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Can Metformin Reduce Weight Gain In Pregnancy?

sharma-obesity-pregnancy5Excessive weight gain during pregnancy is a well-established risk factor for both mother and child.

Now a paper by Argyro Syngelaki and colleagues from the UK, published in the New England Journal of Medicine, suggests that the anti-diabetes drug metformin may limit weight gain in pregnant non-diabetic women with obesity and also reduce the incidence of pre-eclampsia.

The researchers randomised 450 pregnant women with a BMI greater than 35 and no diabetes to either metformin (3 g/day) or placebo from weeks 12-18 weeks of gestation till delivery in a double-blind fashion.

Among the 400 women who completed the study, those on metformin gained about 2 Kg less weight than the placebo group.

There was also an almost 75% decrease in the risk of developing preeclampsia.

Despite these effects, metformin did not significantly reduce the incidence of large-for-gestational-age babies or other adverse neonatal outcomes.

While these findings may be somewhat disappointing with regard to outcomes in the offspring, the reduction in pre-eclampsia is impressive and, if confirmed, could well be an interesting use of this compound in high-risk pregnancies.

@DrSharma
Kelowna, BC

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If Oprah Can’t Why Do You Think You Can?

sharma-obesity-oprah1There are no doubt long-term “success stories” out there – people who just by making (often radical) changes in their diet and activity behaviours have lost a substantial amount of weight AND are keeping it off.

However, there is also no doubt that these people are rare and far between – which is exactly what makes each one of them so exceptional.

I am not speaking of all the people we hear or read about who have lost tons of weight – we hear about their spectacular weight loss – cutting carbs, cutting gluten, going vegan, going paleo, alternate day fasting, running marathons, training for iron man competitions, going on the Biggest Loser or eating at Subway.

What we don’t hear about is the same people, when they put the weight back on – which, in real life is exactly what happens to the absolutely vast majority of “losers”. We hear of their “success” and then we never hear from them again – ever.

Oprah is different! Different because, we have had the opportunity to follow her ups and downs over decades.

When Oprah “succeeds” in losing weight, she does not disappear into the night – no – she puts the weight back right in front of our eyes, again and again and again and again.

Now, comedy writer Caissie St.Onge, in a comment posted on facebook, pretty much summarizes what it is we can all learn (and should probably have learnt a long time ago) from Oprah:

“Oprah is arguably the most accomplished, admired, able person in the world. She creates magic for other people and herself on the regular. So, if Oprah can’t do permanent lifelong weight loss, maybe it can’t be done. Oprah is also crazy rich. If Oprah can’t buy permanent lifelong weight loss, maybe it can’t be bought.”

“I’m not saying you should give up on your dreams of having the body you want. I’m just asking, if you never get that waist, will your life have been a waste? (I see what I did there.) Every day we are bombarded with media, content and products. Special foods and drinks. Programs and plans. None of this shit has ever worked for Oprah and it probably isn’t gonna work for me or you.”

“I know the reason isn’t because you’re weak. If you’re carrying around 10 or 20, or 50 or 150 pounds more than the tiny friend who always calls herself fat in front of you and you don’t kick her in the back of the knee, you’re the opposite of weak. You’re very, very strong in at least two different kind of ways.”

“I realize there are people who are DYING to tell you what they think about what you should do with your body. It always starts with, “No offense but…” or “Not to be mean, but…” And it’s always offensive and mean, but also, you probably say things to yourself every day that are way meaner than what any “well-intentioned” “friend” or internet troll could come up with. You’re gonna have to try harder if you want to beat us at our own game, internet trolls. I would pop someone in the chops if they spoke to me the way I speak to myself. And I would bet all of Oprah’s money that Oprah says mean shit to herself too. Oprah does.”

“You can do what you want. You knew that. But I’m gonna stop wishing that I didn’t have dimples on the backs of my hands or that my ankles were more flattered by strappy shoes. I’m gonna stop telling people that they look great and start telling them what I really mean, that’s it’s nice to see them. And I see you. And I like you so much just how you are right now, and not a year or five years from now when you may or may not be smaller….. Oprah. I’ll love you either way.”

Cassie’s entire post is available here

@DrSharma
Edmonton, AB

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Will Low Oil Prices Lead To An Obesity Spike In Alberta?

Oil-Barrels-with-Red-Arrow-740There is no doubt that the low oil price is pummelling the Alberta economy.

According to the Alberta economic dashboard, in October 2015, Alberta’s seasonally adjusted unemployment rate was 6.6%, up from the 4.4% rate a year earlier and from last month’s 6.5% rate. The youth unemployment rate was 11.6%, up from last year’s 9.0% rate, while male unemployment increased precipitously from 3.6% last October to 7.3% this year.

As no one seems to be expecting a rosier future for this industry, it may well be that many who lost their jobs in the wake of mass oil patch layoffs, will find the coming months (not to mention the festive season) both economically and emotionally challenging.

According to this report, suicide rates from January to June in Alberta this year are up 30% compared to the same period in 2014.

One challenge that may escape notice is the fact that this situation may also lead to significant weight gain in those affected.

Depression, anxiety, food insecurity, insomnia and simply being unable to afford healthy food are all important risk factors for weight gain.

Indeed it is hard to imagine how going from a high-paying job to being unemployed with little immediate hope of recovery will affect families.

