Endodiabology 2007; Issue 1 (February)
Endodiabology.blogspot.com
NORTHEAST NEWSLETTER
FOR SPRs AND BOSSES TRAPPED IN THE NORTHERN DEANERY
FEBRUARY 2007
Editors: Shaz Wahid and Petros Perros
Associate Editors: Freda Razvi, Akheel Syed and Ebaa Al-Ozairi
SPECIALIST REGISTRAR PLACEMENTS (NTN year of training from 1st October 2006)
RVI – Beas Bhatacharya (4), Ravikumar Balasubramanian (3), Sukesh Chandran(3), Subir Ray (3), Ebaa Al-Ozairi (5)
Freeman – Akheel Syed(4), Muthu Jayapaul(4), Khaled Mansur-Dukhan (3)
North Tyneside/ Wansbeck – Latika Sibal (5)/Preeti Rao
South Tyneside – Salman Razvi (5)
Gateshead – Reena Thomas (5)
Sunderland – Peter Carey(5), Chris Rizzo
North Tees/Hartlepool – Ravi Erukalapati(2)/Sony Anthony(5)
Middlesbrough – Jeevan Metafile (2), Shafer Kamarrudin (1), Srikanth Mada
Carlisle – Kerry Livingstone (1)
Bishop Auckland/ Durham – Arun(5)/ Asgar Madathil (3)
NGH/QEH – Ibrahim M Ibrahim (5)
Research with numbers (supervisor) – Andrew Advani (4 – Toronto), Chandima Idampitiya (2 – Srilanka), Arutchelvan Vijayaraman (3 – Prof Home), Eelin Lim(4 – Prof Taylor)
MEETINGS / LECTURES / ANNOUNCEMENTS
21st February 2007 Society for Endocrinology Clinical Cases Meeting, Royal Society for Medicine, London SFE website
22nd February 2007 Society for Endocrinology visiting Professor Andrea Dunaif, RVI, 10-2pm. Contact Richard Quinton
5th - 8th March 2007 BES 2007, ICC, Birmingham. SFE website
10th March 2007 Association of Physicians meeting, RVI. Contact Roy Taylor
14th - 16th March 2007 DUK APC 2007, ICC, Glasgow. DUK website
22nd March 2007 North East & Cumbria Diabetes Research Network Launch, St. James Park. Contact Leonie Walker
28th March 2007 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
19th April 2007 28th Novo Nordisk Symposium from 2pm, Lumley Castle. Contact Sally Marshall
3rd May 2007 Northern Endocrine & Diabetes Summer CME, Queen Elizabeth Hospital, Gateshead. Contacts Reena Thomas or Arut Vijayaraman
8th - 11th May 2007 25th Anglo Danish Dutch Diabetes Group meeting, Denmark. Contact Katharine Owen or John Porter or Peter George
9th May 2007 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
11th - 12th May 2007 20th European Diabetic Nephropathy Study Group meeting, Edinburgh. Contact Carol Forsblom
16th May 2007 Northern Diabetes Audit Group, following NRDSAG, 2.30pm Collingwood College, Durham. Contact Dr Narayanan
16th - 17th May 2007 ABCD Spring Meeting, Chester, ABCD website
2nd - 5th June 2007 ENDO 2007, Toronto, Canada. Contact ENDO email or ENDO website
12th June 2007 Joint Trainers and Trainees meeting, Board room, 1730-1900, Medical School. Contact Shahid Wahid
22nd - 26th June 2007 American Diabetes Association 67th Annual Scientific Sessions, Chicago, USA. Contact ADA email
9th July 2007 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
17th - 21st September 2007 43rd EASD Annual meeting, Amsterdam. Contact EASD website
19th September 2007 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
8th October 2007 Northern Endocrine & Diabetes Autumn CME, James Cook University Hospital. Contacts Reena Thomas or Arut V
5th - 7th November 2007 Society for Endocrinology Clinical Update 2007, Manchester. Contact SFE website
21st November 2007 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
28th November 2007 Northern Endocrine Region Research and Audit Group annual meeting, Lumley Castle, Durham 2pm-8pm. Contact Shaz Wahid
TRAINING ISSUES
Joint Trainers & Trainees meeting The annual T&T meeting will be held on Tuesday 12th June 2006 1715hrs The Board Room Newcastle Medical School.
