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Tuesday, February 16, 2010

SMBG Research, Or The Lack Of It


Nearly three years ago I challenged the authors of a particularly poor paper titled "Impact of self monitoring of blood glucose (SMBG) in the management of patients with non-insulin treated diabetes: open parallel group randomised trial" in the British Medical Journal to conduct a study based on Test, Review, Adjust.

When I first read Jennifer's Test, Test, Test I used to wonder why a study of that method had never been performed.

Of course now, with a little more experience, the reasons are fairly obvious to me. To start with, no researchers are even vaguely aware of the technique. That is apart from the fact that the results are unlikely to lead to increases in medication sales. Over five years ago, back when I naively thought someone would listen, I rang the Australian offices of Roche and Lilly to suggest it. They were polite and totally uninterested. I thought that at least the major test-strip manufacturers may have a vested interest. Apparently not.

My response to that paper was another small attempt to interest somebody in the appropriate field in the concept. But I have to be realistic; not many researchers read the "Rapid Responses" and Farmer et al certainly were not going make any attempt to prove themselves wrong.

The idea surfaced again today when Stuart, a Type 1 diabetic on the dLife forum, posted this very interesting question:

"If you wanted someone to explore something, to do a STUDY on a subject(s) about our diabetes, what do you want them to research? What areas do YOU want to know far more about that don't seem to be being done??? "

He had some very interesting replies. You can read them here. I would like to expand slightly on my answer there.

There are so many areas of diabetes crying out for research. There are some that have never been studied at all, including those dealing with diet modified by structured testing or similar methods which can lead to minimal medication or insulin needs. At the moment research tends to be focused on finding new medications or new ways to use old medications. In the real world "who pays the piper calls the tune".

No researchers are asking us, the diabetics, "what should we be researching?"

My own area of interest is just one of many possibilities. Despite understanding the reasons I still find it hard to believe that after more than three decades of home self-testing of blood glucose by diabetics no medical researcher, anywhere, has researched the use of structured self-testing for dietary modification to reduce blood glucose excursions.

Thousands of type 2 diabetics like myself have been "researching" the method personally and reporting their individual successes on many different forums since before I was diagnosed eight years ago, but we don't count in professional medical and research terms. We are diabetics, not scientists and our reports are anecdotes, not data.

I will offer the basic idea. Who knows, maybe there is a bright scientist out there looking for a PhD subject who has the ability to find a grant or research funds.

I propose a study comparing two groups of type 2 diabetics, all within their first 12 months of diagnosis. The only exclusion criteria would be that none should be using insulin or an insulin-stimulating medication such as a sulfonylurea at the commencement of the study.

Group 1, control, would be treated as individuals by their physicians and other specialists in exactly the same way as the present guidelines for their country. For example that would be the ADA or AACE and American Dietetic Association guidelines in the USA, Diabetes Australia here, or the NICE/NHS guidelines in the UK.

Group 2 would would also be treated as individuals by their physicians and other specialists in exactly the same way as the present guidelines for their country with the exception of dietary and testing guidelines. Instead, they would be given basic dietary guidelines to understand the differences between carbohydrates, fats and protein and their effect on blood glucose levels, and would also receive training and support in using feedback from peak post-prandial blood glucose testing to modify diet and lifestyle. The method taught would be based on the technique described in Test, Review, Adjust. If that needs clarification I am available as a consultant :)

The period of study would be three months initially, with weekly support and review to record indicators for both groups for the first four weeks, then monthly for the next two months with a preliminary report prepared after three months. Periodic follow-up review and reports would be performed at 12 months, five years and ten years. Indicators recorded would include A1c, fasting and peak post-prandial blood glucose levels, lipids, weight, blood pressure and any others the researchers felt valuable.

The five year and ten year reports would follow up all the earlier results and also include morbidity and mortality and any differences in progression to, or of, diabetes complications.

An inexpensive pilot study would not need very large populations and could be restricted to the first three months. The results of that could support further study over the longer period with a larger population.

