Apolipoprotein M and Risk of Type 2 Diabetes
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Apolipoprotein M and Risk of Type 2 Diabetes. / Hajny, Stefan; Christoffersen, Mette; Dalila, Nawar; Nielsen, Lars B.; Tybjaerg-Hansen, Anne; Christoffersen, Christina.
I: Journal of Clinical Endocrinology & Metabolism, Bind 105, Nr. 9, 2020, s. 3046-3057.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Apolipoprotein M and Risk of Type 2 Diabetes
AU - Hajny, Stefan
AU - Christoffersen, Mette
AU - Dalila, Nawar
AU - Nielsen, Lars B.
AU - Tybjaerg-Hansen, Anne
AU - Christoffersen, Christina
PY - 2020
Y1 - 2020
N2 - Context: Recent studies have discovered a role of apolipoprotein M (apoM) in energy metabolism, and observational analyses in humans suggest an association with type 2 diabetes. The causal relationship remains however elusive.Objective: To investigate whether reduced plasma apoM concentrations are causally linked to increased risk of type 2 diabetes.Design: Prospective study design analyzed by Mendelian randomization.Setting and participants: Two cohorts reflecting the Danish general population: the Copenhagen City Heart Study (CCHS, n = 8589) and the Copenhagen General Population Study (CGPS; n = 93 857). Observational analyses included a subset of participants from the CCHS with available plasma apoM (n = 725). Genetic analyses included the complete cohorts (n = 102 446). During a median follow-up of 16 years (CCHS) and 8 years (CGPS), 563 and 2132 participants developed type 2 diabetes.Main outcome measures: Plasma apoM concentration, genetic variants in APOM, and type 2 diabetes.Results: First, we identified an inverse correlation between plasma apoM and risk of type 2 diabetes in a subset of participants from the CCHS (hazard ratio between highest vs lowest quartile (reference) = 0.32; 95% confidence interval = 0.1-1.01; P for trend = .02). Second, genotyping of specific single nucleotide polymorphisms in APOM further revealed a 10.8% (P = 6.2 x 10(-5)) reduced plasma apoM concentration in participants with variant rs1266078. Third, a meta-analysis including data from 599 451 individuals showed no association between rs1266078 and risk of type 2 diabetes.Conclusions: The present study does not appear to support a causal association between plasma apoM and risk of type 2 diabetes.
AB - Context: Recent studies have discovered a role of apolipoprotein M (apoM) in energy metabolism, and observational analyses in humans suggest an association with type 2 diabetes. The causal relationship remains however elusive.Objective: To investigate whether reduced plasma apoM concentrations are causally linked to increased risk of type 2 diabetes.Design: Prospective study design analyzed by Mendelian randomization.Setting and participants: Two cohorts reflecting the Danish general population: the Copenhagen City Heart Study (CCHS, n = 8589) and the Copenhagen General Population Study (CGPS; n = 93 857). Observational analyses included a subset of participants from the CCHS with available plasma apoM (n = 725). Genetic analyses included the complete cohorts (n = 102 446). During a median follow-up of 16 years (CCHS) and 8 years (CGPS), 563 and 2132 participants developed type 2 diabetes.Main outcome measures: Plasma apoM concentration, genetic variants in APOM, and type 2 diabetes.Results: First, we identified an inverse correlation between plasma apoM and risk of type 2 diabetes in a subset of participants from the CCHS (hazard ratio between highest vs lowest quartile (reference) = 0.32; 95% confidence interval = 0.1-1.01; P for trend = .02). Second, genotyping of specific single nucleotide polymorphisms in APOM further revealed a 10.8% (P = 6.2 x 10(-5)) reduced plasma apoM concentration in participants with variant rs1266078. Third, a meta-analysis including data from 599 451 individuals showed no association between rs1266078 and risk of type 2 diabetes.Conclusions: The present study does not appear to support a causal association between plasma apoM and risk of type 2 diabetes.
KW - apolipoproteins
KW - type 2 diabetes
KW - genetics
KW - mendelian randomization
KW - CORONARY-HEART-DISEASE
KW - INSULIN-RESISTANCE
KW - ASSOCIATION
KW - PLASMA
KW - RECEPTOR
KW - CHOLESTEROL
KW - METABOLISM
KW - LIPIDS
KW - APOM
U2 - 10.1210/clinem/dgaa433
DO - 10.1210/clinem/dgaa433
M3 - Journal article
C2 - 32621749
VL - 105
SP - 3046
EP - 3057
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 9
ER -
ID: 251646004