842 2016 10 1 41 10 [ ] (AGHD) (VAI) C (hs-crp) 6(IL -6) 40 AGHD 40 (BMI) (WHR) VAI (WHtR) (LAP) (HOMA-IR) (HOMA- ) (LDL-C)/ (HDL-C) (TC)/HDL-C (TG)/LDL -C AGHD BMI (WC) WHR (FINS) HOMA- HOMA- IR TC TG LDL-C/HDL-C TC/HDL-C hs-cpr IL-6 VAI HDL-C (P<0.05) VAI WC WHR (SBP) FINS HOMA- HOMA-IR TG LDL-C/HDL-C TC/HDL-C TG/ LDL-C hs-cpr IL-6 (P<0.05) hs-crp IL-6 VAI Pearson VAI WC BMI WHR WHtR AGHD VAI [ ] [ ] R584.2 [ ] A [ ] 0577-7402(2016)10-0842-06 [DOI] 10.11855/j.issn.0577-7402.2016.10.10 Correlation of visceral adipose levels and cardiovascular risk factors for disease in patients with adult growth hormone deficiency LI Qing, LIU Chan, XIA Jia-jia, LI Lin-man, XIE Xin, ZHENG Xiao-ya, REN Wei * Department of Endocrinology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China * Corresponding author, E-mail: weiren67@aliyun.com This work was supported by Chongqing Science and Technolog y Commission of Chongqing People's Livelihood Scientific and Technological Innovation Projects (cstc2015shmszx1067) [Abstract] Objective To explore the correlation of visceral adipose index (VAI) with anthropometrics, glycolipid metabolism markers, high-sensitivity C-reactive protein (hs-crp) and interleukin-6 (IL-6) in patients with adult growth hormone deficiency (AGHD). Methods A total of 40 AGHD patients from First Affiliated Hospital of Chongqing Medical University and 40 healthy adults from physical examination centre (control group), matched with age and gender, were enrolled in present study. The general anthropometrics and blood biochemical indexes were collected and compared between the two groups. Waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHtR), and visceral adipose index (VAI) were examined, and homeostasis model assessment-insulin resistance (HOMA-IR), homeostasis model assessment -cell function (HOMA- ), LDL-C/HDL-C, TC/HDL-C and TG/LDL-C between the two groups were calculated. Results Compared with control group, the levels of BMI, WC, WHR, fasting insulin (FINS), HOMA-, HOMA-IR, triglyceride (TG), LDL-C/HDL-C, TC/HDL-C, hs-cpr, IL-6 and VAI were significantly higher, but those of HDL-C were lower in AGHD group (P<0.05). There was a positive correlation between VAI and all the factors including WC, WHR, FINS, HOMA-, HOMA-IR, TC, LDL-C/HDL-C, TC/HDL-C, TG/LDL-C, hs-crp and IL-6 (P<0.05). Multiple linear regression analysis revealed that hs-crp and IL-6 were the independent risk factors of VAI. Pearson correlation index analysis showed that VAI was more correlated with lipid metabolism and inflammatory cytokines than with WC, BMI, WHR and WHtR. Conclusion VAI is significantly higher in AGHD patients than in healthy people, [ ] (cstc2015shmszx1067) [ ] [ ] 400016( ) [ ] E-mail weiren67@aliyun.com