I can also see other possible studies. For example, the possibility of combining Gannon and Nuttall's LoBAG20 or LoBAG30 diet with the above study as the starting diet for Group 2 is one that intrigues me. But it may be unwise to put too many variables in the mix. One thing at a time.

My area of interest may be quite different to yours. If you were the person asked by the researchers "what do you want us to study?" what would your answer be?

Cheers, Alan

Everything in Moderation - Except Laughter

Wednesday, February 03, 2010

Good Targets, Bad Methods

There has been a lot of discussion in the media and the blogosphere about an Early Online Publication in the Lancet on 27 January 2010.

Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study

"Methods
Two cohorts of patients aged 50 years and older with type 2 diabetes were generated from the UK General Practice Research Database from November 1986 to November 2008. We identified 27 965 patients whose treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents, and 20 005 who had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity were identified as important confounding factors, and Cox survival models were adjusted for these factors accordingly


[snip]

Interpretation

Low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events. If confirmed, diabetes guidelines might need revision to include a minimum HbA1c value."

What has saddened but not surprised me is that the reaction in on-line medical discussions has been much the same as that when the ACCORD and ADVANCE studies appeared. No-one has questioned the methods used to attain targets, all appear to accept that there may be a problem with attempting to aim for tight targets for type 2 diabetics. Thus, the targets are bad and should be eased.

I was not going to write about it because so many others have, but eventually I responded in Present where a doctor posed the following question based on this study: "Are we treating our patients to death?"

This was my response to the doctors.

The answer depends, of course, on the method of treatment and the individual nature of your patient's diabetes.

All of these studies, including ACCORD, ADVANCE and these recent ones have a common thread. They presume that the only way the physician can reach lower A1c and blood glucose goals in a patient is by medication. None of them consider using lifestyle – diet and exercise - changes to complement minimal medication or insulin to achieve those goals.

You all presume that a patient would not use diet and exercise. And, of course, to some degree you are correct, especially when the most generally prescribed diet is directly counter-productive for achieving better A1cs and blood glucose levels.

So you prescribe diet and exercise, the numbers go up, you presume non-compliance and prescribe metformin or a sulf or add insulin, they keep going up so you increase those and add more meds. But you also stress that the patient should eat more carbohydrates – and less fat - to be absolutely sure there are no hypoglycemic episodes as a result of the sulfs or the insulin and so the cycle continues, chasing it's tail.

Lower blood glucose and A1c targets do not cause higher mortality and morbidity. I have read success stories from many thousands of pro-active diabetics of all types on many forums since I was diagnosed eight years ago who have clearly demonstrated the opposite is true.

On the other hand, over-medication to attempt to counter poor dietary advice DOES cause higher mortality and morbidity; that is the consequence these studies are showing.

The solution? First, stop promoting the terrible “heart-healthy” high-carbohydrate AHA diet to your patients, or allowing the dieticians you send your patients to to do so. Instead, suggest that the patient use their meter at their post-prandial peak blood glucose timing to find out what foods are killing them and they will quickly reduce those foods, and their levels, and substitute others. The technique is described here:
http://loraldiabetes.blogspot.com/2009/04/test-test-test.html

Some patients will do that and succeed; some will need further medication, but much less than you usually prescribe. And others will be non-compliant whatever you prescribe. They are the ones to prescribe higher medication to – but they are also the ones you should set easier targets for. Because they are the ones dying from over-medication.


Cheers, Alan.

Everything in Moderation - Except Laughter.

Saturday, October 31, 2009

Cholesterol, Fats, Carbs, Statins and Exercise


The following random thoughts are just that - my thoughts, not facts. However, I have provided some selected cites for most of them. If you think I have been a little selective, I agree - I'm human and will spin things my way. So I've also given links to some medical search engines at the foot if you would like to do some further reading. Just one rule: papers funded by pharmaceutical companies, especially statin manufacturers, or written by authors with links to those companies have little credibility with me.

