S. Werner, K. Brismar, P. Eneroth and L. Wetterberg
S Soderberg, B Ahren, M Eliasson, B Dinesen, K Brismar and T Olsson
OBJECTIVE: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. METHODS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin. RESULTS: Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels. CONCLUSIONS: Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.
AM Bennet, K Brismar, J Hallqvist, C Reuterwall and U De Faire
OBJECTIVES: To evaluate the relationship between levels of serum insulin, the homeostasis model assessment (HOMA) and IGF-binding protein-1 (IGFBP-1) as factors related to myocardial infarction (MI) risk, and their interaction with lifestyle-related risk factors. DESIGN: The Stockholm epidemiology programme (SHEEP), a case-control study, consisting of 749 first-time MI cases (510 men, 239 women) and 1101 healthy controls (705 men, 396 women) was used. METHODS: The risk of developing MI was assessed by calculating odds ratios (OR) and synergistic interactions (SI) between serum insulin, IGFBP-1, HOMA and other variables related to MI risk (including smoking) in men and women. RESULTS: Subjects with elevated levels of insulin and HOMA (>75th percentile) had increased MI risks when compared with individuals with low levels. ORs for elevated insulin and HOMA (adjusted for age and residential area) for men: insulin 1.6 (95% confidence interval (CI) 1.3-2.1) and HOMA 1.5 (95% CI 1.1-1.9) and for women: insulin 2.1 (95% CI 1.5-2.9) and HOMA 1.9 (95% CI 1.3-2.8). Women with low levels of IGFBP-1 (<10th percentile) showed a tendency towards elevated MI risk even if this was not statistically significant (OR 1.5 (95% CI 0.9-2.6)). Smokers with high levels of serum insulin had greatly increased MI risk (OR for men: 4.7 (95% CI 3.0-7.2) and OR for women: 8.1 (95% CI 4.5-14.8)). SI scores based upon these interactions were statistically significant. CONCLUSIONS: These results might have preventive cardiovascular implications as they clearly suggest that subjects with insulin resistance are particularly susceptible to the hazards of smoking.
S B Catrina, R Rotarus, I R Botusan, M Coculescu and K Brismar
IGF binding protein-1 (IGFBP-1) is essential for IGF-I bioavailability. High levels of IGFBP-1 are encountered in critically ill patients and are a good predictor marker in acute myocardial infarction. The mechanisms responsible for the elevated IGFBP-1 levels in these conditions are still unclear. Interestingly, high levels of vasopressin have been reported in the above-mentioned conditions.
To study the effect of vasopressin on IGFBP-1 in humans.
Placebo-controlled cross-over study in patients with central diabetes insipidus (CDI) in whom potential interference from endogenous vasopressin secretion is minimized. After a 3-day desmopressin washout period, each patient received i.v. saline on day 1 and desmopressin (3 μg) on day 2. Blood samples were taken after administration, every 2 h during the whole night, starting at 2000 h.
Patients and setting
Fourteen inpatients with CDI in an endocrinology department of a university hospital.
Serum IGFBP-1 increased within 4 h after 1-desamino-8-d-arginine vasopressin (DDAVP) by 375±73%, compared with a spontaneous fasting increase by 252±46% following placebo administration (P<0.05). No changes were registered in the levels of either classically regulators of IGFBP-1 (insulin, glucagon, and cortisol) or of IGF-I and glucose. The decrease in plasma osmolarity induced by DDAVP did not precede the increase in IGFBP-1.
DDAVP increases serum levels of IGFBP-1. Further investigation is essential to unravel the clinical potential of this interaction in conditions associated with high IGFBP-1 levels.