Med J Chin PLA, Vol. 41, No. 10, October 1, 2016 843 and it shows a strong correlation with many risk factors for cardiovascular diseases. [Key words] adult growth hormone deficiency; visceral adipose index; cardiovascular diseases (adult grow th hormone deficiency AGHD) [1] [2] [3] [4] [5-6] [7] AGHD AGHD AGHD [8] [9-10] [12-14] (waist circumference WC) [15] AlkaMeSy WC (body mass index BMI) (triglyceride TG) (highdensity lipoprotein-cholesterol HDL-C) (visceral adipose index VAI) [16] [17] VAI [16-19] AGHD VAI AGHD AGHD VAI C (high sensitivity C-reactive protein hs- CRP) 6(interleukin-6 IL -6) VAI AGHD 1 1.1 2011 6 2013 9 40 AGHD AGHD>2 ( 14 26 50.5 11.0 ) 6 32 8 AGHD 40 49.5 10.1 AGHD AGHD ( ) 3 1. 2 AG H D 2011 (growth hormone research society GRS) [20] AGHD GH <5.0 g/l AGHD GH <3.0 g/l AGHD( GH 3.0 g/l) GH <3.0 g/l AGHD BMI<25kg/m 2 GH <11.0 g/l AGHD GHRH + BMI 25~30kg/m 2 GH <8.0 g/l AGHD BMI>30kg/m 2 GH <4.0 g/l AGHD 2 AGHD +2 3 3 1.3 1.3.1 WC 0.1cm 0.1kg 1 WC 0.1cm 5min 1.3.2 ( 12h 8h) (fasting serum glucose FPG) (fasting ser um insulin FINS) (TC) TG HDL -C ( lowdensity lipoprotein-cholesterol LDL-C) 1.3.3 BMI= / 2 ( kg/m 2 ) (waist hip ratio WHR)=WC/ (waist height ration WHtR)=WC/ (homeostasis model
844 2016 10 1 41 10 a s s e s s m e n t o f i n s u l i n resis t a n c e HOM A -I R ) HOMA-IR=FPG(mmol/L) FINS(mU/ml)/22.5 (homeostasis model assessment index for insulin secretion HOMA- ) H O M A - = F I N S (m U / m l ) 2 0 / [F P G (m m o l / L) 3.5] [14] [ VAI=WC/39.68 +(1.88 BMI) TG/1.03 1.31/HDL VAI= WC/36.58+(1.89 BMI) TG/0.81 1.52/HDL] 1.4 SPSS 17.0 Kolmogorov-Smirnov x±s Mann-Whitney Pearson VAI P<0.05 2 2. 1 AG H D BMI WC WHR WHtR (P<0.05) (P>0.05 1) 2.2 AGHD 1 AGHD (n=40) Tab.1 Comparison of anthropometrics between control and AGHD group (n=40) Item Control group AGHD group P Male/Female 14/26 14/26 Age (year) 49.48 10.12 50.53 10.95 0.219 Height (m) 1.58 0.07 1.59 0.06 0.683 BMI (kg/m 2 ) 21.25 1.78 23.87 3.39 0.000 Body fat percentage (%) 30.55 4.96 31.26 3.39 0.066 Waist circumference (cm) 75.08 8.60 85.30 12.37 0.000 Waist-hip ratio 0.82(0.75, 0.85) 0.89(0.83, 0.96) 0.000 Waist-height ratio 0.48(0.43, 0.52) 0.53(0.47, 0.57) 0.000 SBP(mmHg) 117.68 15.95 121.90 18.53 0.278 DBP (mmhg) 77.80 8.90 85.3 12.37 0.858 FINS HOMA- HOMA-IR TG LDL/HDL-C TG/LDL -C TC/HDL -C hs-cpr IL -6 VAI HDL -C (P<0.05) FPG LDL -C (P>0.05 2) 2.3 VAI AGHD Pearson VAI W C WHR FINS HOM A - HOM A -I R TG hs-crp LDL -C/HDL -C TC/HDL -C TG/ LDL -C (P<0.05 3 1) BMI DBP FPG 2 AGHD VAI (n=40) Tab.2 Comparison of clinical biochemical indexes and VAI between control and AGHD group (n=40) Index Control group Case group P value FPG (mmol/l) 5.38 0.34 5.26 0.77 0.379 FINS (mu/ml) 5.57 1.80 8.50 2.22 0.000 HOMA- 48.16(34.63, 62.16) 100.86(66.11, 162.60) 0.000 HOMA-IR 1.06 (0.81, 1.37) 1.83(1.62, 2.31) 0.000 TC (mmol/l) 4.77 0.83 5.02 1.31 0.317 TG (mmol/l) 1.26 0.40 1.78 0.65 0.000 HDL-C (mmol/l) 1.40 0.31 1.07 0.43 0.000 LDL-C (mmol/l) 2.56 0.79 2.68 0.93 0.545 LDL-C/HDL-C 1.74(1.48, 2.35) 2.47(1.82, 3.70) 0.000 TC/HDL-C 3.27(2.93, 4.17) 4.77(3.73, 6.29) 0.000 TG/LDL-C 0.49(0.35, 0.58) 0.64(0.49, 0.850 0.096 hs-crp (mg/l) 0.47(0.31, 0.76) 2.57(1.48, 3.59) 0.000 IL-6 (pg/ml) 3.50(2.05, 5.13) 5.12(3.48, 