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Dr. Jones: Why can't a woman be more like a man? In the musical "My Fair Lady," Professor Higgins for singing his frustrations in his research project to turn Eliza into a proper lady. But in healthcare the, difference is important. This is Dr. Kirtly Jones from Obstetrics and Gynecology at University of Utah Health Care and this is The Scope.

Announcer: Covering all aspects of women's health. This is "The Seven Domains of Women's Health" with Dr. Kirtly Jones on The Scope

Dr. Jones: Men and women aren't the same. However, in the history of research into health outcomes in medicine, men's biology was the default mode. Except in Obstetrics and gynecology, of course. Researchers were wary of including women in the studies because they knew that there could be variations in how the body worked and how drugs were metabolized during the menstrual cycle. And men, of course, were the same every day, which was not quite true.

Also, women might become pregnant and for untested drugs undergoing research into dosing and side effects, that would be a problem until drug safety was established. So we counted on men to go into the risky drug development battlegrounds, but not anymore. Gender health medicine has become a significant focus at the National Institutes of Health. Research funding requires that a woman be included where appropriate. For instance, not necessary on prostate research but very important in diabetes research. Okay. Well, what are some of the differences?

Body size. Of course, we know that men are often bigger than women, but not always. If body size alone were a bigger factor, we should be dosing drugs by body mass index, or body surface area or just weight. But body size does predict lung size, heart size, artery size and kidney size and the size of the organs may predict how it metabolizes drugs or how it's affected by disease. For instance, a woman's heart vessels are smaller and they might clog up a little more easily and more quietly. Women are less likely to have a massive heart attack and more likely to quietly have heart damage leading to heart failure.

What about body composition? Women carry more fat than men, usually. This may affect how some drugs are stored. Some drugs are distributed in water and some are bound by fat. This can be somewhat important in anesthetic agents, which are fat soluble and might be taken up by fat in women leading to a lower effect per weight in women.

Anatomic shape. Well, we know girls are curvy, but some girls are more curvy than others. Most women have a different hip configuration than men. They have wider hips and that is hip bones, not just fat on the hips. This means that the angle from the hip to the knee is bigger and men's legs are straighter from the knee to the hip. Now, this is important in the rate of knee injuries in female athletes, which is greater than men. And a knee replacement in women doesn't have to be smaller, it has to have a different angle. This is important for your orthopedic surgeon to know.

Absorption. We absorb pills through our stomach in our intestines. Women have slightly less stomach acid and slightly lower gut transit time, which can make some drugs stay around longer to be absorbed more. Of course, there are some men who have lower stomach acid and lower transit times as well.

Metabolism. Women make more of certain kinds of metabolic enzymes in the liver, particularly women on oral hormonal contraception or women who are pregnant. This is particularly important in certain anti-seizure drugs, which may be less effective in women and doses may need to be changed. On the other hand, women have smaller kidneys and less kidney function as they age. So drugs metabolized by the kidneys can hang around much longer in older women.

Another important difference is in narcotics, for which women have a greater effect at lower doses. The same thing with alcohol, women have a greater effect at lower doses. The same is true for some prescription sleeping pills, for which the FTAs implemented labeling to make sure that doctors and patients know that women should be prescribed lower doses.

Now there is the "we don't know why" core category, one of my favorite categories. In this category, we don't really know why there is a difference. We don't know why women have less serotonin than men in their brains. So anti-depressants and anti-anxiety drugs like selective serotonin reuptake inhibitors, SSRIs, have a greater effect, are more effective in depressed women than in depressed men.

All these differences can lead to different side effects in women compared to men. Women have more side effects in drug studies than men. They have more nausea as a side effect. So what should we do about this as clinicians and as patients? First, we should be wary of assuming that all men are alike and all women are alike. We've already been in trouble to say all people are the same, they're all like men. But not all women are the same and not all men are the same. The differences between men and women are evident when we look at large groups of each sex, but individuals may be larger, smaller more or less fat, have different metabolisms than average for their sex.

If our medicine isn't working in the way we hoped, we should take a look at the individual and ask if different dosing or a different drug should be better. If you're having a side effect from a drug, you should let your clinician know. If you're being prescribed a drug or a course of the action like physiotherapy or joint replacement, you should ask your clinician if there are differences between men and women and how should their recommendations be modified.

I read a research study from Japan where there words like "obese" or "fat" or "overweight" were flashed in front of the eyes of men and women in functional FMRI. In men, the brain activity went right to the language center of the brain. "What was that word?" In women, the brain activity went all over to the language center, to the emotion center, to the judgment center. I hope they didn't spend too much money on that study because every woman and man I know could have told them that women are different than men.

