Lifestyle or Environmental Influences and Their Interaction With Genetic Susceptibility on the Risk of LADA

Abstract

BackgroundLADA is a common form of diabetes described as a mix between type 1 and type 2 diabetes. Understanding of how genes and environmental factors interact in the development of LADA is central for future efforts to prevent the disease. This review aims to synthesize the literature on lifestyle factors linked to LADA risk and discuss their potential interaction with genetic susceptibility.FindingsCurrent knowledge on environmental risk factors for LADA is primarily based on observational data from Scandinavian populations. Increasing evidence suggest that lifestyle factors promoting type 2 diabetes such as obesity, sedentariness, low birth weight and smoking, is implicated in the risk of LADA. Data from mendelian randomization studies support that the link between LADA and obesity, low birth weight and smoking is causal. Limited evidence indicates that dietary factors including consumption of red meat, coffee and sweetened beverages may increase the risk while consumption of alcohol and omega-3 fatty acids may reduce the risk. Several lifestyle factors, including smoking and obesity, seem to interact with human leukocyte antigen genes associated with autoimmunity, conferring much stronger effects on disease risk among those exposed to both factors.SummaryAvailable studies suggest that lifestyle modification has the potential for prevention of LADA, particularly for individuals with high risk of disease such as those with genetic susceptibility. Research into risk factors of LADA is however limited, confirmations are warranted, many factors remain to be explored, and there is a need for intervention studies to assess causality

Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?

“…Lastly, there may be important differences in the pathogeneses of LADA and type 1 diabetes. Although risk variants within the HLA region confer the strongest genetic risk of LADA, the association is weaker than with type 1 diabetes 40 and subsequently, the autoimmune reaction tends to be milder in LADA, as illustrated by slower insulin‐deficiency progression and lesser need for insulin treatment at the time of diagnosis 1 . While several studies have linked infections to type 1 diabetes in genetically susceptible children, 8,12,19 we observed no association when restricting the analyses to high‐risk HLA carriers.…”

“…The clinical diagnosis of LADA and type 1 diabetes can be preceded by the presence of diabetesrelated autoantibodies, which is an early sign of the underlying autoimmune pathogenesis. [4][5][6] Moreover, LADA is likely to result from an interaction between environmental and genetic risk factors, 1 but little is known about such environmental risk factors.…”

“…Latent autoimmune diabetes in adults (LADA) is the most common form of autoimmune diabetes with an adult onset 1 and is estimated to account for 3%–14% of all diabetes in adults 2 . Genetically, LADA resembles type 1 diabetes, with the highest genetic risk conferred by certain HLA DR‐DQ haplotypes 3 .…”

Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis

“…3 p for the comparison between LADA low and LADA high individuals. 4 Available for 64% of cases (LADA n = 392, type 2 diabetes n = 1251). 5 Available for 85% of cases (LADA n = 471, type 2 diabetes n = 1713).…”

“…Regarding genetic susceptibility, LADA resembles type 1 diabetes with most of the genetic risk being conferred by HLA haplotypes [3]. Knowledge about modifiable risk factors is limited, but the findings of the small number of studies conducted to date suggest that dietary factors may be of importance in the development of LADA [4].…”