Should Newly Diagnosed Diabetics Attempt to Lose Weight?

People with newly-diagnosed type 2 diabetes are faced with difficult decisions about weight loss.

They are often pushed to lose weight with the promise that this will improve their long-term health. The implication is that if they don't lose weight and change their lifestyle, they will surely have a heart attack and die sooner than later. Some care providers (and insurance companies) pressure new diabetics into weight loss programs through strong-arm tactics, shaming, and penalties.

However, the evidence is less than clear on the pros and cons of weight loss for diabetes. 

Short-term research seems to suggest benefits, but long-term research is much less clear. Some research even suggests potential harms. Let's talk about the benefits and risks.

The Look AHEAD Trial 

The Look AHEAD trial is the biggest example of the trade-off of pros and cons. It used an intensive life-style intervention to encourage intentional weight loss in type 2 diabetics. The trial was done with 5,145 people in 16 centers in the United States.

Details of the Study

Unlike most weight-loss trials, this one was long-term; major evaluations were done at 4 years and 8 years, but the study had a "median of 9.6 years of intervention and a maximal follow-up of 11.5 years." Participants were between the ages of 45 and 76 years old, and had to have a BMI over 25. 60% were women, and just over a third were from minority groups.

About half had a BMI under 35, with only about 22% from the heaviest group (BMI over 40). This means study participants skewed towards the lighter end of the BMI spectrum.

Participants were carefully selected to include those deemed most likely to lose weight successfully, including those who had prior intentional weight losses of more than 5% of bodyweight and who were highly motivated to lose weight. This detail is important because the trial does not represent a typical cross-section of the population and therefore may not be broadly applicable to those who do not fit the participant profile.

In this program, participants in the intensive lifestyle arm were asked to lose at least 10% of their body weight (with the hope that this would mean that study-wide, the group would lose on average a 7% weight loss goal). Participants were paid $100 each year to complete an annual weigh-in.

A lot of data from weight loss studies is pretty meaningless because of high drop-out rates. However, in this study, about 88% stayed through the eight-year post assessment. This relatively high completion rate gives more strength to this study.

The intensive lifestyle treatment arm was intense. For the first 4 months, participants were given meal-replacement shakes for 2 meals per day and snack bars for between meals. These were provided for free. They did eat one meal of real food per day but were encouraged to eat low-fat and low-calorie in that meal. After the first 4 months, participants were encouraged to continue using meal-replacement shakes for 1 meal per day for the rest of the first year and beyond, but it's not clear how many did or for how long.

After the first year, the focus was on maintaining weight loss and exercise levels, as well as offering additional support and interventions to those who did not achieve weight loss goals. 8-10 week "refresher" programs were offered each year to help refocus those who were regaining or who wanted additional help. So the program was not just about an initial weight loss program, but also about frequent re-do programs as needed.

Caloric goals were 1200-1500 calories for those less than 250 lbs. and 1500-1800 for those more than 250 lbs. Those who did not meet weight loss goals were encouraged to take Orlistat, a weight loss medication which was provided for free, although many did not choose to take it. They were also offered "more intensive behavioral interventions" to meet weight loss goals.

Participants were also encouraged to increase their exercise levels over time and had access to gym memberships, exercise equipment, and/or personal trainers. Participants were screened to make sure they were fit enough to do the exercise required so the study group did not include the sickest and most unfit diabetics. Participants were to slowly work up to a total of at least 175 minutes of exercise each week (about 3 hours per week), or about a half-hour of exercise per day, so the exercise requirements were not excessive. Most used walking as their preferred form of exercise.

Participants were asked to record food intake religiously and were encouraged to attend individual and group meetings regularly (individual meetings 1x/month and group meetings 3x/month for the first six months; individual meetings 1x/month and group meetings 2x/month after that). They were encouraged to weigh themselves daily at home and to weigh in at the group meetings. After the initial weight loss emphasis period was over, regular monthly meetings were encouraged and there were reminders about the program by email and texts. As noted previously, those not meeting weight loss goals had additional programs, behavioral interventions, and medications made available to them.

Weight Loss Results

The weight loss results from the study were mixed.

Overall, the intensive life-style intervention group managed to lose just 4.7% of their baseline weight at the end of 8 years. This is more than the diabetes support and education (DSE) group, which lost 2.1% in comparison, but it's not exactly impressive.

A 5% long-term loss is necessary to be deemed "clinically significant" in the medical literature. So by the evaluation calculated at 8 years, the study did not achieve a clinically significant weight loss.

However, when the study was terminated in 2012, the overall loss of the intervention group was about 6%, short of its goal of a 7% loss overall but squeaking by the 5% cutoff for clinical significance. This means the study authors could claim one of the very few long-term weight loss study success stories, but really, the "success" depends on when you looked at the data.

