Monday, September 29, 2008

Endodiabology-October 2008



Editors: Shaz Wahid and
Petros Perros (
Associate Editors: Arut Vijayaraman, Shafie Kamarrudin, Beas Bhattacharya, 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- Ravikumar Balasubramanian (5)
· NGH/QEH- Freda Razvi (5)
· Research with numbers (supervisor)- Eelin Lim(5-Prof Taylor)

· 6-8th October 2008 Society for Endocrinology Clinical update, Bristol. Contact
· 17th October 2008 DUK 2009 abstract deadline.
· 12th November 2008 North East Obesity Forum meeting. Obesogenic environment.
· 12th November 2008 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
· 15th November 2008 BES 2009 abstract deadline.
· 26th November 2008 Northern Endocrine Regional Research and Audit Group (NERRAG) annual meeting, Lumley Castle, Durham. Contact
· 27th November 2008 58th British Thyroid Association Annual meeting, London, .
· 27th and 28th November 2008 (29th November 2008 is SpR meeting) ABCD Autumn Meeting, London,
· 27th and 28th November 2008Insulin Pump Course, James Cook University Hospital. Apply on line at
· 10th December 2008 RCP Updates in G(I)M, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
· 14th January 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
· 26th January 2009 Northern Endocrine & Diabetes Winter CME, Freeman Hospital.
· 10th February 2009 SfE Clinical Cases meeting, London. Contact .
· 11th-13th March 2009 DUK Annual Professional Conference, Birmingham. Contact
· 16th – 19th March 2009 BES 2009, Harrogate. Contact .
· 18th March 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
· 29th April 2009 RCP Acute Medical Emergencies, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
· 7th-8th May 2009 ABCD Spring Meeting, Bristol,
· 11th May 2009 GIM training ½ day, Freeman Hospital. Contact Lorraine Waugh 0191 223 1247
· 24th June 2009 Northern Endocrine & Diabetes Summer CME, Freeman Hospital.
· 12th October 2009 Northern Endocrine & Diabetes Autumn CME, James Cook University Hospital

Confusing paperwork The transitional period between SpR and StR training remains confusing and is especially hindered by the JRCPTBs poor communication and awful paperwork sent to the trainees. There will have to be separate instructions for the RITAs (old SpRs) and ARCPs (the new StR breed). As an example a new educational supervisor report was published by the JRCPTB the week before this years ARCPs/RITAs. The TPD now at least has some time to look at all the documents and ultimately produce separate instructions for regional use.
Acute Medicine Level 2 training for SpRs For next years ARCPs/RITAs any SpR who has not had their PYA will be expected to have 4 ACAT assessments and 4 Mini-CEXs 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 specifically in relation to Acute Medicine, 4 CbDs 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 . 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 although it is still possible to link with this site using the old 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, 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.
ANOTHER CURRICULUM Trainees who have been recently appointed now have a new curriculum for both the specialty, Acute Medicine to Level 2 and a generic curriculum. Essentially there is no difference other than the sections being reorganised into the subsections of OBJECTIVE/COMPETENCY, KNOWLEDGE, SKILLS, ATTITUDE. They are essential reading and can be accessed on .
The GOLD Guide This replaces the Orange guide, and is the definitive guide to all aspects of training in the UK. It can be accessed on . A massive document that I delve into when the need arises, e.g. interdeanery transfers.
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.
Personal Development Plans (PDPs) Following the ARCPs all trainees will have their report. It is essential that this report is used to construct a PDP when starting your new post from 1st October. The format used should be standard template circulated by Shaz Wahid.
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.
Training Committee Chair- Jola Weaver,; Regional Speciality Advisor- Richard Quinton, ; Programme Director- TBC ; Consultant member-Shaz Wahid,; Consultant member-Jean MacLeod,; Consultant member (Research Advisor)-Simon Pearce,; Consultant member-Simon Eaton,; Consultant member-Nicky Leech; SpR representative- Arutchelvan Vijayaraman ; SpR representative- Jeevan Mettayil

· Congratulations to Simon Ashwell on his recent marriage to Amelia Lake.
· Akheel Syed has moved onto a Locum Consultant post in Salford.
· Welcome to Naveen Siddaramaiha (NTN) and Yayha Maghoub (LAT) onto the rotation.
· Shaz Wahid will be stepping down from 1st November 2008 as TPD having completed his tenure.
· Congratulations to Emma Peralta on winning the Prize for best SPARROWS presentation.

