Markers of cholesterol metabolism as biomarkers in predicting diabetes in the Finnish Diabetes Prevention Study.
OBJECTIVE
We examined the effect of serum markers of cholesterol synthesis and absorption on the incidence of type 2 diabetes (T2D) in the randomized Finnish Diabetes Prevention Study (DPS). We also explored a possible interaction of ABCG8 rs4299376 on sterol levels and lifestyle intervention.


RESULTS
We conducted a prospective cohort study including overweight, middle-aged people with impaired glucose tolerance at baseline who participated in the randomized DPS. The primary outcome of the DPS was the diagnosis of T2D based on repeated oral glucose tolerance tests (OGTTs). After active intervention (median of four years, 1994-2001), non-T2D participants were further followed until T2D diagnosis, dropout or the end of 2009. Of these, 340 participants who had β-sitosterol, campesterol, lathosterol and desmosterol measured by gas chromatography-mass spectrometry during the active four-year follow-up and who were not using cholesterol lowering medications were analysed. Surrogate indexes of insulin sensitivity (IS) and secretion were calculated from an OGTT. In adjusted models, plant sterols during the four-year follow-up were associated with lower T2D incidence during the extended eight-year follow-up (HR for 1-SD change in β-sitosterol and campesterol: 0.76 [0.63-0.92], and 0.81 [0.67-0.99], respectively). Lathosterol levels were associated with higher T2D incidence (HR: 1.35 [1.13-1.62]). These associations, though, were not independent of IS. There was an interaction between rs4299376 and study group on β-sitosterol (p = 0.001) and campesterol (p = 0.004) levels during the follow-up.


CONCLUSIONS
Markers of low absorption and high synthesis of cholesterol were associated with the risk of developing T2D, mostly ascribed to IS.
Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. Electronic address: vanessa.laaksonen@uef.fi.
V D F
VD
de Mello
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
J
J
Lindström
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Department of General Practice and Primary Health, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland; Vaasa Central Hospital, Vaasa, Finland.
J G
JG
Eriksson
The Diabetes Centre, Finnish Diabetes Association, Tampere, Finland; Science Center, Tampere University Hospital, Tampere, Finland.
P
P
Ilanne-Parikka
Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital and Oulu Health Centre, Oulu, Finland.
S
S
Keinänen-Kiukaanniemi
Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland.
J
J
Pihlajamäki
Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Center for Vascular Prevention, Danube-University Krems, Austria.
J
J
Tuomilehto
Institute of Public Health and Clinical Nutrition, Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Research Unit, Kuopio University Hospital, Kuopio, Finland.
M
M
Uusitupa
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D002784:Cholesterol / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000517:prevention & control*; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000150:complications; D011446:Prospective Studies; D013261:Sterols / Q000378:metabolism
C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D015415:Biomarkers; D013261:Sterols; D002784:Cholesterol
Cholesterol metabolism; Insulin sensitivity; Lifestyle; Plant sterols; Type 2 diabetes