Recently the FDA has issued an alert about the possible connection between some diabetes medications and heart failure. The drugs in question, Onglyza and Nesina, are relatively new diabetes medications that have surged in popularity. These medications are among a class of dipeptidyl peptidase-4 inhibitor (DDP-4) drugs. 

The FDA is warning that these drugs may increase the risk of heart failure especially in those that are already vulnerable, namely those with existing cardiovascular or kidney disease. There are also combination medicines (Kombliglyze and Kazano) that have these medicines in them. 

This announcement follows the review of two cardiovascular-outcomes trials. In one of the trials there was a 27% increase in the rate of the first hospitalization for heart failure and possible increase in all-cause mortality. A third trial involving another DPP-4 inhibitor called Januvia appears to not show the same issue although I would be skeptical of prescribing that medicine as well considering it is in the same class of medicines.

This announcement re-emphasizes that need for patients to seek alternative means of treating their diabetes.

However, the real focus should be on prevention. Insulin resistance and elevated insulin levels precede the development of diabetes by many years. See the chart below. 

From the previous post found here I hope everyone understands more about cholesterol and why we need it.

I am afraid that this next post requires a little high school chemistry but bear with me as I think you will find it of great benefit. 

Let's start with the high school chemistry. Anybody who has tried to clean a greasy pan with water has realized very quickly that fat and water don't mix. In order for the grease to "dissolve" in the water it needs soap. 

The same thing is true of cholesterol. The cholesterol in our bodies needs a special particle called a lipoprotein to carry it in our blood otherwise it will not dissolve properly. This particle contains proteins called apoproteins,  phospholipids, cholesterol, cholesteryl esters, and triglyercides (fat).  See the figure below. 

The apoproteins serve several functions including binding to cell receptors where the cargo needs to be dropped off. Apolipoproteins come in different forms. Two of the major forms are apoliprotein A-1 (apoA-1) and apolipoprotein B (apoB).

The majority of apoB in our body is found on low-density lipoprotein. You might know this particle by the term "LDL" or the "bad" cholesterol. ApoA-1 is found on high-density lipoprotein otherwise known as "HDL" or "good" cholesterol. For every one particle of LDL there is one particle of apoB (specifically apoB100). 

The density of lipoproteins are defined by their lipid-protein ratio. In terms of lipoproteins there are 5 main classes or densities. These include chylomicrons and high (HDL), Intermediate (IDL), low (LDL), and very low-density lipoproteins (VLDL). HDL is the smallest and most dense followed by LDL, IDL, VLDL, and chylomicrons. Chlyomicrons, VLDL, and IDL have the most fat content and LDL has the most cholesterol. See the figure below. 

Interestingly the cholesterol concentration increases and triglyercide concentration decreases as the size of lipoproteins decrease. 

The reason for this is that chylomicrons and VLDL come loaded with fatty acids from the gut and liver respectively. As they move throughout the body they release their fats to the muscle and adipocytes (fat cells) and shrink. As they do so they morph into IDL and then some eventually make it into LDL particles. As they shed fat they become more concentrated in cholesterol. 

Unfortunately, it is the LDL that can penetrate and deliver cholesterol to the arterial walls leading to atherosclerosis. It is also LDL that returns cholesterol back to the liver. 

The problem of the cholesterol dumping from LDL is the critical issue that we will discuss in the future. 

Stay tuned for part 3 in a few days. Also, I would like to acknowledge that I have gotten much of this information from Dr. Attia and his excellent blog. If you would like a personalized assessment of your cardiac risk factors and cholesterol numbers feel free to schedule a consultation. 

Of course, each individual case is different and the advice in this post should not substitute for getting a consultation with your doctor. ​​