Should young, healthy people with type 1 diabetes take statins?

I encountered this question a couple months ago in a consult and intended to blog about it then, but relatively little trial data was available. I would have essentially been giving my own off-the-cuff opinion. That's very unsatisfying to me, and probably to the reader.

As background: we tend to think of type 1 diabetes as more a need for hormone replacement (insulin) than as a disease state requiring the complex management that type 2 diabetes requires. That is to say that type 1 diabetes, for all the unpleasantness it causes for people, is easier on the blood vessels as a general rule than type 2 diabetes. The ADA has a statement in its guideline that "For patients with diabetes aged <40 years with additional atherosclerotic cardiovascular disease risk factors, consider using moderate-intensity or high-intensity statin and lifestyle therapy." It's a category C recommendation, meaning it's mostly opinion and has a less-than-spectacular evidence base. It also doesn't differentiate between type 1 and type 2 diabetes. Similarly, a joint statement by the ADA and the AHA states that "Adults with T1DM who have abnormal lipids and additional risk factors for CVD (eg, hypertension, obesity, or smoking) who have not developed CVD should be treated with statins." Both statements argue against the routine use of statins in young healthy type 1 diabetics.

But a recent study from the New England Journal helps us with the question of statins in kids, and throws in ACE inhibitors for good measure. Investigators led by M. Loredana Marcovecchio and Scott T. Chiesa randomized 443 kids between 10 and 16 years with type 1 diabetes and urine albumin-to-creatinine ratios in the upper third of "normal" to some combination of ACE inhibitor, statin, and placebo. Creatinine is a consistently excreted product of muscle metabolism that serves as a nice comparator for other things the kidney excretes. So even if you drink a lot of water and dilute the amount of albumin in your urine, we can look at it compared to the similarly diluted creatinine and see if you're excreting too much.

Anyway: the investigators used a 2 x 2 trial design, meaning that there were ultimately four groups: placebo-placebo, placebo-ACEi, placebo-statin, and ACEi-statin. The statin was atorvastatin 10 mg daily, and the ACEi was quinapril 10 mg daily (after titration). They were most interested in the change in albumin excretion (that is, how much protein spilled through the kidneys into the urine). They assessed this according to that same measure, the albumin-to-creatinine ratio in the urine, from three early-morning urine samples obtained every 6 months over about two and a half years. They also looked at secondary outcomes like the new development of microalbuminuria (that is, the new appearance of protein in the urine), worsening of eye disease, changes in kidney function, blood lipid levels, and measures of cardiovascular risk. For the cardiovascular risk, they did ultrasounds of the carotids to measure the thickness of the vessels (carotid intima–media thickness) and measured levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine in the blood. Both of these are generic markers of vascular risk.

After an average of 2.6 years, no benefits were found within the ACEi group, the statin group, or the ACEi+statin group compared to placebo. Unsurprisingly, the ACEi group had a much lower incidence of new microalbuminuria, but "in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94)." Also unsurprisingly, the use of statins resulted in lower cholesterol levels (including, unfortunately, HDL). But neither drug had significant effects on carotid intima–media thickness, C-reactive protein, kidney function, or progression of eye disease.

So we can take away from this small-ish study that, at least in a short amount of time in pretty healthy twelve-year-olds (the subjects were excluded if they had genetically bad lipid levels; the participants' average A1c was ~8.3% and their average blood pressure was 116/65 mmHg), there was no benefit to statins or ace inhibitors. This study will influence my recommendations to patients and other docs in the future. The kicker, naturally, is that many young people with type 1 diabetes have imperfect blood sugar control. What about those who can't get their diabetes controlled? It's a tougher call in that case, and this study didn't address it. 

What's with all the arrows?

You’re back! I guess the random link dumps and talk about what a tightrope we're all on health-wise didn't scare you off. Where to start today's post, then? Let’s start with the name. Why “Double Arrow Metabolism?”

I grew up on a farm in south central Kansas. Our farm raised cattle, at least until I was 13-14 years old or so. According to WikiPedia, branding, in the form of burning a pattern into animals’ hair and skin, has been performed since at least ancient Egyptian times to identify cattle. The Wild West of the 1970s and '80s hadn't changed the practice. Our farm’s brand was the double arrow, two vertical arrows arranged in parallel, each with an arrowhead on each end. You can see it splattered all over this site:

Everything in Kansas leans to the right.

Everything in Kansas leans to the right.

Now, this may be simple coincidence, but as you may recall from post #2, I’m an endocrinologist, a hormone and metabolism specialist. And if there’s a medical specialty that loves arrows, it’s endocrinology:

There was a time when I could draw this from memory. Then I decided that God gave us Google images for a reason. Now that space is taken up by happier memories.

There was a time when I could draw this from memory. Then I decided that God gave us Google images for a reason. Now that space is taken up by happier memories.

Wow! Converting cholesterol to hormones takes a lot of arrows. And chicken wire. Maybe now you can see how, when my world shifted from the windy, sun-drenched agrarian plains of southern Kansas to the fluorescent, air-conditioned, mint-scented hallways of medical academia, sometimes my studies reminded me of home. And not to get sentimental, but that two-headed arrow has always looked like it wanted to move. It reminds me of freedom of movement back and forth between phases or choices. Or, in my case, over the last couple of years, movement away from those fluorescent-lit hallways back to the outdoors and back in contact with people, not just patients.

So: Double Arrow Metabolism.

It’s not particularly catchy. It doesn’t follow the craze of single-word names out there (Spruce) or baby noises (Hulu) or left-out vowels (Scribd, Flickr) or any of the other internet weirdness. It hasn't been tested for SEO or "optimized" (I hate that word) through Google Ad Words. It hasn't been A/B tested.

But it’s honest. And since I’m looking to connect with people and not necessarily just to optimize search engine results, I like the homage to my past. Plus, metabolism is a cheap way to sound smart without using a word people can’t pronounce (if I'm looking to throw out unpronounceable words, I think I've covered that with the diagram above).

I promise that I’ll get back to discussing the path toward medical, financial, and health independence soon. But first a couple of observations: you shouldn't let the process of getting yourself healthier intimidate you. Just as not every new business name has to follow the naming conventions of Silicon Valley, not every healthy person has to be an athletic coastal hipster foodie or a lycra-covered sex kitten. I mean, if that’s what you are, then great. Magazines apparently can’t shoot enough pictures of you:

Backstreet's back, alright!

Backstreet's back, alright!

But you can just as easily be a middle-aged, slightly frumpy guy like me who decided to paddle himself out of the vortex we talked about in post #1. And you can be as happy as that guy is at how it feels to have your feet planted on dry land.

rss Block
Select a Blog Page to create an RSS feed link. Learn more