1589. 4209 UKPDS patients with newly diagnosed type 2 diabetes were randomly assigned to receive either conventional therapy (dietary restriction) or intensive therapy (either sulphonylurea or insulin or, in overweight patients, metformin) for glucose control. In post-trial monitoring, 3277 patients were asked to attend annual UKPDS clinics for 5 years, but no attempts were made to maintain their previously assigned therapies. Annual questionnaires were used to follow patients who were unable to attend the clinics, and all patients in years 6 to 10 were assessed through questionnaires. Seven prespecified aggregate clinical outcomes from the UKPDS on an intention-to-treat basis, according to previous randomization categories, were examined. Between-group differences in HbA1c levels were lost after the first year. In the sulphonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related end point (9%, P=0.04) and microvascular disease (24%, P=0.001), and risk reductions for MI (15%, P=0.01) and death from any cause (13%, P=0.007) emerged over time, as more events occurred. In the metformin group, significant risk reductions persisted for any diabetes-related end point (21%, P=0.01), MI (33%, P=0.005), and death from any cause (27%, P=0.002). This seminal study has shown that despite an early loss of glycaemic differences, a continued reduction in microvascular risk and emergent risk reductions for MI and death from any cause were observed during 10 years of post-trial follow-up. A continued benefit after metformin therapy was evident among overweight patients. In other words “in the long run improving glycaemic control matters for cardiovascular risk reduction and every little helps”-a true legacy effect in keeping with the follow-up of the seminal DCCT study.

Increased Prevalence of Tricuspid Regurgitation in Patients with Prolactinomas Chronically Treated with Cabergoline. Annamaria Colao et al,(JCEM 93: 3777–3784, 2008). Objective of this observational, case-control study was to evaluate prevalence of cardiac valve regurgitation in cabergoline-treated patients with prolactinomas. Fifty treated patients (44 women and six men) and 50 sex- and age-matched control subjects participated; 20 de novo patients were also studied. In the treated patients, the last cabergoline dose was 1.3 ± 1.3 mg/wk (<1 mg/wk in 44%, 1–3 mg/wk in 46%, and >3 mg/wk in 10%). Treatment duration was 12–60 months in 32% and more than 60 months in 68%. The cumulative (milligrams x months of treatment) dose of cabergoline ranged from 32–1938 mg (median 280 mg). In de novo patients, treated patients, and controls, the prevalence of mild regurgitation of mitral (35, 22, and 12%, P = 0.085), aortic (0, 4, and 2%, P = 0.59), tricuspid (55, 30, and 42%, P = 0.13) or pulmonary (20, 12, and 6%, P = 0.22) valves was similar. Conversely, the prevalence of moderate tricuspid regurgitation was higher in the treated patients (54%) than in de novo patients (0%) and controls (18%, P < 0.0001). Moderate tricuspid regurgitation was more frequent in patients receiving a cumulative dose above the median (72%) than in those receiving a lower dose (36%, P = 0.023). A higher systolic (P = 0.03) and diastolic blood pressure (P < 0.0001) was found in patients with than in those without moderate tricuspid regurgitation. Moderate tricuspid regurgitation is more frequent in patients taking cabergoline (at higher cumulative doses) than in de novo patients and control subjects, but the clinical significance of this finding has not been established. A complete echocardiographic assessment is indicated in patients treated long term with cabergoline, particularly in those requiring elevated doses.





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