GUEST EDITORIALS

UKPDS: a Message of Hope and aNeed for ChangeThe results of the huge United Kingdom ProspectiveDiabetes Study, which recruited 5102 patients and lastedmore than 20 years, have clearly demonstrated themagnitude of the risks of hypertension and hyper-glycaemia in Type 2 diabetes mellitus and the beneficialeffects of achieving optimal control of both.1–6

The exposition of the harmful effects of high bloodpressure and blood glucose was impressive. Risks ofboth macrovascular and microvascular damage increasedsubstantially for every 10 mmHg increase of systolicblood pressure and for every 1 % increase of HbA1c.The increases were documented for any diabetes-relatedend-point (macrovascular and microvascular diseasetogether), diabetes-related deaths, myocardial infarction,stroke and microvascular complications (retinopathy andalbuminuria). The risks were additive and reachedalarming levels when both these prime factors wereelevated. There was no threshold level of risk for eitherblood pressure or blood glucose.

The considerable benefits of ‘tight control’ aiming fora blood pressure of less than 150/85 and fasting plasmaglucose of less than 6 mmol l−1 are at last clear cut. Therisks for most (but not all) of the end-points listed aboveare reduced, sometimes substantially. It is to be expectedthat macrovascular end-points benefit most by bloodpressure control and the achievement of a mean bloodpressure of 144/82 (systolic pressure 10 mmHg belowthat of the less intensively treated group) resulted inreduction in risk of diabetes-related deaths (32 %), stroke(44 %) and indeed all diabetes-related end-points. Riskof myocardial infarction was reduced (but not quitesignificantly) by tight blood glucose control but not byblood pressure control.

The decrease in the risk of microvascular end points,especially the need for photocoagulation, by improveddiabetes control is impressive enough (25 %) but theimportance in this regard of blood pressure control isimportant for clinicians to know—the risk of microvascu-lar end-points is reduced by 37 % (again, predominantlydue to reduction in need for photocoagulation), with anaccompanying reduced risk of 47 % of vision decliningby three lines, as a result of protection from maculardisease. The evolution of microalbuminuria is alsoinfluenced by glycaemic control (reduced risk after 9years), while neuropathy seems, as in other studies, tobe most resistant. It is only after 15 years that anybeneficial effect on biosthesiometer measurements (butnot heart rate variation) may be observed.

The inexorable deterioration of the diabetic state whichoccurs over a decade regardless of treatment mode mustconcern all doctors and make them aware of the seriouschallenges which they and their patients face in trying

895CCC 0742–3071/98/110895–02$17.50 1998 John Wiley & Sons, Ltd. DIABETIC MEDICINE, 1998; 15: 895–896

to achieve ‘tight control’. Yet despite the obviousprogression of the disease, a clear difference of HbA1c

of 0.9 % was maintained throughout the UKPDS (themean HbA1c in the ‘tight control’ group was 7.0 %compared with 7.9 % in the conventionally treatedgroup). It is of course this insidious decline and the slowrate of progression of complications that makes the studyof their evolution and the benefits of treatment socomplex: significant benefits of blood glucose controlneed almost a decade, although effectiveness of bloodpressure control is observed sooner. The implications ofthese observations must be considered when determiningthe appropriateness of ‘tight control’.

Answers to questions regarding added efficacy ofdifferent forms of treatment for diabetes have at last beenanswered by UKPDS. The importance of tight bloodglucose control is clearly the key and all means ofachieving it have the same effect. The use of insulin per seconfers neither additional advantages nor disadvantages,while the use of sulphonylureas does not lead toadditional risks. (Chlorpropamide did perform worse, asits use was associated with a rise in blood pressure overthe years). Metformin used alone for overweight patientsis very effective, more so apparently than when used incombination with sulphonylureas, where some conflictingevidence raises new questions but does not indicate anyneed to change its present use where glycaemic controlis optimal. The role of diet, exercise and weight reductionremain, of course, paramount in treatment of Type 2diabetes. It is helpful for physicians to know that ACEinhibitors or b blockers are equally effective in achievingthe benefits of lowering blood pressure which are soclearly described in this group of patients.

