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… Read More »
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.
A recent CMAJ article, by Ian Mosby and Tracey Galloway from the University of Toronto argues that one of the key reasons why we see obesity and diabetes so rampant in Canada’s indigenous populations, is the fact that widespread and persistent exposure to hunger during the notorious residential school system may have metabolically “programmed” who generations toward a greater propensity for obesity and type 2 diabetes. There is indeed a very plausible biological hypothesis for this, “Hunger itself has profound consequences for childhood development. Children experiencing hunger have an activated hypothalamic–pituitary–adrenal stress response. This causes increased cortisol secretion which, over the long term, blunts insulin response, inhibits the function of insulin-like growth factor and produces long-term changes in lipid metabolism. Through this process, the child’s physiology is essentially “programmed” by hunger to continue the cycle of worsening effects, with their bodies displaying a rapid tendency for fat-mass accumulation when nutritional resources become available.” While the impact of hunger may well have been one of the key drivers or metabolic changes, the authors failed to acknowledge another (even more?) important consequence of residential schools – the impact on mental health. Oddly enough, in a blog post I wrote back in 2008, I discussed the notion that the significant (and widespread) physical, emotional, and sexual abuse experienced by the generations of indigenous kids exposed to the residential school system would readily explain much of the rampant psychological problems (addictions, depression, PTSD, etc.) present in the indigenous populations across Canada today. The following is an excerpt from this previous post: This disastrous and cruel [residential school] policy resulted in much pain and despair in the First Nations’, Inuit and Metis people that lasts to this day (known as the “generational effect”). Sexual, physical and mental abuse was widespread; students were broken in heart and spirit; culture and identities were destroyed. Much (if not all) of what ails the Aboriginal peoples of Canada can be traced back to this policy – including possibly issues that affect Aboriginal health to this day. It is no secret that obesity and its consequences (e.g. diabetes) are rampant amongst the Aboriginal peoples of Canada. While poverty, breakdown of traditional lifestyle and culture and even genetic factors (thrifty genotype) have all been implicated in this, I wonder how much the misery caused by the residential school program had to contribute. Early traumatic life experiences including sexual, mental and physical… Read More »
Managing weight in patients with type 2 diabetes (most of who have significant overweight or obesity) is always challenging, not least because many medications used to treat diabetes can also promote weight gain. Now, a paper by Judy Shiau and colleagues from the University of Ottawa, in a paper published in the Canadian Journal of Diabetes, present the results of a retrospective cohort study (1992 to 2009) of weight, glycemic control and diabetes medications changes in 317 patients with obesity and type 2 diabetes at 6 months on a low-calorie diet program. The program (week 1 to week 26) included mandatory weekly group sessions led by a dietitian, behaviour therapist or exercise therapist. All patients received OPTIFAST ®900 as full meal replacements (MR) starting at week 2. Patients consume 4 MR shakes per day for a total of 900 kcal per day, a regimen that is high in proteins (90g/day) and moderate in carbohydrates (67 g/day). Patients with initial body mass indexes (BMIs) of 33 kg/m2 or higher commited to 12 weeks of full MRs, while patients with initial BMIs below 33 started with 6 weeks of full MRs and the option to increase to up to 12 weeks of full MRs. Once patients completed their full MR regimen, there was a 5-week transition period to regular food, typically followed by a maintenance diet, as determined in a one-on- one dietitian counselling session. As glycemic control improved with weight loss, anti-diabetes medications were adjusted or discontinued, thereby stopping any weight-gain-promoting medications first. As the authors note, “At 6 months, both groups had lost 16% of their weight, and the decreases or discontinuations of medications were 92% sulfonureas, 87% insulins, 79% thiazolidinediones, 78% alpha-glucosidase inhibitors, 50% meglitinides, 33% dipeptidyl peptidase-4 (DPP-4) inhibitors and 33% metformin. At 6 months, compared with baseline, A1C levels improved significantly and at 6 months, 30% of patients were no longer taking diabetes medications and had significantly better percentages of weight loss compared with those taking medications (18.6% vs. 16%; p=0.002).” Thus, this paper shows that, a low-calorie meal replacement program can substantially improve glycemic control and reduce the need for anti-diabetes medications. Unfortunately, as participants were transitioned to community care at 6 months, little is know about how long these effects last. Nevertheless, with the increasing availability and use of weight-neutral or even weight-reducing anti-diabetes medications, one may expect that some of these effects can be… Read More »
Last week I was an invited plenary speaker at the 1st International Diabetes Expert Conclave (IDEC2017) held in Pune, India. This 3-day event, organised by Drs. Neeta Deshpande (Belgaum), Sanjay Agrawal (Pune) and colleagues, brought together well over 900 physicians from across India for a jam-packed program that covered everything from diabetic food disease and neuropathy to the latest in insulin pumps and devices – all in a uniquely Indian context. I, of course, was there to speak on obesity, which featured prominently in the program. Topics on obesity ranged from the potential role of gut bugs to bariatric surgery. While Dr. Allison Goldfine, former Director of Clinical Research at the Joslin Diabetes Center in Boston spoke on the latest developments in anti-obesity pharmacotherapy (delivering her talk via Skype), I spoke about obesity as a chronic disease and the need to redefine obesity based on actual indicators of health rather than BMI. During my visit in Pune, I also had the opportunity to visit with my friend and colleague Dr. Shashank Shah, whose bariatric surgical center in Pune alone performs about 75 to 100 bariatric operations per month – a remarkable number by any standards. Of course, the overwhelming number of talks were given by Indian faculty (there being only a handful of select invited international faculty at the meeting), and I did come away most impressed by the breadth and depth of knowledge presented by the local speakers. Diabetes care certainly appears to be in good hands although the sheer number of patients with diabetes (estimated at about 70 million, which I assume to be a rather conservative assessment), would provide a challenge to any health care system. On the obesity front, things are a lot less rosy, given that (as everywhere else) obesity has yet to receive the same level of professional attention and expertise afforded to diabetes or other chronic diseases. Thanks again to the organisers for inviting me to this exciting meeting and congratulations on an excellent event that bodes well for the 2nd Conclave planned for 2018. @DrSharma Edmonton, AB