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DIRECT Remission of Type 2 Diabetes in Primary Care?

There is no reasonable argument against the fact that excess weight gain is one of the key drivers of diabetes risk, and it should come as no surprise to anyone, that losing weight (though bariatric surgery or otherwise) dramatically improves glycemic control in people living with type 2 diabetes.

So what exactly can we learn from the DIRECT study published by Michael Lean and colleagues in The Lancet?

For one, this is a large cluster-randomised trial of obesity intervention conducted entirely in a non-specialist primary care setting with significant weight loss (at least 15 Kg) and diabetes remission (defined as glycated haemoglobin (HbA1c) of less than 6·5% after at least 2 months off all antidiabetic medications) as the pre-defined primary outcome at 12 months.

In the intervention centres, a nurse or dietitian (as available locally) was given a total of 8 h structured training by the study research dietitians experienced in the Counterweight-Plus program.

Initial weight loss was induced with a total diet replacement phase using a low energy formula diet (825–853 kcal/day) for 3 months (extendable up to 5 months if wished by participant), followed by structured food reintroduction of 2–8 weeks (about 50% carbohydrate, 35% total fat, and 15% protein), and an ongoing structured programme with monthly visits for long-term weight loss maintenance.

Given the primary care non-specialist setting of this trial, the key findings (as summarized by the authors), were perhaps surprising:

“Just less than a quarter of participants in the intervention group achieved weight loss of 15 kg or more at 12 months, half maintained more than 10 kg loss, and almost half had remission of diabetes, off antidiabetic medication….Remission was closely related to the degree of weight loss maintained at 12 months, with achievement in 86% of participants with at least 15 kg weight loss, and 73% of those with weight loss of 10 kg or more. 28% of all eligible individuals volunteered to participate,17 and 79% completed the intensive total diet replacement phase…”

In general, the intervention was well tolerated with 117 out of 150 participants (78%) in the intervention group completing the intervention.

So here are the key learning from DIRECT:

For one, there should no longer be any doubt that “remission” of Type 2 diabetes is possible in a substantial number of patients, if we can help them achieve and sustain significant weight loss – the odds of experiencing remission are directly proportional to the amount of weight lost.

Secondly, using a strategy of low-calorie diets and behavioural intervention (allowing ample room for individual preferences) appears feasible in a primary care setting, delivered by health professionals with modest training in obesity management.

Obviously, as anyone who has seen weight loss before is well aware, the challenge in obesity management is more in keeping the weight off than in losing it in the first place. Although sustaining significant weight loss over 12 months is notable, one cannot but wonder how well the participants will do in keeping the weight off in the years to come. This is of course recognised by the researchers, who intend to follow the participants over the next 4 years.

Although a very low calorie diet may not be everyone’s cup of tea, given that the only other intervention that comes anywhere close to the results reported in this paper is bariatric surgery, the findings of this study are indeed notable.

Personally, I would assume that combining the dietary intervention presented in this study with additional pharmacological management may well prove sustainable in the long-term with benefits not just for diabetes control.

I say this because the complex biology of obesity dictates that individuals living with obesity will need a lot more than willpower and hope to sustain meaningful weight loss over time.

@DrSharma
Edmonton, AB

 

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Diagnosis and Treatment of Obstructive Sleep Apnea in Adults

In follow up to yesterday’s guest post by Christy Turer on her challenges in getting timely diagnostics and treatment for a patient with severe obstructive sleep apnea (OSA), it appears timely that this week’s issue of the Canadian Medical Association Journal (CMAJ) features a full-length update on the diagnosis and treatment of OSA in adults.

As  Cheryl Laratta form the University of British Columbia and colleagues point out, OSA) is likely underdiagnosed in Canada with lack of appropriate treatment putting many at risk of poor quality of life, comorbidity, motor vehicle crashes and increased health care utilization.

Clinical features include daytime sleepiness, unrefreshing sleep or fatigue, frequent nocturnal waking due to choking or gasping, nocturia, morning headaches, poor concentration, irritability and erectile dysfunction. Bed partners may report snoring or witnessed apneas. Atypical symptoms, more frequently reported by women, include insomnia, impaired memory, mood disturbance, reflux and nocturnal enuresis.

However, as the authors point out, the correlation of symptoms with disease severity is poor, which is why it is important for physicians to be alert to milder symptoms and screen individuals who present with known risk factors like overweight/obesity, increased neck circumference and nasopharangeal crowding. Importantly, while the presence of these features increases pre-test probability, neither history nor physical examination are enough to rule out OSA.

A number of questionnaires (e.g. Berlin Questionnaire, STOP-Bang, etc.) are available to assist in screening patients.

