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Departments of Vascular Medicine (T.B.T., G.M.D.-T., F.L.J.V., D.W.E.), Sport Physiology (W.R.d.V.), and Endocrinology (H.P.F.K.), University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands; and Institut National de la Santé et de la Recherche Médicale Unit 551 (T.B.T.), Hopital Pitié-Salpetrière, 75651 Paris, France
Address all correspondence and requests for reprints to: T. B. Twickler, M.D., Institute National de la Santé et de la Recherche Médicale Unit 551, Hopital Pitié-Salpetrière, 83 Boulevard de lHopital, 75651 Paris, France. E-mail: Th.B.Twickler{at}azu.nl.
Increased cardiovascular mortality due to premature atherosclerosis is a clinical feature in the adult-onset GH deficiency (AGHD) syndrome. Inflammation is a key feature in atherogenesis and may be triggered by postprandial lipoprotein remnants. We hypothesized that increased postprandial lipoprotein remnant levels in AGHD may be associated with an inflammatory response. In this case-control study, 10 AGHD patients [6 males and 4 females; age, 48 ± 9 yr; body mass index (BMI), 26.9 ± 2.6 kg/m2] and 10 healthy control subjects (matched for age, BMI, gender, baseline lipid levels, and apolipoprotein E genotype) were included. They all ingested an oral fat load. Fasting and postprandial levels of plasma remnant-like particle-cholesterol (RLP-C; 0.31 ± 0.13 mmol/liter and 4.14 ± 1.37 mmol/liter·h in GHD; 0.18 ± 0.06 mmol/liter and 2.56 ± 1.02 mmol/liter·h in controls, respectively) were significantly increased in AGHD patients compared with control subjects. The median inflammatory cytokines, IL-6 and TNF-
, were higher in the fasting [3.9 (range, 3.111.9) pg/ml and 6.8 (range, 2.527.6) pg/ml, respectively] and postprandial [151.7 (range, 87.0294.3) pg/ml·24 h and 289.9 (range, 87.5617.6) pg/ml·24 h, respectively] states in AGHD than in controls [fasting, 0.9 (range, 0.25.2) pg/ml and 2.8 (range, 2.55.7) pg/ml; and postprandial, 54.5 (range, 11.50126.5) pg/ml·24 h and 118.3 (range, 81.2243.1) pg/ml·24 h, respectively]. In addition, postprandial profile of RLP-C and IL-6 in AGHD and in the total group were significantly associated (r2 = 0.44, P < 0.05; and r2 = 0.38, P < 0.01, respectively). In conclusion, the increased postprandial RLP-C level in GHD is associated with an inflammatory response that may result in increased susceptibility for premature atherosclerosis.
Financial support for this work was obtained by Novo Nordisk BV (Alphen A/d Rijn, The Netherlands). Grants were obtained from the foundation De Drie Lichten and the Netherlands Organization for Scientific Research (NWO). T.B.T. received the Poste Verte Fellowship of the Institute National de la Santé et de la Recherche Médicale, France, and a travel fellowship of the International Atherosclerosis Society.
Abbreviations: AGHD, Adult-onset GHD; apo, apolipoprotein; AUC, integrated area under the curve; AUIC, area under the incremental curve; BMI, body mass index; CV, coefficient of variance; GHD, GH deficiency; IMT, intima media thickness; LDL, low-density lipoprotein; NF-
B, nuclear factor-
B; OFLT, oral fat loading test; RLP-C, remnant-like particle-cholesterol; TG, triglyceride.
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