Friday, June 02, 2006

It's Your Heath - What are you Going to Do About It?

With the recently published estimate that one in three Americans either have diabetes or impaired fasting glucose (pre-diabetes) the alarms are sounding that we must modify our lifestyle or face the consequences. The oft-repeated recommendations include losing weight, eating less calories, eating less fat and increasing physical activity. To be clear, losing weight can and will improve health. Eating fewer calories does result in weight loss and increased activity does have a positive effect on glycemic control.

To convince you that complying with the recommendations will prevent or delay the onset of diabetes if you eat less fat as part of your calorie reduction isn't necessary even though a number of studies are being referenced as "proof" such a dietary modification works best.

Some background - the American Diabetes Association (ADA) sets the standard for evaluating test results and diagnosis of pre-diabetes or type II diabetes. Since October 2003, the ADA maintains that normal fasting blood sugar is 100mg/dL or lower; pre-diabetes is greater than 100mg/dL but less than 126mg/dL; and diabetes is a reading greater than 126mg/dL. They also maintain a series of values for testing of glucose tolerance - when levels of blood sugar remain at or below 140mg/dL after an oral glucose challenge, the person is said to have a normal glucose response; blood sugars greater than 140mg/dL but less than 200mg/dL indicate impaired glucose tolerance (pre-diabetes); and blood sugars higher than 200mg/dL indicate diabetes is present.

With these numbers in mind, let's take a look at the evidence from the studies the ADA references to see how well the recommendations are at preventing progression of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Heck, let's even see if the dietary recommendations can reverse IFG or IGT!

Let's really see if the ADA's claim that "Research has also shown that if you take action to manage your blood glucose when you have pre-diabetes, you can delay or prevent type 2 diabetes from ever developing;" and that, "People with pre-diabetes can expect to benefit from much of the same advice for good nutrition and physical activity. The links on this page are cornerstones of successful management of pre-diabetes."

The ADA states that the Diabetes Prevention Program study "conclusively showed that people with pre-diabetes can prevent the development of type 2 diabetes by making changes in their diet and increasing their level of physical activity. They may even be able to return their blood glucose levels to the normal range." [emphasis mine]

How about we take a look?

The study was published in the New England Journal of Medicine in 2001. It provides an interesting look at how three different approaches may influence the development of diabetes in those with pre-diabetes. The researchers recruited 3,234 individuals to participate and randomly assigned them to three groups - 1,082 were in the placebo group (control); 1,073 were in the Metformin group; and 1,079 were in the lifestyle intervention group - instructed to increase activity to 150-minutes per week and modify diet as per ADA recommendations and lose 7% of their body weight.

There were indeed differences at the end of the study - 28.9% of the control group progressed to a diagnosis of diabetes; 21.7% of the Metformin group progressed to a diagnosis of diabetes; and 14.4% of the lifestyle intervention group progressed to a diagnosis of diabetes. Basically, those individuals who followed the lifestyle intervention had a 58% less chance of developing diabetes than those who did nothing.

Impressive, isn't it?

The researchers concluded "Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin."

Something important to keep an eye on - the lifestyle intervention did not prevent diabetes in everyone who followed the recommendations. In fact, the researchers point out that to prevent one case of diabetes, seven individuals would have to follow the intervention program in three years. "To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program."

So, while statistically there was a risk reduction of 58% in those following the lifestyle intervention, the program worked for one in seven individuals over the three year period.

Tuck that number away in your head - one in seven over three-years - for later.

More importantly though - did the lifestyle intervention have a positive effect on fasting blood sugars and HbA1C over the study period? Those in the study all started with impaired glucose tolerance, which we'll address in a moment. Did the FBG and HbA1C improve over time with lifestyle modifications?

Initially, at the six-month and one-year follow-ups there were dramatic changes for those who modified their lifestyle - impressive improvements in fasting blood glucose (FBG). At baseline those in the lifestyle intervention group had an average FBG of 106.3mg/dL which declined over the first year to just a hair above 100mg/dL. After the first year, their fasting blood glucose levels rebounded however, so for the first year the diet and exercise did have a positive effect - but that was lost over time as fasting blood glucose did a rebound and ended higher at the conclusion of the study than at baseline. So, after three years of the lifestyle intervention, while they weren't diabetic, those in the intervention group experienced an overall negative effect on fasting blood glucose - it worsened over time.

