Do you have renal insufficiency, are on dialysis or have a transplanted kidney and are diabetic at the same time? Then this article is very important for you. It explains the most important basics about sugar metabolism. It also tells you which medications you should be careful with if you have impaired kidney function and at what point the medication dose should be adjusted.
Contrary to popular belief, sugar is not fundamentally bad. Glucose, for example - also known colloquially as dextrose - is the most important energy supplier for your body. But as the saying goes, the dose makes the poison. So it's always a matter of not taking in too much sugar through your diet. The World Health Organization (WHO), for example, recommends reducing the amount of sugar per day to less than 10% of your total energy intake. The most difficult thing is that you often don't know exactly how much sugar is actually in your food - especially if you like to reach for ready-made foods. Unfortunately, these often contain a lot of sugar.
Did you know that foods such as potatoes, bread and pasta also contain sugar molecules, even though they don't taste sweet? As you know, they contain a lot of carbohydrates. You've probably heard that name before. If you look at carbohydrates under a microscope, they consist of small sugar molecules. The carbohydrates contained in your bread, for example, are broken down into individual sugar molecules by digestive juices in your intestines and then absorbed into your blood. The amount of sugar in your blood can be measured as a blood glucose value. From there, your blood transports the sugar to your body cells.
Diabetes
But just because the sugar molecule from your blood knocks on your cell door doesn't mean it will be let in. The key to letting it in is held by the doorman - the hormone insulin. To understand these relationships in more detail, we must now distinguish between type 1 and type 2 diabetes.
Type 1 diabetes
If you have type 1 diabetes (=diabetes mellitus type 1), your body - or more precisely the pancreas - cannot produce enough insulin. The sugar can therefore not be absorbed by your cells as usual and remains in your blood. This phenomenon usually occurs in childhood or adolescence and is often marked by extreme thirst and frequent urination. In the blood, sugar levels can be measured as blood glucose levels. Too little insulin then means higher blood sugar levels, which in turn can damage your vessels and organs.
Type 2 diabetes
In type 2 diabetes (=diabetes mellitus type 2), your cells are totally annoyed because insulin is constantly knocking on the cell door. In addition to a genetic component, little exercise and an unfavorable diet favor the development of type 2 diabetes. As a result, the body often has to deal with far too much sugar for years on end. To get all the sugar into the cells, more insulin is produced.
What would you do if the same person kept getting on your nerves and knocking on your door? Probably stop responding. That's exactly what can happen to your cells and insulin - at some point they stop reacting as they usually do. In medicine, this is known as insulin resistance. At some point, your cells become resistant to the effect of insulin. After a certain time, your pancreas becomes so exhausted from constantly producing insulin that insulin production decreases. Less insulin subsequently means that more sugar remains in your blood. As a result, your blood sugar level rises above the healthy range.
Low blood sugar (=hypoglycemia)
But not only too high blood sugar levels (=hyperglycemia) are a problem for your body and your health. Too little sugar in your blood (=hypoglycemia) can also be dangerous. When there is not enough sugar in your blood your cells - especially the nerve cells in your brain - lack the necessary energy to function well. This can manifest itself in the form of tremors, restlessness, confusion, and even unconsciousness. To prevent this from happening so quickly, your body can store glucose and also produce it itself. The production of glucose takes place mainly in the liver and in your kidneys.
What do diabetes and kidneys have to do with each other?
To keep blood sugar levels under control, people who have diabetes often require medication. With kidney disease, your kidney often don't function quite as well as they do in people with healthy kidneys. As you probably know, one important job of your kidney is to clean your blood.
Thus, your kidney is also responsible for the breakdown and elimination of many medications. If your kidney function decreases, then your medications often stay in your body for a longer period of time and work longer. In addition, there are medications that can additionally damage your kidneys, thereby further decreasing their function. Therefore, depending on your kidney function, you may not be allowed to take some medications at all, or the amount may need to be reduced. But don't worry - your medical team will take care of you and optimally adjust your medication to your needs.