The 7 habits of highly effective people-personal change and management SHAZ WAHID. I recently undertook the latter course and have read the book by Stephen Covey. This is what “management” training should be. It relates to the importance of personal management before moving onto management of others/situations. The first 3 habits are about being “proactive”, “having the end in mind” and “putting first things first”-all add up to a private victory. Once mastered one can practice the habits of “think win-win”, “seek first to understand” and “synergise”-all adding up to an effective public victory. Of course in the NHS we need to know what PCT, PBR, PBC, Foundation Trust, etc stand for and work. But, true “management” is about practicing the 7-habits effectively so that we can fullfil our potential as leaders. The 7th habit is “sharpen the saw” and it is about refreshing ones heart, mind, body and soul on a regular basis so that the 1st 6-habits can be practiced effectively. I have been really impressed by this, to the point I have devised a training programme for the Acute Medicine StR that will be rotating through South Tyneside and not to forget the SpR/StR in DM&ENDO. I hope you are intrigued and will try the 7-habits. I have bought the 7-habits of highly effective teenagers book for my 15 year old daughter, of course, but whether she is one of the frogs who actually jumps off the log or simply chooses to remains to be seen.

Rescue of Addison’s Disease Study (RADS)-Simon Pearce RADS is a groundbreaking Newcastle University study, that has been funded by the Medical Research Council. RADS will examine the possibility that autoimmune Addison's disease (AAD) may be a curable condition, rather than a disease that is simply controlled by hormone replacement. Although we generally assume that the autoimmune attack inevitably destroys all the adrenal cortex in autoimmune Addison’s disease, it is possible that the autoimmune attack could be modified. A key feature of AAD is that it is often diagnosed at a stage when subjects have low but detectable serum cortisol. As adrenal tissue is highly plastic, the residual steroidogenic tissue may be sufficient to regenerate normal steroid secretion under the powerful ACTH drive, if the autoimmune process can be arrested.
RADS is a pilot study of rituximab (B lymphocyte depletion) therapy in an attempt to rescue adrenal steroidogenic capacity in ten subjects with early autoimmune Addison's disease: within 1 month of diagnosis. During the first twelve weeks of treatment, additional glucocorticoid therapy (prednisolone) will be given to ensure wellbeing and to rest the steroidogenic apparatus that is the target of the autoimmune attack. Glucocorticoids will be gradually withdrawn, in a controlled fashion, and adrenal function re-evaluated at 13, 26, 39 and 52 weeks. The primary endpoint will be restoration of steroidogenic function as judged by conventional endocrine indices of adrenocortical function. Additional outcomes; 21-hydroxylase autoantibody titres, B cell counts, adverse events and patient wellbeing will be assessed. B cell depletion may ameliorate the autoimmune attack against adrenal cells, potentially allowing a state of immune tolerance to be restored with subsequent regeneration of adrenal steroidiogenic capacity. The importance of this study lies in the possibility of informing the treatment of type 1 diabetes and other autoimmune endocrinopathies, as well as the potential benefit to the Addison’s participants.
All participant treatment and follow-up will be carried out at the Clinical Research Facility, Royal Victoria Infirmary, Newcastle. There will be no payment to participants, but travel expenses to the RVI will be reimbursed.
If you have a suitable potential participant, please discuss the study with them, let them have the patient information leaflet and contact Simon Pearce, 0191-2418674 (office), 07811-902282 (mob) or