DIABETES & ENDOCRINOLOGY PIMD WEBSITE Our specialty web section is now available on the PIMD website. Click onto the specialty training tab then follow to Diabetes & Endocrinology. This site is essential reading, especially for RITA preparation.
Registering with JCHMT/PMETB It is essential that all new SpRs (even LATs) register with the PMETB (used to be JCHMT). Not doing so means your training is not counted and you cannot have a RITA.
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 the JCHMT website. As of October 2005 Multisource feedback (MSF) and Directly Observed Procedural Skills (DOPS) have been formally introduced and Mini Clinical Evaluation Exercise (Mini-CEX) will go live from October 2006. 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 RITA purposes, e.g. MSF Summary Form.
Mini-CEX documentation Mini-CEXs are compulsory from 1st October 2006. When undertaking a Mini-CEX retain 1 copy for yourself, give 1 copy to your Mini-CEX supervisor and have 1 copy available for the RITA panel. The Programme Director will retain this copy for the PIMD. Make sure that a Mini-CEX RITA summary is also completed for your RITA in May 2007.
MSF documentation It is essential that the SpR does not see any original MSF forms from individuals as it is an anonymous exercise. Make sure that the official MSF RITA summary form is completed and 1 copy made available for the RITA panel. This will be retained by the Programme Director for the PIMD.
MMC From Jan 2007 all applications for Higher Specialist Training have been co-ordinated nationally via electronic applications. Our specialty will be given a list of applicants by March 2007. There will be a structured interview for vacancies on the rotation from August 2007 on the 13th April 2007 with a second round interview on 22nd June 2007. The interview will involve 2 structured question stations broadly covering portfolio discussion and clinical scenarios. There will be Lay and Trainee involvement in the selection process.
RITAs 2007 The RITAs will be held on Weds-Thurs 16th-17th May 2007 with the post RITA feedback meeting on Friday 18th May 2007. The PYA RITA and Quality assurance RITAs will be held on Friday 25th May 2007. Finalised timetables and instructions have been circulated, they should be followed to the letter. This year it is mandatory for each SpR to have submitted a MSF and 4 Mini-CEXs post May 2006 for the RITA panel. Only SpRs who have already undertaken a PYA are excused the latter unless they have been asked to do so as one of their PYA targets. Furthermore it is mandatory for ALL SpRs (unless you have already had your PYA) to submit evidence of competence in at least 6 of the core topics. However, note that those of you undertaking a PYA are expected to have evidence in your portfolio/log book of competence in at least 90% of the core topics. It is essential that you read the documentation on the PIMD Diabetes & Endocrine website in relation to assessment (see above).
Taught Programme Following guidance from PMETB having a taught specialty programme will be one of the quality indicators of any training programme. The STC plan the following:
-Formally recognise the annual NERRAG meeting and the bi-annual Diabetes Audit Group meetings as part of the taught programme in the region alongside the 3 annual days of the NED CME programme. This will require the STC to keep records of the programme and the register and allocate a mandatory 75% attendance record for the year for all SpRs at their RITAs. The Programme Director is in the process of liaising with the meeting organisers.
-After much debate the STC have agreed to introduce mandatory essay writing. The provisional plans are that every June, 4 compulsory and 1 optional essays based on the core Diabetes and Endocrine topics will be circulated amongst SpRs and made compulsory for all SpRs who have not had a PYA at the RITAs in May or are not in their final year. Essays 1 and 2 should be returned to the relevant markers by 1st December 2006 and Essays 3 and 4 to the relevant markers by 1st March 2007. Once marked the essays will be returned with either of the following Grades:
A – Excellent. SpR demonstrates wider reading with an understanding and interpretation of the evidence base. There is also an understanding of the degree of variability when it comes to clinical practice due to individual pt variance. The theory is completely stated in the SpRs answers.
B – Good. The theory is completely stated in the SpRs answers with some demonstration of wider reading, but not fully interpreted. Also, no real indication was given in the answers as to patient variability when it comes to management.
C – Satisfactory. The key theory is completely stated in the SpRs answers in rather “text-bookish” style with very little evidence of wider reading and little attempt at interpretation of the evidence base.
D – Needs attention. Key theory is missing from the SpRs answers with no demonstrable evidence of wider reading or interpretation of the evidence base.
