Abstract
High cardiovascular mortality in patients with type 1 diabetes (T1DM) is widely recognized. Paradoxically, these patients have been shown to have elevated HDL-C and reduced apoB-containing lipoproteins. The purpose of this investigation was to further characterize the lipoprotein composition in T1DM and to assess the role that lipases and adipokines may play in these differences.
T1DM patients (89) attending the Diabetes Clinic at the University of Miami and 42 healthy controls were recruited. Clinical characteristics, lipoprotein composition (by ultracentrifugation and HPLC), leptin, and adiponectin were measured in the full cohort, while a subgroup had LPL and hepatic lipase measured.
Subjects were predominately Caucasian and Hispanic. HgbA1c's were above goal while their mean duration of diabetes was >20years. LPL was 2-fold elevated in diabetic women versus controls (+107%{p=0.001}) with no difference in men. Hepatic lipase was reduced 50% {p<0.001} in women but increased 50% {p=0.079} in men. Leptin was similar to controls in women but reduced in men (−60%{p<0.001}). Adiponectin was elevated in both genders (men: +55%{p=0.018}; women: +46%{p=0.007}).
LDL-C was reduced in both diabetic men (−33%{p<0.001}) and women (−24%{p<0.001}) while HDL-C trended higher only in men (+13%{p=0.064}). Both total apoB (men: −31%{p<0.001}; women: −17%{p=0.016}) and triglycerides (men: −49%{p<0.001}; women: −31%{p=0.011}) were reduced in both genders while total apoA-I was increased in both (men: +31%{p<0.001}; women: +19%{p=0.008}). Both men and women had increases in LpA-I (+66%{p<0.001}; +40%{p=0.001}) which accounted for essentially the entire increase in HDL mass. VLDL lipids (men: −53→70%; women: −31→57%) were lower as was apoB (particle number) in men (−51{p<0.001}) with a similar trend in women (−35%{p=0.066}). Cholesterol esters in the particle core were depleted in both genders relative to both apoB (men: −41%; women: −37%) and triglycerides (men: −38%; women: −34%) (all{p<0.009}). There were similar differences in IDL.
HDL-L lipids (except triglycerides) (men: +45→74%; women: +49→77%{p<0.006}), apoA-1 (men: +162%; women: +117%{p<0.001}), and apoA-II (men: +64%{p=0.008}; women: +55%{p=0.014}) were higher in T1DM patients. These differences produced dramatic increases in LpA-I (men: +221%; women +139%{p<0.001}) and total HDL-L mass (men: +85%; women: +78%{p<0.001}). ApoM (men: +190%; women: +149%{p<0.001}) was also dramatically increased. Conversely, HDL-D lipids were lower in both genders (−20%→50%) while apoA-I was not different in either. ApoA-II was lower only in the diabetic women (−25%{p=0.015}).
LPL activity correlated primarily with IDL(−), LDL(−), HDL-L(+), and HDL-D(−) only in the women. HL correlated weakly with VLDL(+), LDL(+), HDL-L(−), and HDL-D(+) in women but had much stronger correlations with VLDL(−), IDL(−), and HDL-L(+). Adiponectin correlated with VLDL(−), IDL(−), LDL(−), HDL-L(+), and HDL-D(−) in women but only HDL-L(+) and HDL-D(−) in men. Leptin correlated with very few parameters in women but did correlate weakly with several HDL-L(−) and HDL-M(−) parameters.
Lipoprotein composition and adipokine concentrations in both genders as well as lipase activities in the women would be expected to reduce the atherosclerotic risk in these patients with T1DM. These data suggest that there are functional lipoprotein abnormalities responsible for their CV risk that are not reflected in their plasma concentrations.
