editorial

© 2002 Diabetes UK.

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Blackwell Science, Ltd

Continuing education

EDITORIAL

Continuing educationContinuing education

Have you ever had that sinking feeling when your patient asksyou a searching and pertinent question that reveals a distinctgap in your knowledge? Where do you turn for information?Do you have a systematic strategy for searching out an evidence-based answer? If you answered ‘yes’, ‘my old Oxford textbook’and ‘well no, not really’, then you obviously need to read AndrewBooth’s article ‘Finding current best evidence: putting the 4Ssinto searching’

.

Andrew lays out a systematic approach thatallows you, in the minimal time, to gather all the informationyou need, framed around your patient asking you therelative risks and benefits of angioplasty vs. bypass graftingin a diabetic population—you may, of course, have the answerto this one at you fingertips, but even if you do you probablydo not have an overall strategy for finding evidence-basedinformation.

Rayaz Malik’s article may initially seem to be exploring amajor philosophical controversy, but in ‘Life after LIFE’—ourcommentary on the recently published

L

osartan

I

ntervention

f

or

E

ndpoint reduction study—he helps us to define more clearlythe role of angiotensin receptor blocking drugs in the manage-ment of patients with diabetes and hypertension. Should webe using them more often in place of ‘older’ therapies?

How do you give your patients ‘Lifestyle advice’? Do youtorture them with tales of horrendous complications if they do

not comply? Do you give them 10 minutes of advice in the newpatient clinic and then not return to the subject ever again? Ordo you give them sequential motivational interviews and a step-by-step behavioural change programme thereby empoweringyour patient? Perhaps you do none of these—but what is thebest way to ensure that your patient adopts a healthier lifestyle?Chas Skinner and Ian Lawrence guide you towards an improvedapproach to ‘Lifestyle modification in Type 2 diabetes’ in ourClinical Practice Question section.

Have you got experience in using continuous glucosemonitors? Can they help you and your patient improve metaboliccontrol? In ‘Horizons’ Pankaj Vadgama and his co-authorsexplain what is currently available, how they work, theirpotential limitations and what may soon be coming our way.

Finally, why not brush up on the latest literature with theminimum of effort by looking at our ‘What’s new in thejournals?’ section. Here you will find articles on improvingglycaemic control, the prevention of diabetes, obesity and more.

As always,

Continuing Education

aims to serve your needsand answer your questions. We welcome your views, comments,questions and even criticisms. Please contact us at HTTP://www.mediabetes.com

Martin Gibson for the Editorial Panel

LEARNING AND TEACHING SKILLS


Finding current best evidence: putting the 4Ss into searching

A. Booth

School of Health and Related Research (ScHARR), University of Sheffield, UK

A diabetic patient’s questions about the relative risks andbenefits of coronary artery bypass grafting (CABG) vs. per-cutaneous transluminal coronary angioplasty (PTCA) leaveyou feeling uncertain about your knowledge. You havelittle time to update yourself. How would you set aboutdoing so?

Almost instinctively we turn to those sources that arereassuringly familiar or immediately accessible [1]. However,other important criteria, such as the reliability of informationcoupled with its currency, point towards alternative routes inour quest for current best evidence. Our information-seekingstrategy must trade off reliability against ease of access so thatwe look for the highest-level resource available for the problemthat we have identified [2]. Consequently, proponents of

evidence-based healthcare propose a ‘4S’ hierarchical model ofsearching [3] (Box 1).

The ‘4S’ model for finding current best evidence

Top of the evolutionary pyramid are

Systems

, clinical decisionsupport systems with contextualized evidence plugged into‘sockets’ in the individual patient record. In the absence of suchreadily digestible information we turn to Level 2 of the pyramid,

Synopses

. In so doing we recognize that busy clinicians donot have time to take in all the findings from an original studyor systematic review. A brief information-rich synopsis providesa ‘clinical bottom-line’ for a particular patient while supplyingpointers to more detailed evidence for continuing professionaldevelopment when the occasion allows. Proceeding to Level 3we arrive at

Syntheses

(systematic reviews of the literature,

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typically generalizing findings from several studies to a broadrange of patients). Finally, we identify individual

Studies

(randomized controlled trials or other appropriate primarystudy designs, addressing specific patient groups but morelimited in terms of generalizability).

Starting with a well-focused question

Before turning to the sources identified above, we recognizethat our search for evidence will prove fruitless if our questionis poorly specified or inadequately focused. We thereforebreak our scenario down into four components in termsof who (Patient), what (Intervention), compared with what(Comparison Intervention) and how measured (Outcomes)—the so-called PICO anatomy [4]:

Patient:

Cardiovascular disease in diabetes.

Intervention:

CABG.

Comparison:

PTCA.

Outcomes:

Risks and benefits.We must also recognize that, while it is acceptable to note

down abbreviations in our strategy, information retrieval systemsare more readily geared to these terms being entered in full,reducing ambiguity or confusion.

Systems

Although Prodigy guidance may not necessarily be available atour desktop [5] we can access this Department of Health-fundedevidence base via its website (HTTP://www.prodigy.nhs.uk/).Checking the topic list we discover that diabetes is yet to becovered. However, we note a context-sensitive facility to allowus to tailor guidance by age and sex, an invaluable feature onceappropriate information has been collated. As implied earlier,the balance of our efforts now concentrates on Synopses,Syntheses and Studies from our model.

Synopses

First among sources of synopses is

Clinical Evidence

[6].Produced by BMJ Publishing and previously available in 6-monthly book and CD-ROM formats, this invaluable resource

is accessible to NHS staff via the National electronic Libraryfor Health (NeLH) [7]. Relevant evidence is organized insections entitled ‘Cardiovascular disorders’ and the morespecific ‘Cardiovascular disease in diabetes’. Hence we discoverthat subgroup analysis in a randomized controlled trialinvolving 353 people with diabetes found that CABG reducedall-cause mortality more than PTCA at both 5 years [8,9] and7 years [9,10]. Another important source,

UpToDate

(availableon CD-ROM and the Internet at HTTP://www.uptodate.com),provides an evidence-based textbook chapter on ‘Coronaryartery revascularization in diabetes mellitus’. Finally we turnto

Best Evidence

, a collected resource of one-page summariesof major articles printed in the secondary journals

ACPJournal Club

and

Evidence Based Medicine

. Here we learnthat diabetic CABG patients have a greater 5-year survival ratethan those assigned to PTCA (15.1%, confidence interval (CI)1.4–28.9%) [8,11] and that, furthermore, CABG has a trendtowards lower cost [12,13].

Syntheses

With most routes leading to papers from the Bypass Angio-plasty Revascularization Investigation (BARI) trial [8,10,13],we strongly suspect that there is no Cochrane systematicreview on our topic, an impression readily confirmed bychecking the

Cochrane Library

(available free to NHS staffvia the NeLH). Nevertheless, numerous additional sourcesof systematic reviews exist, and searching the NHS Centre forReviews and Dissemination’s

Database of Abstracts of Reviewsof Effectiveness

(DARE),

NHS Economic Evaluation Data-base

(NHS EED) and

Health Technology Assessment

(HTA)database (HTTP://nhscrd.york.ac.uk) yields potentially usefulreferences. Such Syntheses typically cover a broader researchquestion, such as CABG vs. PTCA in general [14], with specificconsideration of subsets of patients, such as those withdiabetes, often subsumed within a larger text.

Studies

At the level of individual Studies we find that more recenttrials or analyses enhance our knowledge by following up

Box 1 The ‘4S’ model for finding current best evidence

Description ExamplesSystems Integrate and concisely summarize research evidence

through linkages to an electronic patient recordProdigy

Synopses Provide exactly enough evidence from reviews or trials to support a clinical action

Clinical Evidence, Best Evidence, Evidence-Based Medicine

Syntheses Summaries based on rigorous searching, explicit review and systematic assembly of evidence

Cochrane Database of Systematic Reviews

Studies Reports of individual trials or studies, usually identified through bibliographical details

Cochrane Controlled Trials Register, Medline Clinical Queries and SUMSearch



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supplementary, more specific questions. For example, does theuse of stents tip the balance back in favour of PTCA? [15], andwhat is the protective effect of prior CABG compared withPTCA in diabetics who suffer an acute myocardial infarction[16,17]? The

Cochrane Controlled Trials Register

(within the

Cochrane Library

) is the largest source of such trials, largereven than Medline, and yields important recent trials [18]. TheClinical Queries interface to the PubMed version of Medlineallows us to restrict subject-relevant articles only to thosewith a rigorous research design [19].

