Format

Send to

Choose Destination
Diabetes Care. 2018 Oct 23. pii: dc180431. doi: 10.2337/dc18-0431. [Epub ahead of print]

A Type 1 Diabetes Genetic Risk Score Can Identify Patients With GAD65 Autoantibody-Positive Type 2 Diabetes Who Rapidly Progress to Insulin Therapy.

Author information

1
National Institute for Health Research Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K.
2
Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K.
3
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands.
4
Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, U.K.
5
Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands.
6
Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, the Netherlands.
7
Molecular Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands.
8
National Institute for Health Research Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, U.K. angus.jones@exeter.ac.uk.

Abstract

OBJECTIVE:

Progression to insulin therapy in clinically diagnosed type 2 diabetes is highly variable. GAD65 autoantibodies (GADA) are associated with faster progression, but their predictive value is limited. We aimed to determine if a type 1 diabetes genetic risk score (T1D GRS) could predict rapid progression to insulin treatment over and above GADA testing.

RESEARCH DESIGN AND METHODS:

We examined the relationship among T1D GRS, GADA (negative or positive), and rapid insulin requirement (within 5 years) using Kaplan-Meier survival analysis and Cox regression in 8,608 participants with clinical type 2 diabetes (onset >35 years and treated without insulin for ≥6 months). T1D GRS was both analyzed continuously (as standardized scores) and categorized based on previously reported centiles of a population with type 1 diabetes (<5th [low], 5th-50th [medium], and >50th [high]).

RESULTS:

In GADA-positive participants (3.3%), those with higher T1D GRS progressed to insulin more quickly: probability of insulin requirement at 5 years (95% CI): 47.9% (35.0%, 62.78%) (high T1D GRS) vs. 27.6% (20.5%, 36.5%) (medium T1D GRS) vs. 17.6% (11.2%, 27.2%) (low T1D GRS); P = 0.001. In contrast, T1D GRS did not predict rapid insulin requirement in GADA-negative participants (P = 0.4). In Cox regression analysis with adjustment for age of diagnosis, BMI, and cohort, T1D GRS was independently associated with time to insulin only in the presence of GADA: hazard ratio per SD increase was 1.48 (1.15, 1.90); P = 0.002.

CONCLUSIONS:

A T1D GRS alters the clinical implications of a positive GADA test in patients with clinical type 2 diabetes and is independent of and additive to clinical features.

PMID:
30352895
DOI:
10.2337/dc18-0431

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center