Having the opportunity to be one of the 21,000 attendees at this years American Diabetes Association 68th Scientific Sessions in SanFrancisco created a mix of emotions. Being the only diabetes specialist nurse in the SPARROW group was, at first somewhat nerve-racking, however those feelings were soon replaced with exhilarating thoughts of having such a fantastic opportunity to attend a conference of this size and being able to learn about cutting edge clinical research and studies. The theme of this year’s conference was Type 2 diabetes and cardiovascular disease, with most sessions reflecting this. Although all sessions attended were equally as interesting as each other, one or two were memorable for various reasons. One such session being the Banting Memorial lecture, presented by Ralph DeFronzo, in which he highlighted the need to intervene earlier. He presented his rather controversial (and expensive!) intervention of lifestyle + TZD + Metformin + Exenatide to a crowd of mixed responses.
Another interesting session was that of self-monitoring blood glucose in which it was concluded that the success of this is dependant upon the interest of the patient as well as the interest/ time dedicated by the provider. We need to teach patients not only how to monitor blood glucose levels, but how to translate the results into action in terms of self-care.
Dr Gallen presented a marvellous session on Hypoglycaemia during exercise with practical tips to help manage insulin therapy and blood glucose levels both during and after exercise.
Although the education sessions were plentiful and interesting, opportunities to learn about the latest products serving diabetes were available in the exhibit hall. Being a keen pump enthusiast, I was interested to learn more about the OmniPod, an insulin delivery system launched in the USA in 2005 consisting of an integrated insulin reservoir, personal device manager and blood glucose meter. A system which looks both exciting and at the forefront of pump technology.
Attending the conference, as part of the SPARROW GROUP was a truly superb experience, an opportunity I would urge all DSN’s to take up in the future.

SPARROWS REPORT-Vijayaraman Arutchelvam (SpR)
When I made my itinerary for the scientific programme, I chose to attend the sessions discussing the glycaemic target in Type 2 Diabetes. ACCORD, ADVANCE and VADT were the three studies presented in ADA exploring the benefits (!) of tight glycaemic control.
ACCORD was a randomized controlled trial with a double 2 by 2 factorial design. All cause death rate was high in the intensive therapy group (HR 1.22) prompting the glycaemic arm to be stopped. ADVANCE a factorial randomized trial showed no significant reduction in CV outcome but reduction in nephropathy incidence. VADT, a prospective randomized trial showed increased CV death in the intensive therapy group.
Of the three big studies 2 demonstrated clear negative results with 1 being neutral in terms of macro vascular outcome. This modified my practice that I learn to be reassured with an HbA1c target of 7% rather than 6.5% in long standing type 2 diabetes. These studies also demonstrate the problem with weight gain and the importance of achieving a good glycaemic control early. Table: Three outcome studies in Type 2 diabetes-see appendix A
SPARROWS REPORT-Ravikumat Erukalapati
I am summarising my key learning points from some of the sessions that I attended.
A.) Great Protein Debate
I found the debate stimulating and thought provoking.
Problems with high protein intake in Diabetic patients:
· ↑ proteinuria
· ↑ RBF, GFR, intraglomerular pressure
· ↑ rate of progression of kidney failure
· Increases acid load on kidney
· Promotes osteoporosis (↑ calciuria)
· Induces anorexia
In favour of high protein diet are:
· Not ↑ plasma glucose
· ↑ Insulin response
· No need to ↑ CHO or fat in diet
· ↓ appetite, ↑ satiety
· ↑ weight loss, maintains lean mass
· ↓ Chol, LDL, Trigs
· ↓ BP
· ↓ CV events
My take-home message:
· High protein diet is not necessarily bad for Diabetic patients and might in fact be beneficial. RCTs are needed in this area.
· Protein requirements for patients with Diabetic Nephropathy cannot be generalised. Their protein requirements have to be dealt by a specialist dietician individually.
· Daily protein requirements are better expressed if ‘gm/kg body wt’ is used instead of ‘% of diet’.
B.) Pregnancy sessions
· Evidence available so far suggests that Insulin analogues are safe in pregnancy
Lispro- several Obs. Studies
Aspart- one large RCT
Glargine- Obs. Studies
Levemir- Ongoing RCT
· CI for Metformin- small fetus, severe preeclampsia, sepsis
C.) Newer classes of pharmacologic agents for treatment of Hyperglycaemia.
SGLT2 Inhibitors
· Sodium Glucose Cotransporter Type 2 Inhibitors
· Dopagliflozin, Remogliflozin, Phase 3 trials
· Mechanism of action- Glycosuria
· SE - Transient Hyperkalaemia, salt wasting, dehydration, energy deficit, wt↓, polyuria, polydipsia, recurrent UTIs
Glucokinase Activators
· Potential use in T2DM
· Mechanism of action- ↑ Hepatic glucose utilisation, ↑ Insulin secretion
· SE- Hypoglycaemia , Steatosis, Hepatic Glycogen deposition, weight gain
Glucagon receptor Antagonists
· Gluconeogenesis ( Alanine, Lactate, Pyruvate ) and Glycogenolysis contribute to plasma glucose
· Latest data suggests that 60% of glucose output is due to Gluconeogenesis
· Blocking glucagon action in rodents ↓hepatic glucose production
· SIRT1 activating compounds
· Anti senility agents
· Resveratrol (GSK)
· Similar products in Red wine- if you can drink 1000 bottles/day !!
Due to space constrains, I have not detailed the other sessions and also my Alcatraz prison experience!