The fact that they were dancing around the 5% cutoff is more impressive than most long-term weight loss programs. Still, remember that this was among people pre-selected to be the most likely and highly motivated to lose weight.

The difference between the 4.7% at 8 years and the 6% at termination certainly suggests that there was a fair amount of yo-yoing going on. Did people really lose the weight and keep it off consistently, or were they bouncing all over the place constantly in the meantime? The most likely scenario was that there was a significant initial loss, followed by the typical slow regain, which the participants then fought by once again diving back into weight loss efforts, over and over again. However, we'd need access to the data of all the participants over the entire study length to confirm how often that was the pattern.

One of the more notable and highly publicized results of the study was that 50.3% of the intensive lifestyle group managed to lose 5% or more and 26.9% managed to lose 10% or more of their baseline weight at 8 years. Again, many of these were probably bouncing around rather than achieving a sustained loss, but even so, that's a fair success story.

But let's be fair. Half of the intervention group did manage to lose more than 5% of their baseline weight, but of course this also means that half did not, despite the very intensive interventions. Slightly more than one-fourth managed to lose at least 10% of their baseline weight, but of course, that also means that three-quarters of the intensive treatment group did not. So while the success rates were higher than most long-term studies, they are hardly a ringing endorsement of the success rates of weight loss.

The 8-year follow-up study also showed that 26.4% of intensive lifestyle participants had gained weight over their baseline weights. That's significant; over one-fourth of the weight-loss group actually ended up heavier than they started.

However, of those who lost at least 10% of their baseline weight in the first year, "only" 14% had gained weight over their baselines by year 8. This means that those who lost the most at first were less likely than others to end up heavier than they began.

The study shows that significant weight loss of around 5% is possible for some diabetics with intensive interventions. However, it also showed that even with intensive interventions, extensive weight loss was very difficult and do not work long-term for many. It seems to have translated more to a lot of yo-yoing around. Whether those people were better off for the yo-yoing is an ongoing question.

Frankly, I'd love to see more reporting on the group of those who yo-yo'd around and those who ended up heavier than they started. What were their outcomes? That's the real question for those of us with strong histories of weight cycling; would we be better off trying to lose weight, even if we regained it, or are we worse off yo-yoing around?

Still, the Look AHEAD study is often touted as proof of the importance of a weight loss for new diabetics and a refutation of the criticism that weight loss is usually unsuccessful. Half of the intensive lifestyle participants managed around a 5% loss, after all, and a quarter managed a 10%+ loss.

On the other hand, one analysis suggested that the Look AHEAD authors were putting too much of a positive spin on weight loss in the study and concluded:

The NEJM article states that this study represents that the “weight loss achieved in the intervention group is representative of the best that can be achieved by current lifestyle approaches.” If so, it’s a pretty meager showing for a highly-motivated population receiving an Über-Intensive-Lifestyle Intervention. These results should be the starting point for a broad re-assessment of behavioral lifestyle interventions...A ‘scientific society’ should confront the data and lead the discussion for re-assessment instead of putting the proverbial lipstick on a pig.

Health Results

What's most important is not how much weight people lost or didn't lose, but rather how this affected their health. The answer is that it's a mixed bag.

The Good News

Those who lost weight and managed to keep it off in the Look AHEAD trial did show some health improvement, as study promoters loudly proclaimed afterwards. That is very good news for those who lost weight.

They had improved blood sugar and lipid levels, less sleep apnea, less liver fat, less incontinence, improved sexual function, and better physical mobility. That's no small feat.

Some did reduce their risk for chronic kidney disease, which is quite important since kidney disease is a major issue for diabetics.

These health improvements are nothing to sneer at and do make a case for considering weight loss after a diagnosis of diabetes.

The So-So News

Newly diagnosed diabetics are often pushed into weight loss with the idea that this can "cure" their diabetes, so it's important to look at this outcome as well. However, "cure" is the wrong word; "remission" is a more appropriate word for what usually happens.

Some who lost weight in the Look AHEAD program did have some remission of their diabetes status in the first four years, at least for a while. However, the study noted that "absolute remission rates were modest" because only 3.5% managed to achieve and sustain diabetes remission for four years.

So while long-term diabetes remission was possible, it was achieved by only a few, even at only four years. Most often, diabetes remission was a temporary state of affairs, if it happened at all, and definitely not a "cure."

However, let's not forget that for some, blood sugar levels and other health markers did improve, even if it didn't result in total remission, so the focus shouldn't be only on remission.

The Mostly Bad News

The most important result was that while the trial resulted in modest health improvements, intentional weight loss did NOT reduce the rate of cardiovascular events in this group. 

