What is New Onset Diabetes After Transplant?

New-onset diabetesafter transplantation, often referred to as NODAT, is when a person who was not previously diabetic develops diabetes after receiving an organ transplant. It’s a common condition that presents after organ transplants and it increases the chances of getting infections and the overall death rates.

International guidelines on NODAT were established in 2003. These guidelines recommend that NODAT should be diagnosed based on the criteria for type 2 diabetes, as set out by the American Diabetes Association. Therefore, these guidelines hint at using an altered version of these criteria to identify NODAT and high blood sugar levels in people who have had a kidney transplant.

What Causes New Onset Diabetes After Transplant?

Patients with certain risk factors for type 2 diabetes are more likely to develop New-onset diabetes after transplantation (NODAT). These risk factors can be grouped into two categories: nonmodifiable and modifiable risk factors.

Nonmodifiable risk factors are ones that patients cannot change, like their age, ethnicity, family history of diabetes, the presence of certain genetic factors, and their pre-diabetes status.

In terms of age, research has found that the chance of developing NODAT is 2.2 times higher in those over 45 years old compared to younger individuals.

People of Black and Hispanic descent are more likely to develop NODAT than those of White descent. This might be due to the different ways certain medications, like tacrolimus, affect different ethnic groups, or due to genetic differences.

Individuals with a family history of diabetes, and those carrying certain genetic variants, are more likely to develop NODAT. Specific genetic variants linked to higher NODAT risk include those in the genes HLA A28, A30, B27, Bw42, SLC30A8, KCNQ1, TCF7L2, KCNJ11-Kir6.2, and NFATc4. In pre-diabetes conditions like fasting blood sugar levels between 90 and 100 mg/dL, patients need to be carefully monitored after organ transplant and advised on lifestyle modifications to avoid developing diabetes.

Modifiable risk factors, or risks that patients can do something to change, include obesity and the use of certain post-transplant medications.

Obesity can increase the risk of NODAT by promoting inflammation and disrupting normal insulin function. This can lead to insulin resistance and diabetes. In transplant recipients, low levels of a hormone called adiponectin, which typically helps protect against diabetes, is also a risk factor for developing NODAT.

Certain medications, including corticosteroids and calcineurin inhibitors (CNI), prescribed after organ transplantation can increase NODAT risk. These medications affect insulin sensitivity and glucose transport, leading to higher blood sugar levels. Patients receiving tacrolimus treatment are particularly at a higher risk of NODAT, though this effect can reverse if the medication is discontinued.

Patients who have low magnesium levels after transplant, a condition known as hypomagnesemia are also at a higher risk for NODAT. Calcineurin inhibitors can lead to this condition by inhibiting the body’s ability to absorb magnesium.

Infections and inflammation, such as those caused by Hepatitis C virus (HCV) and cytomegalovirus (CMV), can also contribute to the development of NODAT. Both these infections can affect insulin function, and in the case of HCV, patients treated with tacrolimus are at even higher risk.

Risk Factors and Frequency for New Onset Diabetes After Transplant

NODAT, or New Onset Diabetes After Transplant, tends to occur more frequently in Black and Hispanic recipients than White ones, likely due to different genetic factors. The frequency of NODAT in the U.S. is reported to be around 9.1% three months after a transplant, 16% at one year, and 24% three years post-transplant.

It’s also important to know that NODAT can occur at different rates depending on the type of transplant:

4 to 25% of kidney transplant recipients
2.5 to 25% of liver transplant recipients
4 to 40% of heart transplant recipients
30 to 35% of lung transplant recipients

If you have a liver transplant and also have an HCV infection, your risk of NODAT can increase to between 40% and 60%. There’s considerable variability in the rate of NODAT after a kidney transplant too, with it being between 7% and 30% in the first year. The majority of organ recipients (around 76.5% of them), develop NODAT within the first three months after transplant. After six months, the rate of diabetes in transplant receivers is about the same as in those who have not had a transplant.

