Practice Update: Endocrinology | Volume 1. Number 2. 2016

DIABETES

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EXPERT OPINION Diabetes landscape in Australia is fast evolving Interview with Prof Sof Andrikopoulos

it could very well be that if we have better gut health we may be able to prevent a lot of the chronic diseases we see today. Closing the loop in type 1 diabetes We’re making huge strides in type 1 diabetes with the closed loop system, or the artificial pancreas, being so close to reality. The artificial pancreas, which combines an insulin pump with glucose and a continuous glucose monitor, will reduce glycaemic excursions, preventing an increase in HbA 1c and complications as a result of better plasma glucose control. I find this absolutely fascinating. The artificial pancreas will save lives; it will not only prevent diabetes complications but actually save lives. References 1. Zinman B, Wanner C, Lachin JM, et al. N Engl J Med 2015; 373:2117–2128. 2. Marso Sp, Daniels GH, Brown-Frandsen K, et al. N Engl J Med 2016; 375:311–322. 3. Department of Health. Australian National Diabetes Strategy 2016–2020. Commonwealth of Australia 2015. Canberra: DoH 2016. www.health.gov. au/internet/main/publishing.nsf/content/3AF935DA210DA043CA257EFB 000D0C03/$File/Australian%20National%20Diabetes%20Strategy%20 2016-2020.pdf (accessed 8 August 2016). 4. Sonnenburg JL and Bäckhed F. Nature 2016;535:56–64.

Professor Andrikopoulos speaks with Carolyn Ng on the evolving landscape in the treatment of type 2 diabetes, a need for a national strategy to prevent diabetes, exciting research that could better our understanding of diabetes as a chronic disease, and the prospect of an artificial pancreas system and its impact on patients with type 1 diabetes. O ne of the biggest conversation points in diabetes these days is around the impact of the newer diabetes drugs such as empagliflozin and liraglutide on cardiovascular

We need to implement the recommendations of the Aus- tralian National Diabetes Strategy to prevent the burden of diabetes, not just on the health system in Australia but also on the country’s economy. We are well aware of the statistics: there are 1.7 million people in Australia with diabetes; 280 in- dividuals are diagnosed with diabetes each day; and the indirect cost to the national economy is $14.6 billion annually in loss of income as a result of the disease. These are big numbers. Prevention of diabetes is therefore a conversation we need to have. The key stakeholders – the Australian Diabetes Society, Australian Diabetes Educators Association, Royal Australasian College of Physicians, and the Department of Health – need to come together and come up with a national strategy for the prevention of diabetes. Getting to the root of diabetes While there is evidence of a strong genetic predisposition, we don’t as yet know the exact causes of diabetes. In type 1 diabetes, we know that there are major genetic loci that are more prevalent in people getting type 1 diabetes. In the last 15–20 years, that genetic load has reduced and there seems to be a lot of environmental factors that may be contributing to the accelerated rate of type 1 diabetes such as insulin resistance or overweight. Can we prevent type 1 diabetes? I think we can by fully understanding the mechanism of the disease: why the body’s immune system attacks and kills beta cells resulting in insulin deficiency which then causes diabetes. The topic of epigenetics and its role in predisposing someone to diabetes, whether type 1 or type 2, is of particular interest to me. First, what are the epigenetic changes that cause type 2 diabetes and second, what are the environmental influences that cause epigenetic changes. Can we as clinicians intervene? Can we reduce or remove these environmental influences; avoid the epigenetic changes and thereby prevent the onset of diabetes? Another emerging research area is looking into the gut mi- crobiota and how these predispose us to chronic diseases such as diabetes. An interesting paper published in Nature 4 recently reported that gut microbiota can influence human metabolism, predisposing to obesity and potentially triggering diabetes. So

mortality. The EMPA-REG OUTCOME trial 1 for example reported that patients with type 2 diabetes taking empagliflozin had a 38% significantly (P < 0.001) lower risk of death from CV disease compared with patient on placebo. This is big result. The other big study is the LEADER trial 2 , results of which were released at the recent American Diabetes Association meeting. It reported similarly positive outcomes among type 2 diabetes patients taking liraglutide – a marked reduction in death from CV disease compared with patients on placebo. These are significant results in that it’s the first time we’re seeing glucose-lowering drugs confer CV protection. The ques- tion now then is how do we use these drugs in the treatment algorithm? For the Australian Diabetes Society, our main chal- lenge is informing ourselves to apply what we now know from these studies in the appropriate management of our patients with type 2 diabetes. Both empagliflozin and liraglutide are approved in Australia, with empagliflozin also subsidised on the Pharmaceutical Benefits Scheme as second-line and triple therapy, and as add-on to insulin. The question that remains to be answered is whether we can use these clinical trial data and apply them to all patients with diabetes? The entry point for these clinical trials is that patients have had to have a prior CV event or a strong predisposition to CV events. Does this mean that these drugs are only useful in diabetes patients with established CV disease or can they be used to prevent patients from a CV event? National strategy needed for diabetes prevention Preventing diabetes is still a challenge at a national level. The Australian National Diabetes Strategy 2016–2020 3 document has dedicated a whole section on the prevention of diabetes. Is it appropriate to talk to patients about lifestyle modification at the prediabetes stage? It probably is. Can we use pharmaco- therapy to prevent the conversion of prediabetes to diabetes? Well we currently don’t have any drug that is indicated for prediabetes. Do we need a national strategy for the prevention of diabetes? I think we do.

Professor Sof Andrikopoulos is President of the Australian Diabetes Society, Head of the Islet Biology and Metabolism Research Group at the Department of Medicine, University of Melbourne, and Editor-in- Chief of the Journal of Endocrinology and Journal of Molecular Endocrinology.