E – Fail. No attention has been given to key theory and the basics are dangerously incorrect. The latter could result in unsatisfactory clinical practice.
As well as the grade the marker will provide a short comment as to what improvements could be made. Any SpR scoring a C or D will have their answers reviewed by the TPD or STC chair or RSA, and a separate meeting organised with the TPD. Also, if they have not already done so they will be asked to submit the optional essay. The essays should be made available for the RITAs in May.
This process will provide a structured tool to aid SpR learning whilst at the same time allowing assessment and the use of targeted remedial supervision. It will also be less labour intensive for the already stretched fraternity of trainers. For the moment the plan is for the markers to be taken from the Consultants on the STC. More details will be presented at the joint T&T meeting on 12th June 2007.
Training Committee Committee Chair – Jola Weaver; Regional Speciality Advisor – Richard Quinton; Programme Director – Shaz Wahid; Consultant members – Jean Macleod, Simon Pearce (Research Advisor), Simon Eaton and Ronan Canavan; SpR representatives – Arutchelvam Vijayaraman and Andrew Advani.
NEW FACES ON THE SCENE
Welcome to Chris Rizzo as a new SpR to the region.
Welcome to Rahul Nayar as the new Consultant at Sunderland. You may remember him more affectionately as Raz when he was on the rotation as a SpR.
NEWS FROM THE NORTHEAST
Congratulations to Salman Razvi on obtaining his MD with a commendation and a prize for the best poster at the November Society for Endocrinology London meeting.
Congratulations to David Woods on his Consultant Post(s) at Newcastle & Northumbria.
Congratulations to Arun on his Consultant Post at Darlington.
Congratulations to Andrew Advani for his award of a Fellowship from the Pathological Society of Great Britain for his studies in Toronto.
Simon Eaton is now the Chair of the NRDSAG. We would like to take this opportunity of thanking Jola Weaver for her hard work in this role over the last 5-years.
LETTERS
Contributions for this section can include meeting reports, research experiences, book reviews, experiences abroad, and anything else you feel may benefit trainees and trainers around the region. The success of this section really does depend on YOU.
Withdrawal of intramuscular thyroxine hits headlines in France – Petros Perros
Politicians, endocrinologists, journalists, patient-led organisations, pharmaceutical industry and thyroid patients were engaged in passionate exchanges recently in France. The story goes like this. Roche decided to withdraw a preparation of thyroxine that can be administered intramuscularly, as the market for this is extremely small. In fact it is so small that patients in the UK do not seem to have a need for it. In the centre of this controversy featured Karine, a young woman who had a thyroidectomy when a teenager, then became hypothyroid and apparently could not be managed with oral thyroxine. No matter how high the dose, her hypothyroidism failed to respond. So she happily self-injected thyroxine for years until the giant multinational decided to scrap the product. She now attends her endocrinologist daily for an intravenous injection of thyroxine (still available in France from another manufacturer), but as she pointed out on national French TV, her veins are now messed up and her endocrinologist has recommended a portacath, which she is soon to have in order to continue her life-saving treatment. Apparently there are several patients like her in France going through the same ordeal. This made a good media story and the portrayal of the patient as the victim of corporate ruthlessness angered French public opinion.
Thyroxine malabsorption is well described in conditions like coeliac disease. Interference of thyroxine absorption by a variety of medications is also recognised. The few patients I have known with severe malabsorption including patients with short bowel syndrome (some could barely sustain their nutrition orally) managed their hypothyroidism perfectly adequately on oral thyroxine albeit 3-5 times normal replacement doses.
Many of us have seen patients who seemingly take their thyroxine, yet the TSH is sky high and no matter how much the dose is increased, the TSH won’t budge. None of the ones I have come across ended up on parenteral thyroxine, though. Come to think of it, they quietly disappeared from my clinic when the possibility of non-compliance (sorry non-adherence) was hinted to them. Perhaps they have emigrated to France. If my cynical instinct is correct, I feel sorry for the endocrinologist and for the patient-led organisations for being taken for a ride, but most of all I am sorry for patients like Karine whose power of persuasion sets their doctors off into a spiral of escalating medical intervention.
TRISH STUDY – Simon Pearce
Dear Colleagues,
Just to let you know that the TRISH study is up and running, and to thank you for your efforts so far in putting suitable patients forward. We have appointed Anne O'Brien as a Clinical Coordinator who will be working Monday and Tuesday mornings each week on the study.
