PracticeUpdate: Endocrinology

CONFERENCE COVERAGE

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Patients with diabetes are more likely to overuse than to underuse acetylsalicylic acid In large primary care settings, patients with diabetes are more likely to overuse

Prediabetes is associated with white matter atrophy in the MAASTRICHT study Prediabetes and type 2 diabetes have been associated with white matter hyperintensities and white matter atrophy, and type 2 diabetes with brain atrophy, as indicated by smaller white matter volumes. T his finding of a cross-sectional, comparative study of magnetic resonance and fluid-attenuated inversion recovery weighted images was reported at the EASD 2016 meeting. Marnix.J.M. van Agtmaal, MD, of Maastricht University Medical Center, The Nether- lands, explained that type 2 diabetes mellitus associated with brain atrophy and cerebral small vessel disease is believed to involve cerebral microvascular dysfunction. He said, “The epidemic of type 2 diabetes is a major health problem, and prevention of its complications is important. The brain is a major target for the effects of type 2 diabetes. Patients with type 2 diabetes are at increased risk of stroke, cognitive impair- ment, dementia, and depression.” “Moreover, age-related structural brain changes on MRI, such as markers of cerebral small vessel disease and brain atrophy, are more common in patients with type 2 diabetes. Little is known, however, about the pathophysiology of these structural brain changes.” “In light of the growing diabetes epidemic, the identification of factors contributing to structural brain changes is paramount. Microvascular dysfunction has been implicated in the aetiology of cerebral small vessel disease and brain atrophy in type 2 diabetes. Little is known about structural brain changes before the onset of type 2 diabetes, so preventing these changes is problematic.” “Since it has not been determined whether individuals with prediabetes harbour struc- tural brain changes,” Dr vanAgtmaal asserted, “we hypothesised that cerebral small vessel disease and brain atrophy are present in prediabetes. Answering this question is important because cerebral small vessel disease and brain atrophy are preventable. After the brain has undergone structural damage, however, the consequences are irreversible.” Dr van Agtmaal and colleagues set out to determine whether prediabetes and type 2 diabetes are associated with white matter hyperintensities, a proxy of cerebral small vessel disease, and brain atrophy in a general population age 40–75 years. The Maastricht Study is a population-based cohort study with an oversampling of participants with type 2 diabetes (the present analysis, n = 2243; mean age 59.2 ± 8.2 years; 45.6% females). A total of 1372 subjects had normal glucose metabolism, 347 had prediabetes, and 524 had type 2 diabetes. White matter hyperintensity, white matter, grey matter, and cerebrospinal fluid volumes were determined relative to intracranial volume using automated segmentation of T1, T2, and fluid-attenuated inversion recovery weighted magnetic resonance images. The association between glucose metabolism status and tissue volumes was assessed by linear regression analysis and adjusted for age, sex, body mass index, systolic blood pressure, total-to-high-density lipoprotein-cholesterol ratio, triglyceride levels, and edu- cational level. Prediabetes and type 2 diabetes were associated with a smaller white matter volume after full adjustment. The regression coefficient ( β ) of white matter volume was –0.305 (–0.569; –0.041), P < 0.001 and –0.628 (–0.876; –0.380(, P < 0.001. No association was found between prediabetes and type 2 diabetes grey matter volume. Type 2 diabetes was associated with a larger cerebrospinal fluid volume (0.723 [0.450; 0.995], P < 0.001), while prediabetes was not. Prediabetes and type 2 diabetes were associated with a larger white matter hyperin- tensity volume ( β 0.122 [0.15– 0.228], P = 0.05 and 0.228 [0.127; 0.328], P < 0.001). Dr vanAgtmaal concluded that prediabetes and type 2 diabetes are associated with larger white matter hyperintensity volumes. In addition, while type 2 diabetes is associated with a smaller white matter volume, while type 2 diabetes is associated with a smaller white matter volume and a larger cerebrospinal fluid volume. These data may indicate that, in

