Doctor's Review: Medicine on the Move

October 24, 2017

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Conference proceedings: 15th Annual CDA/CSEM

Coping with Canada's sugar high

In medicine, there are specialities where our knowledge seems to grow at a glacial pace, and little changes from one year to the next, while in other fields the therapeutic advances come so thick and fast it's hard to keep up. And then there’s diabetes, which increasingly feels like a desperate rearguard action against an onrushing public health disaster. So far, it's a battle we're losing.

That was the key message heard at the Vancouver Convention Centre October 10 to 13, at the 15th Annual Conference of the Canadian Diabetes Association/Canadian Society of Endocrinology and Metabolism. The CDA believes that over 3 million Canadians currently have diabetes, and a further 6 million have prediabetes, of whom half will progress to clinical disease. That's twice their estimate from a decade ago, and the CDA projects that one in three Canadians will have diabetes or prediabetes by 2020. “But this does not have to be our future,” said Michael Cloutier, CDA president. “We’ve identified steps that can be taken now that could dramatically reduce the incidence and seriousness of diabetes while we continue to work towards a cure.”

Patient, heal thyself

Curing diabetes was not completely off the agenda. Noted American researcher Dr Carla Greenbaum laid out several promising avenues of research in type 1 diabetes. But in type 2 disease, this was a conference that heard more from the trenches of frontline treatment than it did from the research labs of academe. In coming to grips with an epidemic, public health measures come to the fore. The focus of Canadian endocrinologists is on slowing the growth of diabetes in those populations where it has made the fastest inroads: children, First Nations, and women. And the name of the game is one that will elicit a sigh of resignation from doctors everywhere: lifestyle modification.

Canada's future may or may not turn out ugly, but it's certainly looking somewhat chubby. "It's time obesity is taken more seriously by the medical profession," said keynote speaker Dr Alissa Zentner.

Canada now has Clinical Guidelines for the Management of Obesity, but the actual treatment of obesity is mostly left to unsupervised private weight-loss programs. The CDA believes this approach is self-defeating since obesity is, as the title of Dr Zentner's presentation said, The Disease That Begins It All.

Patients who fail to manage their own weight are all too likely to end up managing their own diabetes. Ontario has led the way on teaching self-management through Diabetes Education Centres (DECs) that typically offer individual counselling on issues like glucose self-monitoring and healthcare utilization. But research led by Dr Baiju Shah of Toronto's Institute for Clinical Evaluative Sciences showed that the 82 percent of Ontario DEC patients who received individual counselling actually had poorer outcomes than the minority who learned to control their disease in group sessions. The same team found that as DECs increasingly take on the counselling of patients with prediabetes, some are running short of places for patients with the actual disease.

Sliding off track

Reducing the harm of diabetes demands early and focused intervention in the youngest patients. But Dr Shazhan Amed of Vancouver's Child and Family Research Institute found dismal results when his team followed all British Columbia youth under 20 diagnosed with T2D and measured adherence to clinical practice guidelines in their treatment. On a rating scale from 1 (poor adherence) to 4 (optimal care), the average score was 1.85 in the first year after diagnosis, and it only went downhill from there, dropping both with age and time since diagnosis. The transition to adulthood is a time when care should be optimal. It clearly isn't.

Adherence to guidelines also seems poor at the other end of the age spectrum. It's recommended that patients aged over 65 start an ACE inhibitor or ARB in the year after starting on an oral antidiabetes drug. But Dr Line Guénette of the University of Laval and colleagues found that, among 43,700 over-65 T2D patients in Quebec, only 31 percent did so. Uptake was even lower in the 75-plus age group, who stood most to benefit from cardiovascular protection. Worse still, the rate of adherence seems to be falling, not climbing, since 2005. One unusual finding of this study was that rural patients, at least in this respect, got more optimal treatment more often than their urban counterparts.

It's doubly regrettable when patients aren't treated according to Canadian diabetes guidelines because these have been rated by the Johns Hopkins University Evidence-Based Practice Review Center as one of the best diabetes guidelines in the world, behind only Britain's. The current set dates from 2008, but they are updated regularly. A complete new set is expected in 2013. One area that needs work is to ensure their compatibility with kidney disease guidelines since the two diseases so often overlap — up to 50 percent of CKD patients have diabetes — and a patient with both diseases would currently be getting contradictory nutritional advice from the two guidelines. The guidelines will also discuss statins whose FDA labelling now includes a warning about blood sugar elevation. Some statin trials have reported slightly higher rates of new-onset diabetes, but like FDA, the CDA takes the view that statins' cardiovascular benefits outweigh their metabolic risks.

The drugs are working

There has been no shortage of new T2D treatments in recent years and while none has delivered any sort of breakthrough in glycemic control, the latest generation does seem to be holding up better post-approval than some previous entries. In the studies presented in Vancouver, Liraglutide’s antiglycemic and weight loss effects were well preserved in two studies of patients with renal impairment. It was also found to suppress post-prandial triglyceride and apolipoprotein B48 responses after a fat-rich meal.

The new basal, ultra-long action insulin degludec was also tested in kidney patients, including ESRD patients both with and without dialysis. Its pharmacokinetics remained reassuringly stable in all of these groups.

Finally, the DPP-4 inhibitors are showing evidence of a cardioprotective effect beyond their antiglycemic function. Saxagliptin-treated rats with induced myocardial infarction appeared to recover more completely than those taking liraglutide or placebo. This may be due to the DPP-4 inhibitor's ability to prevent the degradation of stromal cell-derived factor-1 (SDF-1), an anti-apoptotic and proangiogenic chemokine that appears in ischemic injury.

Cushing's disease

It's not all diabetes all the time at an endocrinology conference. Two studies threw a light on stark inter-provincial differences in the treatment of Cushing's disease. In Ontario, transsphenoidal surgery (TSS) is the clear standard, used in 79 percent of patients and achieving 76 percent disease control. Only 6 percent underwent bilateral adrenalectomy (BLA), with a poor 32 percent disease control rate, while 12.7 percent used medical therapy, of whom 39 percent achieved disease control.

In Quebec, by contrast, TSS and BLA are relied upon equally, used in 23 percent and 21 percent of patients, respectively. Medical therapy is used in 25 percent, mostly ketoconazole and fluconazole. Ontario appeared to achieve better disease control, but patients in both provinces struggled with a high frequency of comorbidities.

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