One-stop shops

Increasingly the three lower tiers of the ‘4S’ pyramid areaccessed through a single interface. For example, the TRIPdatabase [20] indexes Internet sources of synopses, synthesesand studies, presenting the results of each within separatecategories. A US alternative, filtering materials from PubMed,the National Guidelines Clearinghouse and several e-textbooks,is SUMSearch [21], provided free by the Society for GeneralInternal Medicine. Ultimately, the National electronic Libraryfor Health will provide a comparable one-stop function forNHS staff [7].

Summary

Experience of using the ‘4S’ approach, both generally andspecifically within this scenario, suggests that the evidence baseis an uneven patchwork [21,22]. Some sources are accessiblevia multiple routes while others are available only through asingle access point. You should therefore apportion a realisticamount of search time, avoiding being too superficial or, atthe other extreme, being sidetracked into non-productive linesof enquiry [20]. Ironically, the optimal trade-off of quality vs.time was provided by

Clinical Evidence

, an instant accesspaper handbook, also available in both CDROM and Internetformats. In contrast, the single most immediately useful sourcewas a Scottish Intercollegiate Guidelines Network (SIGN)guideline [23] accessed third-hand via

SUMSearch

and thenthe US National Guidelines Clearinghouse. This well-referencedsource resolves our scenario thus:

‘Patients with diabetes mellitus undergoing PTCA have ahigher complication rate and a lower procedural success rateand long-term survival compared to non-diabetic patients.Similarly, patients with diabetes mellitus have an increasedrisk of graft occlusion, post operative myocardial infarctionand a decreased survival following CABG. The BARI trialhas suggested that, amongst diabetic patients, CABG wasassociated with better survival than PTCA’ [23].

References

1 Smith R. What clinical information do doctors need?

BMJ

1996;

313

:1062–1068.

2 Shaughnessy AF, Slawson DC, Bennett JH. Becoming an information

master: a guidebook to the medical information jungle.

J Fam Pract

1994;

39

: 489–499.3 Haynes RB. Of studies, syntheses, synopses and systems: the ‘4S’

evolution of services for finding current best evidence.

ACP J Club

2001;

134

: A11–A13.4 Richardson WS. The well-built clinical question: a key to evidence-

based decisions.

ACP J Club

1995;

123

: A12–A13.5 Purves IN. PRODIGY: implementing clinical guidance using

computers.

Br J General Prac

1998;

48

: 1552–1553.6 Godlee F, Smith R, Goldmann D. Clinical evidence.

BMJ

1999;

318

:1570–1571.

7 Muir Gray JA, Lusignan S. National Electronic Library for Health.

BMJ

1999;

319

: 1476–1479.8 The Bypass Angioplasty Revascularization Investigation (BARI)

Investigators. Comparison of coronary bypass surgery with angio-plasty in patients with multivessel disease.

N Engl J Med

1996;

335

:217–225.

9 Sudlow C, Lonn E, Pignone M, Ness A, Rihal C. Coronary PTAversus CABG for multivessel disease.

Clin Evidence

2002;

7

: 136–138.

10 The Bypass Angioplasty Revascularization Investigation (BARI)Investigators. Seven-year outcome in the Bypass AngioplastyRevascularization Investigation (BARI) by treatment and diabeticstatus.

J Am Coll Cardiol

2000;

35

: 1122–1129.11 Malenka DJ. Bypass surgery and angioplasty led to similar 5-year

mortality rates in multivessel coronary artery disease.

Evidence-Based Med

1997;

2

: 21.12 Schulmann KA. The 5-year cost of coronary angioplasty was lower

than that of bypass surgery only in patients with 2-vessel coronarydisease.

ACP J Club

1997;

127

: 25.13 Hlatky MA, Rogers WJ, Johnstone I, Boothroyd D, Brooks MM,

Pitt B

et al

. For the Bypass Angioplasty Revascularization Investi-gation (BARI) Investigators. Medical care costs and quality oflife after randomization to coronary angioplasty or coronary bypasssurgery.

N Engl J Med

1997;

336

: 92–99.14 Johansson SR, Brorsson B, Bernstein SJ. Coronary artery bypass graft

and percutaneous transluminal coronary angioplasty—a literaturereview and ratings of appropriateness and necessity. Swedish Councilon Technology Assessment in Health Care (SBU), 1994.

15 Huynh T, Eisenberg MJ, Deligonul U, Tsang J, Okrainec K,Schechter D

et al.

Coronary stenting in diabetic patients: results fromthe ROSETTA registry.

Am Heart J

2001;

142

: 960–964.16 Dunlap J.

Type of revascularization affects survival in diabeticswith acute MI

[Infopoem] Available at: http://www.infopoems.com/poems/jc070008.htm

17 Detre KM, Lombardero MS, Brooks MM, Hardison RM, Holubkov R,Sopko G

et al.

The effect of previous coronary-artery bypass surgeryon the prognosis of patients with diabetes who have acute myocardialinfarction.

N Engl J Med

2000;

342

: 989–997.18 Kurbaan AS, Bowker TJ, Ilsley CD, Sigwart U, Rickards AF.

Difference in the mortality of the CABRI diabetic and nondiabeticpopulations and its relation to coronary artery disease and therevascularization mode.

Am J Cardiol

2001;

87

: 947–950.19 Booth A, O’Rourke AJ. SUMSearch and PubMed: 2 Internet-based

evidence-based medicine tools.

ACP J Club

2000;

132

: A16.20 Booth A. Evidence based medicine. In: Mackenzie B.

Medicine andthe Internet

, 3rd edn. Oxford: Oxford University Press, in press2002.

21 Booth A. Sifting for evidence. A guide to EBHC on the Internet. In:Kiley R, ed.

A Guide to Healthcare Resources on the Internet.

London: Royal Society of Medicine Press, 2001; 11–18.22 Booth A, O’Rourke AJ EBM Notebook: searching for evidence:

principles and practice.

Evidence-Based Med

1999;

4

: 133–136.23 Scottish Intercollegiate Guidelines Network. Coronary revasculari-

sation in the management of stable angina pectoris. A nationalclinical guideline. Edinburgh: SIGN, 1998.



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CLINICAL PRACTICE QUESTION


Lifestyle modification in Type 2 diabetes

T. C. Skinner and I. G. Lawrence

University Hospitals of Leicester NHS Trust, Leicester, UK

Consider the following

A 60-year-old man of Indo-Asian origin is referred withrecently diagnosed Type 2 diabetes. He is obese, body massindex being 32 kg/m

2

, and readily admits to a sedentary life-style, using his car whenever possible and taking no regularphysical exercise. His family are similarly overweight, and heis not unduly concerned by his weight, apart from havingheard some of the treatments for diabetes may make him moreoverweight. He is also hypertensive, blood pressure being154/86, and has dyslipidaemia (total cholesterol 5.6 mmol/ l,HDL-cholesterol 0.7 mmol/ l and triglycerides 3.5 mmol/ l).His HbA

1c

is 8.0% (reference range 4.0–6.1%), and hisgeneral practitioner presents his case to you, with the followingquestions:• Have lifestyle modification interventions been shown tomake any long-term differences regarding glycaemic control,weight and cardiovascular parameters in Type 2 Diabetes?• If so, which models have been shown to be effective andwould be feasible in routine clinical practice?• What are the core requirements of a lifestyle modificationprogramme, and have any been customized to ethnic minoritygroups?• Should therapeutic interventions be delayed, or run inparallel with a lifestyle modification programme?

Long-term impact of lifestyle modification interventions in Type 2 diabetes

Most guidelines on the management of Type 2 Diabetes incor-porate dietary modification and physical activity goals, but itis important to consider whether there is any robust evidencethat interventions delivered in a real-world context can makea long-term difference. The difficulty is that the vast majorityof published psycho-educational interventions seem to take aquick fix or inoculation approach to lifestyle modification.That is, they provide relatively brief interventions that aresupposed to change a patient’s lifestyle completely. Unfortunately,we know this does not really work, as most people can stick toa diet for a short time, but then revert back to their old lifestyle.

