Diabetes guidelines: easier to preach than to practise?

The number of adults with diabetes worldwide is predicted to increase from 135 million in 1995 to 300 million in 2025.1 Diabetes is associated with a significantly increased risk of mortality, predominantly from cardiovascular disease.2 Intensive treatment of glycaemia, blood pressure and serum lipids has been shown to delay the onset and progression of complications in type 1 and type 2 diabetes.3-9 Similarly, intensive intervention targeting multiple risk factors reduces the risk of cardiovascular disease and microvascular complications both effectively and significantly in individuals with type 2 diabetes.10 Despite widespread reporting of these trial findings, their incorporation into clinical guidelines and subsequent implementation in routine practice is a challenge, with treatment targets sometimes unrealistic and difficult to meet.11 This is evidenced by a recent study of the management of type 2 diabetes in an urban Australian community, which reported that very few patients achieve recommended targets for glycaemic control.12

The aim of this audit was to review the outpatient management of glycaemia, blood pressure and lipids in a Sydney teaching hospital and to assess whether current treatment targets were being met. This is of particular interest as the director of the diabetes centre at this hospital (L V C) has co-authored diabetes management guidelines for general practitioners,13 and both senior authors (D J C and L V C) have published recommendations for diabetes management.14

Demographic and BMI characteristics of patients included in this audit are shown in Box 1.

Despite strong evidence that intensive control of cardiovascular risk factors reduces morbidity and mortality in type 1 and type 2 diabetes, our study of an outpatient diabetes clinic population revealed that a large number of patients were not achieving recommended treatment targets.

Over the past two decades, large, prospective, randomised studies have incontrovertibly demonstrated that intensive glycaemic control in patients with type 1 and type 2 diabetes delays the onset and progression of microvascular complications, such as retinopathy, nephropathy and neuropathy, and that glucose-lowering with metformin reduces the risk of macrovascular disease events in overweight patients with type 2 diabetes.3,5,6 Furthermore, in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study, it was recently reported that, after 17 years of follow-up, participants with type 1 diabetes who previously had been treated intensively with insulin in the Diabetes Control and Complications Trial (DCCT) had a 42% lower risk of cardiovascular disease events compared with patients who previously had been treated conventionally.4 Given this strong evidence base, the ADA has recommended a target HbA1c of < 7%,15 and the new Joint British Societies’ guidelines (JBS 2) published in December 2005 recommended a target HbA1c of < 6.5%.16 As highlighted by our study and other studies reported in the literature,17-22 these targets are increasingly difficult to achieve (Box 2).

When interpreting our results, it is important to appreciate that HbA1c values in the clinic population described in this study are likely to be skewed to higher values, as the clinic population comprises mainly patients referred by general practitioners with poorly controlled or newly diagnosed type 1 and type 2 diabetes, or those recognised to have complications. Therefore, the study population represents a select group of patients, and our results may not be representative of patients with diabetes in the wider Australian community.

Our results should also be considered in the context of the findings of the United Kingdom Prospective Diabetes Study (UKPDS), in which median HbA1c values over 10 years were 7% in the intensively treated group.5 This result indicates that half of the intensively treated patients failed to achieve this glycaemic target, despite their participation in an intensive-treatment diabetes study. It is therefore not surprising (and perhaps even encouraging) that 30% of patients with type 2 diabetes in our clinic population had an HbA1c < 7%. It should also be noted that, although about half of the participants with type 1 diabetes in the intensive arm of the DCCT achieved an HbA1c ≤ 6.05% one or more times during the study, fewer than 5% of participants maintained an average value below this target, despite an intensive effort with full resources, expert staff and patient compliance.3 Nonetheless, our results illustrate that, with currently available therapies, many patients fail to reach recommended treatment targets. Indeed, clinicians appreciate that, for many patients, individualised recommendations may be more appropriate.23

