Pregnancy After Bariatric Surgery - How Long Should You Wait?

After bariatric surgery, it is recommended to wait at least 12-18 months (with some guidelines recommending to wait two full years) before considering pregnancy.  This is because rapid weight loss and a higher risk for nutritional deficiencies occurs during this phase, which may be a poor environment for fetal development. However, a recent study suggests that waiting two years may not be enough.

The study, published in JAMA Surgery, looked at data from women and their infants in Washington state who had had bariatric surgery (n=1859), and compared them to women and their infants who had not had bariatric surgery (n=8437).  They found that babies who were born to mothers who had had bariatric surgery had a 57% higher risk of prematurity, 25% higher risk of needing to be admitted to the NICU, 93% higher risk of being small for gestational age.

However, when 4 years or more had elapsed since bariatric surgery, the risk of these outcomes was lower when compared to women where 2 years or less had elapsed.  Specifically, the risk for babies born less than 2 years after bariatric surgery was 48% higher for prematurity and 54% higher for NICU admission, compared to babies born to mothers where 4 years or more had elapsed (the difference for being small for gestational age was not significant). For babies born in the 2-4 year window after bariatric surgery, the authors note that the prevalence of prematurity and NICU admission was not meaningfully different from babies born to women who had not had bariatric surgery.

So how do we interpret these data? Well, we already knew that the risks identified in this study exist for babies born to mothers after bariatric surgery, but we need to remember that there are benefits to pregnancy outcomes after bariatric surgery as well - for example, less babies born large for gestational age, less labor and delivery complications, lower risk of C section birth, lower risk of gestational diabetes and high blood pressure in pregnancy.  However, based on these data, it may be better to wait even longer than two years after bariatric surgery before conceiving.

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Poke Free Blood Sugar Monitor Helps Prevent Lows

On behalf of my patients who struggle with the discomfort of having to poke their fingers to check their blood sugars every day, I am super excited about a new poke-free technology that will hopefully be approved in Canada soon – the Freestyle Libre.  With this glucose monitoring system, a small patch is applied to the upper arm with a tiny filament underneath which inserts under the skin.  Wave your glucose monitor over the patch and voilà! – the last 8 hours of blood sugars, including current blood sugar, are transmitted to your monitor for evaluation.  Not only that, but it tells you the current trend in sugar (ie if your blood sugar is on its way up, down, or stable).

In the first randomized controlled trial of this device, it has now been show that monitoring with the Libre helps patients with type 1 diabetes prevent hypoglycemia (low blood sugars).  The study, published in The Lancet, randomized 241 patients with good blood sugar control to the Libre vs usual monitoring with finger pokes.  They found that over 6 months, people using the Libre spent 38% less time with low blood sugars than people using standard finger pokes.  (Despite this benefit, people using the Libre still spent a shocking 2 hours per day with low blood sugar, compared to 3.3 hours per day for people taking finger pokes - so clearly a better monitoring approach is only part of the solution.)

Ten patients reported concerns related to the sensor, primarily itching, allergic reaction, or redness at the site (not out of keeping of the usual risk of reactions to medical devices that stick to the skin).  Some aspects of quality of life were reported to be improved as well – not surprising,  since studies have shown that people with diabetes who have had severe low blood sugar in the past fear this occurring again as much as they fear blindness as a complication of their diabetes.

It would be interesting for this study to be repeated in people with type 2 diabetes, and also to compare the Libre to the continuous glucose monitoring system.

Bottom Line: The Libre would be a strong addition to our blood glucose monitoring options for diabetes in Canada.

Disclaimer: I have received honoraria as a continuing medical education speaker and consultant from the makers of the Freestyle Libre (Abbott). 

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www.drsue.ca © 2016

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Want A Lower Calorie Meal To Go?

For those days when you know you're going to need to eat on the run, it can be especially hard to resist the temptations of the take-out restaurant or deli that you hit up for your lunch.  A great way to cut calories on those days was proven in a recent study - order well ahead!

The study, published in the Journal of Marketing Research, found that longer delays between placing a lunch order and eating lunch was associated with a reduction in calorie content of the order, with 38 calories less ordered per hour of delay between the order and lunchtime.  They also found that people who ordered lunch immediately before eating had the highest calorie content of their order - about 100 calories more than someone ordering earlier in the day.

Ordering lunch soon after breakfast may be the best time to order, perhaps because of fullness from breakfast, or perhaps because it's easier to think about exerting self control over our future selves than our present selves.  Perhaps the stress of the day hasn't yet taken hold in the earlier morning, allowing us to make healthier lunch choices (stress can cause us to eat more and crave unhealthy foods).  Whatever the reason, try ordering lunch when you get to the office in the morning, and let me know how it goes via comments to this post!

Thanks to my friend Bob for the heads' up on this study!