The same disturbing trend is seen with regard to the HbA1c levels. Initially HbA1c improved only to rebound over time with the follow-up levels higher than baseline - HbA1C worsened over time.

So, what about glucose tolerance - the measure of how well an individual metabolizes glucose when given an oral challenge?

At the start of the study, every person participating had impaired glucose tolerance. During the one-year follow-up a considerable percentage - about 50% - had GTT test results which showed normal glucose tolerance. However, much like the rebound experienced with fasting blood glucose and HbA1c levels, we find a similar decline over time with glucose tolerance.

While the ADA likes to cite this study as definitive, "conclusive" proof that lifestyle modification will prevent diabetes - the reality is that this study shows you'll probably experience some significant improvements initially, but with rebound trends evidenced in the data, progression toward diabetes is being delayed not stopped. Yes, that's better than uninterrupted progression - but shouldn't we be looking for a way to reverse what we now call "pre-diabetes" so that the risk of diabetes isn't just reduced, but eliminated?

As I said before, a number of studies are cited to convince you to follow the ADA recommendations if your fasting blood glucose or glucose tolerance tests show "pre-diabetic" values.

The newest one to hit the media is the one I already wrote about - High-fibre, low-fat diet predicts long-term weight loss and decreased type 2 diabetes risk: the Finnish Diabetes Prevention Study. While my previous article didn't explore the findings relative to glucose testing, let's take some time today to review that data.

Like the Diabetes Prevention Program study, the Finnish Diabetes Prevention study also recruited individuals with impaired glucose tolerance. This trial was a bit longer than the ADA study, an average follow-up of 4-years. Of the 500 individuals who completed the study term, 114 were diagnoised with diabetes along the way (one in five). Where the data is interesting is the difference in baseline values of those who developed diabetes and those who did not.

In those who remained free of an official diagnosis of diabetes (based on testing results), their baseline fasting blood glucose averaged 108mg/dL and their GTT results averaged 158.4mg/dL. They did have impaired glucose tolerance, and if we were to use today's accepted standard for impaired fasting glucose (100mg/dL or higher) they also had impaired fasting glucose. This study used the older standard of 110mg/dL so those participating were not considered having impaired fasting glucose.At the end of the study period, their fasting blood sugars remained at 108mg/dL - so there was no improvement there; their glucose tolerance did improve somewhat, to 145.8mg/dL - but they remained pre-diabetic with impaired glucose tolerance. Impaired glucose tolerance is impaired glucose tolerance - the intervention did not reverse this state.

They differed from those who did develop diabetes - specifically their blood test levels were lower than those who developed diabetes during the study. At baseline, those who went on to develop diabetes started with higher average fasting blood glucose levels averaging 117mg/dL - over time that rose to 127.8mg/dL; their initial baseline glucose tolerance was poorer also. At baseline those who developed diabetes averaged 169.2mg/dL readings after a glucose challenge which rose to 208.8mg/dL over time.

So while this study is being offered up as proof that consumption of dietary fat and fiber are significant predictors of progression of developing diabetes, let's not forget that those that did not develop diabetes continued to have impaired glucose tolerance. They actually started the study with better odds - their fasting blood sugars and glucose tolerance were lower at baseline than those that progressed to diabetes! The researchers don't discuss this in their paper though.

From these two studies we clearly see that a lifestyle modification, as per the ADA recommendations, can delay onset of diabetes - but that's just slowing it down, not preventing or stopping it from developing. Don't get me wrong - delaying is better than nothing....but, are we looking at all avenues available - perhaps one that doesn't just delay onset of type II diabetes, but reverses the pre-diabetic state so the individual has normal readings when tested.

Should we just forget the long-term consequences of elevated fasting blood sugar or impaired glucose tolerance? Remember neither of the above studies changed the state of impaired glucose tolerance or improved fasting blood sugars or lowered HbA1C levels.

Should we ignore that study after study points to the increased risks associated with impaired fasting glucose and impaired glucose tolerance - insulin resistance, dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation, hypercoagulability and increased risk for heart disease and stroke! Isn't reversing the pre-diabetic state the goal we should be after rather than simply maintaining such a health-damaging state?

Are we willing to admit defeat?

Are we going to continue to ignore evidence that we can reverse the pre-diabetic state?