This was a major disappointment for the study, especially given that its main hypothesis was that losing weight would result in fewer major events such as heart attacks or death.

Unfortunately, the intervention had NO effect on events like heart attacks, stroke, or death due to cardiovascular causes. In fact, the investigators terminated the study two years early because the lack of effect on the most important endpoints was so remarkable.

Critics contend that the lack of effect was seen because the "Diabetes Support and Education" (DSE) control group developed much less heart disease than the authors predicted. Many attributed this to the fact that many in the control group were put on statin medications, but whether this was the source of the difference is debatable.

On the other hand, a recent secondary analysis of the data showed that those who lost at least 10% of their initial weight did have some improvement in cardiovascular outcomes. Those who lost at least 10% of their baseline weight in the first year had a 21% reduced risk of the primary outcome (heart attacks, strokes, death from heart disease, or hospitalization for angina) and a 24% reduced risk of the secondary outcome (congestive heart failure, medical interventions like bypasses etc., and total mortality). A significant improvement in fitness levels also improved secondary outcomes but just missed achieving clinical significance in primary outcomes.

These are not huge improvements, mind, but they are improvements, so many doctors still feel that it's worth promoting significant weight loss in newly diagnosed diabetics, aiming for at least a 10% loss.

On the other hand, there were other disappointments. Weight loss did not lessen the rate of development of Atrial Fibrillation, an irregular heartbeat that can lead to strokes and other problems. That's another major disappointment.

Nor did the Look AHEAD trial interventions improve cognitive functioning. In fact, the authors noted:

There was some evidence of trends for differential intervention effects showing modest harm in [Intensive Lifestyle Intervention] participants with greater body mass index and in individuals with a history of cardiovascular disease.

That's a little alarming and should be investigated more. Quality of life matters. Based on what doctors have been saying for years, one would expect that a significant loss should improve cognitive functioning, not harm it. This definitely needs further research.

Another recent follow-up from the Look AHEAD trial also showed that those who regained weight or were weight cyclers in the trial had worse physical functioning scores by the end of the trial. That's a big deal. For some the intervention was clearly harmful.

And some research suggests that those who lost weight may also have issues with bone loss. The last thing diabetics need to add is more health problems like easily broken bones or osteoporosis.

So, bottom line, if you were part of the roughly one-fourth who lost a lot of weight at the beginning of the trial and were able to maintain that loss, there might have been some very modest improvements in cardiovascular outcomes, but certainly not the scope that they were hoping for.

For most who did not have a huge difference in weight, the intervention did not offer any improvement in cardiovascular outcomes or death rates.

And if you were part of the group that regained or were significant weight cyclers, you might actually have ended up worse off than you started.

So it seems the outcome depends on which group you were in. How do you predict which group you would likely be a part of? That's the $64,000 question.

Other Studies Like Look AHEAD

Of course, the Look AHEAD study is not the only one out there that has looked at weight loss and diabetes. It's just the one with the most-closely examined data.

Generally speaking, several studies show that for those who can maintain their weight loss, they have benefits like lower blood sugar and needing fewer medications. But what about those who do not maintain the weight loss?

One 2008 study found that even those who largely regained an initial weight loss had better glycemic control and blood pressure than those who were weight-stable after 3 years. (In this study, only 12.2% of newly diagnosed diabetics lost a clinically significant amount of weight, and most regained it all by the end of the study.)

However, other studies have not always found benefits if weight is regained. A 2015 study found that even only a partial regain after initial weight loss largely wiped out any improvements in blood sugar regulation.

In addition, a recent major Scottish study found that while sustained weight loss improved blood glucose control, strong weight variability was associated with poorer outcomes and poorer survival rates among recently-diagnosed diabetics. The authors concluded:

Our results suggest that weight loss or being weight stable with little weight variability early after diabetes diagnosis are associated with better glycaemic control...With respect to mortality and cardiovascular outcomes, although weight change at 2 years was a weak predictor, major weight variability appeared to be the more relevant factor.

And a recent long-term Danish study of newly-diagnosed diabetics also found that long-term intentional weight loss in diabetics did not improve all-cause mortality or cardiovascular-related morbidity and mortality in those followed for 19 years after diagnosis. The best prognosis was in those who maintained their weight.

So the idea that intentional weight loss automatically improves outcomes and prolongs lives among diabetics certainly can be questioned. It seems to help improve glucose control for those who lose a substantial amount of weight and keep it off long-term, but for those who yo-yo up and down or who regain the weight, the benefits are far more questionable and may even be harmful.

Summary

Most diabetes guidelines recommend lifestyle intervention (including an emphasis on losing weight as well as increasing exercise) for newly diagnosed diabetics.

Diabetes studies often state strongly weight-centric things like, "Weight management may be the most important therapeutic task for most obese Type 2 diabetic individuals."