To assess how well your kidneys are actually functioning, the estimated glomerular filtration rate (=eGFR) is often used. This value indicates how much blood your kidneys cleans per minute. The higher the value, the better your kidney function. Your eGFR therefore also plays the decisive role in determining which diabetes medications you can still take or when the dose must be adjusted.
Kidneys can also be directly affected by diabetes. In diabetic kidney disease, the filtering function of the kidneys is disrupted and the kidney tubules (effectively the tubes of your urinary system) can become damaged. This leads, among other things, to a decrease in eGFR and to more protein in your urine (=proteinuria).
Overview of the most important diabetes medications
As mentioned above, impaired kidney function can affect the function of your medications. As a result, you may no longer be allowed to take certain medications at all, or you may only be allowed to take a smaller amount. But what exactly does this mean for your diabetes medications? Here is a brief overview. Please note: There are far too many different medications to give a complete picture here. That is why we have only listed the most common groups of medications. By the way, a drug group is a set of drugs that work in the same way. However, they may differ in their active ingredient.
Insulin
People with type 1 diabetes have to inject the hormone insulin into their body, because their pancreas cannot produce enough of the hormone itself. Since you consume a large part of the sugar in your diet, the amount of insulin you need and when you inject it often depends on what you eat. If you inject too much insulin, you may suffer from hypoglycemia. In this case, the ratio between insulin and blood sugar is not balanced, and not enough sugar remains in the blood to bridge the time between meals.
In the case of type 2 diabetes, your pancreas often still produces insulin itself. Other medications and, above all, a healthy lifestyle can often help you get a better grip on your sugar balance. However, if these measures no longer work, insulin will also be used at some point in type 2 diabetes.
There are also various types of insulin. They differ primarily in how long they work. When you use which insulin and in what quantity is very individual. Therefore, your diabetologist will usually work out an insulin plan for you, which you should follow as closely as possible.
Insulin is mainly broken down in your liver, but your kidneys and even your muscles can also break down insulin. As you can already guess from reading the article, insulin is broken down more slowly when your kidneys are not working so well. This means that insulin works longer. Basically, this is not directly a bad thing. It often means that you have to inject insulin less frequently. If dialysis takes over the task of your kidneys, the whole thing becomes a bit more complicated. Dialysis often does not take place every day. Then your insulin schedule may be different depending on whether you go to dialysis that day or not. One small upside to dialysis is that you often need to inject less insulin on dialysis days than on non-dialysis days to keep your blood sugar in a healthy range. But don't worry, you can get more detailed information and help in this case from your medical team.
Biguanide
The word biguanide probably sounds so foreign to you that you'll have trouble remembering it. Biguanides (e.g. metformin) are used to lower blood sugar levels in type 2 diabetics. The drug does this by ensuring that less sugar is absorbed through the intestines. It also slows down the production of sugar in the liver, thereby also reducing blood sugar levels.
This process is usually good for your physical health if you have diabetes. Biguanides in combination with a reduced kidney function, however, can unfortunately in some cases lead to overacidification (=acidosis) of the blood. You do not need to know exactly how this happens. Often not even your attending physicians know. It is only important that you know that in many cases biguanides should no longer be taken if your eGFR is less than 30 mL/min. If your eGFR is between 30 and 60 mL/min, your doctor will most likely adjust the dose accordingly.
Sulfonylureas
If your pancreas produces less insulin in type 2 diabetes, so-called sulfonylureas (e.g. glibencamide, gliclazide, glimepiride) can boost production again in many cases. However, they are also excreted via the kidney. Therefore, most may no longer be used when eGFR is less than 30 mL/min. For some drugs, however, it is sufficient to reduce the dose. Your treating physician has the exact overview of this. If you are interested in knowing more, ask at your next appointment. It is also important to mention that sulfonylureas (like insulin) can lead to hypoglycemia. It is best to ask your doctor how you should deal with this.