If a transplant recipient is on higher doses of medication to suppress their immune system post-transplant, they also have a greater chance of developing NODAT.

Signs and Symptoms of New Onset Diabetes After Transplant

As with diabetes (DM), many patients with New Onset Diabetes After Transplant (NODAT) don’t experience noticeable symptoms. Most of these patients are identified due to routine blood sugar monitoring and increased blood sugar levels in lab tests after their transplant surgery. This is why blood glucose testing is recommended for all transplant patients as part of their post-transplant screening. This approach helps in identifying NODAT at an early stage. The symptoms of NODAT are the same as those of diabetes in non-transplant patients, and may include increased urination, increased thirst, increased hunger, weight loss, blurry vision, nerve pain, numbness in the limbs, and signs of infection.

Increased urination
Increased thirst
Increased hunger
Weight loss
Blurry vision
Nerve pain
Numbness in the limbs
Signs of infection

The doctors will perform a physical exam that includes checking the vital signs, hydration level, a detailed eye examination, vascular and neurological examinations, and a foot assessment. The findings of the physical exam may not necessarily reveal anything out of the ordinary, but physical signs of damage to end-organs might be observable.

Testing for New Onset Diabetes After Transplant

Predicting NODAT, or New-Onset Diabetes After Transplant, can be done by looking at specific risk factors like obesity and pre-diabetic conditions. Some researchers believe that checking the body’s early response to insulin (insulin resistance) and its overall insulin sensitivity might help predict this condition, but these methods are not universally accepted.

The criteria for diagnosing NODAT are the same as for diabetes mellitus (DM). This includes symptoms of diabetes with a random blood sugar level of 200 mg/dL or more, fasting blood sugar level of 126 mg/dL or higher on multiple occasions, or a blood sugar level of 200 mg/dL or more two hours after an oral glucose tolerance test (OGTT). The OGTT is the best method for diagnosing NODAT, especially soon after organ transplantation.

In the first three months following a transplant, it’s not reliable to use a HbA1c test (which measures average blood sugar over several months) to diagnose NODAT due to changes in red blood cell function. However, after three months, a HbA1c level of 6.5% or higher can help diagnose NODAT. However, many experts do not recommend using the HbA1c test alone to screen for NODAT in the first year after transplantation.

It’s important to identify NODAT early to reduce the risk and complications of diabetes. Medical professionals usually test all organ transplant patients for NODAT, with weekly tests in the first month, then at 3, 6, and 12 months post-transplant. After the first year, the chance of developing NODAT decreases, and annual screening is recommended.

Treatment Options for New Onset Diabetes After Transplant

Post-transplant hyperglycemia, or high blood sugar after a transplant, can be caused by the stress of surgery, pain, and high doses of immune-suppressing drugs. It’s important to detect hyperglycemia early because managing blood sugar levels well can improve the long-term health of both the patient and the transplanted organ.

The main goal of managing post-transplant hyperglycemia is to control blood sugar levels and lower the risk of complications. Firstly, doctors should consider non-drug methods to reduce blood sugar. For example, they could change the immune-suppressing drugs the patient is taking to ones that have less of an effect on blood sugar, or change the dose of these drugs. Sometimes, reducing the dose of a steroid drug soon after the transplant can control blood sugar without the need for further treatment.

However, doctors need to weigh this against the risk of the body rejecting the new organ. If changing lifestyle factors and the dose of immune-suppressing drugs don’t control blood sugar levels enough, then medication could be required. Many patients need insulin therapy to manage high blood sugar after surgery. Because doses of immune-suppressing drugs and the patient’s diet can change often in hospital, blood sugar levels can fluctuate. Intravenous insulin, which is given directly into a vein, can be a good initial treatment because the dose can be easily adjusted and it’s safe to use when the new organ is still settling in.

The choice between insulin and other drugs that lower blood sugar depends on how high the patient’s blood sugar levels are. Once blood sugar is under control or the patient is discharged from the hospital, the doses of injected insulin can be turned into subcutaneous (under the skin) doses based on the intravenous doses. If a patient needed a low dose of insulin in the hospital, they could switch to oral blood sugar-lowering drugs when they’re discharged.

