Latent autoimmune diabetes may increase risk for complications vs. type 2 diabetes
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Key takeaways:
- All-cause mortality risk for adults with LADA is similar to that with type 2 diabetes.
- CVD risk may be higher with LADA than type 2 diabetes, depending on CVD history and autoimmunity level.
Adults diagnosed with latent autoimmune diabetes have similar morality risk and a higher risk for diabetic retinopathy than adults with type 2 diabetes, according to findings published in Diabetes Care.
In a population-based study, researchers compared data from adults newly diagnosed with latent autoimmune diabetes (LADA), a hybrid form of diabetes that involves both autoimmunity and type 2 diabetes characteristics, with those diagnosed with type 1 diabetes or type 2 diabetes. The researchers found adults with LADA may have higher risks for outcomes such as cardiovascular disease and retinopathy as well as worse glycemic control than those with type 2 diabetes, but the risks vary based on autoimmunity level.
“Our findings are important because LADA is common, but frequently misdiagnosed as type 2 diabetes and understudied,” Sofia Carlsson, PhD, associate professor in epidemiology at Karolinska Institutet in Sweden, and Yuxia Wei, MSc, a PhD student in the Institute of Environmental Medicine at Karolinska Institutet, told Healio. “Our findings point at the need to improve glucose management in LADA and to consider both the presence and levels of autoantibody when treating individuals with LADA.”
Carlsson, Wei and colleagues obtained data from the Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes (ESTRID) on 550 adults with LADA (mean age, 59.6 years), 2,001 adults with type 2 diabetes (mean age, 63 years) and 2,355 adults without diabetes (mean age, 58.8 years). Data from 1,573 adults with type 1 diabetes were obtained from Sweden’s National Diabetes Register (mean age, 47.7 years). Blood samples were collected to obtain glutamic acid decarboxylase (GAD) antibody and C-peptide levels. Adults were considered to have LADA if they had a GAD antibody level of 10 IU/mL or higher and a C-peptide level of more than 0.3 nmol/L. Adults with LADA who had a GAD antibody level of at least 250 IU/mL were placed in a high autoimmunity group, whereas those with a lower level were placed in a low autoimmunity group. Clinical data and medication use were collected from national registers. The primary outcomes were all-cause mortality and incidence of CVD, severe diabetic retinopathy and severe diabetic nephropathy.
Low autoimmune LADA linked to higher risks
During a median follow-up of 5.9 years, there were 509 participants who died, 386 cases of incident CVD, 190 cases of diabetic retinopathy and 77 cases of diabetic nephropathy. Among the LADA group, 49 adults died, 35 had incident CVD, 74 had diabetic retinopathy and 10 had diabetic nephropathy.
Adults with LADA (HR = 1.44; 95% CI, 1.03-2.02), type 1 diabetes (HR = 2.31; 95% CI, 1.75-3.05) and type 2 diabetes (HR = 1.31; 95% CI, 1.03-1.67) had higher risks for all-cause mortality than those without diabetes. The higher risk for death was observed among adults in the low autoimmunity LADA group (HR = 1.74; 95% CI, 1.18-2.57), but not those with high autoimmunity.
Among those with no CVD at baseline, adults in the high autoimmunity LADA group (HR = 1.67; 95% CI, 1.04-2.69) and those with type 2 diabetes (HR = 1.53; 95% CI, 1.17-2) had a higher risk for incident CVD than people without diabetes. Compared with type 2 diabetes, the risk for CVD was similar in the high autoimmunity LADA group, but lower for those in the low autoimmunity LADA group (HR = 0.52; 95% CI, 0.3-0.91). Among adults with CVD at baseline, the risk for CVD rehospitalization was higher for adults with low autoimmunity LADA (HR = 2.78; 95% CI 1.48-5.25) compared with adults without diabetes.
“We found that the risk profiles for mortality and cardiovascular diseases in individuals with LADA differed by levels of autoimmunity,” Carlsson and Wei said. “Those with lower levels of autoimmunity had higher prevalence of CVDs at diabetes diagnosis and had excess risk of recurrent CVDs and death after diabetes diagnosis. In comparison, those with higher levels of autoimmunity were more likely to experience first cardiovascular events after diabetes diagnosis.”
LADA linked to higher risk for diabetic retinopathy
Adults with both low autoimmunity LADA (HR = 2.12; 95% CI, 1.43-3.14) and high autoimmunity LADA (HR = 2.41; 95% CI, 1.62-3.59) had a higher risk for diabetic retinopathy than those with type 2 diabetes. No associations were observed for diabetic nephropathy.
Ten years after diagnosis, the percentage of adults with an HbA1c of less than 7% was 58% in the type 2 diabetes group, 43% in the low autoimmunity LADA group, 32% for adults with type 1 diabetes and 31% among those with high autoimmunity LADA. Within 6 months of diagnosis, 34.7% of all adults with LADA required insulin compared with 5.2% of those with type 2 diabetes. Adults with LADA or type 1 diabetes had better blood pressure and lipid control than the type 2 diabetes group.
Of adults with high autoimmunity LADA, 18.6% with an HbA1c above target were not receiving insulin 3 years after diagnosis. Of those with LADA and high LDL cholesterol, more than 60% were not receiving statins at 3 years. Of those with LADA who did not reach BP control targets at 5 years, more than 20% were not receiving antihypertensive medication.
Carlsson and Wei said there were several limitations to their research. They noted that the study was underpowered to examine the risk for diabetic nephropathy. They said the study was conducted only in Sweden, and more studies are needed in other countries to find out whether the findings differ in different health care systems and with more diverse populations. Carlsson and Wei added that future studies should examine the impact of different treatment strategies on LADA prognosis.
For more information:
Sofia Carlsson, PhD, can be reached at sofia.carlsson@ki.se.
Yuxia Wei, MSc, can be reached at yuxia.wei@ki.se.
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