Meeting of minds at the 2016 ADS–ADEA annual meeting

Prof Andrikopoulos says an interesting topic that will be dis- cussed at this year’s meeting, one topic of many, is on the use of technology in the management of diabetes. “We are excited to host a number of high profile international speakers including Professor John Pickup of the King’s College London, a technology specialist who’ll be talking about the closed loop pumps making headlines in diabetes. We’ll also be discussing clinical data from the latest trials such as the LEADER trial; so hot topics and very timely discussions that will be relevant to healthcare professionals with an interest in diabetes.” The ADS–ADEA 2016 Annual Scientific Meeting will be held at the Gold Coast, 24–26 August. For more information visit www.ads-adea.org.au

JOURNAL SCAN Text message support increases weight loss in patients with prediabetes Diabetes Care Take-home message • In this randomised controlled trial, researchers analysed the ef- ficacy of text message support in achieving weight loss in 163 patients offered diabetes prevention program classes. Patients in the text message group lost more weight compared with the control group (mean 2.6 vs 0.6 pounds; P = 0.05). Furthermore, a higher rate of patients in the text message group achieved 3% weight loss (38.5% vs 21.5%; P = 0.02). • Text message support improved weight loss in patients with prediabetes, highlighting the importance of engaging patients in weight loss programs. Abstract

JOURNAL SCAN Life-years lost to diabetes Diabetes Research and Clinical Practice Take-home message

at diagnosis from 20.0 years for those diagnosed before age 20 years to no difference for those diagnosed after 80 years. Hazard ratios for mortal- ity decreased from 3.03 (95%CI 2.41–3.80) for those with diabe- tes diagnosed before 20 years to 1.04 (95% CI 0.78–1.39) for those diagnosed after 80 years. The estimate of life-years lost associated with diabetes was much higher among those with pre-existing cardiovascular dis- ease (20.3 years) than among those without cardiovascular disease (8.5 years). CONCLUSIONS The effect of diabetes on survival depends on age at first diagnosis of diabetes and the presence of pre-existing diseases. The life- years lost are higher for those with diabetes diagnosed at younger ages. This study pro- vided the updated estimates of life-years lost associated with diabetes in the United States. Life-years lost associated with diabetes: An individually matched cohort study using the US National Health Inter- view Survey data . Diabetes Res Clin Pract 2016;118:69–76, Z Wang, M Liu.

• This matched case-control study looked at years of life lost to diabetes in the United States; adults with diabetes had a lifespan 10.5 years shorter than matched controls. Life-years lost to diabetes decreased as age at diabetes diagnosis increased; those diagnosed before 20 years of age lost 20 years whereas those diagnosed after 80 years of age lost no years. In people with pre-existing CVD, 20.3 life-years were lost compared with only 8.5 years in those without CVD. • “Life-years lost to diabetes varies by age at diagnosis and comorbidities, and the results of this study provide clini- cians with estimates that are useful for counselling patients, prognostication, and weighing health risks.” Abstract

compared with 38.5% in the inter- vention group (95% CI 27.7–49.3) (absolute difference 17.0%; P value 0.02). Mean glycated haemoglo- bin (HbA 1c ) increased by 0.19% or 2.1 mmol/mol (95% CI -0.1 to 0.5%) and decreased by 0.09% or 1.0 mmol/mol (95% CI -0.2 to 0.0%) in the control group and inter- vention participants, respectively (absolute difference 0.28%; P = 0.07). Stratification by language demonstrated a significant treat- ment effect in Spanish speakers but not in English speakers. CONCLUSIONS Text message sup- port can lead to clinically significant weight loss in patients with pre- diabetes. Further study assessing effect by primary language and in an operational setting is warranted. Text message support for weight loss in patients with pre- diabetes: a randomized clinical trial . Diabetes Care 2016 Aug 01;39:1364-1370, HH Fischer, IP Fischer, RI Pereira, et al.

invitation to DPP classes as de- fined by the Centers for Disease Control and Prevention, or to the text message-augmented intervention group, which also received text messages adapted from the DPP curriculum for 12 months. RESULTS Mean weight decreased 0.6 pounds (95% CI -2.7 to 1.6) in the control group and 2.6 pounds (95% CI -5.5 to 0.2) in the inter- vention group (P = 0.05). Three percent weight loss was achieved by 21.5% of participants in the control group (95% CI 12.5–30.6),

OBJECTIVE Although the benefits of in-person Diabetes Prevention Program (DPP) classes for diabe- tes prevention have been dem- onstrated in trials, effectiveness in clinical practice is limited by low participation rates. This study explores whether text message support enhances weight loss in patients offered DPP classes. RESEARCH DESIGN AND METHODS English- and Spanish-speaking patients with prediabetes (n = 163) were randomised to the control group, which only received an

status, pre-existing cardiovas- cular disease and pre-existing cancer. All-cause mortality from original surveys to 31 December 2011 and median survival ages were estimated for those with diabetes and their matched controls. RESULTS Overall median survival age for adults with diabetes was 10.5 years shorter than that for matched controls without diabetes. Estimated life-years lost associated with diabetes decreased with increasing age

AIM Previous estimates of life- years lost to diabetes are highly inconsistent. This study pro- vided the updated estimates of life-years lost to diabetes in the United States. METHODS Each of a nation- ally representative sample of 21,829 adults with diabetes in the US National Health Inter- view Survey 1997–2009 was individually matched to one without diabetes by age, sex, race, survey year, BMI, smoking

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