Archive for the 'Uncategorized' category

A Doctor Deals: Metformin

Jul 14 2015 Published by under Diabetes, Uncategorized

Structure of Metformin

Structure of Metformin

The first-line treatment for type 2 diabetes (DM2) is Metformin. First synthesized in the early 1920s, the discovery of insulin a few years later eclipsed these agents, at least for a time. In the latter part of the 20th century medicine rediscovered these drugs, and they entered clinical use. Despite becoming the standard of care for DM2, it took 30 years to figure out how Metformin works!

Human studies show that its major action is reduction of glucose production in the liver. When we eat, nutrients of all types enter the bloodstream and make a first stop in the liver for metabolism. The liver can convert these other molecules to glucose, our circulating fuel for cells, via a process called gluconeogenesis (literally new glucose).  Patients with DM2 have twice the rate of gluconeogenesis in the liver as nondiabetic people. Metformin for 3 months can normalize this process.

Metformin also has beneficial effects on levels of fats in the bloodstream and uptake of glucose by muscles. Unlike many therapies for DM2, patients usually do not gain weight with Metformin; indeed, many experience weight loss.

AMPK-regulated enzymes circled

AMPK-regulated enzymes circled

One documented cellular mechanism involves AMP-activated protein kinase (AMPK), a protein that functions in a number of metabolic processes. These include lipid (fat) synthesis, muscle glucose uptake, and control of a number of enzymes in the gluconeogenesis process (diagram to the right).

Zhou et al showed that Metformin activated AMPK in liver cells, leading to decreased fatty acid and lipid production (which in turn increases the sensitivity of the liver cell to insulin). Inhibition of AMPK blocks Metformin's beneficial effects on gluconeogenesis, so activation of AMPK also provides an explanation for this beneficial effect.

So have we answered the mystery of Metformin? Of course not!

Metformin has one obvious, often troubling, side effect: diarrhea. For myself and a number of friends who take it, the first dose induced events not unlike the clean-out for a colonoscopy (ask your 50+ year-old friends about the joy of colonoscopy prep). Some folks have ongoing diarrhea that limits therapy with the drug; in most patients, like yours truly, the problem eventually resolves (or becomes less problematic).

Why does Metformin cause intestinal problems? We really do not know. Some have suggested that it reduces intestinal absorption of glucose which could contribute to changes in stool pattern. Its effects on the liver may also change stuff downstream in the gut. Some have suggested that these intestinal effects may be beneficial as well, through changes in the microbiome.

For a drug that's a century old, there is still a lot we do not know about Metformin. At least we know it works!


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Jun 19 2015 Published by under Uncategorized

logo-aamc.gif-dataI have finally dug into the latest AAMC dataset on the status of women in academic medicine. The website AWEnow (Academic Women for Equality Now) will be featuring these updates over the coming weeks. Today I posted the overall scores for the nation.

Good news: The overall share of women in leadership has increased over 4 years (3 datasets).

Bad news: At this rate, I will be 94 when women hold half the leadership positions in academical centers.

Go see my pretty graph here!

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A Doctor Deals: Thoughts from #2015ADA

Jun 08 2015 Published by under Diabetes, Uncategorized

Boston revere 220x175

As usual for this time of year, I am at the annual scientific sessions of the American Diabetes Association. For four days I have been hobnobbing with others interested in diabetic nephropathy, learning about new stuff, and hanging out with my spouse in Boston.

This year brought a new perspective. I am now living with diabetes myself.

The diagnosis provided no big surprise. My fasting glucose levels had been “impaired” for about 10 years, a clear indicator that this could happen. I would start a diet, compulsively recording every bite and calorie I ate. This resulted in a few pounds coming off, but as soon as I failed to track food, it came right back. I had generally resigned myself to plus sizes for the rest of my life.

A few months back I established care with a new doctor. Basic lab work showed a somewhat higher glucose than before. Oops. I got back on the wagon to try and fix that by my next labs. I had some additional motivation as well. My daughter got engaged at Christmas, and I really wanted to drop some tonnage before taking family photos. I thought I would get it all fixed.

Unfortunately, I failed. Or at least my pancreas did. My HbA1c, a measure of the amount of hemoglobin with glucose glommed onto it, was 6.8%. Anything above 6.5% means you have diabetes.

Knowing stuff like this does not help

Knowing stuff like this does not help

My brain spent a few minutes in denial. Perhaps if I got more aggressive and lost some more weight, this would go away…? Luckily, I had put on my big girl panties and dealt with it by the time the doctor came in to discuss my next steps.

So this was my first year attending the diabetes meetings as a doctor, a scientist, and a patient living with the disease. In the near future I will write more about dealing with diabetes. It's especially sobering when you know stuff about your pathology...


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The Mirror of Egelivirp

May 06 2015 Published by under Uncategorized

Click for source site

Click for source site

In one of the Harry Potter books, the protagonist (I won't say hero; I felt Hermione should have had top billing) finds a mirror. In it, he sees himself and his family. His friends do not see the same image, though. They see other things of their dreams.

