B. Foger et al., EFFECTS OF PANCREAS TRANSPLANTATION ON DISTRIBUTION AND COMPOSITION OF PLASMA-LIPOPROTEINS, Metabolism, clinical and experimental, 45(7), 1996, pp. 856-861
In type I (insulin-dependent) diabetic patients, peripheral hyperinsul
inemia due to subcutaneous insulin treatment is associated with increa
sed high-density lipoprotein (HDL) cholesterol, and also with an alter
ed surface composition of HDL. Pancreas grafts also release insulin in
to the systemic rather than into the portal venous system, giving rise
to pronounced peripheral hyperinsulinemia. We hypothesized that if pe
ripheral hyperinsulinemia is responsible for high HDL cholesterol and/
or altered surface composition of HDL in diabetic subjects, similar ch
anges in the lipid profile should be present in pancreas-kidney transp
lant recipients (PKT-R). Using zonal ultracentrifugation, we isolated
HDL(2), HDL(3), very-low-density lipoprotein (VLDL), intermediate-dens
ity lipoprotein (IDL), and low-density lipoprotein (LDL) from fasting
plasma of 14 type I diabetic PKT-R, eight nondiabetic kidney transplan
t recipients (KT-R), and 14 healthy control subjects and determined th
e level and composition of the above lipoproteins. HDL(2) cholesterol
was increased in PKT-R as compared with KT-R and healthy controls (bot
h P < .05), whereas HDL(3) cholesterol was unchanged. However, an alte
red lipoprotein surface composition was evident in PKT-R: HDL(2), HDL(
3), and LDL were enriched in unesterified cholesterol ([UC] PKT-R v KT
-R, P = .13, P < .005, and P < .05, respectively; PKT-R v controls, al
l P < .005); HDL was enriched in phospholipids; and LDL was depleted o
f phospholipid. KT-R, in contrast, showed no changes in lipoprotein su
rface composition but a substantial triglyceride enrichment of HDL(2)
as compared with PKT-R and healthy controls (both P < .05). LDL size a
s determined by gradient gel electrophoresis was increased in PKT-R co
mpared with controls (P < .005). The plasma concentration of cholester
yl ester (CE) transfer protein (CETP), involved also in phospholipid t
ransfer, was increased in both transplant groups compared with healthy
controls (both P < .05). Insulin concentrations in fasting plasma wer
e directly related to CETP levels and to the weight-percentage of UC i
n HDL(3), and inversely to the weight-percentage of phospholipids in L
DL (all P < .05). We explain the increase in HDL(2) cholesterol and LD
L size in PKT-R by their high lipoprotein lipase (LPL) activity confer
ring an excellent capacity to clear chylomicron triglycerides. Effecti
ve handling of postprandial triglycerides, high HDL(2) cholesterol, an
d predominance of LDL pattern A, respectively, are established indicat
ors of a low risk of atherosclerosis. However, it is presently unclear
what effects the compositional changes on the surface of HDL and LDL
may have on cardiovascular risk in clinically stable PKT-R. Copyright
(C) 1996 by W.B. Saunders Company