Follow me on

Do SGLT-2 Inhibitors Change Fat Metabolism?

sharma-obesity-blood-sugar-testing2Since the introduction of SGLT-2 inhibitors (“gliflozins” or “glucoretics), as an insulin-independent treatment for type 2 diabetes, that works by blocking glucose reabsorbtion in the kidney resulting in loss of glucose (and calories) through the kidney, much has been written about the (albeit modest) weight loss associated with this treatment.

Several studies have documented that the weight loss leads to a change in body composition with an often significant reduction in fat mass.

Now, Giuseppe Daniele and colleagues, in a paper published in Diabetes Care, show that treatment with these compounds may enhance fat oxidation and increase ketone production in patients with type 2 diabetes.

The researchers randomized 18 individuals with type 2 diabetes to dapagliflozin or placebo for two weeks.

As expected, dapagliflozin reduced fasting plasma glucose significantly (from 167  to 128 mg/dL).

It also increased insulin-stimulated glucose disposal (measured by insulin clamp) by 36%, indicating a significant increase in insulin sensitivity.

Compared to baseline, glucose oxidation decreased by about 20%, whereas nonoxidative glucose disposal (glycogen synthesis) increased by almost 50%.

Moreover, dapagliflozin increased lipid oxidation resulting in a four-fold increase in plasma ketone concentration and and a 30% increase in fasting plasma glucagon.

Thus, the authors note that treatment with dapagliflozine improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production.

While this may explain the recent observation of a greater (albeit still rather rare) incidence of ketoacidosis with the use of these compounds, these findings may also explain part of the change in body composition previously noted with SGLT-2 treatment.

While this still does not make SGLT-2 inhibitors “weight-loss drugs”, there appears to be more to the fat loss seen with these compounds than just the urinary excretion of glucose.

@DrSharma
Edmonton, AB

Comments

Metformin Attenuates Long-Term Weight Gain in Insulin-Resistant Adolescents

metformin-300x217The biguanide metformin is widely used for the treatment of type 2 diabetes. Metformin has also been shown to slow the progression from pre to full-blown type 2 diabetes. Moreover, metformin can reduce weight gain associated with psychotropic medications and polycystic ovary syndrome.

Now, a randomised controlled trial by M P van der Aa and colleagues from the Netherlands, published in Nutrition & Diabetes suggests that long-term treatment with metformin may stabilize body weight and improve body composition in adolescents with obesity and insulin resistance.

The randomised placebo-controlled double-blinded trial included 62 adolescents with obesity aged 10–16 years old with insulin resistance, who received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months.

Of the 42 participants (mean age 13, mean BMI 30), BMI was stabilised in the metformin group (+0.2 BMI unit), whereas the control group continued to gain weight (+1.2 BMI units).

While there was no significant difference in HOMA-IR, mean fat percentage reduced by 3% compared to no change in the control group.

Thus, the researcher conclude that long-term treatment with metformin in adolescents with obesity and insulin resistance can result in stabilization of BMI and improved body composition compared with placebo.

Given the rather limited effective options for addressing childhood obesity, this rather safe, simple, and inexpensive treatment may at least provide some relief for adolescents struggling with excess weight gain.

@DrSharma
Edmonton, AB

Comments

Can Planned Cheating Help You Stick With Your Diet?

pepperoni-pizza-slice-3Many diet plans praise the importance of strict adherence to whatever the storyline of the diet happens to be. This includes tips on what foods to avoid or to never eat. Indulging in these “forbidden” foods, is considered cheating and failure.

Now, research by Rita Coelho do Vale and colleagues, published in the Journal of Consumer Psychology, explores the notion that planned “cheats” can substantially improve adherence with restrictive diets.

Using a set of controlled dietary experiments (both simulated and real dieting), the researchers tested the notion that goal deviations (a more scientific term for “cheats”) in the plan helps consumers to regain or even improve self-regulatory resources along the goal-pursuit process and can thus enhance the likelihood that the final goal is attained.

That, is exactly what they found:

Compared to individuals who followed a straight and rigid goal, individuals with planned deviations helped subjects regain self-regulatory resources, helped maintain subjects’ motivation to pursue with regulatory tasks, and (3) has a positive impact on affect experienced, which are all likely to facilitate long-term goal-adherence.

Thus, the authors conclude that, “…it may be beneficial for long-term goal-success to occasionally be bad, as long it is planned.