9.64) 0.000 VAI 1.43(1.00, 2.33) 2.94(1.80, 4.70) 0.000 3 VA I Pearson Tab.3 The Pearson correlation indexes between VAI value and anthropometrics, glycolipid metabolism markers and inflammatory cytokines Item Pearson value (r) P Waist circumference (cm) 0.365 0.001 Waist-hip ratio 0.376 0.001 FINS (mu/l) 0.419 0.000 HOMA- 0.404 0.001 HOMA-IR 0.389 0.000 TG (mmol/l) 0.668 0.000 LDL-C/HDL-C 0.659 0.000 TC/HDL-C 0.760 0.000 TG/LDL-C 0.400 0.000 hs-crp (mg/l) 0.545 0.000 IL-6 (mg/l) 0.318 0.004 L D L - C hs - CR P IL -6 VA I ( 0.080 0.301 P<0.05) YVAI=1.491+0.080 IL-6+0.301 hscrp 2.4 WC BMI WHR WHtR VAI AGHD WC BMI W H R WHt R VA I Pearson WC LDL -C/HDL -C BMI LDL -C/HDL -C TG WHR LDL - C/HDL - C TG WHtR TG VA I TC/HDL - C TG/LDL - C L D L - C / H D L - C TG hs - C R P IL - 6 (P<0.05) TC ( 4)
Med J Chin PLA, Vol. 41, No. 10, October 1, 2016 845 4 AGHD WC BMI WHR WHtR VAI Pearson Tab.4 The Pearson correlation indexes between VAI value, BMI, WC, WHR, WHtR and anthropometrics, lipid metabolism markers and inflammatory cytokines Item 2.000000000 1.000000000 0.000000000 1.000000000 2.000000000 1.40000000 1.20000000 1.00000000 0.80000000 0.60000000 0.40000000 0.20000000 Pearson value (r) WC BMI WHR WHtR VAI TC/HDL-C 0.098 0.109 0.074 0.019 0.760 (1) TG/LDL-C 0.244 0.114 0.179 0.034 0.400 (1) LDL-C/HDL-C 0.308 (1) 0.331 (1) 0.371 (1) 0.267 0.659 (1) TC 0.103 0.123 0.245 0.003 0.194 TG 0.225 0.446 (1) 0.310 (1) 0.393 (1) 0.668 (1) hs-crp (mg/l) 0.053 0.016 0.015 0.101 0.545 (1) IL-6 (mg/l) 0.004 0.062 0.027 0.085 0.318 (1) (1)P<0.001 1 VAI hs-crp IL-6 Fig.1 Correlation between VAI and hs-crp, IL-6 (hs-crp and IL-6 were transformed by common logarithm) 3 R 2 Linear=0.251 0.00 2.00 4.00 6.00 8.00 10.00 VAI R 2 Linear=0.055 0.00 2.00 4.00 6.00 8.00 10.00 VAI HDL -C AGHD [21] TC/HDL -C LDL -C/ HDL -C TG/HDL -C TG HDL -C [22] AGHD TG LDL -C/HDL -C TG/ LDL-C TC/HDL-C HDL-C (P<0.05) VA I TG LDL-C/HDL-C TG/LDL-C TC/HDL-C [23] VAI [24] AGHD VAI FINS HOMA-IR HOMA- AGHD VAI [7,25] hs-crp IL-6 [26] hs-crp [27] [28] IL-6 [29] AGHD hs-crp IL -6 Person VAI hs-crp IL-6 hs-crp IL -6 VAI VAI hs-crp IL -6 hs-crp IL-6 VAI AGHD VAI Amato [16] VAI BMI WC WHR WHtR [30-32] AGHD BMI WC WHR W Ht R BMI WC WHtR WHR VAI hs-crp IL -6 WHt R [ 3 3 ] WHtR TG Am a t o [ 1 6 ] VA I
846 2016 10 1 41 10 BMI WC WC T G TC / H D L - C TG / L D L - C LDL - C / HDL -C TC hs-crp IL -6 BMI LDL -C/HDL -C TG TC/HDL -C TG/LDL -C TC hs-crp IL -6 VAI TC / H D L - C TG / L D L - C LDL - C / H D L - C TG hs - CR P IL -6 TC VA I BMI WC WHR [ 3 0 ] WHR [15] VAI AGHD VAI VAI WC BMI WHR WHtR VAI AGHD AGHD AGHD VAI AGHD [1] Cen J, Gu F. Interpretation of guidelines on the diagnosis and treatment of adults with growth hormone deficiency[ J]. Chin J Pract Intern Med, 2011, 31(8): 608-612. [,. [ J]., 2011, 31(8): 608-612.] [2] M u r r a y R D, A d a m s J E, S h a l e t S M, e t a l. A d u l t s w i t h par tial grow th hormone deficienc y have an adverse body composition[ J]. J Clin Endocrinol Metab, 2004, 89(4): 1586-1591. [3] Abs R, Feldt-Rasmussen U, Mattsson AF, et al. Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults a KIMS database analysis[ J]. Eur J Endocrinol, 2006, 155(1): 79-90. [4] Rosén T, Wirén L, Wilhelmsen L, et al. Decreased psychological wellbeing in adult patients with growth hormone deficiency[ J]. Clin Endocrinol (Oxf ), 1994, 40(1): 111-116. [5] R o s e n T, B e n g t s s o n B A. P r e m a t u r e m o r t a l i t y d u e t o cardiovascular disease in hypopituitarism[ J]. Lancet, 1990, 336(8710): 285-288. [6] Tomlinson JW, Holden N, Hills RK, et al. Association between premature mor tality and hy popituitarism. West Midlands Prospective Hypopituitar y Study Group[ J]. Lancet, 2001, 357(9254): 425-431. [7] Erfurth EM, Bulow B, Eskilsson J, et al. High incidence of cardiovascular disease and increased prevalence of cardiovascular risk factors in women with hypopituitarism not receiving growth hormone treatment: preliminary results[ J]. Growth Hormone IGF Res,1999, 9(Suppl A): 21-24. [8] Xia JJ, Zheng XY, Li LM, et al. Correlation between atherogenic index of plasma level and metabolism components in adult growth hormone deficiency patients[ J]. Med J Chin PLA, 2014, 39(12): 975-980. [,,,. [ J]., 2014, 39(12): 975-980.] [9] Cuneo RC, Salomon F, McGauley G A, et al. The grow th hormone deficiency syndrome in adults[ J].Clin Endocrinol (Oxf ), 1992, 37(5): 387-397. [10] Weaver JU, Monson JP, Noonan K, et al. The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitar y adults[ J]. J Clin Endocrinol Metab,1995, 80(1): 153-159. [11] Rosen T, Wilhelmsen L, Bengtsson BA. Altered lipid pattern explains increased cardiovascular mortality in hypopituitary patients with growth hormone deficiency[ J]. Clin Endocrinol (Oxf ),1998, 48(4): 525-526. [12] Després JP, Lemieux I. Abdominal obesity and metabolic syndrome[ J]. Nature, 2006, 444(7121): 881-887. [13] DeNino WF, Tchernof A, Dionne IJ, et al. Contribution of abdominal adiposit y to age-related differences in insulin sensitivity and plasma lipids in healthy non obese women[ J]. Diabetes Care, 2001, 24(5): 925-932. [14] Br üünsgaard H, Pedersen BK. A ge-related inf lammator y cytokines and disease[ J]. Immunol Allergy Clin North Am, 2003, 23(1) :15-39. [15] Pouliot MC, Després JP, Lemieux S, et al. Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women[ J]. Am J Cardiol, 1994, 73(7): 460-468. [16] Amato MC, Giordano C, Galia M, et al. Visceral Adiposity Index: are liable indicator of visceral fat function associated with cardiometabolic risk[ J]. Diabetes Care, 2010, 33(4): 920-922. [17] Zhang Y, Zhang SH, Gong LL, et al. The relationship between lipid accumulation product, visceral adiposity index and highsensitivity C-reactive protein in healthy adults[ J]. Med J Chin PLA, 2013, 38(3): 225-229. [,,,. C [ J]., 2013, 38(3): 225-229.] [18] Knowles KM, Paiva LL, Sanchez SE, et al. Waist circumference, body mass index, and other measures of adiposity in predicting cardiovascular disease risk factors among Peruvian adults[ J]. Int J Hypertens, 2011, 2011: 931402. [19] Amato MC, Verghi M, Galluzzo A, et al. The oligomenorrhoic phenotypes of polycystic ovary syndrome are characterized