The inclusion criteria are simple: Age 65 years or more; TSH = 0.1 or less on 2 samples 3 months apart, normal free thyroid hormones; Compos mentis.
The main exclusions are: AF (but paced rhythm is fine) and obvious drugs causing the low TSH.
If you think you have suitable subjects, just let me know by email, or contact Anne (her number is 0191-2227793). In the first instance we will arrange for suitable patients to receive the information sheet, and then offer a screening visit if they think that they might take part. The study is being run in the RVI Clinical Research Facility and we will book them a taxi or offer their travelling expenses.
SPARROWS 2006 – Ana Jokanowitch.
Bariatric surgery in patients with type 2 diabetes – what is the evidence? Short term studies have demonstrated that moderate weight loss improves insulin resistance and normalises fasting glycaemia [1]. Reducing body weight is therefore a cornerstone of diabetes management. But how often do we succeed? Compliance with lifestyle changes is poor. A few pharmacological agents are hardly more efficient. Bariatric surgery has been advertised as an effective weight loss treatment. However, this raises a series of important questions. What advice do we give to our obese diabetic patient who considers undergoing this procedure? What evidence do we have for surgical vs. pharmacological treatment of obesity? Does bariatric surgery improve diabetes control in obese type 2 diabetic patients?
Until two years ago, we had no data comparing medical and surgical approaches to weight loss and the relative benefits and risks of surgical approaches were uncertain. At the 66th ADA Annual Scientific Sessions David Flum, MD, MPH from the University of Washington argued strongly in favour of bariatric surgery as the only available treatment, which can actually reverse type 2 diabetes.
He presented data from a meta-analysis showing that 77% of individuals with type 2 diabetes had complete resolution of diabetes through sustained weight reduction [2]. Furthermore, a separate meta-analysis of effectiveness and adverse events associated with surgical treatment of obesity concluded that bariatric procedures in current use were performed with an overall mortality rate of less than 1% [3]. In the Swedish Obese Subjects study, a 10-year follow-up of individuals undergoing bariatric surgery, 36% of subjects with diabetes had resolution of diabetes compared with 13% of matched control subjects [4]. The only randomised trial which examined the treatment of mild to moderate obesity with laparoscopic adjustable gastric banding has found that after a 24-month treatment programme, surgical treatment using laparoscopic adjustable gastric banding was more effective than intensive medical programme in reducing weight (21.6 vs. 5.5% of initial weight, p<0.001),>[5].
During the session I learned about the differences between procedures most commonly used such as gastric bypass and laparoscopic adjustable gastric banding. Underlying mechanisms and achievable weight loss following each of these procedures are different with only the first one causing malabsorption and change in gut peptides. The same is true for the rate and the severity of complication, which is again greater for the bypass surgery. However, gastric bypass achieves greater weight change than gastric banding.
In summary, despite the lack of randomised, blinded, controlled trials, there is sufficient evidence to support surgery as a more effective modality for weight loss and control of diabetes in patients with a BMI of 35 or greater. This is in agreement with the latest position statement from the American Diabetes Association published in Diabetes Care in September this year: ‘Bariatric surgery may be considered for some individuals with type 2 diabetes and BMI > 35 kg/m2 and can result in marked improvements in glycaemia. The long-term benefits and risks of bariatric surgery in individuals with pre-diabetes or diabetes continue to be studied.’
References
1. Petersen, K.F., et al., Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes, 2005. 54(3): p. 603-8.
2. Buchwald, H., et al., Bariatric surgery: a systematic review and meta-analysis. Jama, 2004. 292(14): p. 1724-37.
3. Maggard, M.A., et al., Meta-analysis: surgical treatment of obesity. Ann Intern Med, 2005. 142(7): p. 547-59.
4. Sjostrom, L., et al., Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med, 2004. 351(26): p. 2683-93.
5. O'Brien, P.E., et al., Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial. Ann Intern Med, 2006. 144(9): p. 625-33.
