Improving cardiovascular risk in type 2 diabetes: time to get personal

Type 2 diabetes is a heterogeneous disease characterized by varying degrees of insulin resistance, insulin deficiency, genetic and environmental contributions. With increasing evidence of individual variation in response to treatments, personalizing both the therapy and the treatment target to the individual should produce improved outcomes. Diabetes is a growing global health challenge, with an estimated 451 million people affected worldwide in 2015, expected to rise to 642 million by 2040.1 At least 90% have Type 2 diabetes; for these patients, the risk of developing hypertension is doubled and cardiovascular disease is the leading cause of death. Over the last 30 years, advances in understanding the underlying mechanisms contributing to this cardiovascular burden in the diabetic population have led to interventions focussing on aggressive control of blood pressure, lipids, and blood glucose. In most developed countries, as the number of people living with diabetes has reached epidemic proportions, the routine review and management of patients with Type 2 diabetes has shifted from hospitals to primary care, with the aim of providing greater continuity of care while reducing costs. In this issue, Grenier et al. report from the Diabetes Mellitus Status in Canada (DM-SCAN) Survey. Using data collected from primary care physicians across Canada, the control of cardiovascular risk factors in Type 2 diabetes patients was compared in those with and without coronary artery disease (CAD). Among 4994 patients, target levels for all three risk factors of blood pressure, lipids, and glucose control were achieved in only 15.4% of those with CAD and 12.0% for patients without. Similar poor attainment has been reported from the USA, where 14.3% achieved all three targets2 and in a study of eight European countries3 where the figure was just 6.5%. In England and Wales, results were slightly better with 41% of patients at target for all three parameters, though only 27% of patients aged below 40.4 Why should this be and how should we respond? At first thought, the obvious approach to tackle the substantially increased cardiovascular morbidity and mortality associated with diabetes would seem optimizing glucose control. However, landmark studies in both Type 1 diabetes and in recently diagnosed and longstanding Type 2 diabetes failed to demonstrate significant benefit of intensive glucose control on cardiovascular risk, despite showing beneficial effects on the risk of microvascular complications (nephropathy, neuropathy, and retinopathy). Only after prolonged post-trial follow-up did the cardiovascular benefits become apparent, even though the differences in HbA1c between the intensively treated and the conventionally treated groups were not maintained. This ‘metabolic memory’ or legacy effect of earlier improved glucose control having a beneficial effect on the future incidence of cardiovascular disease persisted for up to 30 years in Type 1 diabetes patients, producing a 30% reduction in cardiovascular disease.5 In patients recently diagnosed with Type 2 diabetes who received intensive glucose control, 10 years post-trial there was a 15% risk reduction for myocardial infarction and 13% reduction in risk of death.6 Yet, this may not be the case for all patients. The Action to Control Cardiovascular Risk in Diabetes Study Group study was terminated early due to 22% excess deaths in the intensively treated group with a mean HbA1c of 6.4%.7 In trials where patients were older, had longer duration of diabetes, and possessed other cardiovascular risk factors, hypoglycaemia was 2–3 fold more common with intensive treatment.7–9 Hypoglycaemia doubles cardiovascular risk and poses a particular risk in the elderly causing falls, accidents, cognitive decline, and cardiac events. Thus tight glucose control may be less beneficial or even deleterious in older patients who have a long duration of diabetes and are more likely to have other vascular risk factors. Glycaemic targets should therefore be tailored to the individual to balance risk and benefits. For those with newly diagnosed diabetes and no vascular disease a more aggressive HbA1c target of 6.5% (48 mmol/mol) may be appropriate; for older patients, those with a longer duration of diabetes, vascular complications or prone to hypoglycaemia, a target HbA1c of 8.0% (64 mmol/mol) might be considered. For the frail elderly, those with cognitive impairment or limited life expectancy, a target HbA1c of 9.0% (75 mmol/mol) may be more appropriate. Of note in the DM-SCAN study, the CAD patients had a median age of 71 and a long duration of diabetes (median 10 years), but the median HbA1c was just 7.1%, which may explain why this group had almost double the hypoglycaemia rate of those without CAD (12.3 vs. 6.5%). In fact, over 90% of CAD patients had an HbA1c target of 7.5% or less, despite one-third having other macrovascular disease and over a quarter having albuminuria. Perhaps then, we should not be too worried that so few reached the target HbA1c, but instead concerned that the HbA1c target chosen was inappropriately low for these patients. In some countries, primary medical practitioners are rewarded by financial incentives for achieving ever lower HbA1c targets. In light of current evidence, such schemes should be revised to avoid inappropriately tight HbA1c targets for patients for whom they may pose a risk. Despite this focus on HbA1c and glycaemic control, addressing blood pressure and lipids has a much greater effect on cardiovascular risk. To prevent one cardiovascular event, the number of individuals needed to be treated for 5 years is 119 for intensive glucose lowering to reduce HbA1c by 0.9%, 44 for 1 mmol/L reduction in cholesterol, and 34 for a 10/5 mmHg reduction in blood pressure.10 A recent meta-analysis involving over 100 000 patients demonstrated that for every 10 mmHg reduction in systolic blood pressure there was an associated 11% reduction in coronary risk and a 13% reduction in risk of death.11 Again, the target should be individualized with a target systolic pressure of 130 mmHg for many, but for younger patients with less risk of side effects of drug therapy, those with a higher risk of stroke or albuminuria a lower target of 120 mmHg may be more appropriate. Having one, two, or all three risk factors on target incrementally lowers the cardiovascular risk.12 Why then do so few patients achieve the desired levels of the three risk factors? One reason proposed is healthcare professionals' reluctance to initiate or step-up treatment when clinically indicated. This ‘clinical inertia’13 particularly applies to delays in starting insulin therapy for Type 2 diabetes. Causes are complex, involving both healthcare professional and patient factors. Healthcare professionals report lack of knowledge and training, insufficient consultation time, and anxieties about inducing hypoglycaemia. Patient factors also involve fear of hypoglycaemia, but in addition poor compliance with treatment and concern about potential weight gain. Depression coexisting with diabetes is associated with poorer diabetes self-management. Furthermore, both healthcare professionals and patients tend to overestimate the quality of care provided, wrongly perceiving that care is improving. Strategies to overcome clinical inertia include comprehensive primary care education programmes, specialist support and virtual clinics14—all demonstrated to improve quality of community diabetes care, regular feedback on performance, effective clinical information systems, and proactive patient appointment reminders. Consultations where nurses assist the primary care physician are more effective as nurses are more likely to educate and monitor patients and be perceived as better communicators. With abundant evidence of the benefit of tackling cardiovascular risk factors in Type 2 diabetes patients and international consensus on the targets to be achieved,15 the challenge is how to ensure these are addressed appropriately in the face of an ever-increasing diabetes population. Concentrating on those factors which produce most benefit with least risk—lipids and blood pressure—should be the priority. Glycaemic control is important but must be addressed safely. In the 1992, US presidential election Bill Clinton's campaign strategist coined the phrase ‘the economy stupid!’ to remind campaigners to stay focussed on this key message. In this year of another US presidential election, perhaps the diabetes cardiovascular mantra should replace the false economy of ‘one-size-fits-all’ with ‘this time its personal’. Conflict of interest: none declared.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.