Maintaining a positive spirit – necessary for eating healthy, engaging in physical activity and healthy sleep – will clearly be a challenge.

So while it may take some time for “official” statistics regarding overweight and obesity to change, I would not be surprised to see numbers go up.

Unfortunately, when this happens, people putting on the extra pounds will likely face the same blame and shame for “making poor choices” as everyone else who is struggling with this problem faces everyday.

As medical professionals, we need to acknowledge that unemployment and the worries that come with it can make our patients more susceptible to weight gain – let us not miss the opportunity for prevention.

If you’ve been affected by the economic downturn and this is affecting your health, please feel free to leave a comment.

@DrSharma
Edmonton, AB

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Do Low-Calorie Sweeteners Affect Energy Intake Or Promote Weight Gain?

sharma-obesity-artificial-sweeteners1Yesterday, I posted about the interesting study by Madjd and colleagues suggesting that drinking water may be better for weight loss than drinking diet beverages.

But what exactly is the evidence that low-calorie sweeteners (of which there are many) may actually have non-caloric effects on energy intake or body weight?

This is the topic of a systematic review by Peter Rogers and other members of the European International Life Sciences Institute published in the International Journal of Obesity.

The authors assessed both animal and human studies involving the consumption of low-calorie sweeteners in conjunction with an ad libitum diet.

In 62 of 90 animal studies exposure to low-calorie sweeteners did not affect or decreased body weight. Of 28 studies that did report increased body weight, 19 compared compared low-calorie sweeteners with glucose exposure using a specific ‘learning’ paradigm.

In humans, 12 prospective cohort studies found inconsistent associations between the use of low-energy sweeteners and body mass index, with overall minimal effects at best.

A meta-analysis of short-term randomized controlled trials (involving 129 comparisons) showed reduced total energy intake for low-calorie sweetener versus sugar-sweetened food or beverage consumption before an ad libitum meal (about −94kcal per day), with no difference versus water (−2kcal per day).

These findings were consistent with energy intake observations in sustained intervention randomized controlled trials (10 comparisons), a meta-analysis of which (with study durations ranging from 4 weeks to 40 months) showed that consumption of low-calorie sweeteners versus sugar led to relatively reduced body weight (nine comparisons), and a similar relative reduction in body weight compared to water (three comparisons).

Thus, contrary to what is often stated in popular media or even by some experts, there is little if any evidence either from animal or human studies that the use low-caloric sweeteners has any measurable impact on energy intake (other than reducing total caloric intake) or body weight.

Thus, the authors conclude that

“Overall, the balance of evidence indicates that use of low-energy sweeteners in place of sugar, in children and adults, leads to reduced energy intake and body weight, and possibly also when compared with water.”

Obviously, even this analysis is not going to silence the sceptics, who will continue to claim that somehow low-calorie sweeteners are still messing up your energy intake or metabolism.

However, it may be fair to conclude that if indeed such effects exist, their magnitude is likely marginally and of doubtful clinical significance.

I will continue recommending that my patients do their best to replace sugar with non-caloric sweeteners if giving up their liking for sweet foods or beverages is not an option.

@DrSharma
Edmonton, AB

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Does Altered Immune Function Cause Obesity?

sharma-obesity-adipose-tissue-macrophageThe role of proinflammatory cells in adipose tissue as a determinant of insulin resistance and altered metabolic function is now well known.

However, there is also new data suggesting that altered immune function may well be an important causal step in the accumulation of excess fat and related metabolic abnormalities.

Two studies, both in animal models, point to a role of perforin, a cytotoxic effector molecule primarily released by CD8+ T cells and natural killer (NK) cells to eliminate infected or dangerous cells via the perforin-granzyme cell death pathway. In rare cases of humans with impaired perforin-dependent cytotoxic function, one often sees excessive T-cell activation, severe hyper-inflammation and possibly death.

The first study by Xavier Revelo and colleagues from the University of Toronto, published in Diabetes, perforin-deficient mice (Prf1null), which show early increased body weight and adiposity, glucose intolerance, and insulin resistance when placed on high-fat diet (HFD) were shown to have an increased accumulation of proinflammatory IFN-γ–producing CD4+ and CD8+ T cells and M1-polarized macrophages in visceral adipose tissue.

Furthermore, transfer of CD8+ T cells from Prf1null mice into CD8-deficient mice (CD8null) resulted in worsening of metabolic parameters compared with wild-type donors, thus demonstrating a role for T-cell function in insulin resistance associated with visceral adipose tissue.

In a second independent study by Yael Zlotnikov-Klionsky and colleagues from the Weizmann Institute of Science in Rehovot, Israel, published in Immunity, showed that animals selectively lacking perforin-rich granules in their dendritic cells, progressively gained weight and exhibited features of metabolic syndrome, an effect that could be completely prevented by T cell depletion.

Both studies show that the immunoregulatory protein perforin appears to be an important regulator or body weight and metabolic function – a finding, which may well open a new door biological drivers of obesity.

Incidentally, perforin also plays a role in auto-immune diseases and this finding may thus provide a link between the common occurrence of obesity in people with auto-immune disease and has led some authors to even suggest that obesity itself may be a form of auto-immune disease.

While the therapeutic options will certainly not be as simple as replacing low levels of perforin, understanding exactly how immune function ties into the regulation of body weight may eventually lead to novel targets.

@DrSharma
Edmonton, AB

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