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Interviewer: Older adults are at a higher risk for death if they have low levels of bicarbonate in their blood. Bicarbonate, it's the main ingredient in baking soda. We'll talk about that next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Kalani Raphael, a nephrologist and Associate Professor of Internal Medicine at the University of Utah and at the Salt Lake City VA. Dr. Raphael, tell me about the main finding of your study. It's pretty interesting.

Dr. Raphael: In this study, we were looking at the association between serum bicarbonate levels and mortality in a generally healthy older population. The basic finding from our study was that in people with low bicarbonate levels, they had a higher risk of death and their risk of death was about 24%, 25% higher over a mean follow-up period of about 10 years or so.

Interviewer: So that's pretty significant. What is bicarbonate?

Dr. Raphael: Bicarbonate is very important in the body for maintaining your pH levels in a normal range. In order for our cells and our organs to work normally, the pH needs to be kept at a range of about 7.40.

Interviewer: So people with low bicarbonate would have blood that's more acidic. Why might that be unhealthy?

Dr. Raphael: The bicarbonate levels could be low for two main reasons. One is it could be because the kidneys are holding on to too much acid and your bicarbonate levels fall. That's something we call metabolic acidosis. Or the reason the bicarbonate level could be low is because the lungs are breathing off too much carbon dioxide and your bicarbonate levels fall as a compensatory response is what we call that.

So we're not exactly sure why the bicarbonate levels were low in these people. If I had to guess, I would say that the most likely reason the bicarbonate levels are low is because of an impaired ability of the kidney to get rid of the acid that we need to on a daily basis. The main reason why I say that is because our diets are really high in acid content in these western diets that we have now. We don't consume enough fruits and vegetables in relation to the amount of acid that we intake.

So if I had to guess, I would say that the most likely reason that the bicarbonate levels were low is because of an impaired ability to get rid of acid by the kidneys.

Interviewer: So what caused you to even take a look at that in the first place?

Dr. Raphael: Well, in people with kidney disease, we know that low bicarbonate levels occur quite commonly. It occurs in about 15% of people with kidney disease who aren't yet on dialysis. What we know is that in people with kidney disease who have low bicarbonate levels, they have a higher risk of death and they have a higher risk of progression of their kidney disease to end-stage renal disease or needing dialysis or a transplant in order to survive.

But much less was really known about generally healthy people and so I was interested in whether or not low bicarbonate levels have any association with poor outcomes in people who are otherwise healthy. So that was really the driving force behind this research study.

Interviewer: So do you think measuring bicarbonate levels could be some sort of test or indicator that someone could do to evaluate the healthiness of somebody?

Dr. Raphael: Absolutely. I mean, bicarbonate levels are very commonly measured in clinical practice these days. Bicarbonate levels are measured usually when a physician wants to check on somebody's kidney function. They'll order a chemistry panel or a renal panel. In primary care, I'm not exactly sure how well people look at these levels and I think that one of the things that maybe doesn't attract their attention is they don't really know what it means for that person.

So if you had a healthy person sitting in your clinic who had a bicarbonate value that was low, I think most physicians would say, "Okay. It's low. I'm not sure what to do with that." But I think what this research is showing is that it's probably something we should be paying attention to. But I don't really know quite yet what we should do about that.

Interviewer: Right. Maybe it would be a signal that it's worth taking a second look at this patient to see . . .

Dr. Raphael: Absolutely.

Interviewer: . . . if something else is going on.

Dr. Raphael: Right. So, I think you said it correctly that it's a signal for potentially bad things. That might trigger the physician to look into their kidney function a little bit more or maybe consider underlying lung disease or heart problems in that person.

Interviewer: So do you think more research needs to be done to figure out exactly what this could mean?

Dr. Raphael: Absolutely. The key thing about this research is that these were really healthy people. I mean, they were older folks. They could have had diabetes. They could have had some cardiovascular disease. But they were independently living. They could take care of themselves. They could walk a quarter-mile. They could climb up stairs. These were pretty healthy, older folks.

Interviewer: Right. So not necessarily any other indication that something was wrong, right?

Dr. Raphael: Exactly.

Interviewer: Interesting.

Dr. Raphael: Yep. So I think the next steps are to kind of look into why this cohort had low bicarbonate levels in the first place. Is it an undiagnosed or yet to be determined type of kidney disease or some other underlying lung disease, potentially? Then, I think the next thing also to consider is can we raise the bicarbonate levels in these people with various types of interventions and perhaps improve their outcomes, make them live longer, those sorts of things?

Interviewer: Is there anything else you'd like to add?

Dr. Raphael: The takeaway from this type of research is that we can say that there are associations between bicarbonate levels and outcomes. We can't really say quite yet whether or not people should be changing their diets or taking baking soda. I think that's something that needs to be cautioned against at this point, pending further clinical trials.