SPARROWS 2006 – Peter Carey
Pulmonary Disease and Diabetes Mellitus As part of the Novel Complications of Diabetes symposium, Dr Naresh Punjabi of John Hopkins University discussed pulmonary disease and diabetes mellitus, highlighting the bi-directional relationship that exists between the two conditions. Diabetes mellitus reduces indices of forced expiration, lung volume and diffusion capacity. Cross-sectional data from the Framingham Study had shown that subjects with DM and IFG had lower than predicted pulmonary function, and this was related to HbA1c but not fasting glucose. There was also an interaction with smoking, such that smokers had poorer lung function. The British Women’s Heart and Health Study had also shown a negative correlation HOMA and FEV1 in known T2DM patients. The Copenhagen City Heart Study had shown that the FEV1 and FVC in men and women with diabetes was 8% lower than expected, with this difference comparable to that between smokers and non-smokers. However the longitudinal decline in pulmonary function was similar between those with and without diabetes mellitus.
The NHANES I study had shown that patients with restrictive lung disease (low FVC and FEV1) had an increased risk of diabetes, but COPD and smoking were not associated with future risk. Similarly the Atherosclerosis Risk in Communities Study had shown reduced FVC and FEV1 were associated with an increased incidence of diabetes mellitus, but there was no relationship between the ratio of FEV1/FVC. As the FEV1/FVC ratio is indicative of obstructive lung disease, whilst, alone, low FVC and FEV1 are measures of restrictive physiology, it was proposed that the underlying mechanism for impaired pulmonary function could be due to microangiopathy leading to reduced CO diffusion and reduced capillary blood flow. It was also suggested that diabetes risk and reduced lung function might be determined by a common pathway such as an insult in early life/foetal development or inflammation.
Finally, the association between insulin resistance and hypopnoea/apnoea was discussed. Hypoxia and subsequent arousal from sleep causes insulin resistance and increased insulin levels. The Sleep Heart Health Study had shown that increased apnoeic episodes led to increased fasting hyperglycaemia and lipid abnormalities independent of obesity. Intermittent hypoxia in animal studies leads to increased fasting insulin levels. Continuous Positive Airway Pressure (CPAP) ventilation has been shown to quickly improve insulin sensitivity and reduce HbA1c.
The talk touched only briefly on inhaled insulin but two papers presented during the session on Insulin Delivery (Julio Rosenstock et al and Lois Jovanovic et al) looked at the effect of inhaled insulin on pulmonary function. In type 1 and type 2 diabetic patients treated with inhaled insulin there was an early (within 3 months), small (<2%)>1 and DLCO compared to baseline. However this deterioration in pulmonary function did not progress over a 2 year period.
RECENT PUBLICATIONS FROM THE NORTHEAST
Please send us your recent publication for inclusion in the next newsletter.
1. L Sibal , A Jovanovic SC Agarwal, R T Peaston, RA James, TWJ Lennard, R Bliss, A Batchelor,P Perros. Phaeochromocytomas presenting as acute crises after beta blockade therapy. Clinical Endocrinology 2006; 65(2):186-190.
2. L Sibal, HN Law, J Gebbie, P Home. Cardiovascular risk factors predicting the development of distal symmetrical polyneuropathy in people with Type 1 diabetes: a 9 year follow-up study. Annals New York Academy Sciences 2006;1084: 304-318.
3. L Sibal, HN Law, J Gebbie, UK Dashora, SC Agarwal, Philip Home. Predicting the development of macrovascular disease in people with Type 1 diabetes: a 9-year follow-up study . Annals New York Academy Sciences 2006; 1084:191-207.
4. Thomas TH and Advani A (2006) Inflammation in cardiovascular disease and regulation of the actin cytoskeleton in inflammatory cells: the actin cytoskeleton as a target. Cardiovascular and Haematological agents in Medicinal Chemistry 4, 165-182.
5. Ioannidou-Kadis S, Wright PJ, Neely RD, Quinton R. Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate. Fertility & Sterility. 2006 Nov;86(5):1513.e5-9.