Later, he finds out that he has found the Mirror of Erised, one that shows what the viewer most desires.

Desire, backwards as in a mirror, would be erised.

I believe we need a different mirror, The Mirror of Egelivirp.

(I will give you a minute to spell it out)

This mirror shows nothing like what you desire. It will show you things that you get through your privilege of birth, race, ethnicity, gender, etc.

One of my current frustrations involves explaining to white males how much they take for granted. Others in the world do not get the same respect or even the benefit of the doubt in many situations.

Being a lowly muggle, I cannot make this happen. I just hope someone at Hogwart's reads my blog. We could really use a whole bunch of these Mirrors of Egelivirp.

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The River of Knowledge

Apr 07 2015 Published by under Uncategorized

While at Experimental Biology, I wrote here about a number of presentations of interest. These studies revolved around cool animal models and very basic mechanisms of disease. None of them will result in a change in patient care in the next year (nor perhaps in the next 5 years). All of them are essential to advancing human health, because each is a drop of water in the river of science.

A river flows along, with new streams pouring into it all the time. All these bits of water run together, sometimes slowing to mix in eddies, other times tumbling over rapids and falls, producing a whole new arrangement of the molecules that make up the river. As new flows come together, the pattern of the river may change, its rate increasing. Sometimes a rockslide or a beaver provides an obstacle that stops flow, although ultimately the river will overcome a blockage.

In science, new facts and ideas constantly flow into the world, sometimes bumping into each other and mixing in unexpected ways. Sometimes a technical issue will prevent progress on an idea; at other times, a new tool will speed the flow and move the information flow forward faster.

The important part of the metaphor is that we have no idea what information will be the critical piece that solves a puzzle, just as we cannot call out a particular raindrop or snowflake as the one that overcomes the dam. If we want to make progress, we have to continue to study it all. Eventually, the critical pieces will fall into place.

That's why it's so important to study lots of different science, even if it appears to have no implications that we can use. Down the road, it may provide that critical information that revolutionizes our world. And we simply cannot know until it happens.

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One Week to Boston #ExpBio

Mar 20 2015 Published by under Uncategorized

This time next week I will be in an aircraft nearing the end of my first segment to Boston for Experimental Biology 2015 (#ExpBio is the official hashtag). I am beginning to plan my packing list, and the weather in the northeast is completely depressing.

At least the snow should be clearing...

At least the snow should be clearing...

At least the attendees will be warm, and the science will be hot!

I will once again be an official APS blogger, so expect to see lots of posts, tweets, and updates about the conference.

If you're there and you see me, say hello!


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They MOC Us

Jan 14 2015 Published by under Uncategorized

Maintenance of Certification (MOC) presents a challenge for me and others trained in my time frame. Before my class, physicians took exams after their post-graduate training and obtained life-long certification in their specialty. My class was the first to be issued time-limited certificates in Pediatrics. What has this meant over time as I have sub specialized and grown older?

A lot of money and pain. MOC has proved so tedious that The New England Journal of Medicine featured articles about the practice in its January 8 issue. One, Boarded to Death, was contributed by Paul S. Teirstein, MD, a physician whose petition to change the process has been signed by 19,000 doctors. 

Since I was in the first wave of time-limited physicians, I have a “historical” perspective on this issue. My initial exams in general pediatrics and pediatric nephrology both occurred in hotel ballrooms. Each cost about $1,000 plus time off of work and travel costs. 

General Pediatrics Recertification (Early 1990s)

In my first job I supervised residents on the inpatient pediatrics service each year. When I had to renew my certification, the process cost about $1,000 (similar to the original exam), but otherwise proved pleasing. The exam came on disks that I ran in my own computer. I had a time limit (in weeks) to complete it once I loaded it, but otherwise I could do as much research as I liked. The questions generally dealt with important clinical topics, and I received immediate feedback about the results. There were several things I learned through this process. Stuff not relevant to my life as a nephrologist had been published, and I had completely missed it! I pulled papers and looked stuff up! I learned a lot, and it was easy to fit into my life as an academic clinician-scientist starting up a lab. 

This format cost money and time, but overall I felt the process was rewarding and useful.  If they had stuck with this, I might still be certified in general pediatrics. Yup, it was that good.

First Pediatric Nephrology Recertification (2003)

By this point, the powers that be had decided that an open-source exam was not appropriate. No, we doctors needed a “high-stakes” exam. I had to find a testing center and take a supervised exam. This meant studying and taking off a day of work; lucky for us, most cities with an academic medical center will have a testing center. A few weeks after the exam, I received my score (passing!) and a summary of the question areas and my score for each category. My weakest area was transplantation; not exactly surprising, since other areas of nephrology have always interested me more.  

This format cost money and time. The proctored exam annoyed me; I could not take my jacket or purse into the exam room. Let’s face it, no doctor knows every fact that they need to know. However, the questions dealt with reasonable topics. Any competent nephrologist should be able to pass this exam.