than to underuse acetylsalicylic acid. T his conclusion, based on results of an analysis conducted as part of a primary prevention effort to lower the risk of ath- erosclerotic vascular disease was presented at the EASD 2016 meeting. Lauren Crain, PhD, of HealthPartners Insti- tute, Minneapolis, Minnesota, explained that acetylsalicylic acid is recommended for primary prevention of cardiovascular disease for people with and without diabetes when the risk re- duction outweighs the risk of gastrointestinal haemorrhage. In a primary care setting, the complexity and time required to assess acetylsalicylic acid benefits and risks can result in inappropriate acetylsalicylic acid use through either overuse or underuse. Dr Crain and colleagues set out to assess the appropriateness of acetylsalicylic acid use for primary prevention in diabetes and other patients at high risk of cardiovascular disease in a large primary care setting. As part of a study funded by the US National Institutes of Health to lower the risk of athero- sclerotic cardiovascular disease, Dr Crain’s team implemented electronic clinical decision support algorithms to encourage appropriate acetylsali- cylic acid use. The algorithms recommend acetylsalicylic acid if risk scores for atherosclerotic cardiovascular disease are high and consistent with benefit greater than gastrointestinal bleed risk using criteria from the US Preventive Services Task Force. Coinvestigator JoAnn Sperl-Hillen, MD, speaking from a clinician perspective, said, “The latest aspirin guidelines highlight the need for an individualised approach to aspirin recommenda- tions for primary cardiovascular prevention that balances a person’s benefits and risks.” In the study, acetylsalicylic acid was not rec- ommended if risk reduction was low or if major contraindications were identified (anticoagulant use or a history of intracerebral haemorrhage). Providers were also alerted to the presence of other potential acetylsalicylic acid risks including allergy or intolerance, history of conditions indica- tive of gastrointestinal bleed risk, and concomitant use of nonsteroidal anti-inflammatory drugs. Baseline study data was collected for whether

risk, clinical decision support algorithms recom- mended acetylsalicylic acid for 2484 (62.7%) patients with diabetes and 5341 (76.3%) without diabetes. Among patients for whom acetylsalicylic acid was recommended, the agent was underused in 5171(20.8%) with diabetes and 5638 (74.4%) without diabetes. Among patients for whom the algorithms did not recommend acetylsalicylic acid, the agent was overused in 840 (57.0%) with diabetes and 559 (33.7%) without diabetes. Dr Crain concluded that in this large primary care setting, acetylsalicylic acid was more likely to be overused than underused in patients with diabetes. Those with diabetes who were likely to benefit from acetylsalicylic acid use had higher use rates than similar high cardiovascular-risk patients without diabetes. Those with diabetes who were unlikely to ben- efit from acetylsalicylic acid (risks greater than benefit), however, had higher rates of acetylsali- cylic acid overuse than those without diabetes. Dr Sperl-Hillen said, “Our study suggests that in primary care practice, aspirin use is often not concordant with an individual’s assessed risk and benefit. This is due in part to the lack of available practical assessment tools that can be used in the context of busy clinician practices.” She continued, “Care can be improved through shared decision making facilitated by risk/benefit assessment tools integrated with the electronic health record. We successfully implemented a Web-base, electronic health record – integrated tool to help patients and clinicians quickly as- sess and prioritise cardiovascular risk factors and risk-lowering treatment opportunities. We achieved high use rates for appropriate patients in a primary care setting.” When asked about the team’s further research, Dr Sperl-Hillen replied, “We are studying how well these electronic health record – integrated tools work to improve patient outcomes. Risk information that may be impacted by patient characteristics, such as educational level, health literacy, and numeracy, can be presented in nu- merous ways. A major focus of our work will be to evaluate how different formats of risk assessment information presented to patients and clinicians can influence clinical decisions and patient be- haviours.”

acetylsalicylic acid was algo- rithmically recommended for all patients at their first eligible primary care encounter in 20 clinics from 2012 to 2014. The analysis excluded pa- tients with coronary heart disease and included 3958 adults with diabetes (mean age 54.6 years, mean 10-year risk of cardiovascular disease risk 29.2%) and 7000 adults meeting prespecified criteria for high risk of cardiovascular disease risk without diabetes (mean age 58.5 years, mean 10-year risk of cardiovascular disease 25.6%). Over- and underuse were determined by comparing con- cordance with acetylsalicylic acid algorithm recommenda- tions and documented acetyl- salicylic acid use. For the targeted population at high cardiovascular disease

a middle-aged population, changes in cerebral white matter occur before onset of type 2 diabetes. “We showed in a population-based study, that both prediabetes and type 2 diabetes are associated with cerebral small vessel disease and brain atrophy, independent of major cardiovascular risk factors,” Dr van Agtmaal said. He continued, “The findings sup- port the concept that (micro)vascular structural brain damage precedes the clinical diagnosis of type 2 diabetes and may contribute to the cerebral complications of prediabetes and type 2 diabetes, such as stroke, cognitive decline, and depression.” He added, “We will explore the association of structural brain dam- age with stroke, cognitive decline, and depression. And we will follow up on the participants after 5 years to measure the effects of structural brain damage on mortality and co- morbidity.

Courtesy of EASD 2016

PRACTICEUPDATE ENDOCRINOLOGY