As for diagnosis,

“The gold standard for diagnosis of OSA is attended polysomnography (level I study), which involves collection of seven or more data channels, including electroencephalogram and electrooculogram for sleep staging, electromyogram, electrocardiogram and respiratory channels.”

Less reliably,

“Level III sleep studies record a minimum of three channels of data while the patient sleeps at home. Level III studies usually monitor airflow, snoring, respiratory excursion, body position, heart rate and oxygen saturation, but some validated devices use surrogate measurements for these variables, such as tonometry or actigraphy, and the technology is constantly evolving.51 Level III studies do not record sleep; therefore, severity of OSA is estimated using the respiratory event index, which is the number of desaturation events per hour of total recording time.”

Treatment options include nightly use of a continuous positive airway pressure (CPAP) device or the use of oral devices (for less severe cases). The latter should be custom fitted by a dentist with extensive experience or additional training in dental sleep medicine.

Oddly enough, there is no mention of obesity treatment as an effective measure to manage OSA, given that there is evidence from both medical and surgical obesity treatment studies that document clinically important improvement in OSA with weight loss.

The article also briefly discusses on-going long-term patient management as well as some of the important research issues that remain to be studied regarding the rather complex pathophysiology of this common disorder.

In addition,

“Research into the models of service delivery for OSA, including strategies to improve timely access to care, funding for OSA treatment and patient preference, will be important to improve the care of Canadians with sleep disordered breathing.”

@DrSharma
Edmonton, AB

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Urgent Need For Low-Cost In-Home Diagnostics For Obstructive Sleep Apnea

Christy Turer, MD,  Assistant Professor of Pediatrics, Internal Medicine, and Clinical Sciences at University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA

Today’s guest post comes from Christy Turer, MD,  Assistant Professor of Pediatrics, Internal Medicine, and Clinical Sciences at University of Texas Southwestern (UTSW) Medical Center, Dallas, Texas, USA.  

This week, I saw a 50 year-old female patient with obesity (BMI 44) who desperately needs screening and treatment for obstructive sleep apnea (OSA).

Over the past four years, her heart function (ejection fraction) has declined from >60% to now ~20% with significant pulmonary hypertension, almost certainly related to undiagnosed, untreated OSA based on multiple nightly witnessed apneas.

Although she now sleeps with oxygen, this does nothing for her hypopnea-related, sympathetic overdrive-mediated, cardiac dysfunction.

Without CPAP treatment, her life expectancy is two years or less.

Unfortunately, within the public health system for which I work (county system that offers free or discounted healthcare to poor residents in a metropolitan city, USA), the average wait time for a sleep study is 1-2 years.

To be fair, this patient has had a previous attempt at a sleep study in a sleep lab a couple of years ago. At that time, however, the study was inconclusive, because she could not fall asleep in the sleep lab’s unfamiliar environment.

It is frustrating not being able to help my patients with suspected sleep apnea, especially, when I know that help could be available.

It is high time we had a technological disruption that enables cheap, reliable, in-home OSA assessment for patients.

Christy Turer, MD
Dallas, TX

Dr Turer is a standing member of the US Food and Drug Administration’s Pediatric Advisory Committee, a consultant to the FDA’s Endocrinologic/Metabolic Drugs Advisory Committee, and Past-Chair of the Obesity Society’s Clinical Management of Obesity Section. She has authored numerous scientific articles and lectured widely on primary-care evaluation and management of overweight/obesity and related metabolic comorbidities across the lifespan. Her comments do not reflect the views of UTSW, FDA, or any of her funding sources. 

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Free Webinar: Assessing Body Fat – Taking Obesity Phenotyping To The Next Level

As readers will be well aware, n terms of health risks, fat is not fat is not fat is not fat.

Rather, whether or not body fat affects health depends very much on the type of body fat and its location.

While there have been ample attempts at trying to describe body fat distribution with simple anthropometric tools like measuring tapes and callipers, these rather crude and antiquated approaches have never established themselves in clinical practice simply because they are cumbersome, inaccurate, and fail to reliably capture the exact anatomical location of body fat. Furthermore, they provide no insights into ectopic fat deposition – i.e. the amount of fat in organs like liver or muscle, a key determinant of metabolic disease.

Recent advances in imaging technology together with sophisticated image recognition now offers a much more compelling insight into fat phenotype.

In this regard, readers may be interested in a live webinar that will be hosted by the Canadian Obesity Network at 12.00 pm Eastern Standard Time on Thu, Nov 23, 2017. The webinar provides an overview of a new technology developed by the Swedish company AMRA,  that may have both important research and clinical applications.