The UKPDS also demonstrated that “tight” blood pressure control delayed the development and progression of macrovascular and microvascular disease in type 2 diabetes.7 It is important to note that, despite participation in a clinical trial, only 56% of patients in the “tight control” group and 37% in the “less tight control” group achieved a blood pressure < 150/85 mmHg. More recently, the Heart Outcomes Prevention Evaluation (HOPE) Study Investigators reported that patients with diabetes and at least one other cardiovascular risk factor (not necessarily hypertension) treated with the angiotensin-converting enzyme inhibitor ramipril were less likely to develop the composite endpoint of myocardial infarction, stroke or death from cardiovascular disease, compared with those who received placebo, despite a mean reduction in blood pressure of only 3/2 mmHg.24 Guidelines from the ADA published at the beginning of the year of our survey recommended that patients with diabetes receive anti-hypertensive medication(s) if blood pressure consistently equals or exceeds 140 mmHg systolic or 90 mmHg diastolic, with a treatment target of < 130/80 mmHg.15 This blood pressure target is consistent with recommendations from other expert societies from the United States,25,26 Australia13,27,28 and Europe.16,29-31 Despite this consensus, the current and previous studies17-22 demonstrate that many patients with diabetes do not achieve this treatment target in clinical practice (Box 2).

Primary and secondary prevention trials provide convincing evidence that lipid lowering reduces the risk of cardiovascular disease and death in people with diabetes.9 In 2003, the Heart Protection Study group reported that in 5963 patients with diabetes aged 40–80 years with non-fasting total cholesterol levels > 3.5 mmol/L (half of whom had no history of arterial disease at baseline), 40 mg/day of simvastatin significantly reduced coronary mortality and first non-fatal myocardial infarction.32 The average LDL cholesterol level in diabetic patients treated with simvastatin was ≤ 2.6 mmol/L. More recently, in a primary prevention study of 2838 participants with type 2 diabetes aged 40–75 years, 10 mg/day of atorvastatin led to a 37% reduction in the incidence of major cardiovascular events.33 In contrast, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study recently reported mixed results regarding the effect of fenofibrate on cardiovascular disease events in type 2 diabetes.34

Consistent with the findings from these and other studies,8 the ADA has proposed that statins be commenced for primary prevention in patients with diabetes aged over 40 years if total cholesterol is ≥ 3.5 mmol/L, with an LDL cholesterol target of < 2.6 mmol/L.35 Although a similar target was published by the ADA in the year of our audit,15 our results indicate that only 60% of patients receiving lipid-lowering therapy and 40% of untreated patients had LDL cholesterol levels below this value. These recommendations are consistent with those proposed by other expert groups (Box 3),13,16,28,29,31,35-38 but conflict with Australian Pharmaceutical Benefits Scheme restrictions for the supply of subsidised drugs, which is probably a significant disincentive for the appropriate use of statins in diabetes management.

In conclusion, our survey of over 600 patients with diabetes indicates that there is significant discord between the evidence-based guideline targets formulated and advocated by physicians, and current treatment outcomes in our own clinical practice. Potential barriers to achieving recommended treatment targets include:11,39,40

• reduced patient adherence to prescribed medications because of the number of tablets required to adequately treat vascular risk factors in diabetes, drug interactions and side effects (including hypoglycaemia and weight gain), and inadequate counselling of patients about the benefits and efficacy of primary and secondary prevention of diabetic complications;

• ethnicity and racial factors; and

• prescribing restrictions arising from the reluctance of regulatory pricing bodies to embrace and accept new trial evidence that intensive treatment of cardiovascular risk factors in diabetes significantly reduces the increased morbidity and mortality associated with the disease.

Modification of restrictions by regulatory bodies, the development of medication combinations to reduce polypharmacy, and greater engagement with patients regarding the potential individual benefits and expected adverse effects of medications used to treat glycaemia, blood pressure and lipids may help to modify risk factors in patients with diabetes. However, if resources remain restricted, there may be a need to reassess current treatment recommendations and to prioritise expenditure in order to achieve realistic treatment targets in the increasing number of patients diagnosed with diabetes.