Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes

A pooled analysis in more than 20,000 individuals

Barbara Kollerits, Claudia Lamina, Cornelia Huth, Pedro Marques-Vidal, Stefan Kiechl, Ilkka Seppälä, Jackie Cooper, Steven Hunt, Christa Meisinger, Christian Herder, Ludmilla Kedenko, Johann Willeit, Barbara Thorand, Doreen Dähnhardt, Doris Stöckl, Karin Willeit, Michael Roden, Wolfgang Rathmann, Bernhard Paulweber, Annette Peters & 7 others Mika Kähönen, Terho Lehtimäki, Olli T. Raitakari, Steve E. Humphries, Peter Vollenweider, Hans Dieplinger, Florian Kronenberg

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

OBJECTIVE The human Vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in linewith observations in transgenic mice.We thus investigatedwhether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95%CI 1.12-1.26], P=5.96×10-8). Afaminwas positively associated with IR assessed by HOMA-IR (b 0.110 [95%CI 0.089-0.132], P = 1.37×10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.

Original languageEnglish
Pages (from-to)1386-1393
Number of pages8
JournalDiabetes Care
Volume40
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017
Externally publishedYes

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Type 2 Diabetes Mellitus
Insulin Resistance
Prediabetic State
Odds Ratio
Vitamin E
Transgenic Mice
Meta-Analysis
Glycoproteins
Cohort Studies
Research Design
Prospective Studies
Liver
Incidence

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialised Nursing

Cite this

Kollerits, B., Lamina, C., Huth, C., Marques-Vidal, P., Kiechl, S., Seppälä, I., ... Kronenberg, F. (2017). Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes: A pooled analysis in more than 20,000 individuals. Diabetes Care, 40(10), 1386-1393. https://doi.org/10.2337/dc17-0201

Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes : A pooled analysis in more than 20,000 individuals. / Kollerits, Barbara; Lamina, Claudia; Huth, Cornelia; Marques-Vidal, Pedro; Kiechl, Stefan; Seppälä, Ilkka; Cooper, Jackie; Hunt, Steven; Meisinger, Christa; Herder, Christian; Kedenko, Ludmilla; Willeit, Johann; Thorand, Barbara; Dähnhardt, Doreen; Stöckl, Doris; Willeit, Karin; Roden, Michael; Rathmann, Wolfgang; Paulweber, Bernhard; Peters, Annette; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Humphries, Steve E.; Vollenweider, Peter; Dieplinger, Hans; Kronenberg, Florian.

In: Diabetes Care, Vol. 40, No. 10, 01.10.2017, p. 1386-1393.

Research output: Contribution to journalArticle

Kollerits, B, Lamina, C, Huth, C, Marques-Vidal, P, Kiechl, S, Seppälä, I, Cooper, J, Hunt, S, Meisinger, C, Herder, C, Kedenko, L, Willeit, J, Thorand, B, Dähnhardt, D, Stöckl, D, Willeit, K, Roden, M, Rathmann, W, Paulweber, B, Peters, A, Kähönen, M, Lehtimäki, T, Raitakari, OT, Humphries, SE, Vollenweider, P, Dieplinger, H & Kronenberg, F 2017, 'Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes: A pooled analysis in more than 20,000 individuals', Diabetes Care, vol. 40, no. 10, pp. 1386-1393. https://doi.org/10.2337/dc17-0201
Kollerits, Barbara ; Lamina, Claudia ; Huth, Cornelia ; Marques-Vidal, Pedro ; Kiechl, Stefan ; Seppälä, Ilkka ; Cooper, Jackie ; Hunt, Steven ; Meisinger, Christa ; Herder, Christian ; Kedenko, Ludmilla ; Willeit, Johann ; Thorand, Barbara ; Dähnhardt, Doreen ; Stöckl, Doris ; Willeit, Karin ; Roden, Michael ; Rathmann, Wolfgang ; Paulweber, Bernhard ; Peters, Annette ; Kähönen, Mika ; Lehtimäki, Terho ; Raitakari, Olli T. ; Humphries, Steve E. ; Vollenweider, Peter ; Dieplinger, Hans ; Kronenberg, Florian. / Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes : A pooled analysis in more than 20,000 individuals. In: Diabetes Care. 2017 ; Vol. 40, No. 10. pp. 1386-1393.
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abstract = "OBJECTIVE The human Vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in linewith observations in transgenic mice.We thus investigatedwhether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95{\%}CI 1.12-1.26], P=5.96×10-8). Afaminwas positively associated with IR assessed by HOMA-IR (b 0.110 [95{\%}CI 0.089-0.132], P = 1.37×10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95{\%} CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.",
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T1 - Plasma concentrations of afamin are associated with prevalent and incident type 2 diabetes

