Excessive weight linked to increased LADA risk
medwireNews: Being overweight or obese is associated with a significantly increased risk for the development of latent autoimmune diabetes in adults (LADA), especially when combined with a familial history of diabetes, population-based study data show.
“These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes,” Rebecka Hjort (Karolinska Institutet, Stockholm, Sweden) and co-investigators write in Diabetologia.
The researchers analyzed data from two studies: ESTRID, which is a Swedish population-based case-control study with 425 incident cases of LADA, 1420 incident cases of type 2 diabetes, and 1704 randomly selected control participants; and HUNT, a prospective Norwegian study including 147 people with LADA and 1,012,957 person–years of follow-up (1984–2008).
All participants with LADA were at least 35 years of age at diagnosis and were positive for glutamic acid decarboxylase (GAD) antibodies.
Hjort and co-authors report that, in ESTRID, obese individuals were a significant 2.93 times more likely than those of normal weight to have LADA and a significant 18.88 times more likely to have type 2 diabetes.
The risk for LADA was greater among obese individuals with low GAD antibody levels (below median), at an odds ratio (OR) of 4.25, but remained significant among those with a high GAD antibody level (OR=2.14).
The greatest risks were observed among participants who were overweight and also had a family history of diabetes, at an OR of 4.57 for LADA and 24.51 for type 2 diabetes.
In addition, LADA was associated with weight change over time, with the odds increasing by 10% for every unit increase in BMI since age 20 years.
Indeed, Hjort et al calculated that 31.0% of LADA cases and 81.8% of type 2 diabetes cases in ESTRID could be attributed to being overweight or obese.
Similar, but stronger, associations were observed in HUNT. Specifically, obesity was linked to a 6.07-fold increased risk for LADA, while obesity plus low or high GAD antibodies conferred hazard ratios of 10.00 and 4.58, respectively. Being overweight with a familial history of diabetes was associated with a 7.45-fold increased risk for LADA.
In both studies, BMI was significantly and positively associated with insulin resistance and inversely associated with GAD antibodies. Furthermore, obese individuals with LADA had greater insulin production and were less often receiving insulin treatment than those who were a normal weight.
Hjort and team conclude that their data support “the idea that LADA is a hybrid form of diabetes promoted by genes associated with autoimmunity and lifestyle factors inducing insulin resistance.”
They add that “excessive weight is an important contributor to the development of LADA in a large proportion of individuals” and therefore “weight loss in obese individuals may reduce the risk not only of type 2 diabetes but also of adult-onset autoimmune diabetes.”
By Laura Cowen
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