To start off this week’s post, let’s consider two very real-life scenarios, both of which I see regularly.
Scenario #1: a person with newly diagnosed diabetes is referred to me with quite high sugars (let’s say A1C is 10%, which corresponds to an average sugar of about 14 mmol/L). Their family doctor starts one oral diabetes medication while they are waiting to see me. Their sugars come down to near normal range with just this one medication.
Scenario #2: my next patient has had type 2 diabetes for many years. This person’s A1C is also 10%, with average sugars of about 14. They are started on one additional oral medication while waiting to see me, with some improvement in sugars, but not nearly as much as our first patient in Scenario #1.
Today’s question is: Why do some people’s sugars improve a whole lot with one medication, but others very little?
One of the important issues at play here is whether that person’s insulin-producing beta cell dysfunction is reversible or not. When sugars are very high, the beta cells of the pancreas are in a state of ‘glucolipotoxicity’. This means that the beta cells may still have the capacity to produce lots of insulin, but the high sugars and some types of fatty acids are making them dormant (think of it like they are sleeping). When a medication is started and sugars start to improve, dormant beta cells can wake up again and start making more insulin (ie, reversible beta cell dysfunction). For other people who have a longer duration of diabetes, or a genetic tendency towards more aggressive beta cell decline, their insulin-producing beta cells are not dormant, but are actually just not capable of producing much insulin (ie, beta cell dysfunction that is not reversible). So, when an oral medication is added, there is no dormancy of beta cells to recover.
Another major factor for people with type 2 diabetes and elevated body weight, is whether (and how much) weight loss is occurring with starting the new medication (either by way of lifestyle change, or due to the medication itself, as some diabetes medications also cause weight loss). Fat in the liver increase the liver’s resistance to insulin, and fat deposits in the pancreas impairs pancreatic function as well. With weight loss, fat comes out of ectopic stores (fat stores outside of fat tissue itself), including the liver and pancreas. Consequently, insulin sensitivity of the liver markedly improves, and the pancreas can function better. These processes support an improvement in beta cell function.
There are many other possible mechanisms at play which impact how much sugars will come down with one medication, including which medication is chosen, the presences or absence of other health issues like chronic kidney disease, genetics, and other factors.
We don’t currently have any tests that can predict who will have a big blood sugar improvement with a medication and/or weight loss and who won’t. Blood tests as well as pancreatic imaging techniques are currently under investigation/development in this regard.
BOTTOM LINE: Every person with type 2 diabetes is unique, and the response to treatment will be very individual. Keeping sugars as normal as possible, and managing weight as well as possible, are both important steps to allow the pancreas to function to its best capacity!
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