August 13, 2012

Why Thinner People with Diabetes May Have Worse Outcomes

A study published last week in the Journal of the American Medical Association (JAMA) came up with the conclusion that "Adults who were normal weight at the time of incident diabetes had higher mortality than adults who are overweight or obese."

The study can be found at:

If you have been doing a good job controlling your weight and read only the media reports about this study, you may have found it disturbing. If your doctor is one of those who only reads the "25 words or less" summary of medical findings, you may even hear that losing weight is dangerous for diabetics.

Hermes Florez, MD, PhD. Florez, the director of the division of epidemiology and population health sciences at the University of Miami's Miller School of Medicine, who wrote an editorial about this study  was quoted as saying, ""If you are normal weight, you may be at higher risk from diabetes, especially if your fitness status is not so good."

But even a cursory reading of the methodology used in this study should make it clear that the outcomes for people who were normal weight at their diabetes diagnoses has little to do with their weight or, for that matter, fitness.

The data used in this study came from pooling data from the "Atherosclerosis Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008; Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002-2011."

As you will immediately notice, all but one of these studies go back 20 years or more, to the days before doctors understood that only by lowering blood sugar could people with diabetes avoid diabetic complications. So most of the people who participated in the studies whose data was used in this meta analysis were diagnosed in the bad old days, after which they were likely to have received extremely poor treatment.

How bad? Before the middle 1990s, patients diagnosed with Type 2 almost never were given home blood sugar meters. The only time their blood sugar was measured--fasting--was when they saw their doctor once every few months. Since the only drugs available to treat Type 2 Diabetes were the sulfonylureas which can cause dangerous hypos,  the only concern doctors had about these newly diagnosed people's blood sugar was that it not drop low enough to cause hypos. As a result, doctors encouraged patients to keep their blood sugars high and when they administered A1c tests doctors  saw no problem with patients maintaining A1cs in the 10% range or higher.

So what does this have to do with why their weight at diagnosis might have given normal weight people a higher likelihood of dying over the subsequent decades? Just this: Nowadays those of us who keep up with diabetes are aware that most normal weight adults diagnosed with Type 2 are very likely not to have classic  Type 2. Most have a slow-developing form of autoimmune diabetes called LADA that is very similar to Type 1.

This form of diabetes does not respond at all to the oral drugs that are somewhat effective for Type 2. But back in the days when patients had no way to test their blood sugar after eating and doctors considered A1cs as high as 13% "safe" these patients could go many years without being put on insulin. And even when they were put on insulin, because they didn't have meters, they injected only enough insulin to prevent the sky-high blood sugars that cause the fatal condition, diabetic ketoacidosis. Many patients on insulin still had blood sugars that rose into the 200s and even 300s.

So normal weight people with LADA would have ended up with blood sugars much higher than those of the overweight Type 2s who were more likely to respond to the sulfonylurea drugs and, later, metformin, most newly diagnosed people with diabetes received.

And because we now know that there is a straight line relationship (in large groups of people, at least) between A1c and the likelihood of heart disease, it doesn't take genius to suspect that the explanation for the extra cardiac deaths in the group of normal weight people with diabetes was the those much higher blood sugars they ran due both to misdiagnosis and to the way doctors ignored the damage caused by high blood sugars until the middle of the 1990s.

A second group of normal weight people diagnosed with diabetes as adults who are likely to end up with poor outcomes are people with milder versions of one of the many, unrelated, forms of genetic diabetes that are lumped together under the name MODY.

Many people diagnosed with MODY have family histories of relatives dying young of heart attacks while young and fit. This is probably because exposure to blood sugars that remain over 150 mg/dl for hours each day will over time cause the arteries to become diseased. People with these forms of MODY have had that kind of elevated blood sugar all their lives. But until very recently only those with the worst cases were diagnosed, and the rest, whose genes gave them "pre-diabetes" for much of their lives, lived with abnormal post-meal blood sugars for  many years, and only developed full fledged diabetes much later on in life, perhaps after becoming a bit more insulin resistant.

Because they were thin, doctors didn't consider a diabetes diagnosis when they had symptoms that should have pointed them that way.  (In my 20s, my doctors waved off my highly abnormal glucose tolerance test results as "nothing to worry about" precisely because I was normal weight.)

Some rare forms of genetic diabetes are caused by genes that damage not only blood sugar control but other organs, most notably the kidneys and the mitochondria. Mortality in families that inherit these unfortunate genes have nothing to do with diabetes but with the other organ damage that is due to these gene variants.

But for most people with either MODY or LADA it's pretty clear that if you keep your blood sugars in the normal range (under 140 mg/d--7.7 mmol/L) at all times you can, over time, reverse much of the damage that you have already suffered and avoid the premature heart attacks and kidney failure that carried off so many people diagnosed with diabetes in the past, when they were allowed to run very high blood sugars.


There is also one other reason why thin people diagnosed with diabetes may have a higher risk of dying--one that wasn't addressed by this study's methodology. The journal article states that the data were adjusted for "demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status." However, what was left out was co-morbidities--i.e. the presence of other diseases.

One of the most important comorbidities to be considered is pancreatic cancer, since there is growing evidence that a very early symptom of pancreatic cancer may be the onset of diabetes. This is discussed in the Mayo Clinic web page HERE. A small but important subset of normal weight people who die prematurely with diabetes are people whose pancreases failed because they were infiltrated with cancerous cells.

In addition, many drugs used to treat cancers and life-threatening diseases are capable of causing diabetes, for example the steroids administered during chemotherapy or to treat COPD. Powerful steroids were also prescribed in the past to people with neuromuscular diseases like MS. Data sets like those glommed together in this study can't tell us whether a person was diagnosed with diabetes after a course of chemo or whether they died of cancer, COPD, or MS. So the presence of people in this data pool who were diagnosed with diabetes who also had one of these other life-shortening conditions could also explain a significant amount of the excess mortality this study uncovered.

Whatever the explanation, if you are a normal weight person diagnosed with diabetes, there's no need to panic. If you track your blood sugar after meals with a meter and keep it as close to the normal range as possible, you should do fine. The worst treatment doled out to people with diabetes nowadays is far better than what the people involved in these studies back in the late 70s, 80s and early 90s were given after their diagnoses, and for those of us who pursue normal blood sugars the future should be a lot brighter, no matter what our weight.

P.S. If your doctor tells you there's no point in losing weight because thin diabetics have even more heart attacks than fat ones, find a new doctor. I wouldn't have warned about this in the past, but over this past year I have been sent so many stories about doctors giving idiotic advice based on their having misunderstood a media report about a research study that I no longer assume doctors will even bother to read the full report before changing their practice recommendations.