To achieve a sustainable change in lifestyle, a step-by-stepapproach is required. Only a small number of studies havedelivered lifestyle modification over an extended period and aspart of routine care, but they do offer us some positive modelsto follow. In a study for newly diagnosed diabetic patientsreceiving Intensive Health Education over a 5-year period (25contacts 1:1 and/or group), the intervention group had a lower

fasting blood glucose (8.71 vs. 9.27 mmol/ l,

P

< 0.01), lowerblood pressure (143/87 vs. 154/92 mmHg,

P

< 0.01) and lowerdeath rates (30.6 per 1000 vs. 46.2 per 1000,

P

< 0.01), whilstbeing on fewer hypoglycaemic medications (28% vs. 47%,

P

< 0.01) [1]. Meanwhile, in another study patients completeda short computerized questionnaire at their usual clinic appoint-ments, focusing on their key barriers to dietary self-managementand saturated fat intake [2,3]. This was used to inform goal-setting and problem-solving for changes in eating patterns,and demonstrated reduced serum cholesterol equivalent to oralmedication.

The recent publications demonstrating diabetes preventionin Finnish and North American patients with impaired glucosetolerance have demonstrated the potential benefits of lifestylemodification interventions, but there is scope for furtherstudies in Type 2 diabetes. The United Kingdom ProspectiveDiabetes Study (UKPDS) of course demonstrated that dietarymodification alone was not an effective long-term interventionfor maintaining tight glycaemic control, but this was also thecase for sulphonylurea, metformin and insulin monotherapy[4]. However, it should be noted that in the UKPDS, dietmodification was systematically applied only in the earlystages, again following the inoculation model of lifestylemodification. Furthermore, and just as importantly, medicationtaking and monitoring of diabetes need to be as much of afocus of behaviour change approaches as diet and exercise,given the well-documented low concordance rates [5,6].

Effectiveness and feasibility of different models in routine clinical practice

The literature demonstrates that using a model will result inbetter outcomes than using nothing to guide educational inter-vention, at least in adolescents, but this has not been overtlytested in adults with Type 2 diabetes [7]. Unfortunately thereare no head-to-head evaluations of different models that weare aware. However, there are several key models which havereasonable evidence for their effectiveness (though not neces-sarily in diabetes): cognitive behavioural [8], motivationalinterviewing [9], transtheoretical model (stages of change)[10], behaviour change counselling [11], social learning theory[12] and ‘empowerment’ [13]. The first three of these modelsare quite complex, in that they require a specific set oftechniques to be used dependent on the nature of the assessmentof the patient, and require a great deal of training to be deliveredeffectively. The second three models share a great deal interms of their underlying approach to the issue of lifestylemodification, and focus on the commonality in the vast arrayof effective lifestyle modification models.



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The core requirement of a lifestyle modification programme

There are three areas that need to be considered when lookingat the core requirements of an effective lifestyle modificationprogramme. The first is that the programme is integrated inroutine diabetes care and is an ongoing process. Lifestylemodifications are usually only sustained if they are achieved ina step-by-step process focusing on one or two steps at a time,and thus take time and need continued support.

The second core area is that of the philosophical approachadopted by the health care professional. Where the profession-als thinks they know what is best for the patient, tell the patientwhat they should do and how they should do it, anticipate thepatient’s barriers to change and attempts to tell the patienthow to solve these, little change seems to be achieved. How-ever, where the professionals engage the patient in discussionabout their health, what the patient wants to achieve and howthey want to achieve it, help the patient explore the barriers thepatient anticipates and support the patient’s problem-solvingefforts, then behaviour modification is far more likely. Thishas been termed an ‘empowerment’ philosophy to diabetescare and behaviour change. Getting the patient engaged,involved and investing in their own diabetes care are the keyissues. A simple way to remember this is ARCH: give patientsAUTONOMY where possible, RESPECT their views andfeelings, be CURIOUS about how they think and feel, and beHONEST, gently, about what you think and feel.

The third area is how do you do this, and focusing on import-ance, confidence and competence is a good start. Importanceis about exploring both your own and the patient’s viewsabout the importance of diabetes control and lifestyle issues. Ifit is not important then no change will occur. Talking aboutcomplications and scaring the patient is not a discussion aboutimportance. To engage someone in the need for change, theyneed to understand how things like glycaemic control, bloodpressure and dyslipidaemia are related to complications,and how the different lifestyle recommendations may make adifference. Importance is really focusing on the volitional orwanting element of change: however, wanting is not enough,and we need to support patients in turning these wants intoactions. This is where confidence and competence come in.Several studies now show that just getting individuals tospecify the what, where, when and how of behaviour results ina significant increase in the likelihood of their doing it [14].So help patients be clear about what they need to do to influencetheir risk factors. However, life gets in the way and barrierswill occur. Patients require help to be more confident, one ofthe strongest predictors of behaviour change, and this includesthe anticipation of barriers to change and finding ways toproblem solve these.

If the suggested approach is adopted, the lifestyle modificationprogramme, whether developed 1:1 or in groups, does notneed customizing to ethnic minority groups. It works as it is,although you may need the people delivering the programme

to speak the same language as the patient, but that is all, andeven this can be overcome.

The role of therapeutic interventions in a lifestyle modification programme

The historical management of Type 2 diabetes starts withlifestyle modification, and add medication when this does notwork. The current evidence base does not provide clearsupport for this, and furthermore, the historical approach givesother messages to the p atient. He can gain the perception thatType 2 diabetes is a mild condition, especially when accom-panied by similar messages from health care professionals, andculturally prevalent beliefs in the ethnic majority and minoritythat it is not a serious condition. Moreover, the issue of failureon diet and exercise (or oral hypoglycaemic therapy) can drivea whole host of negative beliefs about the self and contributeto depressed mood, which is a major barrier to behaviourchange.

An individual decision also has to be made as to how longto give lifestyle modification before deciding it is not working,and how to determine that it is not working. Otherwise thereis a risk of the diabetes causing macrovascular and micro-vascular damage, or the development of depression preventinglifestyle change. The commencement of medication of coursedoes not mean the cessation of lifestyle modification. Thereare a lot of conflicting and confusing explicit and implicitmessages within these scenarios, even if just one health care pro-fessional is involved, without bringing in the multidisciplinaryteam.

The roles of lifestyle modification and the aggressive treatmentof glycaemic control, hypertension and dyslipidaemia inType 2 diabetes are thus not mutually exclusive, but comple-mentary. The likelihood is that increasing numbers of patientswill receive metformin, angiotensin converting enzymeinhibitors and statins early in the course of their Type 2diabetes on the basis of large randomized controlled trialspublished over recent years, and successful lifestyle modifica-tion thus incorporates diet, exercise and medications.

The key to resolving these issues is to be honest with thepatient, and be curious about how they would like to managethings, and respect their answers. The patient needs to be helpedto make informed choices about their condition, as ultimatelythey are the ones that are really in charge and control of it,whether through action or inaction.

Practice points

• Few studies have investigated long-term, sustained lifestylemodification interventions in established Type 2 diabetes.• Medication taking and monitoring of diabetes need be asmuch a focus of behaviour change as dietary modification andincreased exercise.• The literature demonstrates no one model of lifestylemodification to be superior to the others.



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• The core requirements of a lifestyle modification programmeare a sustained, step by step approach, an ‘empowered’ patientand a focus on what is important, developing the patient’sconfidence and competence.• A lifestyle modification programme and active treatment ofglycaemic control, hypertension and dyslipidaemia are notmutually exclusive, but complementary.• Successful lifestyle modification incorporates diet, exerciseand therapeutic interventions.

References

1 Hanefeld M, Fischer S, Schemechel H, Rothe G, Schulze J, Dude H

et al.

Diabetes intervention study: multi-intervention trial in newlydiagnosed NIDDM.

Diabetes Care

1991;

14

: 308–317.2 Glasgow RE, Toobert DJ, Hampson SE. Effects of a brief office-based

intervention to facilitate diabetes dietary self-care management.