6. Owen CJ, Kelly H, Eden JA, Merriman ME, Pearce SHS, Merriman TR. Analysis of the Fc-receptor like-3 (FCRL3) locus in Caucasians with autoimmune disorders suggests a complex pattern of disease association. J. Clin Endocrinol Metab 2007; doi:10.1210/jc.2006-2183
7. Manji N, Carr-Smith JD, Boelaert K, Allahabadia A, Armitage M, Chatterjee VK, Lazarus JH, Pearce SH, Vaidya B, Gough SC, Franklyn JA. Influences of age, gender, smoking and family history on autoimmune thyroid disease phenotype. J Clin Endocrinol Metab. 2006; 91: 4873-80
8. Hamdy O, Porramatikul S, Al-Ozairi E. Metabolic Obesity: The Paradox between Visceral and Subcutaneous Fat. Current Diabetes Reviews Volume 2, Number 4, November 2006: 367-373
9. Al-Ozairi E, Miffelbeek RJ, Horton ES. Cardiovascular risk assessment in type 2 diabetes mellitus. Curr Diab Rep. 2006;6(5):333-6.
RECENT PUBLICATIONS IN DIABETES & ENDOCRINOLOGY THAT HIT THE NEWS OR THAT MAY HAVE A SIGNIFICANT IMPACT ON MANAGEMENT
The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyle peptidasae-4 inhibitors in type 2 diabetes. Daniel J Ducker & Michael A Nauck. Lancet 2006; 368:1696-1705.
An excellent review on this exciting new therapy for Type 2 DM. Well worth a read.
Management of Hyperglycaemia in the hospital setting. Silvio E Inzucchi. NEJM 2006;355:1903-1911.
An excellent review of the evidence base around managing this common scenario. Mandatory reading for trainees.
Osteonecrosis of the Jaw-Do bisphosphonates pose a risk? John Bilezikian. NEJM 2006;355:2278-2281 and see clinical picture on page 2348.
An excellent, practical article providing a valuable update on this clinical scenario.
Acromegaly. Shlomo Melmed. NEJM 2006;355:2558-2573.
An excellent review on the pathophysiology and management of acromegaly. Mandatory reading for all trainees.
Drug treatments for obesity: orlistat, sibutramine and rimonabant. Raj Padwal & Sumit Majumdar. LANCET 2007;369:71-77.
An excellent review of the place of these therapies in clinical practice.
Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF. Lancet. 2006 Nov 11;368(9548):1660-72.
The RIO-Diabetes trial assessed the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas. 1047 overweight or obese type 2 diabetes patients (BMI 27-40 kg/m2) with a HbA1c 6.5-10.0% (mean 7.3% [SD 0.9] at baseline) already on metformin or sulphonylurea monotherapy were given a mild hypocaloric diet and advice for increased physical activity, and randomly assigned placebo (n=348), 5 mg/day rimonabant (360) or 20 mg/day rimonabant (339) for 1 year. The primary endpoint was weight change from baseline after 1 year of treatment. Analyses were done on an intention-to-treat basis. 692 patients completed the 1 year follow-up; numbers in each group after 1 year were much the same. Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group (placebo: -1.4 kg [SD 3.6]; 5 mg/day: -2.3 kg [4.2], p=0.01 vs placebo; 20 mg/day: -5.3 kg [5.2], p<0.0001 style=""> Recently at South Tyneside strict guidance on the use of rimonobant have been produced and it should only be prescribed if the following are satisfied:
Patient has a BMI > 27 kg/m2 or waist circumference > 94 cm in males; >80 cm in females
The patient has engaged with the dietetics service and is under active follow-up
The patient is younger than 75 years (not for patients <>
The patient can maintain a level of physical activity that equates to 30-mins per day of brisk walking or more
The patient has had an unsuccessful trial on orlistat (whether it was due to side effects or due to it not maintaining 5% of body weight loss)
The patient has had an unsuccessful trial of sibutramine (whether it was due to side effects or due to it not maintaining 5% of body weight loss) or if subutramine is contraindicated, e.g. hypertension
The patient is not on any treatment for depression/anxiety or has a significant recent (<>
The patient has no active psychiatric health problem, e.g. schizophrenia
The patient is not epileptic
The eGFR > 30 mil/min
There is no liver disease
Patient is not pregnant
If the patient is suitable for rimonobant therapy it should be initiated at a dose of 20mg once a day. The patient should be monitored at 3-monthly intervals with the target of achieving a 5% loss in body weight or a 1 cm reduction in waist circumference at each visit. If the patient develops any symptoms of depression or anxiety rimonabant should be discontinued.
International trial of the Edmonton protocol for islet transplantation. Shapiro AM, Ricordi C, Hering BJ et al N Engl J Med. 2006 Sep 28;355(13):1318-30.