But should all newly-diagnosed diabetics attempt to lose weight? Would some be better off maintaining their weight and working on fitness or other goals? This is a key question in the treatment of diabetes. Frankly, the research is debatable.

Short-term studies often show improvements in various risk factors and blood sugar regulation, sometimes even if weight is regained. That's no small accomplishment. However, many of these studies are notoriously brief and small in scope, often lasting a year or less. Benefits are often lost when participants are analyzed more long-term. You really have to take the short, small studies with a large grain of salt.

Moreover, most interventions in weight loss and diabetes studies do not result in clinically significant weight loss (more than 5%). One review concluded:

The majority of lifestyle weight-loss interventions in overweight or obese adults with type 2 diabetes resulted in weight loss <5% and did not result in beneficial metabolic outcomes.

Larger losses (greater than 10%) seem to have the most benefit long-term, but most participants do not manage such levels of weight loss long-term. The Look AHEAD study did not reach even its 7% weight loss goal, despite quite intensive interventions and a focus on those most likely to succeed. The same review listed above concluded:

Weight loss for many overweight or obese individuals with type 2 diabetes might not be a realistic primary treatment strategy for improved glycemic control.

The bottom line for those who have been diagnosed with type 2 diabetes is that there are no clear answers regarding weight loss. There might be some benefits from losing weight if it is sustained, but then again, there might be some risks as well, including increased fatness for those who regain weight or experience weight cycling. This might negate the short-term benefits of weight loss, especially since weight loss is negligible for most in terms of the most important endpoints like heart attacks, stroke, and death.

Frankly, we need better evidence to guide us. Studies need to:

• Last at least multiple years rather than months ─ at least 5 years is best
• Need to have sufficient participants to have the power to show clinically meaningful results 
• Need to differentiate between weight loss and exercise instead of lumping their effects together in analysis; it may be that increased exercise is far more important for blood sugar regulation and long-term health than weight loss itself (or vice versa)
• Need to investigate whether there are sub-groups who benefit most or who are most harmed by weight loss attempts, instead of assuming similar effects among whole groups
• Need to focus on weight cyclers in particular and see what the relative benefits and risks are for this group, since this is a very likely outcome for many 

So, the question becomes ─ if you are diabetic, do you try to lose weight in hopes that you would be one of the lucky ones who lose more than 10% of weight and keep it off? Or would you be more likely to be among those who regain or cycle? 

New diabetics have several key questions they must ask themselves. They should take a frank and honest look at their own habits, at their weight history, and at their lifestyle. They need to consider whether they think they could fall into that 10% sustained weight loss group, or whether they would be more likely to end up in the weight cyclers or weight gain groups.

In the end, the decision on whether or not to pursue weight loss should always be up to the patient. Patients can be advised of the potential benefits of weight loss, but they must also be advised of the potential risks of weight loss as well.

Guidelines from the American Diabetes Association push weight loss very strongly, but they do have some language tacitly acknowledging (in a rather condescending way) that the decision is up to the patient (my emphasis):

Diet, physical activity, and behavioral therapy designed to achieve 5% weight loss should be prescribed for overweight and obese patients with type 2 diabetes ready to achieve weight loss.

Those people who choose weight loss should be given every support possible, but without making participants' sense of self-worth dependent on their results. In addition, programs need to be extremely careful that they are not promoting eating-disordered behaviors or destroying participants' self-esteem. Many people with eating disorders developed them on well-meaning weight loss programs like these.

Those people who choose not to undertake weight loss should not be treated badly by care providers or penalized financially by insurance companies. Weight loss is a medical intervention, and like any other intervention, patients have the right to informed consent and should be free to accept or decline it without penalty.

Of course, it's always important to point out that you can fine-tune dietary intake and increase exercise without weight loss as your goal. This is the Health At Every Size® approach. Diabetics don't have to choose only between a weight-loss-at-any-cost approach or completely ignoring good nutrition and exercise (as many doctors wrongly assume a HAES® patient will do). There is a happy medium that emphasizes self-care without emphasizing the scale.

Some research suggests that a Mediterranean-style diet (mostly plant-based, low-to-moderate carbohydrate intake, with an emphasis on whole grains, nuts, and healthy fats) may be advantageous to diabetics. More research is needed, but initial studies are promising.

In addition, some people with blood sugar issues find that giving up certain types of foods they are sensitive to (like gluten, dairy, corn, or certain fruits and vegetables) changes their blood sugar responses without necessarily affecting their weight or calorie intake. This is another option some people may wish to explore.

Most importantly, increased fitness has been shown to improve blood sugar levels, insulin sensitivity, and quality of life in diabetics, especially when a combination of aerobic and resistance exercise is used. Thus, an emphasis on exercise, even without concurrent weight loss, may improve outcomes for diabetics.

