medwireNews: Latent autoimmune diabetes in adults (LADA) is associated with similar rates of mortality and cardiovascular disease (CVD) to those seen in patients with type 2 diabetes, and a higher risk for retinopathy, suggests a study published in Diabetes Care.
This was despite LADA being associated with fewer metabolic risk factors than type 2 diabetes, in terms of blood pressure, lipid profiles, obesity, and insulin resistance, say Yuxia Wei (Karolinska Institutet, Stockholm, Sweden) and colleagues.
However, they note that beta-cell function and glycemic control were worse in people with LADA than those with type 2 diabetes, particularly among LADA individuals with high levels of glutamic acid decarboxylase antibody (GADA) and this may therefore outweigh the healthier metabolic profile of these patients.
“Our findings are of clinical importance since improper LADA diagnosis and management may increase the risk of complications and subsequently raise mortality among these patients,” the researchers comment.
The team analyzed data from the Swedish ESTRID study, for 550 people with LADA, 2001 with type 2 diabetes, 1573 with adult-onset type 1 diabetes, and 2355 controls without diabetes. The participants had a mean age of 47.7 to 63.0 years.
Individuals with LADA were stratified according to whether they had high or low autoimmunity (n=275 and 264, respectively), based on a median GADA level above or below 250 IU/mL, respectively.
Over a median follow-up of 5.9 years, 509 participants died. The risk for all-cause death was higher for those with LADA, type 2 diabetes, and type 1 diabetes, compared with individuals without diabetes, with respective hazard ratios (HRs) of 1.44, 1.31, and 2.31 after adjusting for a history of CVD.
The authors point out, however, that among individuals with LADA only those with low autoimmunity had a significantly increased mortality risk compared with controls.
The mortality rate for individuals with LADA was similar to that of people with type 2 diabetes, at 14.4 versus 16.6 per 1000 person–years, giving a nonsignificant HR of 1.13.
New-onset CVD occurred in 386 participants, and relative to controls, the risk was only significantly higher in people with LADA and high autoimmunity (HR=1.67) or type 2 diabetes (HR=1.53). The risk in people with LADA and high autoimmunity was not increased versus those with type 2 diabetes (HR=1.03), whereas it was significantly reduced in those with LADA and low autoimmunity (HR= 0.52) and type 1 diabetes (HR=0.63).
The risk for retinopathy by comparison was around twofold higher among people with LADA versus type 2 diabetes, both for those with high and low autoimmunity (HRs=2.41 and 2.12, respectively). This excess risk was attenuated when glycated hemoglobin (HbA1c) levels were taken into account, but it still remained significantly greater for people with LADA, the researchers note.
“Hyperglycemia is the main cause of diabetic retinopathy, and the results may be explained by worse glycemic control in LADA,” say Wei et al.
Indeed, they remark that “a significant proportion of LADA individuals were not on any glucose lowering treatment.” Approximately 15% of people with LADA and a C-peptide level of 0.7 nmol/L or below or high autoimmunity did not receive glucose-lowering drugs during the course of follow-up, they report, and this was also the case for 25% of people with LADA and low autoimmunity or type 2 diabetes.
“These findings point to the need for improved glucose management of this common but largely unrecognized patient group,” say the investigators, who report that the proportion of individuals achieving the HbA1c target of below 53 mmol/mol (7.0%) declined over time for all the diabetes types.
This was particularly the case for those with LADA and high autoimmunity and those with type 1 diabetes, of whom 31% and 32%, respectively had met the target 10 years after diagnosis. This compared with 43% and 58% of those with LADA and low autoimmunity and type 2 diabetes, respectively.
The researchers say that these findings “point at a need for measuring GADA and C-peptide for better phenotyping and improved management of LADA.”
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