This international trial explored the feasibility and reproducibility of islet transplantation with the use of the Edmonton protocol, by enrolling 36 subjects with type 1 DM, who underwent islet transplantation at nine international sites. Islets were prepared from pancreases of deceased donors and were transplanted within 2 hours after purification, without culture. The primary end point was defined as insulin independence with adequate glycaemic control 1 year after the final transplantation. Of the 36 subjects, 16 (44%) met the primary end point, 10 (28%) had partial function, and 10 (28%) had complete graft loss 1 year after the final transplantation. A total of 21 subjects (58%) attained insulin independence with good glycaemic control at any point throughout the trial. Of these subjects, 16 (76%) required insulin again at 2 years; 5 of the 16 subjects who reached the primary end point (31%) remained insulin-independent at 2 years. Although islet transplantation with the use of the Edmonton protocol can successfully restore long-term endogenous insulin production and glycaemic stability in subjects with type 1 diabetes mellitus and unstable control, insulin independence is not sustainable. The search goes on, although there have been enormous advances over the last 1-2 yrs and the Edmonton protocol has added to the knowledge base.
Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatraemia. Schrier RW, Gross P, Gheorghiade M et al. N Engl J Med. 2006;355:2099-112.
The authors investigated whether tolvaptan, an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis (excretion of electrolyte-free water) might be of benefit in hyponatraemia. The efficacy of tolvaptan was evaluated in patients with euvolaemic or hypervolaemic hyponatraemia. Patients were randomly assigned to oral placebo (223 patients) or oral tolvaptan (225) at a dose of 15 mg daily. The dose of tolvaptan was increased to 30 mg daily and then to 60 mg daily, if necessary, on the basis of serum sodium concentrations. The two primary end points for all patients were the change in the average daily area under the curve for the serum sodium concentration from baseline to day 4 and the change from baseline to day 30. Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days (P<0.001) style=""> It is also well worth reading the accompanying editorial on page 2146. The other vasopressin receptor antagonist is conivaptan. These agents would be very useful in patients with hyponatraemia and underlying CCF, who I find the most difficult to treat and in whom often the prognosis is poor.
Glycaemic durability of rosiglitazone, metformin, or glyburide monotherapy. Kahn SE, Haffner SM, Heise MA et al. N Engl J Med. 2006;355:2427-43. The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycaemic control in type 2 diabetes is not known.
The ADOPT study evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.0 years. The primary outcome was the time to monotherapy failure, which was defined as a confirmed level of fasting plasma glucose of more than 10.0 mmol/l, for rosiglitazone, as compared with metformin or glyburide. Prespecified secondary outcomes were levels of fasting plasma glucose and hbA1c, insulin sensitivity, and beta-cell function. Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide. This represents a risk reduction of 32% for rosiglitazone, as compared with metformin, and 63%, as compared with glyburide (P<0.001 style=""> Does this trial change my practice? NO. Given the small glycaemic benefit of rosiglitazone (with the risk of fluid retention and weight gain) and higher cost, metformin should remain the 1st choice when initiating oral drug therapy for type 2 DM.
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. Belfort R, Harrison SA, Brown K et al. N Engl J Med. 2006;355:2297-307.
The authors randomly assigned 55 patients with impaired glucose tolerance or type 2 diabetes and liver biopsy-confirmed nonalcoholic steatohepatitis to 6 months of treatment with a hypocaloric diet (a reduction of 500 kcal per day in relation to the calculated daily intake required to maintain body weight) plus pioglitazone (45 mg daily) or a hypocaloric diet plus placebo. Before and after treatment hepatic histologic features, hepatic fat content by means of magnetic resonance spectroscopy, and glucose turnover during an oral glucose tolerance test ([14C]glucose given with the oral glucose load and [3H]glucose given by intravenous infusion) were assessed. Diet plus pioglitazone, as compared with diet plus placebo, improved glycaemic control and glucose tolerance (P<0.001), p="0.04)," p="0.008)." p="0.003)," p="0.02)," p="0.008)." p="0.001)," p="0.08).">
Case reports and echocardiographic studies suggest that the ergot-derived dopamine agonists pergolide and cabergoline may increase the risk of cardiac-valve regurgitation by acting on the 5HT2B receptors abundant on cardiac valves causing fibroses similar to carcinoid syndrome and the drug reactions to dexfenfluramine. Two recent studies add to the literature:
Dopamine agonists and the risk of cardiac-valve regurgitation. Schade R, Andersohn et al. N Engl J Med. 2007;356:29-38.