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Type 2 Diabetes Medications Exenatide Weekly and Dapagliflozin Studied In Combination

In the wake of the recent annual European diabetes (EASD) meeting, another important study (and heavy science blog post!) coming your way today.

In the care of people with type 2 diabetes, we have fully 9 classes of glucose lowering medications to choose from in Canada.  While some of these medications can cause weight gain, others are weight neutral, and some can cause weight loss, in addition to improving blood sugar control.  Two classes of medications can cause weight loss, namely the GLP1 receptor agonists, and the SGLT2 inhibitors.  As 90% of people with type 2 diabetes also have overweight or obesity, it is of interest to know whether these two classes of medications can be used together, for even better blood sugar control and greater weight loss.

Two of these medications, the GLP1 receptor agonist exenatide qweekly (Bydureon) and the SGLT2 inhibitor dapagliflozin (Forxiga) have now been studied in combination.  Recently published in The Lancet Diabetes & Endocrinology, the study randomized 695 patients with a baseline hemoglobin A1C of 8-12% to receive either exenatide qweekly, dapagliflozin, or the two medications in combination. 

After 28 weeks, hemoglobin A1C decreased by 1.6% in the exenatide group, by 1.4% in the dapagliflozin group, and by 2.0% in the combination group.   While the medications together were better than either drug alone, the benefit was not additive.  This does not surprise us, as we know that the higher starting A1C, the greater reduction we will see – so to be on two medications together would not expect to give an additive result compared to either medication alone.

The weight loss seen was additive, with a loss of -1.54kg in the exenatide group, -2.19kg in the dapagliflozin group, and -3.41kg in the combination group. Blood pressure reduction also exhibited an additive response, with a systolic BP reduction of -1.3mmHg on exenatide, -1.8mmHg reduction on dapagliflozin, and a full -4.2mmHg reduction on the combination.  These additive benefits make sense, given that each of these medications has a different mechanism of action on weight and blood pressure.

From a safety point of view, side effects that were seen were as expected from what we already know about each of these classes of medications, with no suggestion for any negative side effects of using the two medications in combination.

Finally, we have much awaited data that shows us that these two medications can be used safely in combination, with the result of better diabetes control, and an additive effect on both weight loss and blood pressure.

Disclaimer: I am involved in research trials of GLP-1 receptor agonists and SGLT2 inhibitors.  I receive honoraria as a continuing medical education speaker and consultant from the makers of exenatide and dapagliflozin (Astra Zeneca). 

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www.drsue.ca © 2016

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Diabetes Medication Semaglutide Decreases Cardiovascular Events

Hot off the presses from the New England Journal of Medicine – an emerging type 2 diabetes medication called semaglutide has been shown to decrease cardiovascular events in a high risk population with type 2 diabetes.

The two year study, called the SUSTAIN-6 study and in which I was an investigator, enrolled 3,297 people from 20 countries around the world who had established cardiovascular disease, or at least one cardiovascular risk factor.   They were randomized to receive either semaglutide 0.5mg, semaglutide 1.0mg, or placebo as once weekly subcutaneous injections.

The primary outcome of the study, which was a composite outcome of first occurrence of nonfatal heart attack, nonfatal stroke, or cardiovascular death, was found to be reduced by 26% compared to placebo, with 6.6% of patients on semaglutide experiencing an event, vs 8.9% of patients on placebo.   When we look at these endpoints individually, there was a significant reduction of 39% of nonfatal stroke, whereas the differences in nonfatal heart attack and death were not significant.  

Although all patients in the study were treated to achieve target glycemic control, blood glucose control was better in the semaglutide groups, with hemoglobin A1C reduced by 0.7% and 1.0% in the semaglutide 0.5mg and 1.0mg groups respectively, compared to placebo, despite the fact that insulin needed to be started twice as often in the placebo group than in the semaglutide group.

In terms of other complications that we are aiming to prevent in people with diabetes, rates of new or worsening kidney disease was reduced with semaglutide.  The risk of retinopathic (eye) complications was higher, experienced by 3% of patients on semaglutide vs 1.8% of patients on placebo.  Rarely, achieving glycemic control rapidly (particularly when sugars start off very high) can paradoxically increase the risk of eye complications.  It is not clear if this was the reason in these patients; a direct effect of semaglutide cannot be ruled out.

So what does this mean for the care of people with type 2 diabetes?  The above results suggest that 45 people with type 2 diabetes and high cardiovascular risk would need to be treated for 2 years in order to prevent one cardiovascular event.  In the diabetes world, this is an impressive benefit, similar to the benefit of statins for cholesterol, and also in a similar realm to the two other diabetes medications, empagliflozin and liraglutide, that have been shown to prevent cardiovascular events (read more here and here).  The data showing cardiovascular benefit on all three of these medications has come out within the last year – before that, we did not have definitive evidence that any diabetes medication clearly reduces the risk of cardiovascular events.