Diabetes Care

1996;

19

: 835–842.3 Glasgow RE, La Chance P, Toobert DJ

et al.

Long term effects andcosts of brief behavioural dietary intervention for patients withdiabetes delivered from the medical office.

Patient EducationCounselling

1997;

23

: 175–184.4 UKPDS Group. Intensive blood-glucose control with sulphonylureas

or insulin compared with conventional treatment and risk ofcomplications in patients with type 2 diabetes (UKPDS 33).

Lancet

1998;

352

: 837–853.5 Donnan PT, MacDonald TM, Morris AD for the DARTS/MEMO

Collaboration. Adherence to prescribed oral hypoglycaemic medica-tion in a population of patients with Type 2 diabetes: a retrospectivecohort study.

Diabet Med

2002;

19

: 279–284.6 Evans JMM, Newton RW, Ruta DA, MacDonald TM, Stevenson RJ,

Morris AD. Frequency of blood glucose monitoring in relationto glycaemic control: observational study with diabetes database.

BrMed J

1999;

319

: 83–86.7 Hampson SE, Skinner TC, Hart J, Storey L, Gage H, Foxcroft D

et al.

Behavioural interventions for adolescents with type 1 diabetes:how effective are they?

Diabetes Care

2000;

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: 1416 –1422.8 Campbell EM, Redman S, Moffitt PS, Sanson-Fisher RW. The

relative effectiveness of educational and behavioral instructionprograms for patients with NIDDM: a randomized controlled trial.

Diabetes Educator

1996;

22

: 379–386.9 Smith DE, Kratt PP, Heckemeyer CM, Mason DA. Motivational

interviewing to improve adherence to a behavioral weight-controlprogram for older obese women with NIDDM.

Diabetes Care

1997;

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: 52–54.10 Ruggiero L. Helping people with diabetes change behaviour: from

theory to practice.

Diabetes Spectrum

2000;

13

: 125–132.11 Rollnick S, Mason P, Butler C.

Heath Behaviour Change: a Guide forPractitioners.

London: Churchill Livingstone, 1999.12 Bandura A. Health promotion from the perspective of social cogni-

tive theory.

Psychol Health

1998;

13

: 623–650.13 Skinner TC, Cradock S. Empowerment: what about the evidence?

Pract Diabetes Int

2000;

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: 91–95.14 Orbell S, Hodgkins S, Sheeran P. Implementation and the theory

of planned behaviour.

Personality Social Psychol Bull

1997;

23

:945–954.

Prevention of cardiovascular morbidity with angiotension receptor blockade: life after LIFE

With the impending implementation of the DiabetesNational Service Framework you consider it is time toreview your treatment guidelines and protocols for hyper-tension management. You discover that these were lastupdated in line with the findings of UKPDS and the BritishHypertension Society guidelines issued in 1999. Whilstmost drug types are represented in your portfolio, youfind that angiotensin-II receptor antagonists are barely men-tioned and their role poorly defined. Should you now beusing them more often? Should you be using them in place ofor before the addition of other drug classes? And, are thereany particular subgroups of patients with diabetes that mightbenefit?

Aim

To compare a selective angiotensin-II type-1-receptorantagonist with a

β

-blocker to reduce cardiovascular morbidityand mortality in people with diabetes, hypertension and leftventricular hypertrophy.

Design

Planned subgroup analysis of a randomized controlledtrial.

Setting

International (mainly Nordic, USA).

Patients

One thousand one hundred and ninety-five patientswith diabetes, essential hypertension and signs of left ventri-cular hypertrophy on electrocardiograms, followed up for at

least 4 years (average of 4.7 years). Mean blood pressure afterplacebo run-in was 177/96 mmHg.

Intervention

Losartan or atenolol. Both drugs were titrated from50 mg to a maximum of 100 mg to reduce blood pressure tobelow 140/90 mmHg. Other anti-hypertensive treatments (notincluding the study drug classes) were also permitted. Doubledummy blinding of the two study treatments was used.

Main outcome measures

The primary outcome was a com-posite of cardiovascular death, myocardial infarction and stroke.Other outcome measures included all cause mortality, hospitaladmission and revascularization.

Main results

A similar level of blood pressure control wasachieved in the two groups (losartan 146/79, atenolol 148/79 mmHg). The primary endpoint occurred in 103/586 (18%)of the losartan group and 139/609 (23%) of the atenololgroup, giving a relative risk of 0.76 (95% confidence interval0.58–0.98). Total mortality was 11% and 17%, a relative riskof 0.61 (0.45–0.84).

Conclusion

Losartan was more effective than atenolol inreducing cardiovascular morbidity and mortality, and allcause mortality in patients with diabetes, hypertension and leftventricular hypertrophy. There appears to be additionalbenefit beyond that due to the blood pressure reduction.



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Commentary

R. A. Malik

Department of Medicine, Manchester Royal Infirmary, Manchester, UK

Until recently, no morbidity–mortality study had examinedthe effects of ‘newer’ drugs, like angiotensin-converting enzymeinhibitors, calcium antagonists, and α-blockers comparedwith ‘old’, but well-proven, thiazide diuretics, and β-blockers.The prospective and randomized clinical trials, CAPPP [1],STOP-2 [2], NORDIL [3], INSIGHT [4], and one arm ofALLHAT [5], with a total of approximately 58 000 middle-agedor elderly hypertensive patients, have now been published.In predominantly non-diabetic populations they demonstratethat the primary outcome, composite cardiovascular (CV) death,cerebral stroke, and myocardial infarction, or composite fatalcoronary heart disease and myocardial infarction, is the same,irrespective of the drug used.

However, the publication of results from vascular risk trialsof patients with diabetes should lead us all to rethink ourcurrent choice of therapies offered and implemented in this high-risk group of patients. Thus recommendations for diabeticpatients should be based on evidence from clinical trialsconducted in diabetic patients, as opposed to extrapolationfrom other patient populations.

The Losartan Intervention for Endpoint reduction (LIFE)study provides unique comparative data against standardcurrently recommended therapy [6]. Patients (n = 1195) withdiabetes, hypertension and electrocardiographic evidence ofleft ventricular hypertrophy were assigned to therapy witha losartan (n = 586) or atenolol (n = 609) based therapy.Patients were followed up over 4.7 ± 1.1 years to comparethe effects of each treatment regime on primary outcomes:CV morbidity and mortality (CV death, stroke, or myocardialinfarction). Mean blood pressure fell significantly in bothintervention groups from 177/96 (14/10) mmHg at baselineto 146/79 (17/11) mmHg in the losartan group, and 148/79(19/11) mmHg in the atenolol group. The primary end-pointoccurred in significantly less patients assigned to losartan(103) compared with atenolol (139); relative risk 0.76 (95%confidence interval (CI) 0.58–0.98; P = 0.031). All causemortality was significantly less in the losartan (63) comparedwith the atenolol (104) groups (0.61 (0.45–0.84), P = 0.002).CV deaths were significantly less frequent in the losartan(38) compared with the atenolol (61) group (relative risk0.63 (0.42–0.95), P = 0.028). For an apparently equal degreeof blood pressure reduction losartan was more effective thanatenolol in reducing CV morbidity and mortality in diabeticpatients with hypertension and left ventricular hypertrophy(LVH). Added benefits include a reduction in clinical albuminuria(11% to 8%) in the losartan group compared with no benefitwith atenolol (12% to 11%). Additionally, losartan was sig-nificantly more effective at reversing LVH when assessed

using the Cornell voltage-duration product (P < 0.0001) or theSokolow–Lyon voltage criteria (P < 0.0001).

However, there are limitations to the generalization andapplication of these results to all diabetic patients, as thepatients participating in the trial were middle aged to elderly(age 67.4 (6.8)). They were predominantly white (86%) andonly a minority were black (11%), Hispanic (2%) and Asian(0.9%). At recruitment 24% had previous coronary arterydisease (CAD), 12% cardiovascular disease (CVD) and 7%peripheral vascular disease (PVD), 5% had atrial fibrillation(AF) and 18–22% isolated systolic hypertension (ISH). Fur-thermore, at baseline only 56% of the patients were on therapyto control hyperglycaemia (44% oral sulphonylurea, biguanideor both and 16% were on insulin). Of the patients not on therapy44% are stated to have been given ‘non-pharmacological’treatment; quite what this was is not stated. Twenty-threepercent began to receive therapy during the trial and 21%remained treatment free. Surprisingly 27% of patients in thelosartan group and 32% in the atenolol group were off studydrugs at the end-point or at the end of follow-up.