This is not really that new to those of us, who recommend or use planned “treats” as a way to make otherwise restrictive diets bearable.

Good to see that there is now some research to support this notion.

@DrSharma
Edmonton, AB

Comments

Effectiveness of Exercise Interventions After Bariatric Surgery

sharma-obesity-pedometer2There is no doubt that exercise is good for you and that individuals with obesity, both before and after bariatric surgery (like everyone else), would stand to benefit from increasing their levels of physical activity.

Following bariatric surgery, exercise may be particularly important not just to increase physical fitness, but also to limit the obligatory loss in muscle mass that generally accompanies weight loss.

Now, a study by David Creel and colleagues, published in OBESITY, compares three levels of exercise intervention in patients following bariatric surgery in terms of effectiveness and adherence.

A total of 150 patients undergoing bariatric surgery were randomised to either standard care (SC), pedometer use (P), or exercise counseling group (C).

The standard care group (SC) received no exercise support by the bariatric center beyond a simple educational pamphlet.

Participants in the pedometer group (P) were given a pedometer and a one-page information sheet on using the device to increase physical activity. This handout promoted the progressive attainment of 10,000 steps/day. Individuals were asked to wear their device daily and record date, steps achieved, and whether they wore the device the entire day, part of the day, or not at all. Journals were collected, but no feedback was provided.

Participants in the exercise counselling group (C) were regularly seen at the bariatric centre and counselled by a certified exercise professional using motivational intervention techniques with individual goal setting.

Based on physical activity measurements using an accelerometer over two weeks before and 2, 4, and 6 months postoperatively, there was no difference between the SC and P groups, with a statistically significant but modest increase in daily steps in the C group that emerged at 4 months and was maintained at 6 months (about 1,000 extra steps per day compared to SC).

There was no notable difference in exercise tolerance, which increased in all three groups post surgery.

No group reached the 10,000 steps/day or 150 bout-minutes/week recommended for general health

As may be expected from these rather modest results, no significant differences in weight or weight change were found between groups at any time point.

Thus, these findings suggest that handing out a pedometer and asking patients to journal their activity is no more effective in promoting physical activity, than simply handing out a pamphlet; moreover, even adding in counselling by an exercise professional adds little (if anything) to the outcome.

Although the researchers discuss the possibility that an even more intense intervention may provide more benefit, the modest findings certainly question the effectiveness of activity interventions post surgery.

Certainly, simply handing out pedometers does nothing, and adding in expensive group meetings or meetings with exercise professionals adds little more.

These finding by no means speak against the value of exercise after bariatric surgery – they just speak against the indiscriminate use of expensive healthcare resources, when they achieve little more than can be achieved by handing out a pamphlet.

@DrSharma
Edmonton, AB

 

Comments

What Behaviours Are Important For Optimal Outcomes With Bariatric Surgery?

sharma-obesity-gastric_bypass_roux-en-y3Bariatric surgery is by far the most effective treatment for severe obesity but outcomes vary from one patient to the next.

Now a paper by James Mitchell and colleagues, published in JAMA Surgery, reports on the postoperative eating behaviors and weight control strategies that are associated with differences in body weight seen at 3 years after bariatric surgery.

The study looks at self-reported data from over 2000 participants in the The Longitudinal Assessment of Bariatric Surgery-2 (LABS-2) study, a multicenter observational cohort study at 10 US hospitals in 6 geographically diverse clinical centers in the USA. Participants completed detailed surveys regarding eating and weight control behaviors prior to surgery and then annually after surgery for 3 years.

The researchers assessed 25 postoperative behaviors related to eating, weight control practices, and the use of alcohol, smoking, and illegal drugs.

The three key behaviours associated with poor outcomes were lack of weekly self-weighing, continuing to eat when feeling full more than once a week, and eating continuously during the day.

Thus, a participant who postoperatively started to self-weigh regularly, stopped eating when feeling full, and stopped eating continuously during the day after surgery would be predicted to lose almost 40% of their baseline weight compared to only 24% weight loss in participants who did not adopt these behaviours.

Other behaviours that had negative influences on outcomes included problematic use of alcohol, smoking and illegal drugs.

Thus, as one may have suspected all along, helping patients adopt and adhere to behavioural changes that include self-montioring and mindful eating behaviours can be expected to substantially affect the success of bariatric surgery.

@DrSharmma
Seoul, South Korea

Comments