Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project.
OBJECTIVE
The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes.


METHODS
A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey.


RESULTS
Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently).


CONCLUSIONS
We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
Buschard
K
K
Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark.
Fredman
P
P
Bøg-Hansen
E
E
Blomqvist
M
M
Hedner
J
J
Råstam
L
L
Lindblad
U
U
D015703:Antigens, CD / Q000097:blood*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology; D005260:Female; D005699:Galactosylceramides / Q000097:blood*; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D007790:Lactosylceramides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors; D017678:Sex Distribution; D013433:Sulfoglycosphingolipids / Q000097:blood*; D013548:Sweden / Q000453:epidemiology
D015703:Antigens, CD; D005699:Galactosylceramides; D007790:Lactosylceramides; D013433:Sulfoglycosphingolipids; C009744:CDw17 antigen