Confounding factors may have been the initial rise in bloodglucose in the atenolol group, which almost reached signific-ance compared to the losartan group (P = 0.087).

There was also a 3-mmHg greater reduction in systolicblood pressure and 4% more patients had a systolic bloodpressure < 140 and 3% more had a diastolic BP < 90 mmHgin the losartan compared with the atenolol group.

Nevertheless, these results echo the findings of several recentlarge studies that appear to show benefit beyond achievinga simple reduction in blood pressure using ACE inhibitors(MICROHOPE [7]). Angiotensin receptor blockers (ARBs)will decrease proteinuria [8] and slow progression of renaldisease [9,10] in Type 2 diabetic patients when compared withregimens that do not include an ARB or an ACE inhibitor(Irbesartan Type II Diabetes with Microalbuminuria (IRMAII) [8], Reduction of Endpoints in NIDDM with the Angio-tensin II Antagonist Losartan (RENAAL) [9], Irbesartan TypeII Diabetic Nephropathy Trial (IDNT) [10]).

Together, these results argue for a mechanistic and evidence-based approach to the choice of therapy in patients withdiabetes. Therefore, an ACE-inhibitor or ARB, usually with adiuretic, can be considered as preferred therapy in hypertensivediabetic patients, particularly those with evidence of incipientor established nephropathy.

References1 Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A

et al. Effect of angiotensin-converting-enzyme inhibition comparedwith conventional therapy on cardiovascular morbidity and


© 2002 Diabetes UK. Diabetic Medicine, 19, 1–14

8 Continuing education

mortality in hypertension: the Captopril Prevention Project (CAPPP)randomised trial. Lancet 1999; 353: 611–616.

2 Hansson L, Lindholm LH, Ekbom T, Dahlof B, Lanke J, Schersten Bet al. Randomised trial of old and new antihypertensive drugs inelderly patients: cardiovascular mortality and morbidity the SwedishTrial in Old Patients with Hypertension-2 study. Lancet 1999; 354:1751–1756.

3 Hansson L, Hedner T, Lund-Johansen P, Kjeldsen SE, Lindholm LH,Syvertsen JO et al. Randomised trial of effects of calcium antagonistscompared with diuretics and beta-blockers on cardiovascularmorbidity and mortality in hypertension: the Nordic Diltiazem(NORDIL) study. Lancet 2000; 356: 359–365.

4 Brown MJ, Palmer CR, de Castaigne A, Leeuw PW, Mancia G,Rosenthal T et al. Morbidity and mortality in patients randomised todouble-blind treatment with a long-acting calcium-channel blockeror diuretic in the International Nifedipine GITS study: Interventionas a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356:366–372.

5 Furberg CD, Psaty BM, Pahor M, Alderman MH. Clinical implicationsof recent findings from the Antihypertensive and Lipid-LoweringTreatment To Prevent Heart Attack Trial (ALLHAT) and other studiesof hypertension. Ann Intern Med 2001; 135: 1074–1078.

6 Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire Uet al. The LIFE Study Group. Cardiovascular morbidity and mortalityin patients with diabetes in the Losartan Intervention For Endpointreduction in hypertension study (LIFE): a randomised trial againstatenolol. Lancet 2002; 359: 1004–1010.

7 Heart Outcomes Prevention Evaluation Study Investigators. Effectsof ramipril on cardiovascular and microvascular outcomes in peoplewith diabetes mellitus: results of the HOPE study and MICRO-HOPEsubstudy. Lancet 2000; 355: 253–259.

8 Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S,Arner P. Irbesartan in Patients with Type 2 Diabetes and Micro-albuminuria Study Group. The effect of irbesartan on the develop-ment of diabetic nephropathy in patients with type 2 diabetes. N EnglJ Med 2001; 345: 870–878.

9 Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE,Parving HH et al. RENAAL Study Investigators. Effects of losartanon renal and cardiovascular outcomes in patients with type 2 diabetesand nephropathy. N Engl J Med 2001; 345: 861–869.

10 Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JBet al. Collaborative Study Group. Renoprotective effect of theangiotensin-receptor antagonist irbesartan in patients withnephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860.

What’s new in the journals?

Glycaemic control

Pickup J, Mattock M, Kerry S. Glycaemic control with continuoussubcutaneous insulin infusion compared with intensive insulininjections in patients with type 1 diabetes: meta-analysis ofrandomised controlled trials. BMJ 2002; 324: 705.

A meta-analysis of pump therapy vs. multi-injection regime forType 1 diabetes (600 patients in total). Pump therapy was bet-ter (HbA1c approx. 0.5% lower and insulin dose 7.6 U/dayless), but authors concluded that the differences were smalland that pumps should be reserved for patients with ‘specialproblems’. From the electronic responses to this article it seemsthat many patients do not agree with the latter statement.

Kaufman FR, Gibson LC, Halvorson M, Carpenter S, Fisher LK, Pituk-cheewanont P. A pilot study of the continuous glucose monitoringsystem: clinical decisions and glycaemic control after its use in paedi-atric type 1 diabetic subjects. Diabetes Care 2001; 24: 2030–2034.

This study looked at the use of the continuous glucosemonitoring system (CGMS) (MiniMed, Sylmar, CA, USA) ina specific group of patients, i.e. children either with suboptimalHbA1c as defined by a HbA1c > 8% where hypoglycaemicepisodes were severe, or nocturnal hypoglycaemia with a HbA1c

of < 8%. Forty-seven children were studied with a mean HbA1c

of 8.6% and a mean age of 11.8 years. The youngest child wasonly 2.7 years. The aim of the study was to look at whether theuse of a glucose sensor helped to make or change managementso that HbA1c could be improved. Results show that 3 monthsbefore, and then at 6 months post the census study there was asignificant reduction in HbA1c which was statistically significantat 0.2% but in clinical terms is probably only a modest reduc-tion. Disappointingly, any changes in hypoglycaemic episodesfollowing the glucose sensor are not reported. Another practicalarea of interest was that a mean of three recommendations was

made per patient following the sensor study. Twenty-two per-cent of the children were found to have evidence of the dawnphenomenon and around 25–32% of patients were found tohave post-prandial hyperglycaemia each mealtime. There wasa mean of 1.2 asymptomatic nocturnal hypoglycaemic events.The other interesting fact was that these young children wereall able to tolerate the glucose sensing study.

Wright A, Burden ACF, Paisey RB, Cull CA, Holman RR for the UKProspective Diabetes Study Group. Sulphonylurea inadequacy.Efficacy of addition of insulin over 6 years in patients with type 2diabetes in the UK Prospective Diabetes Study (UKPDS 57). DiabetesCare 2002; 25: 330–336.

UKPDS 57 evaluates the effectiveness of the addition ofinsulin when maximum sulphonylurea therapy proves inadequate(defined as the fasting plasma glucose remaining > 6.0 mmol/ l)in patients with Type 2 diabetes. Over 6 years follow-up, 53%of the sulphonylurea-treated patients required additional insu-lin therapy. Median HbA1c was lower in the sulphonylurea± insulin group compared with the insulin alone group (6.6%vs. 7.1%, P = 0.0066), and more patients achieved a HbA1c

< 7.0% (47% vs. 35%, P = 0.011). There were also fewer majorhypoglycaemic episodes in the sulphonylurea ± insulin group(1.6% vs. 3.2% per annum, P = 0.017), while weight gain wassimilar. The early addition of insulin to maximum sulphonylureatherapy thus improves glycaemic control, without increasinghypoglycaemia or promoting weight gain.

Jones KL, Arslanian S, Peterokova VA, Park J-S, Tomlinson MJ. Effectof Metformin in paediatric patients with type 2 diabetes: arandomized controlled trial. Diabetes Care 2002; 25: 89–94.

