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Review
. 2022 Jun 29:13:917850.
doi: 10.3389/fendo.2022.917850. eCollection 2022.

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

Sofia Carlsson  1
Affiliations
Review

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

Sofia Carlsson. Front Endocrinol (Lausanne). .

Abstract

Background: LADA 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.

Findings: Current 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.

Summary: Available 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.

Keywords: HLA; gene*environment; latent autoimmune diabetes; lifestyle; obesity; smoking.

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Conflict of interest statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Lifestyle factors and LADA-findings from observational studies. Relative risk estimates extracted from references (, , –47).
Figure 2
Figure 2
BMI, birth weight, smoking and the risk LADA compared to type 2 diabetes-findings from Mendelian randomization studies. Odds ratios extracted from references (36) and (48).
Figure 3
Figure 3
Additive interaction between HLA risk genotypes and overweight (BMI >25) on the risk of LADA (28). AP, Attributable proportion due to interaction.
Figure 4
Figure 4
Etiology of LADA.
See this image and copyright information in PMC

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