From the Guidelines
In MODY patients, CGM readings often do not correlate well with A1C levels due to the unique pathophysiology of this genetic form of diabetes, and therefore, both CGM and A1C should be considered together for accurate monitoring and treatment decisions, as suggested by the most recent guidelines 1. The most common forms of MODY, such as HNF1A and GCK mutations, can produce normal fasting glucose levels with postprandial spikes that may not be captured in A1C measurements, which reflect average glucose over 2-3 months. Some key points to consider include:
- Conditions that affect red blood cell turnover, such as hemolytic and other anemias, glucose-6-phosphate dehydrogenase deficiency, recent blood transfusion, use of drugs that stimulate erythropoiesis, end-stage kidney disease, and pregnancy, may result in discrepancies between the A1C result and the patient’s true mean glycemia 1.
- Hemoglobin variants must be considered, particularly when the A1C result does not correlate with the patient’s CGM or BGM levels 1.
- The use of CGM devices should be considered from the outset of the diagnosis of diabetes that requires insulin management, allowing for close tracking of glucose levels with adjustments of insulin dosing and lifestyle modifications 1.
- A1C is currently recognized as the key surrogate marker for the development of long-term diabetes complications, but its limitation is the lack of information about acute glycemic excursions and the acute complications of hypo- and hyperglycemia 1. Some MODY variants, especially GCK-MODY, involve a reset glucose threshold where the body maintains a higher baseline glucose level but with minimal glucose variability, resulting in CGM showing consistently mild hyperglycemia while A1C remains only slightly elevated. Red blood cell lifespan, which affects A1C measurements, may also be different in some MODY patients. For accurate monitoring in MODY patients, treatment decisions should be based on the specific MODY subtype, glucose patterns, and clinical symptoms rather than A1C targets alone, considering the unique pathophysiology of this genetic form of diabetes and the limitations of A1C measurements 1.
From the Research
Reasons for Discordance between CGM and HbA1C in MODY Patients
- The relationship between Continuous Glucose Monitoring (CGM) readings and Hemoglobin A1C (HbA1C) levels can be complex, and several factors may contribute to discordance in Maturity-Onset Diabetes of the Young (MODY) patients 2.
- Studies have shown that CGM metrics, such as mean glucose and glucose management indicator (GMI), may not always correlate with HbA1C levels, especially in patients with certain types of diabetes or those undergoing hemodialysis 3, 4.
- In MODY patients, the unique clinical features of mild fasting hyperglycemia and stable glucose excursion patterns may lead to discrepancies between CGM readings and HbA1C levels 2.
- The use of CGM technology has highlighted the importance of postprandial glucose regulation in MODY patients, which may not be fully captured by HbA1C measurements alone 2, 5.
- Nonglycemic effects on HbA1C, such as red blood cell age, can also contribute to discrepancies between CGM and HbA1C readings 6.
- Combining CGM data with HbA1C measurements may provide a more comprehensive understanding of glucose control in MODY patients, but the accuracy of estimates can vary depending on the duration of CGM monitoring and individual factors 6, 4.
Implications for Clinical Practice
- The discordance between CGM and HbA1C readings in MODY patients highlights the need for careful interpretation of glucose control metrics in clinical practice 3, 4.
- CGM technology can provide valuable insights into glucose excursion patterns and postprandial glucose regulation in MODY patients, which can inform treatment decisions 2, 5.
- The development of new formulas or metrics, such as the CKD-GMI, may help to improve the accuracy of glucose control estimates in patients with certain types of diabetes or those with chronic kidney disease 4.