Don't let diabetes education programs or doctors make you feel like your only choice after a diabetes diagnosis is weight loss. Whether you wish to participate in a weight loss program is your choice.

You can absolutely pursue weight loss if you feel like that is the right option for you, and there are many programs that will help you towards this goal if that's what you want. Just ask for them.

But if you don't wish to hop on the weight loss roller-coaster again, rest assured that there are things besides weight loss you can do to improve your outcomes.

My Take

I'm sure many readers are wondering if I'm writing about this topic from personal experience. No, I'm not diabetic, but there is an extremely strong history of diabetes on one side of my biological family so it is likely I will face a diagnosis at some point. Genetics is not destiny, of course, but it does point to strong probability. As a result, I look at studies like these periodically and debate what would be the best course for me if I did get diabetes at some point.

Personally, my feeling is that weight-loss decisions in diabetes should be made on a case-by-case basis rather than a blanket policy across the board. This is where I differ from experts in both the diabetes field and the size-acceptance field, who tend to be all-or-nothing ("everyone should lose weight" or "no one should ever try to lose weight") about the issue. I say, look at your personal history and habits and use those to guide your decision. 

For those who were once a "normal" BMI and who have simply gained weight due to age and/or poor habits, a weight loss emphasis might make sense. Anecdotally, these seem to be the people who are most successful at long-term weight loss and who benefit the most from it. It's just a returning to what is normal for their body.

Similarly, those who have had poor nutritional habits or an unhealthy relationship with food should be encouraged to improve those, since it is likely that improving these could well result in weight loss and improvements in blood sugar status.

Those who have indulged in foolish or trendy dieting practices (the "grapefruit diet" or similar programs) instead of sensible, moderate approaches might also benefit from trying again with a sensible plan. Whatever changes you make have to be sustainable, not something you do for a little while and then stop. 

However, I strongly suspect that major weight loss efforts are actually counter-productive for those who have been heavy most of their lives, have a long history of weight cycling, and who generally have reasonable habits and intake.

A lot depends on the person's personal weight and dieting history. If a person has a long history of weight cycling and obesity despite reasonable habits, I question the wisdom of subjecting that person to yet another round of dieting or ever-increasing caloric restriction. If they have a history of ending up heavier than they began after most diets, it seems far more likely that the intervention would harm rather than help, so why take that risk? In particular I question the likelihood of sustained weight loss for people who have biological reasons for fatness like lipedema or PCOS.

Also consider the psychological effects of an emphasis on weight loss; if it would harm self-esteem or re-trigger eating-disordered behaviors, then the potential benefits of weight loss may be far overshadowed by the potential harms. I strongly question the use of diets in this context. Eating disorders are very serious, and the potential for harm here is quite high. 

This doesn't mean that there is no role for lifestyle counseling. Habits can be relevant. But emphasis should be placed on HABITS and not on the scale, and lab results and the person's health should guide changes. Furthermore, recent research shows that more aggressive management of medications early in the course of diabetes may improve outcomes. To me, a more sensible course for many might be:

• To encourage an increase in both fitness and strength
• To focus on optimization of lab results through medication management and exercise
• To consult with a medical nutritional specialist who does not focus on weight loss or caloric restriction but rather on refining nutritional habits and discovering "trigger" foods that cause high blood sugar or insulin levels
• To find ways of living that are sustainable long-term and which do not measure a person's worth based on the scale
• [For those who are not yet diabetic but have an extremely strong family history of diabetes (or those who are in the "pre-diabetes" range), to consider medications like metformin as a proactive prevention treatment since research shows that this can lower the risk for diabetes even without weight loss]

Traditional medicine needs to step away from the "shame and blame" model of diabetes management. It needs to acknowledge that genetics play a stronger role in the development of type 2 diabetes and obesity than is generally recognized, and that while lifestyle habits can be relevant, they are not the whole story.

Only when medicine does this will it be able to move beyond the simplistic "every diabetic should lose weight" mentality. While it may be helpful to some, this approach is not helpful to many and may even be harmful to some.

The truth is that the best course of treatment for new diabetics is probably best individualized for each person, based on their personal history and circumstances. And as always, the final decision should be left up to the individual. 

References

Look AHEAD Studies

N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. Look AHEAD Research Group, Wing RR, Bolin P, et al. PMID: 23796131. Full text available here.

