Background
Latent autoimmune diabetes of adulthood (LADA) differs in clinical features from type
2 diabetes. Whether this difference translates into different risks of complications
remains controversial. We examined the long-term risk of microvascular complications
in people enrolled in the UK Prospective Diabetes Study (UKPDS), according to their
diabetes autoimmunity status.
Methods
We did a post-hoc analysis of 30-year follow-up data from UKPDS (UKPDS 86). UKPDS
participants with diabetes autoantibody measurements available and without previous
microvascular events were included. Participants with at least one detectable autoantibody
were identified as having latent autoimmune diabetes, and those who tested negative
for all autoantibodies were identified as having type 2 diabetes. The incidence of
the primary composite microvascular outcome (first occurrence of renal failure, renal
death, blindness, vitreous haemorrhage, or retinal photocoagulation) was compared
between adults with latent autoimmune diabetes and those with type 2 diabetes. The
follow-up ended on Sept 30, 2007. Baseline and updated 9-year mean values of potential
confounders were tested in Cox models to adjust hazard ratios (HRs). UKPDS is registered
at the ISRCTN registry, 75451837.
Findings
Among the 5028 participants included, 564 had latent autoimmune diabetes and 4464
had type 2 diabetes. After median 17·3 years (IQR 12·6–20·7) of follow-up, the composite
microvascular outcome occurred in 1041 (21%) participants. The incidence for the composite
microvascular outcome was 15·8 (95% CI 13·4–18·7) per 1000 person-years in latent
autoimmune diabetes and 14·2 (13·3–15·2) per 1000 person-years in type 2 diabetes.
Adults with latent autoimmune diabetes had a lower risk of the composite outcome during
the first 9 years of follow-up than those with type 2 diabetes (adjusted HR 0·45 [95%
CI 0·30–0·68], p<0·0001), whereas in subsequent years their risk was higher than for
those with type 2 diabetes (1·25 [1·01–1·54], p=0·047). Correcting for the higher
updated 9-year mean HbA
1c seen in adults with latent autoimmune diabetes than in those with type 2 diabetes
explained entirely their subsequent increased risk for the composite microvascular
outcome (adjusted HR 0·99 [95% CI 0·80–1·23], p=0·93).
Interpretation
At diabetes onset, adults with latent autoimmune diabetes have a lower risk of microvascular
complications followed by a later higher risk of complications than do adults with
type 2 diabetes, secondary to worse glycaemic control. Implementing strict glycaemic
control from the time of diagnosis could reduce the later risk of microvascular complications
in adults with latent autoimmune diabetes.
Funding
European Foundation for the Study of Diabetes Mentorship Programme (AstraZeneca).