T2 - A pooled analysis in more than 20,000 individuals

AU - Kollerits, Barbara

AU - Lamina, Claudia

AU - Huth, Cornelia

AU - Marques-Vidal, Pedro

AU - Kiechl, Stefan

AU - Seppälä, Ilkka

AU - Cooper, Jackie

AU - Hunt, Steven

AU - Meisinger, Christa

AU - Herder, Christian

AU - Kedenko, Ludmilla

AU - Willeit, Johann

AU - Thorand, Barbara

AU - Dähnhardt, Doreen

AU - Stöckl, Doris

AU - Willeit, Karin

AU - Roden, Michael

AU - Rathmann, Wolfgang

AU - Paulweber, Bernhard

AU - Peters, Annette

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Raitakari, Olli T.

AU - Humphries, Steve E.

AU - Vollenweider, Peter

AU - Dieplinger, Hans

AU - Kronenberg, Florian

PY - 2017/10/1

Y1 - 2017/10/1

N2 - OBJECTIVE The human Vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in linewith observations in transgenic mice.We thus investigatedwhether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95%CI 1.12-1.26], P=5.96×10-8). Afaminwas positively associated with IR assessed by HOMA-IR (b 0.110 [95%CI 0.089-0.132], P = 1.37×10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.

AB - OBJECTIVE The human Vitamin E-binding glycoprotein afamin is primarily expressed in the liver and has been associated with prevalent and incident metabolic syndrome. These data were in linewith observations in transgenic mice.We thus investigatedwhether afamin concentrations are associated with prediabetes, type 2 diabetes, and insulin resistance (IR). RESEARCH DESIGN AND METHODS Individual-level baseline (n = 20,136) and follow-up data (n = 14,017) of eight prospective cohort studies were investigated. Study-level data were combined using random-effects meta-analyses. Main outcomes were prevalent and incident type 2 diabetes, prediabetes, and IR. Discrimination and reclassification of participants was analyzed for incident type 2 diabetes. RESULTS Mean afamin concentrations between studies ranged from 61 to 73 mg/L. The eight studies included 1,398 prevalent and 585 incident cases of type 2 diabetes. Each increase of afamin by 10 mg/L was associated with prevalent type 2 diabetes (odds ratio [OR] 1.19 [95%CI 1.12-1.26], P=5.96×10-8). Afaminwas positively associated with IR assessed by HOMA-IR (b 0.110 [95%CI 0.089-0.132], P = 1.37×10-23). Most importantly, afamin measured at baseline was an independent predictor for 585 incident cases of type 2 diabetes (OR 1.30 [95% CI 1.23-1.38], P = 3.53 × 10-19) and showed a significant and valuable gain in risk classification accuracy when added to this extended adjustment model. CONCLUSIONS This pooled analysis in >20,000 individuals showed that afamin is strongly associated with IR, prevalence, and incidence of type 2 diabetes independent of major metabolic risk factors or parameters. Afamin might be a promising novel marker for the identification of individuals at high risk for the development of type 2 diabetes.

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