Apolipoprotein M and risk of type 2 diabetes

Stefan Hajny; Mette Christoffersen; Nawar Dalila; Lars B Nielsen; Anne Tybjærg-Hansen; Christina Christoffersen

doi:10.1210/clinem/dgaa433

Apolipoprotein M and risk of type 2 diabetes

Stefan Hajny, Mette Christoffersen, Nawar Dalila, Lars B Nielsen, Anne Tybjærg-Hansen, Christina Christoffersen

Abstract

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 × 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.

Original language	English
Article number	dgaa433
Journal	The Journal of clinical endocrinology and metabolism
Volume	105
Issue number	9
Pages (from-to)	3046-3057
Number of pages	12
ISSN	0021-972X
DOIs	https://doi.org/10.1210/clinem/dgaa433
Publication status	Published - 1 Sept 2020

Keywords

apolipoproteins
type 2 diabetes
genetics
mendelian randomization

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10.1210/clinem/dgaa433

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title = "Apolipoprotein M and risk of type 2 diabetes",

abstract = "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 × 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.",

keywords = "apolipoproteins, type 2 diabetes, genetics, mendelian randomization",

author = "Stefan Hajny and Mette Christoffersen and Nawar Dalila and Nielsen, {Lars B} and Anne Tybj{\ae}rg-Hansen and Christina Christoffersen",

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T1 - Apolipoprotein M and risk of type 2 diabetes

AU - Hajny, Stefan

AU - Christoffersen, Mette

AU - Dalila, Nawar

AU - Nielsen, Lars B

AU - Tybjærg-Hansen, Anne

AU - Christoffersen, Christina

PY - 2020/9/1

Y1 - 2020/9/1

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 × 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 × 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

U2 - 10.1210/clinem/dgaa433

DO - 10.1210/clinem/dgaa433

M3 - Journal article

C2 - 32621749

SN - 0021-972X

VL - 105

SP - 3046

EP - 3057

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 9

M1 - dgaa433

ER -

Apolipoprotein M and risk of type 2 diabetes

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