Are we goiong to contine to dismiss evidence that we can offer individuals diagnoised with type II diabtes an option which may not just stop progression of the disease, but reverse it?

Is there any evidence we can really do this? Or am I just speculating here?

Well, we have dozens of studies that have investigated diets that restrict carbohydrate while allowing either higher intake of protein or fat. We have data that consistently shows following such a diet improves cholesterol (specifically increasing HDL and dramatically reducing triglycerides), enables weight loss with greater satiety and spontaneous calorie reduction, improves blood pressure and increases insulin sensitivity. The data we're lacking is the effect such a dietary approach has on fasting blood glucose and glucose tolerance because few researchers have included these parameters in their study design or haven't specifically followed individuals with pre-diabetes.

The evidence we do have shows much promise. Recently, Dashti et al published Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level - in the April 2006 issue of Molecular Cell Biology. In their 56-week study following obese subjects, they found glucose levels decreased significantly (p=0.0001) from a baseline to end-of-study. In fact, after following the diet for one year, glucose levels were within normal range!

As I said though, there just isn't much data out there to really give us a clear picture about how a carbohydrate controlled diet affects those classified as "pre-diabetic." What we do have is data from studies investigating a controlled-carb or low-carb diet's effect in those with type II diabetes though.

Yancy et al published a small, short-term study in 2005, A low-carbohydrate, ketogenic diet to treat type 2 diabetes, that found statistically significant improvement in fasting glucose in those individuals following a low-carb diet. Over sixteen weeks, 28 individuals with diabetes were recruited to follow a low-carb diet. At baseline the group had an average fasting blood glucose of 163.4mg/dL - after sixteen weeks their fasting blood glucose declined to 136.26mg/dL - still, as a group diabetic.

But, if we dig into the paper, we find that of the 28-individuals in the group, 7 discontinued all medication for diabetes, 10 reduced medication and only 4 required medication at the same level as they did at baseline. Folks, that's one-in-four who improved fasting glucose levels to the point where diabetic medication was no longer needed, and another one-third had to reduce their medication during the diet.

One in four had their diabetes medications stopped during the study. Isn't that better than one in seven maintaining a pre-diabetic state, even though they did not progress to diabetes?

Too bad the study here was only 16-weeks - what would have happened if those in the study were followed for six months? One year? Three years?

But honestly, this isn't "new" information. In fact, back in 1994, JAMA published Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus, in which the researchers concluded that "In NIDDM patients, high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels, which may not be desirable."

Sixteen years ago researchers stated bluntly that a diet high in carbohydrate caused persistent deterioration of glycemic control, and yet it remains the diet of record from the ADA for those who are pre-diabetic or diagnoised with diabetes!

But I digress...

In 2004, Stern et al published a one-year study in the New England Journal of Medicine - The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial, and concluded that "Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glycemic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss."

In those who had diabetes at baseline, the results for those following a low-carb diet were in stark contrast to those following the conventional, low-fat diet. The low-carb group experienced a normalization of their fasting blood sugar levels. At baseline their fasting blood glucose was reported as 9.21mmol/l - by the end of the study, their fasting blood glucose was just 3.66mmol/l. Not only did their fasting blood sugars improve, their HbA1c reading also improved moreso than those following the conventional diet - declining from 7.4 to 6.6 in the low-carb group, but only going from 7.3 to 7.2 in the convential diet group.

With these studies in mind - how do you think they compare with the studies the ADA touts as "conclusive" evidence that a low-fat diet is the gold-standard for pre-diabetes and even those with type II diabetes?

Isn't it time the ADA is called to task and asked why they're dismissing the data from studies showing superior results from alternative dietary approaches?

The data doesn't lie - it is what it is - and it consistently shows that reducing carbohydrate improves glycemic control. Carbohydrate restricted diets don't just have a similar or comparable effect when compared to low-fat diets - the differences are statistically significant - controlled-carb diets result in greater improvement in glycemic control!

With one-in-three adults in the United States at risk or already diagnoised with diabetes, isn't it time we take serious the idea of an evidence-based approach and actually do something to reverse the current trends? Or do we just keep marching down the same path that the data clearly shows will not stop diabetes?

1 comment:

  1. I know your questions are rhetorical but the answer is usually, 'follow the money.'

    What good is the ADA (AHA, AMA, ETC, LOL) if they publish a cure? Look at all the money they would lose. Same algorythm applies to government and politicians.