말기신부전 환자에서 혈청 Insulin-Like Growth Factor-1 농도와 인슐린 저항성과의 관계 = Relationship between Serum Insulin-like Growth Factor-1 Concentration and Insulin Resistance in End-stage Renal Disease Patients

다국어 초록 (Multilingual Abstract)

Background:Insulin resistance is a characteristic feature of uremia and recent studies suggested that it might be one of the causes of muscle wasting. Serum insulin-like growth factor 1 (IGF-1) has been known as one of marker of malnutrition in end-stage renal disease (ESRD) patients. However, there were few studies on the relationship between IGF-1 and insulin resistance.
Methods:We measured serum IGF-1, prealbumin, albumin, plasma insulin and glucose concentration and body composition by dual energy X-ray absorptiometry in 20 non-diabetic ESRD patients who admitted to start dialysis. Homeostasis model assessment method of insulin resistance (HOMA-IR) was used for insulin resistance.
Results:Patients with IGF-1 <200 ng/mL (n=6) had significantly lower body weight (BW), body mass index (BMI), prealbumin (29.8±7.0 vs. 39.7±9.3 mg/ dL, p=0.022), Fat mass, pFat (percent fat mass), pFat-limb and HOMA-IR (1.44±0.59 vs. 3.47±2.22, p=0.04) than those with >200 ng/mL (n=14). IGF-1 showed positive correlations with BMI (r=0.45), prealbumin (r=0.6), Fat-limb (r=0.51), and HOMA-IR (r=0.67). On WHO classification for weight status, IGF-1 seemed to be higher when weight status was increased from underweight (151.8±41.6 ng/mL) to overweight (371.8±109.8 ng/mL) and these trends were similar to those of HOMA-IR. On multivariate analysis, IGF-1 was independent variable for affecting HOMA-IR.
Conclusion:Serum IGF-1 concentration seems to be associated with insulin resistance in ESRD patients and reflect body composition, especially fat mass. (Korean J Nephrol 2005;24(3):375-383)

국문 초록 (Abstract)

배 경:요독증에서 인슐린 저항성이 흔하며 이것이 요독증에서 영양실조로 인한 근육소실과 관련이 있음이 제시되었다. 말기신부전 환자에서 혈청 insulin-like growth factor-1 (IGF-1) 농도가 영양상태의 판정에 도움이 됨을 고려할 때, 혈청 IGF-1 농도가 낮은 영양실조 환자에서 인슐린 저항성이 높을 것으로 추정되나 이에 대해 아직 알려진 바 없어, 본 연구를 시행하였다.
방 법:말기신부전으로 투석을 시작하기 위해 입원하는 비당뇨병 환자 20예를 대상으로 공복시 혈액을 채취하여 IGF-1, prealbumin, 인슐린, 포도당, 알부민 농도를 측정하고 인슐린 저항성 평가는 homeostasis model assessment method of insulin resistance (HOMA-IR)로 계산하였으며, 체조성 평가는 dual energy X-ray absorptiometry를 측정하여 지방량 (Fat), 사지 지방량 (Fat-limb), 제지방량 (LBM), 사지 제지방량 (LBM-limb) 및 체중에 대한 지방량 (pFat), 사지지방량 (pFat-limb) 및 제지방량 (pLBM)의 백분율, 사지에서 지방량/제지방량의 비 (Fat/LBM ratio at limb)를 구하였다.
결 과:혈청 IGF-1 농도가 200 ng/mL 미만인 군에서 이상인 군에 비해 체중, BMI, prealbumin, HOMA-IR, Fat, Fat-limb, pFat, pFat-limb이 의의있게 낮았다. 혈청 IGF-1 농도는 BMI (r=0.45), BW/IBW ratio (r=0.49), prealbumin (r=0.6), Fat-limb (r=0.51), HOMA-IR (r=0.67)과 양의 상관관계를 보였다. WHO 체중분류시 저체중, 정상체중, 과체중, 비만에 따라 혈청 IGF-1 농도가 저체중에서 과체중으로 갈수록 증가하는 경향을 보였다. 선형회귀분석결과 혈청 IGF-1 농도만이 HOMA-IR에 영향을 미치는 독립적인 변수였다.
결 론:말기신부전 환자에서 혈청 IGF-1 농도가 영양상태 판정의 한 인자로서 체조성 중 체내 지방량과 관련이 있고, 인슐린 저항성과는 양의 상관관계가 있을 것으로 사료되나, 많은 수의 영양상태가 나쁜 환자를 대상으로 한 연구가 필요할 것으로 사료된다.

