Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes

AbstractIn the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring.

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Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes

Environment International ◽

10.1016/j.envint.2020.105935 ◽

2020 ◽

Vol 143 ◽

pp. 105935 ◽

Cited By ~ 4

Author(s):

Aidan McGlinchey ◽

Tim Sinioja ◽

Santosh Lamichhane ◽

Partho Sen ◽

Johanna Bodin ◽

...

Keyword(s):

Type 1 Diabetes ◽

Prenatal Exposure ◽

Perfluoroalkyl Substances ◽

Increasing Risk ◽

Serum Phospholipids

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Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study

Autoimmunity ◽

10.1080/08916934.2018.1494160 ◽

2018 ◽

Vol 51 (5) ◽

pp. 221-227 ◽

Cited By ~ 2

Author(s):

Mara Cerqueiro Bybrant ◽

Lena Grahnquist ◽

Eva Örtqvist ◽

Cecilia Andersson ◽

Gun Forsander ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cohort Study ◽

Human Leukocyte Antigen ◽

Tissue Transglutaminase ◽

Human Leukocyte ◽

Population Based ◽

Islet Autoantibodies ◽

Newly Diagnosed ◽

Leukocyte Antigen

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Susceptible and Protective Human Leukocyte Antigen Class II Alleles and Haplotypes in Bahraini Type 2 (Non-Insulin-Dependent) Diabetes Mellitus Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.1.213-217.2005 ◽

2005 ◽

Vol 12 (1) ◽

pp. 213-217 ◽

Cited By ~ 8

Author(s):

Ayesha A. Motala ◽

Marc Busson ◽

Einas M. Al-Harbi ◽

Manal A. A. Khuzam ◽

Emtiaz M. D. Al-Omari ◽

...

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Human Leukocyte Antigen ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Leukocyte Antigen ◽

Insulin Dependent

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

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Human Leukocyte Antigen (HLA) and Islet Autoantibodies Are Tools to Characterize Type 1 Diabetes in Arab Countries: Emphasis on Kuwait

Disease Markers ◽

10.1155/2019/9786078 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Mohamed Jahromi ◽

Ebaa Al-Ozairi

Keyword(s):

Type 1 Diabetes ◽

Human Leukocyte Antigen ◽

Incidence Rate ◽

Disease Onset ◽

Human Leukocyte ◽

Arab Countries ◽

World Health ◽

Leukocyte Antigen ◽

Prospective Longitudinal

The incidence rate of type 1 diabetes in Kuwait had been increasing exponentially and has doubled in children≤14 years old within almost two decades. Therefore, there is a dire need for a careful systematic familial cohort study. Several immunogenetic factors affect the pathogenesis of the disease. The human leukocyte antigen (HLA) accounts for the major genetic susceptibility to the disease. The triggering agents initiate disease onset by type 1 destruction of pancreatic β-cells. Both HLA and anti-islet antibodies can be used to characterize, predict susceptibility to the disease, innovate, or delay the β-cell destruction. Evidence from prospective longitudinal studies suggested that the underlying disease process represents a continuum that begins before the symptoms are clinically evident. Autoimmunity of the functional pancreatic β-cells results in symptomatic type 1 diabetes and lifelong insulin dependence. The autoantibodies against glutamic acid decarboxylase (GADA), insulinoma antigen-2 (IA-2A), insulin (IAA), and zinc transporter-8 (ZnT-8A) comprise the most reliable biomarkers for type 1 diabetes in both children and adults. Although Kuwait is the second among the top 10 countries with a high incidence rate of type 1 diabetes, there have been no proper diagnostic and prediction tools as per the World Health Organization. The Kuwaiti Type 1 Diabetes Study (KADS) was initiated to understand the disease pathogenesis as well as the HLA and anti-islet autoantibody profile of type 1 diabetes in Kuwait. Understanding the disease sequela in a homogenous gene pool and highly consanguineous population of Kuwaitis could help solve the challenges and pathogenesis, as well as hasten the prevention, of type 1 diabetes.

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