ABSTRACT.Purpose: To classify a cohort of 62 patients with vernal keratoconjunctivitis (VKC) in immunologic, functional, and epidemiological terms. Methods: A retrospective chart review was conducted to establish the patients' ethnic origin and to ascertain the results of standard in vitro and in vivo testing for atopic allergy. The latter data were compared with tear Phadiatop A , an allergy screening test, in 31 subjects. Further subgroup analyses included methacholine bronchial provocations, serum screening for chlamydial antibodies and epidemiological calculations of the observed prevalence of VKC in the Stockholm area in 1994. Results: Thirty-seven subjects (59.7%) were sensitised to common allergens. No additional allergic subjects were diagnosed with the tear Phadiatop A test. The serology for ocular chlamydial disease was negative. Only 6 out of 17 subjects displayed bronchial reactivity to methacholine of whom 4 had a history of asthma. VKC was clearly more common in individuals with an Asian and African origin. Conclusions: Sensitivity to allergens is a strong determinant for the disease but in a large proportion of the subjects this immunologic abnormality is absent. The varying prevalence of the condition in different ethnic groups indicates a genetic predisposing factor.

OBJECTIVE -We sought to test the hypothesis that start of insulin glargine with sustained nightly insulin action results in changes in circulating concentrations of IGF-I and IGF binding proteins (IGFBPs) in adolescents with type 1 diabetes-changes that may support improvement of A1C.RESEARCH DESIGN AND METHODS -Twelve pubertal adolescents with type 1 diabetes and initially on NPH insulin were studied during 12 weeks of intensified treatment with glargine.RESULTS -Subnormal IGF-I SD scores on NPH (Ϫ1.8 Ϯ 0.4) rapidly increased and remained 54 Ϯ 9% elevated (P Ͻ 0.001) after 12 weeks on glargine. A1C decreased from 8.3 Ϯ 0.6% to a nadir of 6.9 Ϯ 0.3% (P ϭ 0.002) at 6 weeks and correlated with changes in IGF-I (r ϭ Ϫ0.64, P Ͻ 0.05). The increase in IGF-I did not suppress the mean overnight growth hormone (GH) secretion at 6 weeks. The mean overnight IGFBP-1 levels decreased (P ϭ 0.035), supporting the hypothesis that the nightly hepatic insulin action was increased. Circulating IGF-I increased in the absence of changes in both GH secretion and GH receptor numbers (assessed by growth hormone binding protein), indicating that postreceptor mechanisms are involved. IGFBP-3 proteolysis was decreased.CONCLUSIONS -Increased hepatic insulin action after start of glargine was evident from a decrease in night time IGFBP-1 concentrations. This may improve GH postreceptor signaling, resulting in increased circulating IGF-I. We suggest that even in the absence of changes in GH, increased IGF-I and decreased IGFBP-1 support the improvement of metabolic control.

Human conditions of elevated interleukin-6 (IL-6) and transgenic mice overexpressing IL-6 have increased proteolytic degradation of insulin-like growth factor binding protein (IGFBP)-3. In addition, IL-6 alters the hepatic expression of insulin-like growth factor-I (IGF-I) and the IGFBPs in vitro. The aim of the present study was to investigate whether moderately elevated IL-6 levels have short-term effects on circulating IGF-I, IGFBP-1 and IGFBP-3 proteolysis in vivo. Healthy men received a 3-h IL-6 (n = 6) or saline (n = 6) infusion and blood samples were collected prior to and up to 8 h after the start of infusion. Free IGF-I, total IGF-I, IGFBP-1, insulin and cortisol were measured using immunoassays. Serum IGFBP-3 proteolysis was analyzed by Western immunoblot and by in vitro degradation of ¹²⁵I-IGFBP-3. We found that IL-6 concentrations reaching approximately 100 pg/ml significantly increased IGFBP-1 after the end of infusion in the absence of changes in insulin. In addition, plasma levels of cortisol were increased in response to IL-6 during and after infusion compared to saline. There was no effect of IL-6 on IGFBP-3 proteolysis, total IGF-I or free dissociable IGF-I. These data suggest that moderately elevated levels of IL-6 such as in the post-operative state or after exercise may contribute to increased levels of IGFBP-1. Although this study does not exclude that high levels and/or prolonged exposure to IL-6 may induce IGFBP-3 proteolysis in sepsis or chronic inflammatory disease, it suggests that IL-6 released from exercising skeletal muscle is not directly involved in proteolysis of circulating IGFBP-3.

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Background/Aims: Growth hormone insensitivity syndrome (GHIS) is caused by a defective growth hormone receptor (GHR) and is associated with insulin-like growth factor-I (IGF-I) deficiency, severely short stature and, from adolescence, fasting hyperglycemia and obesity. We studied the effects of treatment with IGF-I in either a 1:1 molar complex with IGFBP-3 (IGF-I/BP-3-Tx) or with IGF-I alone (IGF-I-Tx) on metabolism and linear growth. Methods: Two brothers, compound heterozygous for a GHR gene defect, were studied. After 8 months without treatment, we examined the short- and long-term effects of IGF-I/BP-3-Tx and, subsequently, IGF-I-Tx on 12-hour overnight levels of IGF-I, GH, insulin, IGFBP-1, insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by dual-energy X-ray absorptiometry and linear growth. Results: Mean overnight levels of insulin decreased and IGFBP-1, a measure of hepatic insulin sensitivity, increased on both regimens, but was more pronounced on IGF-I-Tx. Insulin sensitivity by clamp showed no consistent changes. Lean body mass increased and abdominal fat mass decreased in both subjects on IGF-I-Tx. However, the changes were inconsistent during IGF-I/BP-3-Tx. Height velocity was low without treatment, increased slightly on IGF-I/BP-3-Tx and doubled on IGF-I-Tx. Conclusion: Both modalities of IGF-I improved determinants of hepatic insulin sensitivity, body composition and linear growth rate; however, IGF-I alone seemed to be more efficient.