참고문헌 (Reference)

1 "and 3 in children with chronic renal failure relationship to height and glomerular filtration rate The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood" 80 : 2684-2691, 1995

2 "The role of the growth hormone-insulin-like growth factor axis in glucose homeostasis" 20 : 3-15, 2003

3 "The origin of the ideal body weight equations" 34 : 1066-1069, 2000

4 "The growth hormone and insulin-like growth factor axis:Its manipulation for the benefit of growth disorders in renal failure" 12 : 1297-1306, 2001

5 "The Asia-Pacific perspective : redefining obesity and its treatment" 2000

6 "Skeletal muscle fatty acid metabolism in association with insulin resistance,obesity,and weight loss" 277 : 1130-1141, 1999

7 "Serum-free insulin-like growth factor I correlates with clerarance in patients with chronic renal failure" 56 : 2076-2084, 1999

8 "Serum levels of leptin,insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in women with pre-eclampsia,and their relationship to insulin resistance" 18 : 341-348, 2004

9 "Serum insulin-like growth factor-1 levels and potential risk of type 2 diabetes" 60 (60): 131-135, 2003

10 "Roles of insulin-like growth factor-I and growth hormone in mediating insulin resistance in acromegaly" 5 : 181-183, 2002

11 "Relationship of leptin and insulin-like growth factor I to nutritional status in hemodialyzed children" 18 : 1255-1259, 2003

12 "Relation between insulin-like growth factor-I,body mass index,and clinical status in cystic fibrosis" 76 : 304-309, 1997

13 "Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment in normal range weight and moderately obese type 2 diabetic patients" 26 : 2426-2432, 2003

14 "Plasma concentration of IGF-1 is independently associated with insulin sensitivity in subjects with different degrees of glucose tolerance" 28 : 120-125, 2005

15 "Nutritional assessment of children on haemodialysis value of IGF-I" 13 : 1484-1488, 1998

16 "Nutrition in end-stage renal disease" 50 : 343-357, 1996

17 "Nonlinear relationship of insulin-like growth factor -I and IGF-I/IGF- binding protein-3 ratio with indices of adiposity and plasma insulin concentrations Cancer Causes Control 13" 13 : 509-516, 2002

18 "Metabolic acidosis stimulates muscle protein degradation by activating the ATP-dependent pathway involving ubiquitin and proteasomes" 93 : 2127-2133, 1994

19 "Medical consequences of obesity" 89 : 2583-2589, 2004

20 "Insulin-like growth factors and pancreas beta cells" 34 : 249-255, 2004

21 "Insulin-like growth factor-I as a reflection of body composition,nutrition,and puberty in sixth and seventh grade girls" 73 : 907-912, 1991

22 "Insulin-like growth factor-1 therapy in diabetes" 120 : 47-55, 1994

23 "Insulin-like growth factor I correlates with lean body mass in cystic fibrosis patients" 88 : 956-961, 2003

24 "Insulin resistance of uremia" 14 : 272-276, 1989

25 "Insulin resistance in patients with chronic kidney disease" 45 : 275-280, 2005

26 "Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease" 13 : 1894-1900, 2002

27 "Inhibition of insulin action by acidosis" 186 : 964-965, 1963

28 "Impact of an exercise program on arterial stiffness and insulin resistance in hemodialysis patients" 15 : 2713-2718, 2004

29 "IGF-I,a marker of undernutrition in hemodialysis patients" 52 : 39-44, 1990

30 "IGF-I as an early indicator of malnutrition in patients with end-stage renal disease" 67 : 73-81, 1994

31 "Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity:studies in subjects with various degrees of glucose tolerance and insulin sensitivity" 23 : 57-63, 2000

32 "HOMA index to assess insulin resistance in renal failure patients" 89 : 348-349, 2001

33 "Growth hormone, IGF-1 and its binding proteins (IGFBP- 1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis" 60 : 741-749, 2004

34 "Free fatty acids in obesity and type 2 diabetes:defining their role in the development of insulin resistance and beta- cell dysfunction" 32 (32): 14-23, 2002

35 "Factors predicting malnutrition in hemodialysis patients:a cross-sectional study" 53 : 773-782, 1998

36 "Evolution of insulin superfamily:cloning of a hybrid insulin/insulin-like growth factor cDNA from amphioxus" 87 : 9319-9323, 1990

37 "Cellular mechanisms causing loss of mus cle mass in kidney disease" 24 : 484-487, 2004

38 "Body mass index is the most important determining factor for the degree of insulin resistance in non-obese type 2 diab etic patients in Korea" 53 : 142-146, 2004