1. Taylor R. Pathogenesis of type 2 diabetes: Tracing the Reverse Route. Diabetologia 2008 Aug 26. [Epub ahead of print; Full text available under Open Access]

2. Arun CS, Taylor R. Influence of pregnancy on long-term progression of retinopathy in patients with type 1 diabetes. Diabetologia 2008. Jun;51(6):1041-1045. Epub 2008 Apr 8.

3. Trenell MI, Hollingsworth KG, Lim EL, Taylor R. Walking improves lipid oxidation independent of changes in mitochondrial ATP synthesis in people with Type 2 diabetes. Diabetes Care 2008; 31(8):1644-9. Epub 2008 May 16.

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 2008 Sep;57(9):2288-95. Epub 2008 Jun 5.

5. Simon G. Ashwell, Clare Bradley, James W. Stephens, Elke Witthaus, and Philip D. Home Treatment Satisfaction and Quality of Life With Insulin Glargine Plus Insulin Lispro Compared With NPH Insulin Plus Unmodified Human Insulin in Individuals With Type 1 Diabetes Diabetes Care 31: 1112-1117, June 2008.

6. Razvi S, Shakoor A, Vanderpump M, Weaver JU, Pearce SH. The influence of age on the relationship between subclinical hypothyroidism and ischemic heart disease: a metaanalysis. J Clin Endocrinol Metab. 2008 Aug;93(8):2998-3007.

7. Falardeau J, Chung WCJ, Beenken A, Raivio T, Plummer L, Sidis I, Jacobson-Dickman EE, Eliseenkova AV, Ma J, Dwyer AA, Quinton R, Na S, Hall JE, Huot C, Alois N, Pearce SHS, Cole LW, Hughes VA, Mohammadi M, Tsai P, Pitteloud N. 2008 Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in human and mice. Journal of Clinical Investigation. 118: 2832-2831.

8. Advani A, Vaikkakara S, Gill MS, Arun CS, Pearce SHS, Ball SG, James RA, Lennard TJW, Bliss RD, Quinton R, Johnson SJ. 2008 Impact of standardised reporting in adrenocortical carcinoma: a single centre clinicopathological review. Journal of Clinical Pathology. 61: 939-944.

9. Cole LW, Sidis I, Zhang CK, Quinton R, Plummer L, Pignatelli D, Hughes VA, Dwyer AA, Raivio T, Hayes FJ, Seminara SB, Huot C, Alos N, Speiser P, Takeshita A, van Vliet G, Pearce SHS, Crowley WF, Jr, Zhou QY, Pitteloud N. 2008 Mutations in Prokineticin 2 (PROK2) and PROK2-receptor (PROKR2) in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. Journal of Clinical Endocrinology & Metabolism. 93: 3551-9.

10. Al-Ozairi E, Quinton R, Advani A. 2008 Therapeutic response to metformin in an underweight patient with polycystic ovarian syndrome. Fertility & Sterility. 2008 Jan 25. [Epub ahead of print].

