Acetaminophen use in patients with diabetes
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Acetaminophen Use in Diabetes: Safety, Pharmacokinetics, and Glucose Monitoring Interference
Acetaminophen and Continuous Glucose Monitoring (CGM) Interference in Diabetes
Acetaminophen is known to interfere with many continuous glucose monitoring (CGM) systems, causing falsely elevated glucose readings. This interference occurs because acetaminophen is oxidized at the sensor electrode, producing a signal that is not related to actual glucose levels. This effect has been observed in both older and some newer CGM devices, leading to significant clinical implications for people with diabetes who rely on CGM for insulin dosing decisions. The U.S. FDA recommends that insulin dosing should be based on blood glucose meter values, not CGM readings, when acetaminophen has been used, due to this risk of error 128.
However, newer CGM systems, such as the Dexcom G6, have been specifically designed to resist acetaminophen interference. Studies show that the G6 system has a minimal interference effect, with a mean bias well below clinically meaningful thresholds, providing reassurance for patients using both acetaminophen and CGM technology .
Acetaminophen Use Patterns in People with Diabetes
In clinical practice, acetaminophen is commonly used by adults with type 1 diabetes, especially among those on Medicaid plans, where it is frequently prescribed alongside other medications for pain and comorbid conditions. This reflects the higher burden of comorbidities in these populations .
Acetaminophen Safety and Pharmacokinetics in Diabetes
Animal studies have explored how diabetes affects the way the body processes acetaminophen. In rats with insulin-dependent diabetes, urinary excretion of acetaminophen increased, while biliary excretion decreased, but total clearance remained unchanged. Some changes in drug metabolism, such as reduced elimination half-life and altered excretion of certain metabolites, were observed. Insulin treatment reversed some of these changes, suggesting that insulin deficiency can alter how the liver handles acetaminophen .
Another study in rats with type 2 diabetes found that the no-observed-adverse-effect-level (NOAEL) for acetaminophen was the same in diabetic and non-diabetic rats, indicating that preexisting diabetes did not increase the risk of acetaminophen toxicity at therapeutic doses. However, high doses did cause some changes in organ weights and mild tissue changes in both groups .
Acetaminophen, Oxidative Stress, and Antioxidant Systems in Diabetes
Research in diabetic rats shows that acetaminophen can increase markers of oxidative stress, such as malondialdehyde and conjugated dienes, especially after acute toxic doses. Even at therapeutic doses, there is a temporary increase in oxidative stress, but this effect lessens over time. Acetaminophen also impairs the activity of antioxidant enzymes in the liver, with more pronounced effects at toxic doses. These findings suggest that people with diabetes may experience increased oxidative stress when using acetaminophen, particularly at higher doses or with overdose 79.
Acetaminophen and Stroke Risk in Diabetes
The relationship between acetaminophen use and stroke risk in people with diabetes is unclear. Some studies suggest a possible increased risk, while others find no association or even a negative association. The evidence is inconsistent, and more research is needed to determine if acetaminophen use truly affects stroke risk in this population .
Conclusion
Acetaminophen is widely used by people with diabetes and is generally considered safe at therapeutic doses, with no clear evidence of increased toxicity due to diabetes. However, it can interfere with many CGM systems, leading to inaccurate glucose readings and potential risks if insulin dosing is based on these readings. Newer CGM technologies have addressed this issue. There is also some evidence that acetaminophen may increase oxidative stress in diabetes, especially at high doses. The link between acetaminophen and stroke risk in diabetes remains uncertain. Overall, acetaminophen can be used in people with diabetes, but caution is needed with CGM use and high doses.
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