But I think if somebody is interested in keeping their bicarbonate levels at a normal range, I think that the safest way to do that is to look at how much fruits and vegetables they eat because fruits and vegetables are a source of bicarbonate, that bicarbonate largely comes from citric acid in fruits and vegetables, which gets converted by the liver into bicarbonate. We all know that fruits and vegetables have great health benefits for lots of other reasons.

One of the cautions about increasing fruits and vegetables in your diet is in people with kidney disease because those have high levels of potassium and that could cause potassium buildup in people with kidney disease. So I think if somebody is thinking about increasing their fruits and vegetables in their diet to keep their bicarbonate levels in a normal range that they should probably check with their doctor to make sure that it's safe.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: Diabetes and fruit flies; Dr. Carl Thummel, Professor of Human Genetics, is investigating what these insects can tell us about the disease, and some of his findings may surprise you.
Now is this something that happens to flies in nature, or something that you induce in the lab?

Dr. Thummel: It can happen under any circumstances, just like it could with you and me, because all living animals fundamentally need to handle their energy. So we eat three meals a day and we do that because we need the energy to survive. And we take those nutrients; we burn some of them to do what we need to do day to day, just to maintain our normal existence. And we store a whole bunch of it away so that it's available to us when food is not plentiful. And all animals have to do this, so that when we are fasting, or starving under the worst conditions as an animal, we can survive. It's just a fundamental survival mechanism, and there are regulatory systems that control that energy storage and release, and they are the same in a fly or a person.

Interviewer: And what does a fly with diabetes look like?

Dr. Thummel: Diabetes would not necessarily lead to being overweight. A lot of people actually ask whether you can tell your flies are obese, and sadly you can't. But I just wonder if it's because we're not flies.

Interviewer: Yes.

Dr. Thummel: You know, when you look at them, another fly may look at it and say, you look overweight. What's wrong? But when we look at the flies we don't really see them visually as overweight, and it might be because they have an exoskeleton.

Interviewer: Right.

Dr. Thummel: Unlike us, we have a skeleton inside our body; they have a skeleton outside their body that restricts their size to some degree.

Interviewer: Right.

Dr. Thummel: But if you open them up and you look at their adipose deposits you can see that they are indeed loaded with fat. And we can measure that with assays that we use to measure something called triglycerides, which are stored fat. And that's how we quantify it basically.

Announcer: What's the advantage of investigating diabetes in fruit flies?

Dr. Thummel: That's the real question, right? Why would we want to study these disorders that you and I have in this weird little bug system? And that's where the real strength comes in, because fruit flies have so many advantages for genetic and functional studies. They just aren't present in other more complex animal models like mice, or even zebra fish.
This goes back to about 100 years now of fly genetics that's behind this, and thousands and thousands of genetic stocks that are available to us so that we can manipulate the fly's genome basically in any way we want very quickly, and analyze pathways in great detail... far greater than we could do in another model system.

Interviewer: And can you tempt us with any of your findings?

Dr. Thummel: We're excited about our studies with diabetes now, because we have one of the first genetic models of diabetes. We have genetic diabetic models where through mutation these animals are no longer able to release insulin properly in response to glucose, which is what normally happens. You eat a meal, your glucose levels rise, your pancreatic cells sense that and release insulin, and that causes your peripheral tissues to suck up glucose, to store it away or burn it. And the diabetics are unable to do that for various reasons, either an inability to release insulin properly, or an inability to clear glucose properly. And our different genetic models have defects in both of those pathways. They can't sense glucose or release insulin, or they can't clear it properly, in peripheral tissue.
So we can model more than we had actually expected we would be able to do, really model the major forms of diabetes that are out there. And so we're really working hard on trying to figure out the mechanisms that are involved. Many of the genes we identify are conserved throughout evolution, and so we think it'll have direct relevance for human disease.

Interviewer: One thing I notice that you are studying is the transgenerational effect of diabetes, which is a concept that's really fascinating to me. Can you explain what that is and what you're doing?

Dr. Thummel: This goes back to studies in rodent systems over the last decades, but more profoundly to a human study called the Dutch Hunger Winner, which was at the end of the Second World War when the Nazis had a siege on in Holland. And the Dutch were getting much less food than they normally would get. And those children who were born during this period of low nutrient availability later grew up during a postwar period of prosperity under ideal dietary circumstances. And it turned out that when you looked at these as adults the kids whose mom's were not getting enough nutrition had a higher propensity to diabetes and obesity than their siblings did, who where under ideal dietary circumstances.
This was very interesting, because many studies have shown the same thing in rats and mice. And people hadn't really known what to make out of it.

Interviewer: Right, because it's not like traditional genetics. The parents weren't born with a predisposition to diabetes; they acquired it later. But then they still passed it on to their kids.