This paper looks at the use of Metformin in children withType 2 diabetes and was performed in the USA and Eastern


Continuing education 9


Europe. It is of interest that there are increasing numbers ofsubjects of children with Type 2 diabetes reported world-wide,and an increase recently reported in the UK. They looked atsubjects aged between 10 and 16 years, who had a fastingglucose of > 7 but < 13.3, and an HbA1c which was > 7%. Theywere C-peptide-positive and had a body mass index (BMI)> 50th percentile for age. Eighty-two subjects were included inthis randomized control trial where the comparator was pla-cebo. Metformin reduced fasting glucose by 2.4 mmol, andHbA1c at the end of the 16-week study was lower in those onMetformin at 7.5% vs. 8.6% (P < 0.001). Fourteen percent ofthe Metformin group compared with 10% of the placebogroup discontinued before the end of the study. GI upset wasreported in 25% of the Metformin subjects compared with12% of placebo. The dose of Metformin was titrated up to 2 g/day. This is the first RCT of the safety and efficacy of Met-formin in children, and is reassuring in that there were no casesof lactic acidosis. The efficacy appeared to be similar to thatreported in adult subjects and the safety profile similar to thatas reported in adult subjects.

Diabetes Prevention

Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K et al.Prevalence of impaired glucose tolerance among children andadolescents with marked obesity. N Engl J Med 2002; 346: 802–810.

In a study of 167 children and adolescents whose body massindices lay above the upper 95% confidence limit for their age,one-quarter had impaired glucose tolerance and 4% of theadolescents had unsuspected Type 2 diabetes. These extremelyobese young people were markedly insulin-resistant and thosewith diabetes had β-cell failure. This study is important in thatit documents a strong relationship between childhood obesityand diabetes, with its attendant cardiovascular risks, and high-lights the need for public health efforts to prevent diabetes bya healthy lifestyle to start in early life.

Diabetes Prevention Program Research Group. Reduction in theincidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med 2002; 346: 393–403.

This study randomized 3234 patients with impaired glucosetolerance to a lifestyle-modification programme aiming tohelp them lose at least 7% of body weight, metformin 850 mgtwice-daily, or placebo. Over nearly 3 years of follow-up,incidence rates of diabetes (cases per 100 patient years) were11.0 with placebo, 7.8 with metformin, and 4.8 with lifestylechange. Lifestyle change was significantly more effective thanmetformin, which was significantly more effective than placebo.Over 3 years of follow-up, the NNT for lifestyle change was 7,and 14 for metformin. Fifty percent of patients initiallyachieved the target weight loss, and 38% managed to sustainit; some two-thirds of patients in the lifestyle group were sus-taining 2.5 h of exercise per week. These results are promisingfor both pharmacological and lifestyle approaches to diabetesprevention.

Obesity

Serrano-Rios M, Melchionda N, Moreno-Carretero E. Role ofsibutramine in the treatment of obese type 2 diabetic patientsreceiving sulphonylurea therapy. Diabet Med 2002; 19: 119–124.

In a randomized, placebo-controlled study of 134 obese Type2 diabetic patients, those treated with sibutramine lost a mean4.5 kg body weight compared with 1.7 kg on placebo. Waistcircumference was also reduced by sibutramine. There was nosignificant difference in the fall in HbA1c. This study confirmsthat sibutramine, combined with moderate calorie restriction,aids weight reduction even in patients on sulphonylurea,although this did not translate into a worthwhile ameliorationof glycaemic control.

Dixon JB, O’Brien PE. Health outcomes of severely obese type 2 diabeticsubjects 1 year after laparoscopic adjustable gastric banding.Diabetes Care 2002; 25: 358–363.

Fifty consecutive patients (17 men, 33 women) with morbidobesity and Type 2 diabetes were evaluated 12 months afterlaparoscopic adjustable gastric band surgery. Weight fell from137 kg to 110 kg, and body mass index from 48.2 kg/m2 to38.7 kg/m2. There was remission of diabetes in 64% of patients,and improvement in glycaemic control in another 26% patients.HbA1c was 7.8% preoperatively and fell to 6.2% at 12 months.There were also improvements in various cardiovascular riskfactors, sleep, depression, appearance evaluation and health-related quality of life. The complication rate of surgery wasacceptable, and laparoscopic weight-loss surgery should beconsidered as an early intervention for the morbidly obesepatient with Type 2 diabetes.

Pregnancy

Howorka K, Pumprla J, Gabriel M, Feiks A, Schlusche C, Nowotny Cet al. Normalization of pregnancy outcome in pregestational diabetesthrough functional insulin treatment and modular out-patienteducation adapted for pregnancy. Diabet Med 2001; 18: 965–972.

This unrandomized study compared the outcomes of 76diabetic pregnancies treated with extremely intensive educationand supervision starting before pregnancy against historicalcontrol data. Glycaemic control was excellent, as were pregnancyoutcomes. This study adds to the evidence that excellentcontrol improves outcome, though at a level of intensity thatwould be hard to implement widely.

Simmons D, Thompson CF, Conroy C, Scott DJ. Use of insulin pumps inpregnancies complicated by Type 2 diabetes and gestational diabetesin a multiethnic community. Diabetes Care 2001; 24: 2078–2082.

This is an important study for those who manage increasingnumbers of women with gestational diabetes or Type 2 diabetesin those areas where there is a large South Asian population.This study reports the use of an insulin pump in women witheither gestational diabetes or Type 2 diabetes who are insulin-resistant and have difficulty in maintaining adequate glycaemiccontrol. Their criteria for using pump therapy were in womenwho were using > 100 U of insulin as their basal night-timedose, or their preprandial injections failed to provide adequate




control, or if fetal growth remained accelerated despiteoptimal conventional insulin therapy. Their experience in 30such women showed that no women had severe hypoglycaemia.Nearly 80% had improved glycaemic control within 1–4 weeks,and potentially for this difficult to manage group of women,insulin pump therapy would seem to be a reasonable andsafe option.

Cardiovascular

Roffi M, Chew DP, Mukherjee D, Bhatt DL, White JA, Heeschen C et al.Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabeticpatients with non-ST segment elevation acute coronary syndromes.Circulation 2001; 104: 2767–2771.

This meta-analysis evaluated 6458 diabetic patients enrolledin the six large-scale platelet glycoprotein (GP) IIb/IIIa inhibi-tor trials of intervention in non-ST segment elevation acutecoronary syndromes. Platelet GP IIb/IIIa inhibition wasassociated with a reduction in mortality at 30 days from6.2% to 4.6% in diabetic patients, whereas there was nosurvival benefit in 23 072 patients without diabetes (3.0% vs.3.0%). Among 1279 patients having percutaneous coronaryintervention during the index hospitalization, these agentswere associated with a fall in 30-day mortality from 4.0%to 1.2%. The platelet GP IIb/IIIa inhibitors should be stronglyconsidered in diabetic patients with acute coronary syndromes.

Schrier RW, Estacio RO, Esler A, Mehler P. Effects of aggressive bloodpressure control in normotensive type 2 diabetic patients on albumi-nuria, retinopathy and strokes. Kidney Int 2002; 61: 1086–1097.

The Appropriate Blood Pressure Control in Diabetes (ABCD)study compared the effect of intensive vs. moderate diastolicblood pressure control in 480 patients with Type 2 diabetes,who were deemed normotensive (BP < 140/90 mmHg). Over5.3 years follow-up, the mean BP was 128/75 mmHg in theintensive group, and 137/81 mmHg in the moderate group.There was no change in creatinine clearance (P = 0.43), butless patients progressed from normoalbuminuria to micro-albuminuria (P = 0.012) and also from microalbuminuria toovert albuminuria (P = 0.028) in the intensive group. Therewas less progression of diabetic retinopathy (34% vs. 46%,P = 0.019), but no difference in the development of retino-pathy. However, the intensive group had marked reductionin strokes (1.7% vs. 5.4%, P = 0.03), and the results were thesame, irrespective of whether enalapril or nisoldipine was usedas the initial anti-hypertensive therapy.

Patient education

Surwit RS, Van Tilburg MAL, Zucker N, McCaskill CC, Parekh P,Feinglos MN et al. Stress management improved long-term glycaemiccontrol in type 2 diabetes. Diabetes Care 2002; 25: 30–34.