11. Arutchelvam V & Quinton R. 2008 Anaemia in older patients can be secondary to testosterone deficiency. Geriatric Medicine. 38: 272-273.

12. Quinton R, Pearce SHS, Sievenpiper JL. 2008 Sun and melanoma: time to go to get your hat. BMJ. 337: 309.

13. Sievenpiper JL, McIntyre EA, Verrill M, Quinton R, Pearce SHS. 2008 Lesson of the Week: Unrecognised severe vitamins D deficiency. BMJ. 336: 1371-1374. [with Editorial Comment: Deficiency of sunlight and vitamin D: fortification of foods and advice on sensible sun exposure are urgently needed@, pp1318-1319]

14. Vaidya B, Pearce SHS. Management of hypothyroidism in adults. BMJ
2008;337: 284-89.

15. Skinningsrud B, Husebye ES, Pearce SH, McDonald DO, Brandal K, Boe Wolff A, Lovas K, Egeland T, Undlien DE. Polymorphisms in CLEC16A and CIITA at 16p13 are associated with primary adrenal insufficiency. J Clin Endocrinol Metab 2008; 93:3310-7.

16. Pearce SHS. Section VI. Hyperparathyroidism. In Davies TF. Case-based guide to Clinical Endocrinology. Integra Press, 2008 pp169-193.
Including case contributions from Drs. CS Arun, Ebaa Al Ozairi, Ee Lin Lim, Andy James, Muthy Korada, Reena Thomas & Tim Cheetham.

Intensive glycaemic control and cardiovascular disease. Much has been said about this topic following publication of the ACCORD and ADVANCE trials. I would suggest reading Arut’s letter summarising the trials and read from there.
PTH Mutation with primary hyperthyroidism and undetectable intact PTH. Halpern et al. NEJM 2008;359:1182-1183. An interesting case report that should also be read in conjunction with a recent article on the same subject in Clinical Endocrinology.
Extracapsular haemorrhage from a parathyroid adenoma. MC Zillikens & A Wijbenga. NEJM 2008;359:1155. A good clinical picture.

Hypoparathyroidism. Dolores Shoback. NEJM 2008;359:391-403. An excellent practical review well worth a read.

Sievenpiper JL, McIntyre EA, Verrill M, Quinton R, Pearce SHS. 2008 Lesson of the Week: Unrecognised severe vitamins D deficiency. BMJ. 336: 1371-1374. [with Editorial Comment: Deficiency of sunlight and vitamin D: fortification of foods and advice on sensible sun exposure are urgently needed@, pp1318-1319]. An excellent local article that should serve as a reminder to consider vitamin D deficiency.

Precocious Puberty. JC Carel & J Leger. NEJM 2008;358:2366-2377. Essential reading for trainees.

Graves’ Disease. Gregory Brent. NEJM 2008;358:2594-2605. A good update.
A combined presentation of Graves’ disease and Miller-Fisher syndrome. Vetsch et al. NEJM 2008;371:1886. An excellent case report.

Risk assessment and lipid modification for primary and secondary prevention of cardiovascular disease: summary of NICE guidance (Angela Cooper&Norma O’Flynn) & the accompanying controversies report (Francesco Cappucio). BMJ 2008;336:1246-1249. An excellent summary with analysis.

The Addison’s disease dilemma-autoimmune or ALD? M-F Kong et al. Lancet 2008;371:1970. A very good case report that should act as a reminder that not all Addison’s is autoimmune.

Type 1 diabetes, hyperglycaemia, and the heart. Ravi Retnakaran & Bernard Zinman. Lancet 2008;371:1790-1809. A wonderful article reviewing the pathophysiology and possible treatment strategies of heart disease in Type 1 DM-NOT Type 2!

Management of type 2 diabetes; updated NICE guidance (Philip Home et al) & the accompanying controversies report (Stephen Atkin & Chris Walton). BMJ 2008;336:1306-1309. I just could not look at the electronic report hence bought the hard copy, tis big! This is an excellent summary of the guidance with some food for thought. Thankfully, because of my crystal ball gazing the local district guidelines do not need much rewriting.

