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Hemoglobin A1c Has Suboptimal Performance to Diagnose and Monitor Diabetes Mellitus in Patients with Cirrhosis

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Abstract

Background

Glycated hemoglobin A1c (HbA1c) is routinely used to diagnose and monitor type 2 diabetes mellitus (T2DM) in cirrhotic patients. Remarkably, HbA1c may be falsely low in such patients.

Aims

We assessed the diagnostic and monitoring yield of HbA1c in cirrhotic patients with T2DM (DM-Cirr) and without T2DM (NoDM-Cirr).

Methods

We conducted a composite study allocating 21 NoDM-Cirr into a cross-sectional module and 16 DM-Cirr plus 13 controls with T2DM only (DM-NoCirr) into a prospective cohort. Oral glucose tolerance test (OGTT) was performed in NoDM-Cirr. DM-Cirr and DM-NoCirr were matched by sex, age, BMI, and T2DM treatment and studied with continuous glucose monitoring (CGM). Percent deviations from target, low/high blood glucose indexes (LBGI/HBGI) were calculated from CGM, as well as the average daily risk range (ADRR) as a marker of glucose variability.

Results

Overall, HbA1c and OGTT diagnostic yield agreed in 12 patients (57%, ρ = 0.45, p < 0.03). CGM captured 3463 glucose determinations in DM-Cirr and 4273 in DM-NoCirr (p = 0.42). Regression analysis showed an inferior association between HbA1c and CGM in DM-Cirr (R2 = 0.52), when compared to DM-NoCirr (R2 = 0.94), and fructosamine did not improve association for DM-Cirr (R2 = 0.31). Interestingly, cirrhosis and Child–Turcotte–Pugh class accounted for HbA1c variance (p < 0.05). Patients in DM-Cirr were less frequently within target glucose (70–180 mg/dL), but at higher risk for hyperglycemia (HBGI > 9) when compared to DM-NoCirr, and they also showed higher glucose variability (ADRR 13.9 ± 2.5 vs. 8.9 ± 1.8, respectively, p = 0.03).

Conclusion

HbA1c inaccurately represents chronic glycemia in patients with cirrhosis, likely in relation to increased glucose variability.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

NoDM-Cirr:

Cirrhosis but no T2DM

DM-Cirr:

Cirrhosis and T2DM

DM-NoCirr:

T2DM without cirrhosis

OGTT:

Oral glucose tolerance test

HbA1c:

Glycated hemoglobin A1c

CGM:

Continuous glucose monitors

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

TIPS:

Transjugular intrahepatic portosystemic shunt

BMI:

Body mass index

INR:

International normalized ratio

NGSP:

National Glycohemoglobin Standardization Program

NPO:

Nothing by mouth

SD:

Standard deviation

IQR:

Interquartile range

MELD:

Model for end-stage liver disease

MELD-Na:

MELD-sodium

LBGI:

Low blood glucose index

HBGI:

High blood glucose index

ADRR:

Average daily risk range

HOMA-IR:

Homeostatic model assessment for insulin resistance

95% CI:

Confidence interval

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Acknowledgment

We would like to thank Dr. Peter Goulden from the Division of Endocrinology and Metabolism for his kind advice and support during conception and implementation of the study.

Funding

This study was funded in full by a Diabetes Research Grant from the Sturgis Foundation and the University of Arkansas for Medical Sciences College of Medicine Clinician Scientist Program.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Naga S. Addepally, Roberto Martinez-Macias, Mauricio Garcia-Saenz-de-Sicilia & Andres Duarte-Rojo

  2. Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Nayana George

  3. Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA

    W. Ray Kim

Authors
  1. Naga S. Addepally
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  2. Nayana George
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  3. Roberto Martinez-Macias
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  4. Mauricio Garcia-Saenz-de-Sicilia
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  5. W. Ray Kim
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  6. Andres Duarte-Rojo
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Corresponding author

Correspondence to Andres Duarte-Rojo.

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Authors have nothing to disclose

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of our Institutional Review Board (UAMS IRB) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Addepally, N.S., George, N., Martinez-Macias, R. et al. Hemoglobin A1c Has Suboptimal Performance to Diagnose and Monitor Diabetes Mellitus in Patients with Cirrhosis. Dig Dis Sci 63, 3498–3508 (2018). https://doi.org/10.1007/s10620-018-5265-3

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  • DOI: https://doi.org/10.1007/s10620-018-5265-3

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