It is indeed wonderful that we now know that some glucose lowering medications are able to prevent cardiovascular events in people with type 2 diabetes.  While semaglutide has not yet been approved for use, this study suggests that it will be a beneficial addition to our type 2 diabetes treatment armamentarium.

Disclaimer: I have been involved in research trials of semaglutide, other GLP-1 receptor agonists including liraglutide, and SGLT2 inhibitors like empagliflozin.  I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide and liraglutide (Novo Nordisk) and empagliflozin (Boehringer-Ingelheim/Eli Lilly).  

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Barrier to Exercise - Low Sugars in Diabetes

A healthy lifestyle includes exercise, and is part of standard recommendations to most people for maintenance of health and well being.  People with diabetes who take medications that can cause low blood sugar usually have to alter medications and/or food intake to avoid having a low blood sugar induced by the exercise.  A low blood sugar can be a very frightening experience -  sadly, as a recent study shows, the fear of having low blood sugars may actually prevent people with type 1 diabetes from engaging in exercise.

The study, published in the Canadian Journal of Diabetes, surveyed over 500 adults with type 1 diabetes, asking about how they manage their diabetes in the context of exercise.

The majority of these people said that they increased carbohydrate intake before (79%) and after (66%) exercise, and about half of them decreased their meal time insulin before and/or after exercise.  Despite making these adjustments, however, 70% of people reported that they still experience low blood sugars after exercise.  Fear of low blood sugars was identified as a barrier to exercise.

While people with type 2 diabetes were not surveyed in this study, I can attest to the fact that people with type 2 diabetes who are taking medications that can cause low blood sugars (insulin, sulfonylureas, and meglitinides) share these concerns and struggles in preventing low sugars with exercise.

Newer insulins are becoming available to decrease the risk of low blood sugars, and much work is being done to advance the technology in glucose sensing and insulin pump devices as well. For people with type 2 diabetes, medications that do not cause low blood sugar may be an option.    But for those who do take insulin or medications that can cause low sugars, the most important part of avoiding lows around exercise as much as possible is working closely with your diabetes educator to find strategies that work for you.  Each person will be different in terms of what medication they are taking; what kind of exercise is being done and for how long; eating patterns; and how your body responds to that particular exercise.  If you have diabetes and are struggling with preventing lows around exercise, be sure to see your diabetes educator to explore strategies that will work better for you.

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Duodenal Mucosal Resurfacing for Treatment of Type 2 Diabetes?

Our knowledge and understanding about the role of gut hormones in type 2 diabetes continues to grow, as we get a better understanding of the mechanisms involved in the often dramatic improvement in diabetes that is seen after bariatric surgery.  In gastric bypass surgery, we know that at least one of the mechanisms involved is food literally bypassing the first segment of the small intestine, called the duodenum.  This effect may be seen because food is more rapidly delivered to the intestine further down, causing a more powerful release of hormones from the more distal intestine (called the hindgut hypothesis).  However, there may also be an as yet unidentified hormone (or hormones) secreted by the first part of the gut that have an antidiabetic effect, and by having food skip over this part of the gut, this mystery antidiabetic hormone is not released, thereby improving blood sugar control (called the foregut hypothesis).  We do know that the surface of the duodenum in a person with diabetes is altered, with a sort of overgrowth of cells in the duodenal mucosal (called hypertrophy and hyperplasia).

For believers of the foregut hypothesis, a novel approach called Duodenal Mucosal Resurfacing (DMR) is now being studied to see if diabetes control can be improved by doing a sort of 'thinning out' of the lining of the upper part of the intestine.

The first human study of DMR, recently published in the journal Diabetes Care, performed the DMR procedure in 39 patients with type 2 diabetes.  They found an improvement in diabetes control at 6 months post procedure, with greater improvement in those who had a longer segment of the duodenum ablated than those that had a shorter segment treated. Improvement in blood sugars was seen as soon as 1-2 weeks after the procedure, despite no restrictions in diet or calorie intake being recommended.  The improvement in diabetes control was not as powerful as what is seen with gastric bypass surgery, suggesting that there are many additional elements at work in gastric bypass surgery.  The authors also noted that there was some erosion of the improvement in diabetes control at 6 months, so certainly larger and longer studies need to be done to understand what the effect of this procedure is over the long term. There was little weight loss in this study (only a few kg), so the DMR does not hold promise as a weight management strategy.   The procedure was well tolerated overall, though there were three cases of duodenal stenosis that were treated with balloon dilatation.  The authors noted no signals for malabsorption (eg no calcium abnormalities or iron deficiency anemia), but this would need to be evaluated carefully in long term studies as well.

It will be interesting to see further study of the DMR procedure.

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www.drsue.ca © 2016

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