Diagnosis and management of hypocalcaemia. Mark Cooper & Neil Gittoes. BMJ 2008;336:1298-1302. An excellent review and practical update.Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. Sattar N, McConnachie A et al. Lancet 2008;371:1927-1935. The authors investigated to what extent metabolic syndrome and its individual components were related to risk for cardiovascular disease and diabetes in elderly populations, by relating metabolic syndrome (defined on the basis of criteria from the Third Report of the National Cholesterol Education Program) and its five individual components to the risk of events of incident cardiovascular disease and type 2 diabetes in 4812 non-diabetic individuals aged 70-82 years from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER); and, in a second prospective study (the British Regional Heart Study [BRHS]) of 2737 non-diabetic men aged 60-79 years. In PROSPER, 772 cases of incident cardiovascular disease and 287 of diabetes occurred over 3.2 years. Metabolic syndrome was not associated with increased risk of cardiovascular disease in those without baseline disease (hazard ratio 1.07 [95% CI 0.86-1.32]) but was associated with increased risk of diabetes (4.41 [3.33-5.84]) as was each of its components, particularly fasting glucose (18.4 [13.9-24.5]). Results were similar in participants with existing cardiovascular disease. In BRHS, 440 cases of incident cardiovascular disease and 105 of diabetes occurred over 7 years. Metabolic syndrome was modestly associated with incident cardiovascular disease (relative risk 1.27 [1.04-1.56]) despite strong association with diabetes (7.47 [4.90-11.46]). In both studies, body-mass index or waist circumference, triglyceride, and glucose cutoff points were not associated with risk of cardiovascular disease, but all five components were associated with risk of new-onset diabetes. The authors conclude that metabolic syndrome and its components are associated with type 2 diabetes but have weak or no association with vascular risk in elderly populations, and that clinical focus should remain on establishing optimum risk algorithms for each disease separately. This point is eloquently argued by Richard Kahn in the accompanying editorial (Lancet 2008;371:1892-1893) as “another nail in the coffin”.Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomized parallel-group trial. Weng J, Li Y et al. Lancet 2008;371:1753-1760. In this multicentre, randomised trial to compare the effects of transient intensive insulin therapy(continuous subcutaneous insulin infusion[CSII] or multiple daily insulin injections [MDI]) with oral hypoglycaemic agents on beta-cell function and diabetes remission rate; 382 patients, aged 25-70 years, were enrolled from nine centres in China. The patients, with fasting plasma glucose of 7.0-16.7 mmol/L, were randomly assigned to therapy with insulin (CSII or MDI) or oral hypoglycaemic agents for initial rapid correction of hyperglycaemia. Treatment was stopped after normoglycaemia was maintained for 2 weeks. Patients were then followed-up on diet and exercise alone. Intravenous glucose tolerance tests were done and blood glucose, insulin, and proinsulin were measured before and after therapy withdrawal and at 1-year follow-up. The primary endpoint was time of glycaemic remission and remission rate at 1 year after short-term intensive therapy. More patients achieved target glycaemic control in the insulin groups (97.1% in CSII and 95.2%in MDI) in less time (4.0 days [SD 2.5] in CSII and 5.6 days [SD 3.8] in MDI) than those treated with oral hypoglycaemic agents (83.5% and 9.3 days [SD 5.3]). Remission rates after 1 year were significantly higher in the insulin groups (51.1% in CSII and 44.9% in MDI) than in the oral hypoglycaemic agents group (26.7%; p=0.0012). Beta-cell function measured by HOMA B and acute insulin response improved significantly after intensive interventions. The increase in acute insulin response was sustained in the insulin groups but significantly declined in the oral hypoglycaemic agents group at 1 year in all patients in the remission group. This study suggests that early intensive insulin therapy in patients with newly diagnosed type 2 diabetes has favourable outcomes on recovery and maintenance of beta-cell function and protracted glycaemic remission compared with treatment with oral hypoglycaemic agents. There are obvious limitations with extrapolating these results to our own patients, but I will not forget Andrew Advani thinking I was a “nut” when I used a similar approach in patients with clinical features of type 2 diabetes presenting with significant hyperglycaemia to the acute take. I think he changed his opinion when he saw the majority come off insulin and onto either oral agents or diet alone.Effect of financial incentives on inequalities in the delivery of primary clinical care in England: analysis of clinical activity indicators for the quality and outcomes framework. Doran T, Fullwood C, Kontopantelis E, Reeves D. Lancet 2008;372:728-736. The quality and outcomes framework (QuOF) has received much praise and some suggest it has done more for diabetes care than insulin! Make what you wish of it, but what is clear financial incentives have helped improved the processes and outcomes of care in the community allowing specialist teams to branch out into areas they can do justice to. Before you pure Endocrinologists switch off monitoring of thyroxine therapy is in the QuOF. However, incentive schemes can increase inequalities in the delivery of care if practices in affluent areas are more able to respond to the incentives than are those in deprived areas. The authors examined the relation between socioeconomic inequalities and delivered quality of clinical care in the first 3 years of QuOF by analyzing data extracted automatically from clinical computing systems for 7637 general practices in England, data from the UK census, and data for characteristics of practices and patients from the 2006 general medical statistics database. Practices were grouped into equal-sized quintiles on the basis of area deprivation in their locality. The overall levels of achievement, defined as the proportion of patients who were deemed eligible by the practices for whom the targets were achieved, for 48 clinical activity indicators during the first 3 years of QuOF were calculated. The median overall reported achievement was 85.1% (IQR 79.0-89.1) in year 1, 89.3% (86.0-91.5) in year 2, and 90.8% (88.5-92.6) in year 3. In year 1, area deprivation was associated with lower levels of achievement, with median achievement ranging from 86.8% (82.2-89.6) for quintile 1 (least deprived) to 82.8% (75.2-87.8) for quintile 5 (most deprived). Between years 1 and 3, median achievement increased by 4.4% for quintile 1 and by 7.6% for quintile 5, and the gap in median achievement narrowed from 4.0% to 0.8% during this period. Increase in achievement during this time was inversely associated with practice performance in previous years (p<0.0001), but was not associated with area deprivation (p=0.062). These results suggest that QuOF has made a substantial contribution to the reduction of inequalities in the delivery of clinical care related to area deprivation. Before, we put another leaf on QuOFs laurel it is essential to read the balanced accompanying editorial by Barbara Starfield (Lancet 2008;372:692-694) that states do these expensive financial incentive schemes truly reduce suffering? I guess my tune may change if HbA1c ever becomes a performance measure for specialists.