The authors used data from the United Kingdom General Practice Research Database to identify a population-based cohort comprising 11,417 subjects 40 to 80 years of age prescribed antiparkinsonian drugs between 1988 and 2005. A nested case-control analysis within this cohort in which each patient with newly diagnosed cardiac-valve regurgitation was matched with up to 25 control subjects from the cohort, according to age, sex, and year of entry into the cohort was done. Incidence-rate ratios for cardiac-valve regurgitation with the use of different dopamine agonists were estimated by conditional logistic-regression analysis. Of 31 case patients with newly diagnosed cardiac-valve regurgitation, 6 were currently exposed to pergolide, 6 were currently exposed to cabergoline, and 19 had not been exposed to any dopamine agonist within the previous year. The rate of cardiac-valve regurgitation was increased with current use of pergolide (incidence-rate ratio, 7.1; 95%CI, 2.3-22.3) and cabergoline (incidence-rate ratio, 4.9;1.5-15.6), but not with current use of other dopamine agonists. In this study, use of the dopamine agonists pergolide and cabergoline was associated with an increased risk of newly diagnosed cardiac-valve regurgitation.
Valvular heart disease and the use of dopamine agonists for Parkinson's disease. Zanettini R, Antonini A et al. N Engl J Med. 2007;356:39-46.
The authors performed an echocardiographic prevalence study in 155 patients taking dopamine agonists for Parkinson's disease (pergolide, 64 patients; cabergoline, 49; and non-ergot-derived dopamine agonists, 42) and 90 control subjects. Clinically important regurgitation in any valve was found with significantly greater frequency in patients taking pergolide (23.4%) or cabergoline (28.6%) but not in patients taking non-ergot-derived dopamine agonists (0%), as compared with control subjects (5.6%). The relative risk for moderate or severe valve regurgitation in the pergolide group was 6.3 for mitral regurgitation (P=0.008), 4.2 for aortic regurgitation (P=0.01), and 5.6 for tricuspid regurgitation (P=0.16); corresponding relative risks in the cabergoline group were 4.6 (P=0.09), 7.3(P<0.001), p="0.12)." style=""> In my own practice when managing pts on dopamine agonists I undertake an annual screen of FBC, ESR, U&Es and LFTs and consider Echo/CXR/PFTs only if symptoms are present. Because of the large doses used in the above studies compared to the much smaller doses used in my own practice, I do not see the study results necessitating the use of regular echo screening in pts treated with dopamine agonists for prolactinoma. This is open to debate?
The nuclear receptor LXR is a glucose sensor. Mitro N, Mak PA, Vargas L, Godio C, Hampton E, Molteni V, Kreusch A, Saez E. Nature. 2007 Jan 11;445(7124):219-23. Epub 2006 Dec 24.
The liver has a central role in glucose homeostasis, as it has the distinctive ability to produce and consume glucose. On feeding, glucose influx triggers gene expression changes in hepatocytes to suppress endogenous glucose production and convert excess glucose into glycogen or fatty acids to be stored in adipose tissue. This process is controlled by insulin, although debate exists as to whether insulin acts directly or indirectly on the liver. In addition to stimulating pancreatic insulin release, glucose also regulates the activity of ChREBP, a transcription factor that modulates lipogenesis. The authors describe another mechanism whereby glucose determines its own fate. They show that glucose binds and stimulates the transcriptional activity of the liver X receptor (LXR), a nuclear receptor that coordinates hepatic lipid metabolism. d-Glucose and d-glucose-6-phosphate are direct agonists of both LXR-alpha and LXR-beta. Glucose activates LXR at physiological concentrations expected in the liver and induces expression of LXR target genes with efficacy similar to that of oxysterols, the known LXR ligands. Cholesterol homeostasis genes that require LXR for expression are upregulated in liver and intestine of fasted mice re-fed with a glucose diet, indicating that glucose is an endogenous LXR ligand. Their results identify LXR as a transcriptional switch that integrates hepatic glucose metabolism and fatty acid synthesis. This paper was suggested by Dr Simon Pearce
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