Dr. Thummel: You're exactly right. So it means that our own metabolic health isn't just dependent on what we eat and our particular genetics, like we assume. Those are the things we assume are the most important, and they indeed are. But another important factor in our metabolic health is our parents' metabolic health and even our grandparents' or great grandparents.
This has been now receiving a lot of attention. People want to understand the molecular mechanisms behind this non-canonical genetic inheritance, called epigenetic inheritance. And we are tackling it in the fruit fly.

Interviewer: What's an example of how you're approaching that problem in flies?

Dr. Thummel: We have set up stocks of flies that are genetically absolutely identical, so there's no genetic variation in those. And we are taking the parental generation and subjecting them either genetically or through diet to nutrient deprivation; or we're making them conversely obese; too much nutrients. And then we raise their offspring on a normal diet, and we check their metabolic parameters. And we take their offspring and raise them on a normal diet and check their metabolic parameters, and so on.
So we are looking to reproduce the effects in rodents and humans. We have been successful at that, and so now what we're trying to do is get those results reproducible and robust enough so we can start doing molecular studies to get a mechanism.

Interviewer: You've been working with fruit flies for quite a while, and I believe this is sort of a new focus for your lab, a relatively new focus. Why did you decide to make that shift?

Dr. Thummel: As you know, and as everyone knows, over the last ten years we've become very much aware of this increase in both diabetes and obesity in human populations. It's really threatening our health in ways that we never would have envisioned. When I was a kid we could eat Twinkies and drink Coca-cola and we didn't even think about the health consequences of that. It was wonderful.

Interviewer: Yeah.

Dr. Thummel: And now we look at our kids and we actually worry about whether they're drinking too much soda, or are they eating too many junk foods, and indeed, they are. As a population we have more calories available than we need for our day-to-day survival, so we are all living in an epidemic of diabetes and obesity. You can see it around you all the time.
And so this peaked our interest, and really caused us to redirect our research to see how far we could push flies to study those kinds of evolutionarily conserved pathways. And it's been very gratifying to see how well we can model it. Actually it's really surprising, I'll have to say. I am very surprised to see how similar they are.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.

Beat the summer heat when you're pregnant. This is Dr. Kirtly Jones, from the Department of Obstetrics and Gynecology at University of Utah Health, and today on The Scope you'll find out why being pregnant in the summer is miserable and if it can affect your unborn child and what to do to cool down.

Many women actually plan their pregnancies, what a great idea. And they plan their pregnancies not to be pregnant in the summer because they know, from their last August pregnancy that it's miserable to be pregnant in the summer. In the winter when you're pregnant you're warm all the time, it's so great. In the summer you can't cool down.

So what's the problem? You're so big, it's hard to cool down a big thing versus a skinny thing. And the metabolic fires are raging, you are building a baby, you're growing a baby, your cardiac output has increased by almost half, and you are pumping warm blood around your body.

Now when is it dangerous to get overheated? Clearly it's difficult to keep yourself cool when you're so big, have so much blood flow and you're trying to grow a baby. Getting overheated, or hyperthermic can be very dangerous for you and your baby. So sitting like you're a little baby kid who isn't very good at being able to thermoregulate, you don't leave your kid in an overheated car, don't stay in an overheated car, stay in the shade, keep a hat on your head, drink lots and lots of fluids to keep yourself hydrated because your baby, in your tummy, can't control it's temperature. So if your temperature goes up, its temperature goes up and it's not good for you baby.

Now this is what we do to cool down. Try as a fan, now maybe you are lucky and you've got air conditioning in your house, but moving air is one of the best ways to feel cool. Moving air is helpful. I like the personal swamp cooler. So what's the personal swamp cooler? Get a cotton t-shirt, that big baggy one for your pregnancy, get it wet, not soaking wet, but get it wet, squeeze it out so it's kind of damp and then put it on. And in Utah's climate, this won't work for our listeners in Houston, but it will work in Utah, Colorado, Wyoming. That coolness, evaporative coolness, will keep your skin cool and you'll feel so much better.

The other bad thing about being hot when you're pregnant is it makes your feet swell. o already you're all puffed up, you're all puffed out and your feet look like marshmallows, so when it's hot, try to keep your feet up when you're sitting down. Because your feet will just get bigger and bigger and then you're just into your flip flops.

So it's hot in the summer, its bliss in the winter, but if you're pregnant in the summer, here are some tips for you. Keep yourself cool by staying hydrated, drinking cool fluids, staying in front of a fan, keep your feet up so your feet don't puff out, try my own personal swamp cooler, which is a wet cotton t-shirt and sit in front of the fan and you will be cool and the baby is going to come sooner or later. Good luck to you. This is Dr. Kirtly Jones and this is The Scope.

updated: July 8, 2021
originally published: September 24, 2013