General Pediatrics Recertification (Late 1990s)

The general exam now required a secure test center. As my new employer no longer required this certification, I opted out. I simply could not justify the cost of the exam, the cost and time off to take a review course (my only hope to pass), and the other annoyance of something not required. 

Next Pediatric Nephrology Recertification (2013)

By this time, recertification has grown into full-blown MOC. Once again, the cost was around $1,000 for a ten-year period. Requirements over that time included:

  • Maintaining valid, unrestricted state medical license (with its own requirements for continuing medical education hours)
  • Educational and quality improvement modules approved by the Board; these could also count for continuing medical education hours, but might conflict or duplicate other activities required elsewhere
  • Another exam at the testing center

 The medical license is pretty easy; if I don’t have that, being board certified is pretty useless. The educational module could be fulfilled by subscribing to a monthly Question and Answer publication sold by the Board (can you say more money). I enjoy this piece of the effort; I learn stuff. The quality improvement modules proved annoying. The ones relevant to my job duplicated efforts my employer had in place (prescription writing, hand washing, weight control). I got through the two required, but the process was generally useless. The cry about this part resulted in the Board agreeing to certify centers (more money) to produce their own modules. Finally, my exam this time included scanning with a metal detector. The questions seemed more esoteric than before, and when I got my letter, it told me I passed. No feedback on areas that might need improvement. Just a score and the cut-off.

The Future of MOC

Compared to Dr. Teirstein, my lot seems light. He is trying to maintain certification in several subspecialties. The time away from my other duties is less problematic for me, and the educational efforts supplement my other academic activities. When we arrange things so institutional quality projects can count for MOC, that part will also be less problematic.

The point many physicians have made regards the secure exam. Physicians simply do not have to remember information the way they once did. I can pull up drug information and other references on my smart phone in the exam room. If I did need to know which interleukin was secreted by a lymphocyte expressing certain markers (an actual question from my last exam; clinically relevant my ass), I can have the answer in about a minute. I am sure the person who wrote that one (a) studies the immune system and (b) considers it relevant, but I still do not know the answer. No one has yet died from this knowledge gap.

In addition to MOC, our institutions have placed further training burdens on physicians. Time here and there, even at no formal cost, adds up. I especially love reviewing fire safety on an annual basis. RACE never changes, you know.

Some form of ongoing education and certification requirements seem reasonable. I have seen some doctors who have not kept up, and it did affect patient care. However, the current system seems as much about income for the Board as it is about quality of care. We have to be able to make it less of a burden, or physicians will just go without it. And then it serves no purpose.

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Meaningless Use

Jan 12 2015 Published by under Uncategorized

Unfortunately, I have a prior engagement that prevents my participation in a TEDMED Hangout tomorrow. The topic is important: why do we not discuss socioeconomic and other social factors routinely when we know that these items influence health? As the website states:

We’ve all experienced a doctor visit. The physician measures your blood pressure, pulse, breathing, and temperature. They may ask about personal or family history of specific diseases or even inquire about eating or exercise habits. Rarely, however, do they ask about your income or education, access to healthy foods, the safety of your home, or the stability of your personal life. And yet, we know that 40 percent of one’s health is shaped by socioeconomic factors, and only 20 percent by clinical care.

The site implies that these factors could be another vital sign. I would not put them in that category (just as I would not have made pain a vital sign), but I do agree that we don’t think about these things enough. After all, how can my patients follow my advice when

  • The neighborhood may not be safe for outdoor activity that would help the child with weight control
  • The family can only get to a convenience store; if they pay for transportation to a grocer, they have no food money
  • The parent and patient cannot understand the instructions, even after discussion in clinic and reading the written stuff the electronic medical record prints out (meaningful use can be so meaningless)
  • The parent moves the family frequently because of an abusive ex, making support services difficult to maintain

As physicians, our training allows only the most superficial assessment of these issues. We need specialists in these social issues, people known as social workers! However, in the current reimbursement climate, these services often get cut. 

In a time when economic pressures force us to see patients in less and less time, we need to recognize the need for multidisciplinary more than ever. I hope that events like this one can get the conversation going. I also hope that the role of crushing poverty in bad health gets more attention.

One way or another, we all end up paying for these inequalities. 


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End of Vacation

Jan 07 2015 Published by under Uncategorized

Vacation officially ended on January 5, when our son drove back to the tundra and I went back to the office. The patient call backlog did not overwhelm me, and I feel pretty good about the job right now. 

My blogging spirit has not yet caught up with that “put your nose back on the grindstone” mood yet. I have found a couple of nephrology topics that I am reading about for the future. 

For now, I will wish everyone a prosperous new year. 

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Another New Year

Dec 31 2014 Published by under Uncategorized

2015 is almost upon us. I am still enjoying time with my son who is home from college. I am also beginning to work with my daughter to plan her upcoming wedding (FINALLY!!!!!).

Hope your New Year is happy and your resolutions attainable! Last year, I set out to finish my book. AND I DID IT!

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