Relationship between Abdominal Fat Accumulation and Insulin Resistance in Hemodialysis Patients

83 Hypertens Res Vol.31 (2008) No.1 p.83-88 Original Article Relationship between Abdominal Fat Accumulation and Insulin Resistance in Hemodialysis Patients Tomohito GOHDA1), Hiromichi GOTOH1), Mitsuo TANIMOTO1), Michiko SATO1), Hiroaki IO1), Kayo KANEKO1), Chieko HAMADA1), and Yasuhiko TOMINO1) It is well known that obesity and insulin resistance are closely related to the development of type 2 diabetes. However, the exact pathogenic mechanism underlying the insulin resistance in renal disease has not been clarified. The purpose of the present study was to clarify the contribution of abdominal (visceral and subcutaneous) fat accumulation to insulin resistance and various clinical parameters, including C-reactive protein (CRP), in hemodialysis (HD) patients. Visceral and subcutaneous fat areas (VFA and SFA) were evaluated at the umbilical level by CT. Insulin resistance was estimated by the homeostasis model assessment–insulin resistance index (HOMA-IR) in 80 HD patients. Insulin resistance and CRP seemed to be closely correlated with fat-related parameters such as body mass index (BMI), VFA and SFA. HOMA-IR was positively correlated with BMI, VFA, SFA, triglycerides (TG), remnant-like particle (RLP)-cholesterol and CRP in simple regression analysis. In multiple stepwise regression analysis, SFA and RLP-cholesterol were predominant determinants of HOMA-IR in HD patients. Furthermore, CRP was positively correlated with BMI, VFA, SFA, TG, high-density lipoprotein (HDL)-cholesterol, atherosclerosis index (AI), immunoreactive insulin (IRI) and HOMA-IR in simple regression analysis. In multiple stepwise regression analysis, VFA and HDLcholesterol were predominant determinants of CRP in HD patients. In conclusion, insulin resistance and CRP were related to fat-related parameters such as BMI, VFA and SFA in HD patients. Furthermore, the contribution of SFA to insulin resistance was much higher than that of VFA, while the opposite relation was recognized for CRP. (Hypertens Res 2008; 31: 83–88) Key Words: abdominal adipose tissue, obesity, insulin resistance, C-reactive protein, hemodialysis Introduction Obesity and inflammation or obesity and insulin resistance are closely related (1, 2). Overweight individuals commonly demonstrate elevated levels of inflammatory molecules such as C-reactive protein (CRP). High levels of inflammation have been implicated in the pathogenesis of cardiovascular disease (CVD). CRP, an acute-phase reactant protein and a marker of systemic inflammation, is known to be an important predictor of future cardiovascular events or mortality (3, 4). Adipose tissue secretes proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). These cytokines stimulate the production of CRP. About 30% of the total circulating level of IL-6 originates from adipose tissue in healthy Caucasians (5). Thus, adipose tissue is an important factor for the CRP in healthy individuals. Insulin resistance is often observed in patients with renal insufficiency. Accumulation of uremic toxins and metabolic acidosis have been hypothesized as the major causes of the insulin resistance observed in these patients (6, 7). Since most hemodialysis (HD) patients are maintained at an appropriate From the 1)Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan. Address for Reprints: Yasuhiko Tomino, M.D., Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, 2–1–1 Hongo, Bunkyo-ku, Tokyo 113–8421, Japan. E-mail: Received April 30, 2007; Accepted in revised form August 5, 2007. 84 Hypertens Res Vol. 31, No. 1 (2008) Table 1. Characteristics of Hemodialysis Patients Characteristics Number Age (years) Sex (male/female) Duration of HD (months) BMI (kg/m) VFA (cm2) SFA (cm2) Serum total cholesterol (mg/dL) Serum HDL cholesterol (mg/dL) AI Serum triglyceride (mg/dL) Serum RLP-cholesterol (mg/dL) Fasting plasma glucose (mg/dL) Immunoreactive insulin (μU/mL) HOMA-IR CRP (mg/dL) Mean±SD DM Non-DM 80 64.2±12.2 44/36 68.0±65.0 20.1±2.9 91.0±71.6 97.6±79.7 183.5±37.1 53.6±15.0 2.6±1.1 98.7±42.1 4.4±2.3 96.8±22.1 6.3±4.0 1.6±1.1 0.09±0.10 25 67.1±9.9 15/10 38.0±45.2 21.2±3.2 98.6±77.6 108.2±81.1 193.1±34.0 54.2±14.3 2.7±0.9 105.1±43.6 5.4±3.1 116.6±23.1 7.3±3.1 2.1±1.1 0.11±0.07 55 62.9±13.1 29/26 80.8±68.2 19.6±2.6 87.9±68.3 93.2±78.3 179.2±37.9 53.4±15.5 2.6±1.2 95.9±41.5 4.0±1.8 87.3±10.3 5.9±4.3 1.3±1.0 0.09±0.11 n.s. n.s. <0.01 <0.05 n.s. n.s. n.s. n.s. n.s. n.s. <0.05 <0.0001 n.s. <0.005 n.s. DM, type 2 diabetes; HD, hemodialysis; BMI, body mass index; VFA, visceral fat area; SFA, subcutaneous fat area; HDL, high-density lipoprotein; AI, atherosclerosis index; RLP, remnant-like particle; IRI, immunoreactive insulin; HOMA-IR, homeostasis model assessment–insulin resistance index; CRP, C-reactive protein. body mass index (BMI), insulin resistance might be determined in part not only by BMI but also by abdominal fat distribution. Some reports have demonstrated that accumulation of visceral adipose tissue (VAT) is related to insulin resistance, while that of subcutaneous abdominal fat (SAT) is generally not related to insulin resistance (8, 9). HD improves uremic-induced glucose intolerance to some extent. However, the exact pathogenic mechanism underlying insulin resistance in renal disease has not been clarified. The purpose of the present study was to clarify the contribution of abdominal (visceral and subcutaneous) fat tissue accumulation to insulin resistance and various clinical parameters, including CRP, in HD patients. Ltd., Tokyo, Japan) three times a week. Dry weight was determined in each case to achieve a normotensive, edemafree status based on the inferior vena cava diameter, plasma concentration of arterial natriuretic peptide and cardiothoracic ratio. Blood samples for biochemical parameters were drawn before starting HD and in a fasting state. For diabetic patients, blood samples were drawn before taking the morning oral hypoglycemic agents. Informed consent was obtained from all patients before the study onset. The study protocol was approved by the Ethics Committee of Juntendo University School of Medicine. Methods Abdominal fat distribution was determined using abdominal CT at the level of the umbilicus. CT scans were performed with the subject in the supine position using a slip ring CT scanner (Aquilion; Toshiba, Tokyo, Japan). SAT was clearly defined as the extraperitoneal fat between the skin and muscle. Intra-abdominal tissue with the same density as the SAT was defined as VAT. The subcutaneous fat area (SFA) and visceral fat area (VFA) were also measured at the level of the umbilicus. Subjects Eighty HD patients (age 64.2±12.2 years, mean±SD; male/ female 44/36; duration of HD, 68.0±65.0 months) were recruited for this study. The reason for the renal insufficiency necessitating HD was chronic glomerulonephritis in 27 patients (...truncated)