DPP-4 inhibitors
DPP-4 inhibitors (e.g. sitagliptin, vildagliptin, saxagliptin) also increase the secretion of insulin from your pancreas. If your kidney function is impaired, the dose may need to be adjusted. More detailed information is always available from your medical team.
GLP-1 agonists
Drugs from this group also increase the release of insulin in the pancreas. They include, for example, agents such as dulaglutide, exenatide, and liraglutide. The excretion of these drugs via the kidneys is not yet precisely understood. Therefore, as always, a prescription in combination with impaired renal function should be discussed with your medical team. Nausea is common, especially at the beginning of DLP-1 agonist therapy. This usually subsides over time and can be reduced by adjusting the dose (especially at the beginning). Rarely, inflammation of your pancreas may occur. This is indicated by very severe abdominal pain that runs around the front of your abdomen like a belt.
SGLT2 inhibitors
Your kidneys also contribute their part to your sugar balance. Sugar is not normally excreted in your urine, because your healthy kidneys put sugar back into your blood through a transporter. This group of medications is designed to optimally block this transporter so that some sugar is excreted through the urine after all. SGLT2 inhibitors not only improve your blood sugar, but are also used in most kidney diseases, regardless of your blood sugar levels, to slow the deterioration of your kidney function. Therapy with SGLT2 inhibitors can increase risk for urinary tract infections and genital fungal infections. It is best to talk to your healthcare team if you have more specific questions about this medication.
Glinides
Glinides (e.g., rapeglinide, nateglinide) also stimulate your pancreas to produce more insulin. They are derivatives of sulfonylureas. While nateglinide is excreted through the kidneys, this is not true of rapeglinide. This may influence the prescription of these drugs in chronic kidney disease. Like the sulfonylureas, glinides can also cause hypoglycemia. You can always get more specific information from your medical team.
Thiazolidinediones
On with the tongue twisters! In the best case, thiazolidinediones (e.g. pioglitazone) cause your cells to respond better to insulin. Unfortunately, however, taking them can also lead to water retention in the body. You may already know this problem from your kidney disease. If your kidneys are no longer able to excrete enough fluid, it is deposited in your legs or lungs, for example. Your body does not need this extra load. That's why thiazolidinediones are not usually used in people with impaired kidney function. They can also be harmful if you have heart failure and may increase your risk of developing bladder cancer. You can always get more detailed information from your medical team.
Challenges with diabetes & renal insufficiency
Whether you have renal insuffuciency, are on dialysis, or have a transplanted kidney, if your kidney function is limited, it will affect your sugar metabolism and your diabetes medications.
For one thing, you know by now that many medications for diabetes are broken down or excreted through the kidneys or even work in the kidneys, so their effects may be prolonged or altered if your kidneys are not functioning to their full capacity. In addition, your kidneys are also involved to a small extent in making glucose themselves to prevent possible hypoglycemia. If they no longer function as they should, or if dialysis takes over the purification of your blood, then the body's own sugar production is also limited. This can put you at higher risk for hypoglycemia if you have diabetes and impaired kidney function.
However, this can usually be managed quite well by regularly measuring blood sugar. An important note at this point: The long-term blood glucose value HbA1c is no longer as meaningful with impaired kidney function. But don't worry about that - your doctor knows other tricks to monitor your blood glucose metabolism. In addition, your medical team will support you by keeping track of your diabetes medications and, if necessary, replacing them with a more appropriate medication or reducing the dose.
In summary, the risk of hypoglycemia is increased when you have diabetes and impaired kidney function at the same time. Therefore, it is important to keep an eye on kidney function and adjust medications accordingly. To put it simply, your medications and their dosage should usually be checked by your treating nephrologist when your eGFR is below 60 mL/min. At the latest when your eGFR drops below 30 mL/min, there are a number of drugs that should not be given or should only be given in smaller amounts.
As you can see, as a diabetic, you should definitely get an "okay" from your nephrologist if, for example, other doctors or pharmacists suggest additions or adjustments to your medication plan!
