Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case–control study

Hjort, Rebecka; Alfredsson, Lars; Carlsson, Per‐Ola; Groop, Leif; Martinell, Mats; Storm, Petter; Tuomi, Tiinamaija; Carlsson, Sofia

doi:10.1007/s00125-015-3711-8

Cited by 19 publications

(21 citation statements)

References 39 publications

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“…Findings of the studies on lifestyle and risk of LADA compared to type 2 diabetes conducted to date are summarized in Figure 1. In support of a role for insulin resistance and a type 2-like etiology, these studies indicate that LADA may share several risk factors with type 2 diabetes; Excess risk of LADA is seen in relation to overweight (Hjort et al, 2018b), adiposity (Hjort et al, 2018b), low birth weight (Hjort et al, 2015), and sweetened beverage intake (Löfvenborg et al, 2016), whereas the risk is reduced in those with moderate alcohol consumption (Rasouli et al, 2013a, 2014) and high physical activity (Carlsson et al, 2007; Hjort et al, 2018a; Figure 1). The associations are generally weaker for LADA than for type 2 diabetes (Figure 1), which is not surprising since insulin resistance can be expected to be less important in disease progression in the presence of autoimmunity and a more pronounced insulin deficiency.…”

Section: Etiologymentioning

confidence: 82%

Etiology and Pathogenesis of Latent Autoimmune Diabetes in Adults (LADA) Compared to Type 2 Diabetes

Carlsson

2019

Front. Physiol.

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As the heterogeneity of diabetes is becoming increasingly clear, opportunities arise for more accurate assessment of factors influencing disease onset, which may lead to more efficient primary prevention. LADA – latent autoimmune diabetes in adults – is a common, hybrid form of diabetes with features of both type 1 and type 2 diabetes. This review aims to summarize current knowledge on the pathophysiological and etiological overlap and differences between LADA and type 2 diabetes, discuss similarities between LADA and type 1 diabetes and point at future research needs. Studies conducted to date show a clear genetic overlap between LADA and type 1 diabetes with a high risk conferred by variants in the human leukocyte antigen (HLA) region. In contrast, data from the limited number of studies on lifestyle factors available indicate that LADA may share several environmental risk factors with type 2 diabetes including overweight, physical inactivity, alcohol consumption (protective) and smoking. These factors are known to influence insulin sensitivity, suggesting that insulin resistance, in addition to insulin deficiency due to autoimmune destruction of the beta cells, may play a key role in the pathogenesis of LADA. Moreover, this implies that onset of LADA, similar to type 2 diabetes, to some extent could be prevented or postponed by lifestyle modification such as weight reduction and increased physical activity. The preventive potential of LADA is an important topic to elucidate in future studies, preferably intervention studies.

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Section: Etiologymentioning

confidence: 82%

Etiology and Pathogenesis of Latent Autoimmune Diabetes in Adults (LADA) Compared to Type 2 Diabetes

Carlsson

2019

Front. Physiol.

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“…There are no unified criteria for LADA diagnosis and classification, but the criteria used in ANDiU and ANDIS are in line with previous literature . The exception is fC‐peptide, which is used in ANDiU and ANDIS as an indicator of remaining insulin production to separate LADA from T1D . It replaces the insulin therapy criterion (i.e.…”

Section: Methodsmentioning

confidence: 93%

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

Singh

Martinell

Luo

et al. 2019

Clinical and Experimental Immunology

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Summary There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age‐matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)‐35 were measured by enzyme‐linked immunosorbent assay (ELISA). The proportion of CD11c+CD123– antigen‐presenting cells (APCs) was lower, while the proportions of CD11c+CD123+ APCs and IL‐35+ tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3–CD56highCD16+ natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL‐35+ regulatory T cells and plasma IL‐35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL‐35+ regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

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“…In conclusion, having both T1D and T2D in the family is associated with the risk of LADA, and the strong association with FHD-T1D suggests that genes related to autoimmunity are more influential in the development of LADA than those related to T2D. Given this situation, it is noteworthy that, with regard to lifestyle, studies to date indicate that LADA shares several risk factors with T2D, including smoking [38], alcohol consumption (protective) [39] and low birth weight [40]. Taken together, these findings indicate that LADA development is promoted by genes related to autoimmunity and by lifestyle factors that increase insulin resistance.…”

Section: Strengths and Limitationsmentioning

confidence: 96%

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

Hjort

Alfredsson

Andersson

et al. 2017

Diabetes & Metabolism

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Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case–control study

Cited by 19 publications

References 39 publications

Etiology and Pathogenesis of Latent Autoimmune Diabetes in Adults (LADA) Compared to Type 2 Diabetes

Etiology and Pathogenesis of Latent Autoimmune Diabetes in Adults (LADA) Compared to Type 2 Diabetes

Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

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