Intensive treatment is no simple matter. It requiresdedication on the part of the physician and the will tocomply on the part of the patient. Polypharmacy maybe needed to implement tight control and it is estimatedthat one new treatment will need to be added every 4or 5 years. Yet the study shows no overall deteriorationin quality of life as a result of intensified treatment. Onthe other hand, increased anxiety when eye complicationsdevelop is entirely understandable and a clear measureof the life-long tension experienced by people withdiabetes, for whom the benefits of this study are soimportant. Of course, hazards of severe hypoglycaemiaalways exist whenever insulin is needed, affecting about1.8 % of those taking it. Intensive treatment led to asignificant weight gain (mean 2.9 kg), which was greatestfor those taking insulin (4.0 kg).

How should we proceed in tomorrow’s clinic? First,the primary aim must continue to be to ensure the reliefof symptoms and best possible quality of life for our

GUEST EDITORIALSindividual patients. Selection of people to whom tightcontrol policies should be aimed depends on factorswhich may be difficult to define but must at least includea potential predicted lifespan which will allow realbenefits. Second, patients need to be enthusiastic tocomply with treatment and undertake lifestyle changeswhich are not always easy. Physicians should be awarethat tight blood pressure control overall has larger benefitswhich are manifest sooner than those of blood glucosecontrol. We must be careful to avoid doing more harmthan good by inducing anxiety when treatments fail, asthey often do, and we will need to monitor the potentialproblems of polypharmacy—almost inevitable in somepatients—and avoid inappropriate advice. People needto know what is harmful and the clear benefits of goodtreatment. Research needs to seek and implement newand better techniques. Those who cannot cope with therigors of tight control also need to know that their carestill comprises many other facets, not least the continuingimportance and benefits of complications screeningleading to early diagnosis and effective interventions.

Implementation of the findings of the UKPDS willneed a programme of education for all health pro-fessionals, people with diabetes and the public. Themessages must be taken up by government and healthauthorities, because they have important implications forservice provision. With new targets to achieve, there isan even greater need than before for close collaborationbetween primary and secondary care. And it need notbreak the bank—the cost-effectiveness of intensifiedtreatment for Type 2 diabetes compares very favourablywith initiatives such as the implementation of the 4Scholesterol lowering study, population screening forcardiovascular risk, breast cancer screening and cardio-vascular lifestyle advice, and other established healthcare programmes, at least in the UK.

What are the messages? The most important is thatthe aims of treatment for Type 2 diabetes should be setnear normality, at least for patients diagnosed betweenthe ages of 25 and 65. Can we do it? One way towardsthe new goals might be to use the UKPDS study protocolsas guides in clinical practice. We have evidence thatthey work! Involvement of patients is crucial. They must

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1998 John Wiley & Sons, Ltd. Diabet. Med. 15: 895–896 (1998)

be informed of the natural progression of the diseaseand so not regard intensification of therapy over time asworsening of the disease, and physicians must rememberthat the need for increasing therapy may not be due topoor compliance. Insulin should not be considered as apunishment for treatment failure or a last resort for theseverely ill. And the overwhelming message is thatcomplications are not inevitable and can be activelyavoided. Patients themselves can monitor their need forfurther therapy when fasting plasma glucose is over6 mmol l−1 or blood pressure is over 145/85.

UKPDS is a landmark in the history of diabetes.The Oxford team and all their collaborators must becongratulated on their vision, perseverance and hugeachievements over more than 20 years. Now it is up tous to use the results of their labour.

Peter J WatkinsDepartment of Diabetes,

King’s College Hospital, London

References1. UK Prospective Diabetes Study Group. Presentations at

37th annual meeting of the European Association for theStudy of Diabetes, September 11th and 12th 1998,Barcelona, Spain.

2. UK Prospective Diabetes Study Group. Intensive bloodglucose control with sulphonylureas or insulin comparedwith conventional therapy and risk of complications inpatients with Type 2 diabetes mellitus: UKPDS 33. Lancet1998; 352: 837–853.

3. UK Prospective Diabetes Study Group. Effect of intensiveblood glucose control with metformin on complications inpatients with Type 2 diabetes: UKPDS 34. Lancet 1998;352: 854–865.

4. UK Prospective Diabetes Study Group. Tight blood pressurecontrol and risk of macrovascular and microvascularcomplications in Type 2 diabetes: UKPDS 38. BMJ 1998;317: 703–712.

5. UK Prospective Diabetes Study Group. Efficacy of atenololand captopril in reducing risk of macrovascular andmicrovascular complications in Type 2 diabetes: UKPDS 39.BMJ 1998; 317: 713–719.

6. UK Prospective Diabetes Study Group. Cost effectivenessanalysis of improved blood pressure control in hypertensivepatients with Type 2 diabetes: UKPDS 40. BMJ 1998; 317:720–726.