BACKGROUND: Weight loss is recommended for overweight or obese patients with type 2 diabetes on the basis of short-term studies, but long-term effects on cardiovascular disease remain unknown. We examined whether an intensive lifestyle intervention for weight loss would decrease cardiovascular morbidity and mortality among such patients. METHODS: In 16 study centers in the United States, we randomly assigned 5145 overweight or obese patients with type 2 diabetes to participate in an intensive lifestyle intervention that promoted weight loss through decreased caloric intake and increased physical activity (intervention group) or to receive diabetes support and education (control group). The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina during a maximum follow-up of 13.5 years. RESULTS: The trial was stopped early on the basis of a futility analysis when the median follow-up was 9.6 years. Weight loss was greater in the intervention group than in the control group throughout the study (8.6% vs. 0.7% at 1 year; 6.0% vs. 3.5% at study end). The intensive lifestyle intervention also produced greater reductions in glycated hemoglobin and greater initial improvements in fitness and all cardiovascular risk factors, except for low-density-lipoprotein cholesterol levels. The primary outcome occurred in 403 patients in the intervention group and in 418 in the control group (1.83 and 1.92 events per 100 person-years, respectively; hazard ratio in the intervention group, 0.95; 95% confidence interval, 0.83 to 1.09; P=0.51). CONCLUSIONS: An intensive lifestyle intervention focusing on weight loss did not reduce the rate of cardiovascular events in overweight or obese adults with type 2 diabetes.

Obesity (Silver Spring). 2014 Jan;22(1):5-13. doi: 10.1002/oby.20662. Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study. Look AHEAD Research Group. PMID: 24307184. Full text here.

OBJECTIVE: To evaluate 8-year weight losses achieved with intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study...RESULTS: All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012; ≥88% of both groups completed the 8-year outcomes assessment. ILI and DSE participants lost (mean ± SE) 4.7% ± 0.2% and 2.1 ± 0.2% of initial weight, respectively (P < 0.001) at year 8; 50.3% and 35.7%, respectively, lost ≥5% (P < 0.001), and 26.9% and 17.2%, respectively, lost ≥10% (P < 0.001)...CONCLUSIONS: Look AHEAD's ILI produced clinically meaningful weight loss (≥5%) at year 8 in 50% of patients with type 2 diabetes and can be used to manage other obesity-related co-morbid conditions.

Lancet Diabetes Endocrinol. 2016 Nov;4(11):913-921. doi: 10.1016/S2213-8587(16)30162-0. Epub 2016 Aug 30. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Look AHEAD Research Group. PMID: 27595918

...In this observational, post-hoc analysis, we examined the association of magnitude of weight loss and fitness change over the first year with incidence of cardiovascular disease. The primary outcome of the trial and of this analysis was a composite of death from cardiovascular causes, non-fatal acute myocardial infarction, non-fatal stroke, or admission to hospital for angina. The secondary outcome included the same indices plus coronary artery bypass grafting, carotid endartectomy, percutaneous coronary intervention, hospitalisation for congestive heart failure, peripheral vascular disease, or total mortality. We adjusted analyses for baseline differences in weight or fitness, demographic characteristics, and risk factors for cardiovascular disease...FINDINGS: For the analyses related to weight change, we excluded 311 ineligible participants, leaving a population of 4834; for the analyses related to fitness change, we excluded 739 participants, leaving a population of 4406. In analyses of the full cohort (ie, combining both study groups), over a median 10·2 years of follow-up (IQR 9·5-10·7), individuals who lost at least 10% of their bodyweight in the first year of the study had a 21% lower risk of the primary outcome (adjusted hazard ratio [HR] 0·79, 95% CI 0·64-0·98; p=0·034) and a 24% reduced risk of the secondary outcome (adjusted HR 0·76, 95% CI 0·63-0·91; p=0·003) compared with individuals with stable weight or weight gain. Achieving an increase of at least 2 metabolic equivalents in fitness change was associated with a significant reduction in the secondary outcome (adjusted HR 0·77, 95% CI 0·61-0·96; p=0·023) but not the primary outcome (adjusted HR 0·78, 0·60-1·03; p=0·079). In analyses treating the control group as the reference group, participants in the intensive lifestyle intervention group who lost at least 10% of their bodyweight had a 20% lower risk of the primary outcome (adjusted HR 0·80, 95% CI 0·65-0·99; p=0·039), and a 21% lower risk of the secondary outcome (adjusted HR 0·79, 95% CI 0·66-0·95; p=0·011); however, change in fitness was not significantly associated with a change in the primary outcome. INTERPRETATION: The results of this post-hoc analysis of Look AHEAD suggest an association between the magnitude of weight loss and incidence of cardiovascular disease in people with type 2 diabetes. These findings suggest a need to continue to refine approaches to identify individuals who are most likely to benefit from lifestyle interventions and to develop strategies to improve the magnitude of sustained weight loss with lifestyle interventions.

