Use of hemoglobin A1c to identify dysglycemia in cystic fibrosis

Abstract

Background Cystic fibrosis (CF) leads to pancreatic endocrine dysfunction with progressive glycemic disturbance. Approximately 30%–50% of people with CF eventually develop CF–related diabetes (CFRD). Pre-CFRD states progress from indeterminant glycemia (INDET) to impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Screening guidelines recommend inconvenient annual 2-hour oral glucose tolerance tests (OGTTs), beginning at age 10 years. More efficient methods, such as hemoglobin A1C (HbA1c), have been evaluated, but only limited, relatively small studies have evaluated the association between HbA1c and pre-CFRD dysglycemic states. Objective To determine whether HbA1c is an appropriate screening tool for identifying patients with pre-CFRD dysglycemia to minimize the burden of annual OGTTs. Methods This retrospective review evaluated medical records data of all University of Massachusetts Memorial Health System CF patients with an HbA1c result within 90 days of an OGTT between 1997 and 2019. Exclusion criteria were uncertain CF diagnosis, other forms of diabetes, or incomplete OGTT. In total, 56 patients were included and categorized according to OGTT results (American Diabetes Association criteria): normal glucose tolerance, INDET, IFG, or IGT. Associations were evaluated between HbA1c and OGTT results and between HbA1c and pre-CFRD dysglycemic states. Results Mean HbA1c was not significantly different between patients with normal glucose tolerance and those in the INDET (p = 0.987), IFG (p = 0.690), and IGT (p = 0.874) groups. Analysis of variance confirmed the lack of association between HbA1c and glycemia, as mean HbA1c was not significantly different amongst the four categories (p = 0.250). Conclusion There is increasing awareness of the impact of pre-CFRD states, including reduced pulmonary function and nutritional status. Unfortunately, our results do not support using HbA1c as a screening tool for pre-CFRD dysglycemia, specifically INDET, IFG, and IGT. Further studies are warranted to evaluate more efficient screening methods to reduce the burden of annual OGTTs.

ISPAD Clinical Practice Consensus Guidelines 2022: Management of cystic fibrosis‐related diabetes in children and adolescents

“…HbA1c is unreliable in the diagnosis of CFRD because it has low sensitivity for identifying CFRD detected by OGTT 6 , 11 , 137 , 138 and poor ability to differentiate among different glucose tolerance categories. 139 When using ADA criteria for diagnosing diabetes with an HbA1c cut point of 48 mmol/mol (6.5%), many individuals with early CFRD defined by OGTT will be missed. 110 , 140 Historically, HbA1c has been thought to underestimate glycemia in CF, and this has been postulated to be due to increased red blood cell turnover related to chronic inflammation.…”

Continuous Glucose Monitoring as an Additional Tool in Early Cystic Fibrosis-Related Diabetes Monitoring and in Evaluation of Short-Term Sitagliptin Response

“…However, the OGTT is a time-consuming test with a high within-patient variability in CFRD diagnosis [ 12 ]. Alternative tests, such as glycosylated haemoglobin (HbA1c) tests, have not been validated to date as alternatives to the OGTT, as the data are still controversial [ 13 , 14 ]. Continuous glucose monitoring (CGM) is increasingly considered as an additional tool that could improve the early detection of pancreatic endocrine dysfunction [ 15 ] in people with CF.…”