Pathophysiology of T2DM and Cardiovascular Disease



Paul Thompson, MD: Hi, everyone. I’m Dr Paul Thompson. I’m the former chief of cardiology at Hartford Hospital in Hartford, Connecticut. Welcome to HCPLive® Peers & Perspectives®, which is a presentation titled “Evaluating the Diabetes-Cardiology Interface.” I’m lucky enough to be joined today by Dr Robert Busch, who is an internationally known diabetologist and endocrinologist from Albany Medical Center in Albany, New York. We’re going to be talking about that interface between cardiology, endocrinology, primary care, and the very important risk factor for heart disease: insulin resistance and diabetes.

Our goals today are to talk about cardiovascular disease with respect to insulin, glucose, metabolic syndrome, and diabetes management. We’ll discuss the importance of why cardiologists, endocrinologists, and primary care doctors need to know a lot about diabetes. I’m going to give you an example of why that’s important.

There’s something called the Early Acute Coronary Syndrome trial, in which they looked at about 9000 patients in 2013. Of those patients, about 30% had known diabetes. About 10% had diabetes that was easily diagnosable but wasn’t known. An additional 10% had prediabetes.

Bob, can you give us the basic background and the pathophysiology of type 2 diabetes?

Robert Busch, MD: Years before the diabetes starts, the patient is insulin resistant. If you’re insulin resistant, the blood sugar might go up an iota. If blood sugar goes up a bit, the pancreas will sense that and pour out more insulin. You’re insulin resistant to start with, and then you get compensatory insulin secretion. Eventually, the beta cell loses function, either for genetic or other reasons, and starts going bald. It’s not an on-off process as in type 1 diabetes, but the beta cell fades out over time. When that happens, the postmeal sugar goes up, and then the fasting sugar goes up. Until the fasting sugar goes up, some people don’t receive a diagnosis of diabetes. They have already had 10 years of insulin resistance with additional high triglycerides, low HDL [high-density lipoprotein], prehypertension or hypertension, and abdominal obesity. All those other inflammatory conditions are existing, and the patient is going on without knowing they have diabetes. They finally get the diagnosis, and they already have underlying heart disease because of all those other issues that have inflamed the endothelium.

Paul Thompson, MD: Bob, that’s a great point. I see it a lot. I run a lipid clinic, and I see it a lot because I see people who present with triglyceride elevations. What’s unknown is that a lot of those people who present with triglyceride elevations have early diabetes. It’s not known. Their hemoglobin A1C [glycated hemoglobin] can be borderline or normal, yet when you do an oral glucose challenge test, you note that they’re diabetic. One of the themes we need to get across to people today is to go hunting for those prediabetic patients. Why? If you start overglycosylating hemoglobin, you’re also glycosylating a lot of other proteins, including LDL [low-density lipoprotein] cholesterol and apolipoprotein B. Apolipoprotein B is part of LDL cholesterol. Before you present with frank diabetes, you’re already doing a lot of things wrong.

Dr Ralph DeFronzo, who is 1 of the greats in endocrinology and diabetes, always pointed out that when you have prediabetes, that is actually a misnomer because you’ve already lost about 50% of your islet cell insulin-secreting capacity. You’re already well down the pike toward being frankly diabetic. Do you have any comments about that?

Robert Busch, MD: Right, you have to lack beta cell secretion of insulin to get diabetes. If you have a 400-lb patient who is insulin resistant but their beta cells work, they will not get diabetes. Even though insulin resistance is the core defect, you have to lack the beta cell to get diabetes. You’re exactly right. Our cardiologists don’t know as much as you do, so thank you for bringing that up. You’ve lost a lot of beta cell function by the time diabetes is diagnosed.

Paul Thompson, MD: Right. The issue is that it leads to coronary disease. At 1 point, I tried to get the endocrinologists to become part of the cardiology division, because diabetes is a vascular disease. Bob, you belong in cardiology. You should be a cardiologist.

We all know the primary pathophysiology of insulin resistance, but can you just discuss that with us so we’re all at the same starting point? What are the biggest causes of diabetes?

Robert Busch, MD: A big cause is obesity. Genetics cause it. Obesity causes it. There is more insulin resistance in the obese patient, and that is exacerbated by their genetic problems. There are certain drugs that can cause it. One example is steroid therapy. We can have a patient perfectly well controlled, without diabetes or prediabetes. Someone can give them a steroid shot, and all of the sudden, their sugar sails up. It’s typical to get calls at night from patients saying, “My sugar is 400 mg/dL.” The first thing I ask is, “Did anything else change? Did you see the orthopedist today?” Patients say, “Yes, how did you know that?” They got a shot of steroids. Steroids, obesity, and genetic factors are some of the key contributors. There are some other drugs that do that too. Some of the HIV drug treatments can also set off diabetes.

Paul Thompson, MD: I agree with you. The key factor is obesity. I always tell patients that fat fights insulin. If you’re overweight, it doesn’t matter where it is. Abdominal obesity is clearly the worst, but fat fights insulin.

Transcript Edited for Clarity

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