ALTERED RELATION BETWEEN CIRCULATING LEVELS OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 AND INSULIN IN GROWTH HORMONE-DEFICIENT PATIENTS AND INSULIN-DEPENDENT DIABETIC-PATIENTS COMPARED TO THAT IN HEALTHY-SUBJECTS

被引:110
作者
HILDING, A
BRISMAR, K
DEGERBLAD, M
THOREN, M
HALL, K
机构
关键词
D O I
10.1210/jc.80.9.2646
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To investigate whether previously reported increased levels of insulin-like growth factor-binding protein-1 (TGFBP-1) in GH-deficient patients only reflect decreased levels of insulin or are elevated in relation to insulin, diurnal profiles of IGFBP-1 and insulin were determined in plasma from patients with GH levels below 0.2 mu g/L throughout 24 h (n = 23) and compared to profiles from patients with insulin-dependent diabetes mellitus (IDDM; n = 9) and healthy subjects (n = 12). Samples were drawn using a continuous withdrawal technique at 20-min intervals. Levels of IGF-I were determined in one morning sample. As in healthy subjects, serum IGFBP-1 displayed a diurnal variation in GH-deficient as web as in IDDM patients, with lowest levels in the afternoon and evening and a rise with maximum levels during the night and morning. Fasting and 24-h mean levels of IGFBP-1 were significantly higher in GH-deficient patients [61 +/- 12 (P < 0.01) and 39 +/- 6 mu g/L (P < 0.01), respectively] and IDDM patients [72 +/- 18 (P < 0.01) and 45 +/- 9 mu g/L (P < 0.01), respectively] compared to those in healthy subjects (27 +/- 4 and 18 +/- 2 mu g/L, respectively). Fasting levels of IGFBP-1 correlated to 24-h mean values of IGFBP-1 in all groups separately and in the combined group (r = 0.931; P < 0.001). An inverse relationship was found between IGFBP-1 and insulin in GH-deficient patients, both between 24-h mean values (r = -0.756; P < 0.001) and between fasting values (r = -0.721; P < 0.001). Corresponding values for healthy subjects were r = -0.548; P = 0.065 and r = -0.712; P < 0.41, respectively, whereas in IDDM patients the relationship was nonsignificant. Moreover, in GH-deficient patients, the diurnal mean levels of IGFBP-1 were inversely correlated to IGF-I (r = -0.477; P < 0.05) and body mass index (r = -0.450; P < 0.05). When insulin was taken into account, a tendency for a negative correlation between IGFBP-1 and IGF-I (P = 0.054) remained, whereas the relationship to body mass index disappeared. However, IGFBP-1 levels were elevated in relation to insulin levels in GH-deficient patients compared to healthy subjects (F = 48.7; P < 0.001 and F = 32.5; P < 0.001, diurnal mean values and fasting values, respectively). The majority of the IDDM patients had values in the same range as the GH-deficient patients. In conclusion, diurnal mean levels as well. as fasting levels of IGFBP-1 were elevated not only in absolute values but also in relation to insulin levels in GH-deficient patients and IDDM patients compared to values in healthy subjects. Although unexplained, this elevation may influence the bioavailability of IGF in these patients.
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页码:2646 / 2652
页数:7
相关论文
共 42 条
[1]   COMPARISON OF ACID ETHANOL EXTRACTION AND ACID GEL-FILTRATION PRIOR TO IGF-I AND IGF-II RADIOIMMUNOASSAYS - IMPROVEMENT OF DETERMINATIONS IN ACID ETHANOL EXTRACTS BY THE USE OF TRUNCATED IGF-I AS RADIOLIGAND [J].
BANG, P ;
ERIKSSON, U ;
SARA, V ;
WIVALL, IL ;
HALL, K .
ACTA ENDOCRINOLOGICA, 1991, 124 (06) :620-629
[2]  
BANG P, 1992, INSULIN LIKE GROWTH, P151
[3]   INSULIN DIFFERENTIALLY ALTERS TRANSCAPILLARY MOVEMENT OF INTRAVASCULAR IGFBP-1, IGFBP-2 AND ENDOTHELIAL-CELL IGF-BINDING PROTEINS IN THE RAT-HEART [J].
BAR, RS ;
BOES, M ;
CLEMMONS, DR ;
BUSBY, WH ;
SANDRA, A ;
DAKE, BL ;
BOOTH, BA .
ENDOCRINOLOGY, 1990, 127 (01) :497-499
[4]   ABNORMAL REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS IN ADOLESCENTS WITH INSULIN-DEPENDENT DIABETES [J].
BATCH, JA ;
BAXTER, RC ;
WERTHER, G .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1991, 73 (05) :964-968
[5]  
BAXTER RC, 1991, ACTA PAEDIATR SCAND, P107
[6]   RESPONSES OF INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 (IGFBP-1) AND THE IGFBP-3 COMPLEX TO ADMINISTRATION OF INSULIN-LIKE GROWTH FACTOR-I [J].
BAXTER, RC ;
HIZUKA, N ;
TAKANO, K ;
HOLMAN, SR ;
ASAKAWA, K .
ACTA ENDOCRINOLOGICA, 1993, 128 (02) :101-108
[7]   DIURNAL RHYTHM OF GROWTH HORMONE-INDEPENDENT BINDING-PROTEIN FOR INSULIN-LIKE GROWTH-FACTORS IN HUMAN-PLASMA [J].
BAXTER, RC ;
COWELL, CT .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1987, 65 (03) :432-440
[8]   THE INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-1 IN LOW AND HIGH INSULIN RESPONDERS BEFORE AND DURING DEXAMETHASONE TREATMENT [J].
BRISMAR, K ;
GRILL, V ;
EFENDIC, S ;
HALL, K .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1991, 40 (07) :728-732
[9]   EFFECT OF INSULIN ON THE HEPATIC PRODUCTION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 (IGFBP-1), IGFBP-3, AND IGF-I IN INSULIN-DEPENDENT DIABETES [J].
BRISMAR, K ;
FERNQVISTFORBES, E ;
WAHREN, J ;
HALL, K .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 79 (03) :872-878
[10]   INSULIN REGULATES THE 35-KDA IGF BINDING-PROTEIN IN PATIENTS WITH DIABETES-MELLITUS [J].
BRISMAR, K ;
GUTNIAK, M ;
POVOA, G ;
WERNER, S ;
HALL, K .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 1988, 11 (08) :599-602