The talk features Olof Dahlqvist Leinhard, PhD, Chief Scientific Officer & Co-Founder at AMRA and Ian Neeland, MD, a general cardiologist with special expertise in obesity and cardiovascular disease, as well as noninvasive imaging at the UT Southwestern Medical Center in Dallas, US.

Registration for this seminar is free but seats are limited.

To join the live event register here.

I have recently heard this talk and can only recommend it to anyone interested in obesity research or management.

@DrSharma
Edmonton, AB

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Vote of Thanks From The Obesity Chair

Me back in 2007 (note the ETS monthly pass for my then  daily commutes to the RAH)

10 years ago, I was enticed to take up an endowed “Chair” in obesity research and management at the University of Alberta with the task to develop and lead the fledgling bariatric program at the Royal Alexandra Hospital.

The decision to move to the University of Alberta from a prestigious Tier 1 Canada Research Chair in obesity at McMaster University, where my research enterprise was moving along just fine, was largely prompted by the Ontario Government’s bumbling indecision (despite all of my considerable and enthusiastic advocacy efforts on behalf of my patients) about promoting much needed bariatric services in Ontario (as a side note, only six weeks after I had signed on with the University of Alberta, the Ontario government, after much to-and-froing, finally did announce substantial funding for a province-wide bariatric program, which continues to this date as the Ontario Bariatric Network).

Despite my sadness at leaving my most wonderful and supportive colleagues at McMaster University, I have not for a moment regretted my move to Edmonton. Not only did I find another set of as supportive colleagues at the University of Alberta but also the committed and dedicated staff within Capital Health (now part of  Alberta Health Services), all of which enthusiastically supported the creation of a now world-class academic bariatric program in Edmonton. With well over 100 peer-reviewed publications to show for (with a notable mention to the colleagues who helped develop the Edmonton Obesity Staging System and the 5As of Obesity Management), the academic work in obesity was only a rather small part of my activities as “Chair”.

Together with my colleagues at Alberta Health Services, we supported a total of 5 bariatric clinics across the province, all of which are now up and serving Albertans living with severe obesity –  each adapted to local resources and interests. Of these, the Edmonton Adult Bariatric Specialty Program at the Royal Alexandra Hospital of course continues as the flagship program, offering a full suite of behavioural, medical, and surgical treatments for Albertans with severe obesity.

With my move to Edmonton, so did the national office of the Canadian Obesity Network (co-hosted by the University of Alberta and Alberta Health Services). As readers will be well aware, this pan-Canadian network of now well over 15,000 obesity researchers, health professionals, trainees, and now 1000s of public supporters, continues to grow and steadfastly pursue its important mission of promoting obesity research, professional education in obesity management, fighting weight bias and discrimination, and advocating for better access to obesity prevention and management for all Canadian children and adults across the continuum of care.

Now, as the 2nd (non-renewable) 5-year term of my appointment as “Obesity Chair” comes to an end, I can only humbly express my sincere thanks to all of my many colleagues and staff at the University of Alberta and Alberta Health Services for supporting all of my activities. I also send out a sincere vote of thanks to all my patients, who continue to keep me well grounded in the reality of clinical obesity practice.

While I may no longer hold the “Chair”, I will of course continue serving in my role as Professor at the University of Alberta and fully aim to further pursue all of my academic and clinical activities while continuing to advocate for better access to obesity care for Albertans (and all Canadians). I also plan to continue to in my role as Medical Co-Director of Alberta Health Services’ Obesity Strategy.

As the search now commences for a new endowed “Chair” (and I know that the University will be looking for the best possible candidates from across Canada and the world), I look forward to working closely with whoever takes on this role to continue improving care for Albertan adults and children living with obesity.

@DrSharma
Edmonton, AB

 

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Oral Semaglutide Is As Effective For Weight Loss As Injections

Readers will recall, that once-weekly injections of the novel long-acting GLP-1 analogue semaglutide was recently shown (in patients with type 2 diabetes) to result in a rather impressive weight loss.

Now, a phase II dose-finding study comparing various oral doses of semaglutide to subcutaneous injections in patients with type 2 diabetes was just published in JAMA.

The 26-week trial with 5-week follow-up included around 600 patients with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized to once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks.

Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%);

Significant reductions were also seen in body weight with both oral (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg)>

Adverse events (largely consisting of mild to moderate gastrointestinal events) were as expected and relatively comparable between the treatment arms.

Although this was a diabetes study, these findings clearly hold promise for the further development of an oral formulation of semaglutide for the obesity indication.

@DrSharma
Tønsberg, Noway

Disclaimer: I have served as a consultant for Novo Nordisk, the maker of semaglutide. 

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