PracticeUpdate Diabetes Best of 2018

EXPERT OPINION 19

Now, the other thing that can do it is nephrotic syndrome. Nephrotic syndrome, because as you’re losing protein in the urine the liver gets the message, make more protein, and one of the proteins it makes is not just the albumin you’re losing, but ApoB so you can drive up the triglycer- ide levels, and then remember other things that can do it. For example, estrogens can do it, that’s a secondary cause. Alcohol is a big cause of elevate triglyceride levels. And then what we forget is this, people with inflammatory bowel disease and that’s because if you can’t reabsorb bile salts and your bile acids, your triglycerides go up. Bile salts come back to the liver and they suppress triglyceride levels. So I see a lot of young kids, for example with Crohn’s dis- ease and inflammatory bowel disease, who have elevated triglyceride levels because they’re not reabsorbing their bile salts, there’s nothing to come back to the liver and to shut down production. I think I mentioned estrogen. Estrogen can drive up. But also remember that tamoxifen can drive up. Tamoxifen blocks estrogen in the breast, but in the liver it actually acts like estrogen. So, tamoxifen can drive up the triglyceride levels by mimicking estro- gen in the liver. Dr. Caudle: Interesting. And what do you think about the familial hypertriglyceridemia? When should we start getting concerned about that in a patient of ours? Dr. Thompson: Obviously you want to be concerned about familial hypercholes- terolemia. The worst is when you’re born without lipoprotein lipase activity, and so that’s a pretty unusual thing for an adult car- diologist like me to see. So when does that appear? You can almost guess, not always, but you can guess that someone has lipo- protein lipase deficiency when you have a child or a patient who has the history of get- ting pancreatitis when they were about age 2. Now, what’s happening? They’re going off breast milk, they’re coming on cow’s milk, they’re getting exposed to a lot of fat, and so the real severe familial-inherited hypertriglyceridemia gives you clues that it’s there and that is pancreatitis in child- hood early on. Dr. Caudle: That’s interesting. Thank you for that. And finally, what are the current guidelines for the addition of a fibrate to lipid-lowering therapies in patients with car- diovascular disease? Dr. Thompson: So it varies. It varies through- out and nobody argues about when you have triglyceride levels over the level of 500 you add on. I must admit that I and many of the people that work in lipids a lot of the time are more aggressive at low

" You’re going to see a lot more emphasis on triglycerides… Because we’ve cured the LDL problemwith the drugs that we have available, and

levels, and so what do I use to make a decision? Going back to ApoB, every bad particle has one ApoB. You want to know how many bad particles you got? Get an ApoB level. You don’t have to do anything more fancy than that, and so if the ApoB level is much over what I want for an LDL... for example, if I want my LDL at 100, I want my ApoB level somewhere around 110. If it’s much over that then I’ll go chasing that with a lipid-lowering agent, you know, either concentrated fish oil or fibric acid derivative. Dr. Caudle: And finally, is there any new research in this field that might change our approach? Dr. Thompson: Well, there are a bunch of new drugs being developed that work on either ApoC3 or ApoC5, both of which help reg- ulate triglyceride levels, and so there are new drugs coming down the path. You’re going to see a lot more emphasis on tri- glycerides, and why are you going to see more emphasis on triglycerides? Because we’ve cured the LDL problem with the drugs that we have available, and so now we’re looking for residual risk. Residual risk in that the LDL isn’t low enough, residual risk in that it’s triglycerides, residual risk in that it’s inflammation and other things. So you’ll see a lot more emphasis on triglyc- erides because we’ve cured things and because there are new drugs coming. so nowwe’re looking for residual risk. Residual risk in that the LDL isn’t low enough, residual risk in that it’s triglycerides, residual risk in that it’s inflammation and other things. "

level. So if I want the person to have an LDL cholesterol of 70 I want their overall ApoB level, which will include their VLDL and tri- glycerides, I want that under about 80. Let’s talk about the numbers where I pay a lot of attention. As I mentioned, over 1,000 I see that person right away – life-threaten- ing pancreatitis. Over 500 mg/dL, nobody argues that those people ought to be treated with drugs. Between 200 and 500 it’s a bit of a, you know, what do you think you can do? Can you get it downwith statins and eze- timibe, great drugs to lower LDL as well, or do you need to add a fibric acid derivative? The higher the triglycerides, when it’s over 200, the lower my threshold to adding either concentrated fish oil or fibric acid derivative. Dr. Caudle: So let’s talk about secondary causes of hypertriglyceridemia. When should we as clinicians really start thinking about pursu- ing a work-up for secondary causes of high triglycerides, and when should we be also concerned for familial hypertriglyceridemia? Dr. Thompson: Let’s talk about the second- ary causes, and I want to give you the top 3 secondary causes: number 1, diabetes; number 2, diabetes; number 3, diabetes. High triglycerides should make you think that you have early diabetes even when the hemoglobin A1c is not over 6 or what- ever, but you just want to think about it. I do more oral glucose tolerance tests at Hartford Hospital as a cardiologist than the endocrinologists. Why? Because I see these people referred to our Lipid Clinic with ele- vated triglycerides.

Dr. Caudle is a Board- Certified Family Medicine Physician and Assistant Professor in the Department of Family Medicine at Rowan University-School of Osteopathic Medicine in Stratford, New Jersey.

Go to www.practiceupdate.com/c/65261 to watch this interview with Dr. Thompson.

VOL. 2 • NO. 4 • 2018