Obes Sci Pract. 2015 Oct;1(1):12-22. Epub 2015 Sep 14. Body Weight Dynamics Following Intentional Weight Loss and Physical Performance: The Look AHEAD Movement and Memory Study. Beavers KM, Neiberg RH, Houston DK, Bray GA, Hill JO, Jakicic JM, Johnson KC, Kritchevsky SB. PMID: 27453790

OBJECTIVE: To explore the impact of body weight change following intentional weight loss on measures of physical performance in adults with diabetes. DESIGN AND METHODS: 450 individuals with type 2 diabetes (age: 59.0±6.9 years, BMI: 35.5±5.9 kg/m2) who participated in the Look AHEAD Movement and Memory Study and lost weight one year after being randomized to an intensive lifestyle intervention were assessed. Body weight was measured annually, and participants were categorized as continued losers/maintainers, regainers, or cyclers based on a ±5% annual change in weight. Objective measures of physical performance were measured at the year 8/9 visit. RESULTS: Forty-four, 38 and 18% of participants were classified as regainers, cyclers, and continued losers/maintainers. In women, weight cycling and regain was associated with worse follow-up expanded physical performance battery score (1.46±0.07 and 1.48±0.07 vs. 1.63±0.07, both p≤0.02) and slower 20-meter walking speed (1.10±0.04 and 1.08±0.04 m/s vs. 1.17±0.04 m/s, both p<0.05) compared to continued or maintained weight loss. Male cyclers presented with weaker grip strength compared to regainers or continued losers/maintainers (30.12±2.21 kg versus 34.46±2.04 and 37.39±2.26 kg; both p<0.01). CONCLUSIONS: Weight cycling and regain following intentional weight loss in older adults with diabetes was associated with worse physical function in women and grip strength in men.

J Am Geriatr Soc. 2017 Jan 9. doi: 10.1111/jgs.14692. [Epub ahead of print] Effect of a Long-Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study. Rapp SR, et al.; Look AHEAD Research Group. PMID: 28067945

OBJECTIVES: To assess whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function...RESULTS: Assignment to lifestyle intervention was not associated with significantly different overall (P = .10) or domain-specific (all P > .10) cognitive function than assignment to diabetes support and education. Results were fairly consistent across prespecified groups, but there was some evidence of trends for differential intervention effects showing modest harm in ILI in participants with greater body mass index and in individuals with a history of cardiovascular disease. Cognitive function was not associated with changes in weight or fitness (all P > .05). CONCLUSION: A long-term behavioral weight loss intervention for overweight and obese adults with diabetes mellitus was not associated with cognitive benefit.

Studies Other Than Look AHEAD

J Acad Nutr Diet. 2015 Sep;115(9):1447-63. doi: 10.1016/j.jand.2015.02.031. Epub 2015 Apr 29. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ. PMID: 25935570

...A systematic review and meta-analysis was undertaken to answer the following primary question: In overweight or obese adults with type 2 diabetes, what are the outcomes on hemoglobin A1c (HbA1c) from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? Secondary questions are: What are the lipid (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides) and blood pressure (systolic and diastolic) outcomes from lifestyle weight-loss interventions resulting in weight losses greater than or less than 5% at 12 months? And, what are the weight and metabolic outcomes from differing amounts of macronutrients in weight-loss interventions? Inclusion criteria included randomized clinical trial implementing weight-loss interventions in overweight or obese adults with type 2 diabetes, minimum 12-month study duration, a 70% completion rate, and an HbA1c value reported at 12 months. Eleven trials (eight compared two weight-loss interventions and three compared a weight-loss intervention group with a usual care/control group) with 6,754 participants met study criteria. At 12 months, 17 study groups (8 categories of weight-loss intervention) reported weight loss <5% of initial weight (-3.2 kg [95% CI: -5.9, -0.6]). A meta-analysis of the weight-loss interventions reported nonsignificant beneficial effects on HbA1c, lipids, or blood pressure. Two study groups reported a weight loss of ≥5%: a Mediterranean-style diet implemented in newly diagnosed adults with type 2 diabetes and an intensive lifestyle intervention implemented in the Look AHEAD (Action for Health in Diabetes) trial. Both included regular physical activity and frequent contact with health professionals and reported significant beneficial effects on HbA1c, lipids, and blood pressure. Five trials (10 study groups) compared weight-loss interventions of differing amounts of macronutrients and reported nonsignificant differences in weight loss, HbA1c, lipids, and blood pressure. The majority of lifestyle weight-loss interventions in overweight or obese adults with type 2 diabetes resulted in weight loss <5% and did not result in beneficial metabolic outcomes. A weight loss of >5% appears necessary for beneficial effects on HbA1c, lipids, and blood pressure. Achieving this level of weight loss requires intense interventions, including energy restriction, regular physical activity, and frequent contact with health professionals. Weight loss for many overweight or obese individuals with type 2 diabetes might not be a realistic primary treatment strategy for improved glycemic control. Nutrition therapy for individuals with type 2 diabetes should encourage a healthful eating pattern, a reduced energy intake, regular physical activity, education, and support as primary treatment strategies.