The cites are only representative of a lot of general reading. There are many more supporting papers out there. I am happy to hear from anyone with more specific papers on particular aspects - pro or con.

These thoughts are based on my own reading from many various sources over time. Lately I have found them reinforced in Taubes' book "Good Calories, Bad Calories", but most I had read before that from other sources.

1. Eating excessive carbohydrates leads to high triglycerides. The definition of "excessive" may depend on whether or not the diner has diabetes. Triglycerides are one of the three major reported components of the usual lipids panel, the other two being HDL and LDL. One that we should get but often don't is VLDL, the dangerous one; usually that is estimated by dividing the triglycerides by 5 (in mg/dl). But that estimate is very approximate.

2. LDL is considered by the mainstream medical establishment to be the bad cholesterol and most anti-cholesterol meds target that. But high triglycerides, high VLDL and low HDL are actually the ones we should be most concerned about.


3. The absolute number of our LDL is less important than the specific number of certain components of LDL; the dangerous ones are the small, dense particles. High triglycerides usually indicate high proportions of those small dense particles. Better indicators of our lipids health are VLDL and the apolipoproteins A1 and B.

4. ALL of the foods we eat affect our cholesterol levels. EXCESS of carbohydrates OR fats may lead to dyslipidemia.

5. The past research on the relationship between cholesterol and heart disease is misleading at best. There appears to be shaky support for the hypothesis that lowering cholesterol, particularly LDL, improves overall mortality and even less support for the use of statins to do that.

6. Inadequate dietary fat will lead to low HDL.

7. Exercise usually, but not always, helps increase HDL.

8. A low HDL is a better indicator of future cardiac problems than high LDL and apolipoprotein levels are a better predictor than either.

9. Diabetics should aim for a triglycerides to HDL ratio of less than 3.0 in mg/dl or 1.3 in mmol/l.

10. Cholesterol in the foods we eat such as eggs and seafood has an insignificant effect on the cholesterol in our blood stream.

11. Low LDL is also dangerous and can be related to other problems such as Parkinson's Disease, cancer and other causes of early death.

12. There is growing concern that the over-prescription of statins and limited but alarming research into their side effects needs a lot more investigation.

Putting that all together, I no longer worry about the level of fats in my diet for their affect on cholesterol. I am selective in my choices of oils, but for other reasons such as Omega 3 content or eliminating trans-fats. I also found that reducing carbohydrates reduced my triglycerides as well as my blood glucose levels. I also dropped my statin, lipitor, four years ago.

When you look back through that list, some things stand out to me. If I am going to worry about cholesterol at all, the two things that will improve it most are moderating carbohydrates for better triglycerides and increasing exercise for better HDL. It seems a happy coincidence that those are the same two things that improve my blood glucose levels most. Additionally, inclusion of some additional fats in my menu to replace those carbohydrates may also help increase HDL.

For those interested in further reading to support - or refute - my thoughts here are a few useful search engines: Google Advanced Scholar, Medline and Highwire.

Cheers, Alan

Everything in Moderation - Except Laughter.

Footnote:

Here are some additional references for you in no particular order. Most of these papers and articles apply to more than one of the points above, which is why I found it awkward to include them in the body. The titles tend to give the context.

Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance

Effect of Dietary Carbohydrate on Triglyceride Metabolism in Humans

Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance

Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessmentEffect of the Magnitude of Lipid Lowering on Risk of Elevated Liver Enzymes, Rhabdomyolysis, and Cancer

Exercise Prevents the Accumulation of Triglyceride-Rich Lipoproteins and Their Remnants Seen When Changing to a High-Carbohydrate Diet

Effects of Protein, Monounsaturated Fat, and Carbohydrate Intake on Blood Pressure and Serum Lipids

Carbohydrate-Induced Hypertriglyceridemia: An Insight into the Link between Plasma Insulin and Triglyceride Concentrations

A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia

Plasma high density lipoproteins HDL2, HDL3 and postheparin plasma lipases in relation to parameters of physical fitness.