Lipoprotein(a) and incident type-2 diabetes: results from the prospective Bruneck study and a meta-analysis of published literature.
We aimed to (1) assess the association between lipoprotein(a) [Lp(a)] concentration and incident type-2 diabetes in the Bruneck study, a prospective population-based study, and (2) combine findings with evidence from published studies in a literature-based meta-analysis.



We used Cox proportional hazards models to calculate hazard ratios (HR) for incident type-2 diabetes over 20 years of follow-up in 815 participants of the Bruneck study according to their long-term average Lp(a) concentration. For the meta-analysis, we searched Medline, Embase and Web of Science for relevant prospective cohort studies published up to October 2016.



In the Bruneck study, there was a 12% higher risk of type-2 diabetes for a one standard deviation lower concentration of log Lp(a) (HR = 1.12 [95% CI 0.95-1.32]; P = 0.171), after adjustment for age, sex, alcohol consumption, body mass index, smoking status, socioeconomic status, physical activity, systolic blood pressure, HDL cholesterol, log high-sensitivity C-reactive protein and waist-hip ratio. In a meta-analysis involving four prospective cohorts with a total of 74,575 participants and 4514 incident events, the risk of type-2 diabetes was higher in the lowest two quintiles of Lp(a) concentrations (weighted mean Lp(a) = 3.3 and 7.0 mg/dL, respectively) compared to the highest quintile (62.9 mg/dL), with the highest risk of type-2 diabetes seen in quintile 1 (HR = 1.28 [1.14-1.43]; P < 0.001).



The current available evidence from prospective studies suggests that there is an inverse association between Lp(a) concentration and risk of type-2 diabetes, with a higher risk of type-2 diabetes at low Lp(a) concentrations (approximately <7 mg/dL).
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Ellie
0000-0003-0855-9872
E
Paige
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Katya L
0000-0002-9822-1105
KL
Masconi
Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Sotirios
S
Tsimikas
Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
Florian
0000-0003-2229-1120
F
Kronenberg
Department of Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
Peter
P
Santer
Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy.
Siegfried
S
Weger
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Johann
0000-0003-4083-0466
J
Willeit
Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
Stefan
S
Kiechl
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. peter.willeit@i-med.ac.at.|Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. peter.willeit@i-med.ac.at.
Peter
0000-0002-1866-7159
P
Willeit
D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors
D017270:Lipoprotein(a)
Diabetes; Lipoprotein(a); Meta-analysis; Prospective study