NEXT NEWSLETTER Due out beginning of February 2009 so keep the gossip coming.


Blogger Arutchelvam said...

Could I just pick up on the ACCORD, VADT, ADVANCE results and the
comments in ENDODIABOLOGY please.

Firstly there is twice a suggestion that CV deaths were increased in
VADT. Though the results have not been published, my memory from the
presentations is that there was no different between groups. CV
deaths were numerically higher, but the power was way too low for this
to be meaningful - indeed the very analysis is dangerous.

Secondly ACCORD did not show increased deaths. It was stopped because
of a signal of increased death, which generated a p value of 0.04.
This interim observational test should not be regarded as
statistically significant. Indeed most of us would not have stopped
the study on the basis of the results presented in the paper (and
though tight lipped the investigators seem to think the same).

Thirdly you will have seen the UKPDS extension study published since.
Attached for those who have not. It is important to realize that
ACCORD, ADVANCE and VADT are all consistent with the UKPDS findings,
but of course not statistically significant largely because
underpowered (VADT always was, ACCORD because stopped early). The
consistency and power problems can be seem by considering the headline
CV risk reduction in each study (also given in attached slide):
study HR/RR p
ACCORD 0.90 (0.78, 1.04) NS
VADT 0.86 (0.73, 1.04) NS
Advance 0.94 (0.84, 1.06) NS
UKPDS'08 0.84 (0.75, 0.97) 0.01

Someone will no doubt do a meta-analysis on this lot when VADT appears
in print - my bet it that it will be statistically significant.

Comments, as ever, welcome

September 30, 2008 12:02 AM  

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