DC22-2301_CP_GAD_InsulinUse_TableFigure_Supplement_2023Mar14.pdf (815.89 kB)

Differential associations of glutamic acid decarboxylase antibodies (GADA) and C-peptide with insulin initiation, glycemic responses and severe hypoglycemia in patients diagnosed with type 2 diabetes

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posted on 2023-04-19, 16:05 authored by Baoqi Fan, Cadmon K.P. Lim, Emily W.M. Poon, Eric S.H. Lau, Hongjiang Wu, Aimin Yang, Mai Shi, Claudia H.T. Tam, Samuel Y.S. Wong, Eric Kam-Pui Lee, Maggie H.T. Wang, Natural H.S. Chu, Risa Ozaki, Alice P.S. Kong, Elaine Chow, Ronald C.W. Ma, Andrea O.Y. Luk, Juliana C.N. Chan

Objective

We examined the associations of glutamic acid decarboxylase antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses and severe hypoglycemia in type 2 diabetes (T2D).

Research Design and Methods

In 5230 Chinese patients with T2D (mean±SD age: 56.5±13.9 years, diabetes duration (median, IQR): 6 (1-12) years, 47.6% men) enrolled consecutively in 1996-2012 and prospectively observed till 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes.

Results

At baseline, 28.6% had low CP (<200 pmol/L) (n=1494) and 4.9% (n=257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+ and in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI: 1.15-1.84, p=0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, p=0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12) versus -1% in the other 3 groups. The aHR of severe hypoglycemia was 1.29 [(95% CI 1.10-1.52), p=0.002] in the low-CP and 1.38 [(95% CI 1.04-1.83) p=0.024] in the GADA+ group.

Conclusions

There is considerable heterogeneity in autoimmunity and beta-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation while GADA+ and low CP, increased risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.