Doctors, like orange juice, are better with breakfast

When I was a medical student, I thought I wanted to be a radiologist. I love the science. I like the physics of radiation, and my ego was invested in the idea of being a “doctor’s doctor” that other doctors looked to for wisdom and interpretation of diagnostic testing. Radiology checked all those boxes without the ooey-gooey autopsies and whatnot that are part of the daily routine of pathologists.

Then I did a radiology rotation.

I truly did like the science of x-rays and the conversations with other doctors and all the rest. I discovered one problem, though: I could not stay alert for hours at a time in a dark room looking at films. Come two or three o’clock in the afternoon, I would inevitably start to fade. Once, I even nodded off in the radiology suite. So, with the safety of future patients in mind, I decided to go a decidedly more well-lit and upright route, eventually completing a residency in internal medicine and a fellowship in endocrinology, diabetes, and metabolism. If nothing else, the work in endocrinology was ambulatory. If I’m moving, I can’t fall asleep.

I review my personal history as a wind-up for a research paper in JAMA Health Policy this last week (paywall). Investigators looked at records from primary care practices–these studies always pick on primary care docs–to see how likely a patient was to receive a “statin” medication depending on the time of day of his or her appointment. This is no casual question. Viral pandemics aside, cardiovascular disease remains the leading cause of death in the United States. Appropriate use of statin medications like atorvastatin (Lipitor), rosuvastatin (Crestor), and others dramatically reduce the risk of death from any cause in people at risk for heart disease.

Using United States Preventive Services Task Force (USPSTF) guidelines, which state that we should offer statins to anyone with known vascular disease, anyone with a diagnosis of a genetic problem called “familial hypercholesterolemia,” or anyone with a low-density lipoprotein (LDL) cholesterol level of 190 mg/dL or more (among other diseases like diabetes), the researchers found a disturbing trend. Compared with 8 am appointments, which the investigators used as their reference group, the likelihood of getting a statin was lower at all hours except 9 am. And the likelihood of getting a statin pretty consistently fell as the day went on: 88% at 9 am, 63% at 12 pm, and 69% at 3 pm. Overall, you were only 69% as likely to get an appropriate statin prescription in an afternoon appointment as you were in a morning appointment. Here’s the raw, “unadjusted” data:

JAMA Health Policy

JAMA Health Policy

And yes, radiologists make more mistakes later in their shifts, too. But this phenomenon is not limited to doctors. Judges sentence defendants more harshly just before lunch, when they’re hungry, and sentence more leniently after a break. Car crashes peak between 5 and 7 pm. Students taking standardized tests perform better earlier in the day and recover performance after rest. If you’re like me, you may have found that you do your best creative work earlier in the day, and you’re better off going to meetings or working on a task list later in the day.

The wellness industry has long coached patients to get the earliest available appointment of the day, but our reasoning has had more to do with the fact that if you go earlier in the day, you’re less likely to have to wait. With this data, we have to consider not only the time in the waiting room but the outcome of the visit.

[Disclaimer: the Kansas Business Group on Health has CDC funding to encourage appropriate use of statin medications.]

As the Medical Director of the Kansas Business Group on Health, I’m sometimes asked to weigh in on hot topics that might affect employers or employees. This is a reprint of a blog post from KBGH.

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.