This is an important study in 108 patients with Type 2 diabeteswho were undergoing a group diabetes education programme,and had this either with or without stress managementtraining. The group which had additional stress managementtraining as part of their group education programme hada 0.5% lower reduction in HbA1c compared with the groupwhich received standard group education. Looking at particulargroups who may have benefits from the stress management,those with anxiety trait did not actually appear to derive anymore benefit from the training than those with other personalitytraits. Over 30% of the group who were in the stress managementgroup had a > 1% reduction in their HbA1c, while only 12%of the control subjects had a > 1% reduction. The aim of thisstudy was to try to look at where the stress management couldbe implemented in a real-life set-up in a cost-effective way aspart of a group education programme. From this perspective,this study appears to have been successful.

Rickheim PL, Weaver TW, Flader JL, Kendall DM. Assessment ofgroup vs. individual diabetes education. Diabetes Care 2002; 25:269–274.

This study randomly assigned 170 patients with Type 2 diabetesto either group or individual diabetes education, using aconsistent, evidence-based curriculum. Four sequential sessionswere delivered over 6 months, with there being similar improve-ments in knowledge, weight, health-related quality of life andattitudes. Glycaemic control improved in both cohorts, butmore so in the group setting (2.5% reduction in HbA1c vs.1.7% reduction in HbA1c, P = 0.05). The authors thus suggestthat a group setting may provide a more efficient and cost-effective means of diabetes education than individually basedprogrammes.

Levetan CS, Dawn KR, Robbins DC, Ratner RE. Impact of computer-generated personalized goals on HbA1c. Diabetes Care 2002;25: 2–8.

This study looks at the use of a computer-generated personal-ized HbA1c goal on outcome. They looked at 150 patients withdiabetes who were randomized to receive either standard careor intervention inclusive of a computer-generated colour posterwith their HbA1c status and goals along with a personalizedstep to aid in goal achievement. All patients received diabeteseducation during the 3 months before enrolment. HbA1c wasperformed at baseline and at 6 months. In the control group,there was a 0.6% reduction in HbA1c, but in the interventiongroup the fall was 1.08%, therefore a difference of around0.48%. The only concern was that at the end of the studyHbA1c was similar in both groups, but the baseline HbA1c

at the start of the study appeared to be clinically higher inthe intervention group. However, this seems to be a simple toolwhich could be amended and used routinely in the diabetesclinic to help empower and inform patients.




HORIZONS


Advances in continuous in vivo glucose monitoring

E. Leitao, K. Kaushal, A. Gill and P. Vadgama*University of Manchester, Manchester, and *Director of the IRC in Biomedical Materials, Queen Mary University of London, London, UK

A commentary on Boland E, Monsod T, Delucia M, BrandtCA, Fernando S, Tamborlane WV. Limitations of conven-tional methods of self-monitoring of blood glucose. DiabetesCare 2001; 24: 1858–1862.

Introduction

Good glycaemic control is essential to reduce the risk of long-term diabetic complications. This has been demonstrated inpatients with both Type 1 and Type 2 diabetes [1,2]. Patientswith diabetes are encouraged to perform self-monitoring ofblood glucose (SMBG), particularly before meals and atbedtime, using portable capillary blood meters. Such devicesnecessitate painful fingerstick testing by the patient andprovide no information about variations in blood glucoselevels between measurements. Blood glucose levels are rarelymeasured at night, when insulin-treated patients are mostvulnerable to hypoglycaemia. Biochemical nocturnal hypogly-caemia occurs frequently both in adults [3] and children [4–6].Intensive insulin regimens guided by frequent SMBG, such asthose used in the Diabetes Control and Complications Trial(DCCT) [1], can improve glycaemic control and significantlyreduce the risk of microvascular complications, but withan increased incidence of severe hypoglycaemia. Untowardhypoglycaemia remains the greatest obstacle to achieving thestrict glycaemic goals required to prevent the long-termcomplications of diabetes [7]. Postprandial hyperglycaemia,a predictor of macrosomia in gestational diabetes [8] as wellas an independent risk factor for macrovascular complications[9], is another phenomenon that goes undetected by routinepremeal SMBG. Continuous glucose monitoring, by demon-strating these swings in glucose levels in patients with diabetes,is therefore a potentially important adjunct to good diabetesmanagement.

Continuous monitoring devices

Two continuous glucose monitoring systems (CGMS) havenow been approved by the Federal Drug Administration(FDA) [10]: the MiniMed® CGMS (Medtronic MiniMed®

Inc., Northridge, CA, USA) and the GlucoWatch® Biographer(Cygnus Inc., Redwood City, CA, USA). These techniques, ratherthan measuring glucose directly in the blood in line with existingcapillary glucose meters, rely upon interstitial fluid (ISF) that ispresent in subcutaneous tissue either by direct access (MiniMed®)or by extraction through the skin (GlucoWatch®).

The MiniMed® CGMS samples ISF glucose every 10 s andrecords an average glucose value every 5 min for up to 72 h.The Glucowatch® samples ISF glucose by the application of asmall electric current to transfer electrolytes and water throughintact skin. An averaged glucose reading is provided every20 min for up to 12 h. Both devices detect the formation ofhydrogen peroxide from glucose oxidation, using the enzymeglucose oxidase and an amperometric detector [10]. TheMiniMed® device, unlike the GlucoWatch®, provides onlyretroscopic glucose data.

Microdialysis is another technique that has been applied toCGMS. Menarini has recently obtained a CE mark under theMedical device directive, for GlucoDay®, a continuous glucosemonitoring system (A. Menarini Diagnostics, Florence, Italy)that will be available in the market later this year (MenariniGroup press release HTTP://www.menarini.com). This devicesamples ISF via a microdialysis probe and is able to monitorglucose continuously for up to 48 h needing only one point invivo calibration. The glucose values are available immediately,allowing the user to act in order to bring them to normal levels.

There has been some concern that ISF may not equate tochanges in blood glucose levels. However recent research[4,11,12] has shown that there is indeed agreement betweenblood and ISF glucose levels. Therefore, probing ISF forglucose appears to be a viable option with key advantagesover existing SMBG methodologies. These include a reducedrequirement for painful repeat fingerstick tests and, moreimportantly, the tracking of daily fluctuations in glucoselevels. Appropriate therapeutic adjustments can then be madein order to prevent periods of hyper- and hypoglycaemia.

These new technologies are designed to be an adjunct tointermittent SMBG by providing sequential information aboutglucose changes. Currently, they are unable to replace SMBGentirely, since their reliable operation demands intermittentin vivo calibration, e.g. based upon measurements madewith capillary fingerstick meters. This can therefore impartthe potential, inherent 20% error associated with capillarymeters to the CGM device. Interstitial fluid glucose concentra-tion may also lag behind the blood value by up to 18 min [13].

Skin irritation occurs in most patients with the GlucoWatch®

but settles after a few days [14]. Perspiration, which can ofcourse be a manifestation of hypoglycaemia, may affectsensor function. Nevertheless, the device has been shown toimprove detection of hypoglycaemia when used with SMBG.By setting the alert level at 5.6 mmol/ l, the GlucoWatch®

detected 75% of the hypoglycaemic events (defined by a bloodglucose of 3.9 mmol/ l) in contrast to the 14% and 39%obtained from capillary fingerstick measurements performedtwice and four times a day, respectively [15].




Boland et al. [4] demonstrated that the MiniMed® CGMS,in a study of 56 children with Type 1 diabetes, was able todetermine that almost 90% of the postprandial peak glucoselevels were > 180 mg/dl (9.9 mmol/l) and almost 50% were> 300 mg/dl (16.5 mmol/l). Additionally, the sensor revealedthat asymptomatic nocturnal hypoglycaemia (glucose< 3.3 mmol/l) occurred in almost 70% of subjects. Even71% of the daytime hypoglycaemic events were asymptomatic.These findings were only possible through the use of CGM.In a series of children monitored every 5 min overnight, only15% of nocturnal hypoglycaemic episodes resulted in the childawakening and seeking assistance [16]. Moderate hypoglycaemia(symptomatic but requiring no assistance) occurs approximatelyonce a week with conventional therapy and twice weekly withintensive therapy [17]. In the DCCT severe hypoglycaemia(symptomatic and requiring assistance) occurred 19 timesper 100 patient-years with conventional therapy and 62 timesper 100 patient-years with intensive therapy.