Metformin, a drug that improves how the body reacts to insulin, is commonly used and usually safe for most patients. Other drugs that could be used include sulfonylureas, which increase insulin secretion but can lead to weight gain and low blood sugar as side effects, Thiazolidinediones, which improve the body’s glucose tolerance and insulin sensitivity, and DPP-4 antagonists like sitagliptin that enhance the body’s insulin secretion. Because these patients often have an increased risk for low blood sugar and heart disease, the target HbA1c, a measure of long-term blood sugar, is between 7 to 7.5%. Also, using ACEIs or ARBs could lower the risk of post-transplant diabetes in patients with hypertension and heart failure. Doctors should also consider treating any existing infections before the transplant.

Sugar diabetes (Diabetes mellitus)
High blood sugar due to stress (Stress hyperglycemia)

What to expect with New Onset Diabetes After Transplant

Different factors like the type of organ transplant, age, obesity, other heart disease risk factors, and immunity-suppressing drugs can influence the outcome of New Onset Diabetes After Transplantation (NODAT). Research has found that patients with NODAT have a higher mortality rate compared to those with type 2 diabetes. This is because NODAT reduces patient survival by increasing the risk of heart-related events and infections.

Additionally, NODAT is linked to a greater probability of organ rejection and kidney failure after the transplant. In patients with NODAT, studies have found that organ transplant survival rates stand at 48%, compared to 70% in those without NODAT.

Particularly in kidney recipients, heart-related events occur 2 to 3 times more frequently in those with NODAT compared to other patients. Also, the harmful effects on the smallest blood vessels in the body, associated with diabetes, tend to appear more quickly in patients with NODAT than in traditional diabetes cases.

Possible Complications When Diagnosed with New Onset Diabetes After Transplant

New Onset Diabetes After Transplantation (NODAT) can result in complications similar to those associated with traditional diabetes. Even though the effects are similar, the rate at which they occur is significantly faster. In addition to this, the increased risk of organ transplant rejection, higher occurrence of infections, and late cardiovascular events lead to a higher risk of death.

Common complications include:

Neuropathy (nerve damage)
Ophthalmopathy (eye disease)
Nephropathy (kidney disease)
Ketoacidosis (dangerous metabolic state)
Episodes of hypoglycemia (low blood sugar)
Increased risk of transplant rejection
Higher incidence of infections
Late occurrence of cardiovascular events

Preventing New Onset Diabetes After Transplant

It’s crucial to start managing New Onset Diabetes After Transplant (NODAT) even before the organ transplant takes place. This involves informing those awaiting a transplant about the potential risk of developing NODAT and how to avoid it. A key way to prevent NODAT is to prevent weight gain. Shedding some weight can help avoid NODAT in over-sized patients showing pre-diabetes symptoms. For patients with high risk, such as those who are obese, it’s beneficial to mix weight loss with a good diet and regular exercise. Weight loss of 5% to 10% of total body weight is the target, and a dietitian can help guide this process both before and after the transplant. It’s recommended that patients eat a balanced, low-calorie, low-fat diet. Immediately after a transplant, however, weight loss isn’t ideal, as it may slow the healing process.

Upon being diagnosed with NODAT, constant self-monitoring of blood sugar levels and sticking to the treatment plan are key. Patients should also understand the importance of an annual eye exam. This is especially crucial for NODAT patients as their high consumption of corticosteroids and immune-suppressing drugs can speed up the development of cataracts. Regular foot check-ups should also be part of all medical visits. Being on immunosuppressants increases the risk of various infections for NODAT patients. Therefore, staying up-to-date with yearly flu and pneumonia vaccines is critical. If a patient wishes to become pregnant, it’s advised to wait at least a year after the transplant to lower the risk of rejection. The transplant team should be involved during all stages of pregnancy to minimize health risks to both mother and child.