Obes Res Clin Pract. 2015 May-Jun;9(3):266-73. doi: 10.1016/j.orcp.2014.09.003. Epub 2014 Oct 5. Effects of weight regain following intentional weight loss on glucoregulatory function in overweight and obese adults with pre-diabetes. Beavers KM, Case LD, Blackwell CS, Katula JA, Goff DC Jr, Vitolins MZ. PMID: 25293586

OBJECTIVE: To assess the extent to which initial, intentional weight loss-associated improvements in glucose tolerance and insulin action are diminished with weight regain. METHODS: 138 overweight and obese (BMI: 32.4±3.9kg/m(2)), adults (59.0±9.7 years), with pre-diabetes were followed through a 6-month weight loss intervention and subsequent 18-month weight maintenance period, or usual care control condition. Longitudinal change in weight (baseline, 6, 24 months) was used to classify individuals into weight pattern categories (Loser/Maintainer (LM), n= 50; Loser/Regainer (LR), n=51; and Weight Stable (WS), n=37). Fasting plasma glucose (FPG), insulin, and insulin resistance (HOMA-IR) were measured at baseline, 6, 12, 18 and 24 months and model adjusted changes, by weight pattern category, were assessed. RESULTS: LMs and LRs lost 8.3±4.7kg (8.7±4.5%) and 9.6±4.7kg (10.2±4.7%) during the first 6 months, respectively. LM continued to lose 1.1±3.4kg over the next 18 months (9.9±6.5% reduction from baseline; p<0.05), while LRs regained 6.5±3.7kg (3.3±5.3% reduction from baseline; p<0.05). Weight change was directly associated with change in all DM risk factors (all p<0.01). Notably, despite an absolute reduction in body weight (from baseline to 24 months) achieved in the LR group, 24-month changes in FPG, insulin, and HOMA-IR did not differ between WS and LR groups. Conversely, LM saw sustained improvements in all measured DM risk factors. CONCLUSIONS: Significant weight loss followed by weight loss maintenance is associated with sustained improvements in FPG, insulin, and HOMA-IR; conversely, even partial weight regain is associated with regression of initial improvements in these risk factors towards baseline values.

BMJ Open. 2016 Jul 26;6(7):e010836. doi: 10.1136/bmjopen-2015-010836. Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes: a retrospective cohort study. Aucott LS, Philip S, Avenell A, Afolabi E, Sattar N, Wild S; Scottish Diabetes Research Network Epidemiology Group. PMID: 27466237. Full free text found here.

OBJECTIVES: To determine weight change patterns in Scottish patients 2 years after diagnosis of type 2 diabetes and to examine these in association with medium-term glycaemic, mortality and cardiovascular outcomes...PARTICIPANTS: 29 316 overweight/obese patients with incident diabetes diagnosed between 2002 and 2006 were identified with relevant information for ≥2 years. RESULTS: By 2 years, 36% of patients had lost ≥2.5% of their weight. Increasing age, being female and a higher body mass index at diagnosis were associated with larger proportions of weight lost (p<0.001). Multivariable modelling showed that inadequate glycaemic control at 2 years was associated with being younger at baseline, being male, having lower levels of obesity at diagnosis, gaining weight or being weight stable with weight change variability, and starting antidiabetic medication. While weight change itself was not related to mortality or cardiovascular outcomes, major weight variability was independently associated with poorer survival and increased cardiovascular outcome risks, as was deprivation. CONCLUSIONS: Our results suggest that weight loss or being weight stable with little weight variability early after diabetes diagnosis, are associated with better glycaemic control and we identified groups less able to lose weight. With respect to mortality and cardiovascular outcomes, although weight change at 2 years was a weak predictor, major weight variability appeared to be the more relevant factor.

PLoS One. 2016 Jan 25;11(1):e0146889. doi: 10.1371/journal.pone.0146889. eCollection 2016. Intentional Weight Loss and Longevity in Overweight Patients with Type 2 Diabetes: A Population-Based Cohort Study. Køster-Rasmussen R, Simonsen MK, Siersma V, Henriksen JE, Heitmann BL, de Fine Olivarius N. PMID: 26808532

OBJECTIVE: This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI≥25 kg/m2) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients. METHODS: This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (≥40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989-92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers. RESULTS: Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97-1.50, P = 0.10), 1.26 (0.93-1.72, P = 0.14), and 1.06 (0.79-1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all-cause mortality, suggesting the best prognosis for those who maintained their weight. CONCLUSIONS: In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years.