Although a commercial closed-loop device combiningglucose sensing and insulin pump therapy has yet to emerge,significant progress has been made. Glucose sensor research isaimed at producing accurate, minimally or non-invasive deviceswith fast response times and, ideally, no requirement forin vivo calibration. Devices are being developed using a rangeof detection principles; namely amperometric measurement,near infrared spectroscopy and fluorescence. All have limitationsimposed by conditions within body tissues that invariablydegrade function. First, the body’s defence mechanismsbegin to reject any implanted device no matter how minimallyinvasive it is. Second, for optical devices, where light is usedto penetrate tissues and thereby detect and measure glucoseremotely, the complexity, and variability of light scatteringwithin tissues confound reliability of the glucose concentration‘message’ that is brought out by light returned to a detector.

Conclusions

Pre-meal and pre-bedtime testing using conventional capillaryglucose meters may miss glucose excursions in insulin-treatedpatients. Boland et al. [4] clearly demonstrated postprandialhyperglycaemia and nocturnal hypoglycaemia in their sub-jects, despite the presence of a good HbA1c and target pre-mealcapillary glucose levels. Frequent severe hypoglycaemia,particularly in children, can lead to neuropsychologicalimpairment [18]. Hypoglycaemia is the most common adverseeffect of intensive insulin therapy and represents one of thepatient’s greatest fears. The use of CGMS can facilitatetreatment adjustment [19–21] and may result in improvedglycaemic control [20]. Continuous monitoring also helps tomotivate and educate patients [19].

As the biological difficulties associated with sensor technol-ogy are resolved in the coming years, it is hoped that sufficientfunction will be attained such that ultimately fully implantedsensors operating over months or even years will becomeavailable for use.

Summary practice points

• Nocturnal hypoglycaemia and postprandial hyperglycaemiaare common in diabetic patients even when HbA1c levels are good.• These variations in blood glucose levels may go undetectedwith current conventional SMBG techniques.• Intensive insulin regimens increase the risk of hypoglycaemia.• Continuous glucose monitoring systems, such as theMiniMed® CGMS and GlucoWatch® Biographer have beenshown to be beneficial in detecting trends in glucose levelswhen used to supplement standard SMBG techniques.• In addition to allowing facilitation of diabetes treatmentadjustment, CGMS can be a powerful education tool forpatients.

References

1 Diabetes Control and Complications Trial Research Group. Theeffect of intensive treatment of diabetes on the development andprogression of long-term complications in insulin-dependentdiabetes mellitus. N Engl J Med 1993; 329: 977–986.

2 UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared withconventional treatment and risk of complications in patients withtype 2 diabetes. Lancet 1998; 652: 837–853.

3 Gale EAM, Tattersall RB. Unrecognised nocturnal hypoglycaemia ininsulin-treated diabetics. Lancet 1979; i: 1049–1052.

4 Boland E, Monsod T, Delucia M, Brandt CA, Fernando S,Tamborlane WV. Limitations of conventional methods of self-monitoring of blood glucose: lessons learned from 3 days of continuousglucose sensing in pediatric patients with type diabetes. DiabetesCare 2001; 24: 1858–1862.

5 Shalwitz RA, Farkus-Hirsch R, White NH, Santiago JV. Prevalenceand consequences of nocturnal hypoglycaemia among conventionallytreated children with diabetes mellitus. J Pediatr 1990; 116: 685–689.

6 Beregszaszi M, Tubiana-Rufi N, Benali K, Noel M, Bloch J,Czernichow P. Nocturnal hypoglycaemia in children and adolescentswith insulin-dependent diabetes mellitus: prevalence and risk factors.J Pediatr 1997; 131: 27–33.

7 Furlanetto R. Hypoglycaemia and the brain. Diabetes Technol Ther2001; 3: 467–468.

8 De Veciana M, Major CA, Morgan MA, Asrat T, Toohey JS, Lien JMet al. Postprandial versus preprandial blood glucose monitoring inwomen with gestational diabetes requiring insulin therapy. N Eng JMed 1995; 333: 1237–1241.

9 Ceriello A. The postprandial state and cardiovascular disease:relevance to diabetes mellitus. Diabet Metab Rev 2000; 16: 125–132.

10 Kiechle FL. The impact of continuous glucose monitoring onhospital point-of-care testing programs. Diabetes Technol Ther2001; 3: 647–650.

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General description and methods

Aims and editorial philosophy

This section of Diabetic Medicine aims to promote good careof people with diabetes by meeting the educational needs oftrainee and trained professionals. Its goals are to:• Respect adult learning principles.• Report and comment on important changes in the evidencebase of diabetes care.• Explore problems and controversies in care and offer expertsolutions when the evidence base is weak.• Explain scientific concepts and developments that impact ondiabetes care.• Support the readers’ development of study skills.• Promote and report interaction with the readership.• Be concise.

It aims to be rigorous, always clinically relevant, and todraw on the discipline of evidence-based medicine.

Editorial panel

The contents of the Section are contributed or commissionedby a panel whose members are:Dr Melanie Davies, Leicester; Dr Tim Dornan, Salford(Co-ordinating Editor); Dr Martin Gibson, Salford; Dr SallyHollis, Lancaster; Dr Ian Lawrence, Leicester; Dr PaulMcNally, Leicester; Dr John New, Salford.

Publication details

Continuing Education is published three times per annum.Full-text and PDF versions are available to Diabetic Medicinesubscribers on the Blackwell Science Synergy website (http://www.blackwell-synergy.com). The electronic version of the sectionprovides an electronic link to MedLine and, whenever available,to the full electronic text of any original article cited. Anelectronic discussion forum will be linked to the website topromote communication between readers (http://www.mediabetes.com).

Contents

Each issue contains some or all of the following types of article:

Editorial. A brief commentary on the contents of the issueand other matters relevant to continuing education and clinicalpractice in diabetes.

Learning and teaching skills. These commissioned articles ontopics related to professional development aim to help readersdevelop their learning skills.

Clinical practice question. The Editorial Panel commissionsan expert to write a short commentary around a difficultsituation arising in clinical practice. The article begins withself-assessment questions, and then answers them as far asexisting evidence and the experience of the commentatorpermit. The Editorial Panel invites readers to submit questionsand nominate commentators. The electronic discussion forumwill, with time, act as a source of topics.

Today’s evidence. Members of the Editorial Panel screen thefollowing journals for original articles which, in their opinion,have the potential to change clinical practice:

General journals: British Medical Journal; Journal of theAmerican Medical Association; The Lancet; New EnglandJournal of Medicine; British Journal of General Practice;Annals of Internal Medicine.

Specialist journals: Diabetes; Diabetic Medicine; DiabetesCare; Diabetes Research and Clinical Practice; Diabetologia;Endocrine Reviews; Journal of Clinical Endocrinology andMetabolism.

Having identified a paper, the screener scores it for itspotential to change practice, originality, importance andstrength of evidence. At present, the journals are not second-screened. Six months before an issue is due to be published, allarticles identified in the preceding 4 months are ranked. Astructured abstract of the highest-ranking article is prepared,




prefaced by self-assessment questions, and an expert in thefield is commissioned to write a short commentary discussingthe article and putting it in the context of the current medicalliterature, and clinical practice generally. Other articles arecited with a short comment.

Horizons. These articles aim to give a succinct discussionof a new or evolving aspect of basic science that impacts onclinical practice. They are commissioned in response toimportant biomedical developments.

Correspondence. A resume of any important correspondence,electronic and on paper, may be published.

Citation

For citation purposes, each issue will be regarded as a singlearticle; citations should be in the following format: ContinuingEducation. Diabetic Med 1999; 17: 000–000.

Communication with the readership

The Editorial Panel hopes to develop two-way interaction withits readership, through;• The website, electronic discussion forum and use of e-mail.• Publication of correspondence on previously publishedmaterial.

Correspondence from readers is welcomed, both electronicallyon our bulletin board and on paper. Letters should beaddressed to:

Continuing Education, c /o Diabetic Medicine, 25 John Street, London WC1N 2BS, UK.E-mail: [email protected]://www.mediabetes.com


editorial

Documents