Med J Chin PLA, Vol. 41, No. 10, October 1, 2016 847 by a high v i sceral adiposit y index : a likely condition of cardiometabolic risk[ J]. Hum Reprod, 2011, 26(6): 1486-1494. [20] Molitch ME, Clemmons DR, Malozowski S, et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline[ J]. J Clin Endocrinol Metab, 2011, 96(6): 1587-1609. [21] Abdu TA, Neary R, Elhadd TA, et al. Coronary risk in growth hormone deficient hypopituitary adults: increased predicted risk is due largely to lipid profile abnormalities[ J]. Clin Endocrinol, 2001, 55: 209-216. [22] Kimm H, Lee SW, Lee HS, et al. Associations between lipid measures and metabolic syndrome, insulin resistance and adiponectin. - Usefulness of lipid ratios in Korean men and women[ J]. Circ J, 2010, 74(5): 931-937. [23] Bornfeldt KE, Tabas I. Insulin resistance, hyperglycemia, and atherosclerosis[ J]. Cell Metabolism, 2011, 14(5): 575-585. [24] Du T, Yuan G, Zhang M, et al. Clinical usefulness of lipid ratios, visceral adiposity indicators, and the triglycerides and glucose index as risk markers of insulin resistance[ J]. Cardiovasc Diabetol, 2014, 13: 146. [25] Besson A, Salemi S, Gallati S, et al. Reduced longev ity in untreated patients with isolated growth hormone deficiency[ J]. J Clin Endocrinol Metab, 2003, 88(8): 3664-3667. [26] Mo n t a g n a n a M, L i p p i G, D a n e s e E, e t a l. T h e r o l e o f osteoprotegerin in cardiovascular disease[ J]. Ann Med, 2013, 45(3): 254-264. [27] Ridker PM. Evaluating novel cardiovascular risk markers: can we better predict heart attacks.[ J]? Ann Intern Med, 1999, 130(11): 933-937. [28] Welch GN, Loscalzo J. Homocysteine and atherothrombosis[ J]. N Engl J Med, 1998, 338(15): 1042-1050. [29] Aker S, Bantis C, Reis P, et al. Influence of interleukin-6 G-174C gene polymorphism on coronary artery disease, cardiovascular complications and mortality in dialysis patients[ J]. Nephrol Dial Transplant, 2009, 24(9): 2847-2851. [30] Menke A, Muntner P, Wildman RP, et al. Measures of adiposity and cardiovascular disease risk factors[ J]. Obesity (Silver Spring), 2007, 15(3): 785-795. [31] Wildman RP, Gu D, Reynolds K, et al. Are waist circumference a n d b o d y m a s s i n d e x i n d e p e n d e n t l y a s s o c i a t e d w i t h cardiovascular disease risk in Chinese adults.[ J]? Am J Clin Nutr, 2005, 82(6): 1195-1202. [32] Vazquez G, Duval S, Jacobs DR Jr, et al. Comparison of body mass index, waist c ircumference, and waist/hip rat io in predicting incident diabetes: a meta analysis[ J]. Epidemiol Rev, 2007, 29: 115-128. [33] Lee CM, Huxley RR, Wildman RP, et al. Indices of abdominal obesity are better discriminators of cardiovascular risk factors than BMI:a meta-analysis[ J]. J Clin Epidemiol, 2008, 61(7): 646-653. ( 2016-04-22 2016-08-16) ( )