We have determined the phosphorylation pattern of circulating insulin-like growth factor-binding protein-1 (IGFBP-1) in normal subjects and assessed how this changes in pregnancy. Two RIAs employing different monoclonal antibodies (MAbs 6303 or 6305) were used to measure IGFBP-1. In normal subjects, RIA 6303 measured 11-fold higher levels than RIA 6305 (72.8 vs. 6.6 micrograms/L; P < 0.008). However, in amniotic fluid (AF), the two assays gave similar results. Immunoprecipitation of plasma and AF with MAb 6303 and 6305 before nonsodium dodecyl sulfate-electrophoresis and Western ligand blotting revealed different IGFBP-1 isoforms and differential antibody recognition as the cause of this discrepancy. In AF, both MAbs precipitated nonphosphorylated and phosphorylated isoforms, whereas in plasma, only a single highly phosphorylated species, not seen in AF, was observed. This form of IGFBP-1 was precipitated by MAb 6303 only. During pregnancy, the phosphorylation state of IGFBP-1 in the maternal circulation was altered, as nonphosphorylated IGFBP-1 and three lesser phosphoforms were also observed. The appearance of these other variants resulted in a significant increase in IGFBP-1 measured by RIA 6305 (37, 51, and 83 micrograms/L in first, second, and third trimesters, respectively; P < 0.0005 vs. controls). The changes in IGFBP-1 phosphorylation induced by pregnancy may influence the modulatory effects of IGFBP-1 on IGF bioavailability and, hence, fetal growth.
OBJECTIVE -To determine whether Pro-Active Call Center Treatment Support (PACCTS), using trained nonmedical telephonists supported by specially designed software and a diabetes nurse, can effectively improve glycemic control in type 2 diabetes. RESEARCH DESIGN AND METHODS -A randomized controlled implementationtrial of 1-year duration was conducted in Salford, U.K. The trial comprised 591 randomly selected individuals with type 2 diabetes. By random allocation, 197 individuals were assigned to the usual care (control) group and 394 to the PACCTS (intervention) group. Lifestyle advice and drug treatment in both groups followed local guidelines. PACCTS patients were telephoned according to a protocol with the frequency of calls proportional to the last HbA 1c level. The primary outcome was absolute reduction in HbA 1c , and the secondary outcome was the proportion of patients reducing HbA 1c by at least 1%.RESULTS -A total of 332 patients (84%) in the PACCTS group and 176 patients (89%) in the control group completed the study. Final HbA 1c values were available in 374 patients (95%) in the PACCTS group and 180 patients (92%) in the usual care group. Compared with usual care, HbA 1c improved by 0.31% (95% CI 0.11-0.52, P ϭ 0.003) overall in the PACCTS patients. For patients with baseline HbA 1c Ͼ7%, the improvement increased to 0.49% (0.21-0.77, P Ͻ 0.001), whereas in patients with baseline HbA 1c Ͻ7% there was no change. The difference in the proportions of patients achieving a Ն1% reduction in HbA 1c significantly favored the PACCTS intervention: 10% (4 -16, P Ͻ 0.001) overall and 15% (7-24, P Ͻ 0.001) for patients with baseline HbA 1c Ͼ7%.CONCLUSIONS -In an urban Caucasian trial population with blood glucose HbA 1c Ͼ7%, PACCTS facilitated significant improvement in glycemic control. Further research should extend the validity of findings to rural communities and other ethnic groups, as well as to smoking and lipid and blood pressure control. Diabetes Care 28:278 -282, 2005A worldwide epidemic of type 2 diabetes is threatening to overwhelm the capacity of health care service providers. There is good evidence that tight blood glucose, blood pressure, and lipid control can markedly reduce the adverse impact of type 2 diabetes and deliver substantial health benefits (1-4). Reviews of implementation strategies to achieve these treatment targets indicate that a multifaceted approach is most successful (5). Although a stepped-care program based on guidelines, education of primary care professionals, and support from secondary and intermediate care specialists has achieved appreciable improvements in blood pressure and lipid control in the Salford area, it has failed, thus far, to improve blood glucose control (6).Chronic disease management programs seem to be most successful when they support treatment adherence and self-efficacy (7-10). Attaining type 2 diabetes treatment targets requires appreciable pharmacologic intervention (1,3,4). However, good blood glucose control may be particularly difficult because of the s...
OBJECTIVE:This study compared lean children at high risk (HR) and low risk (LR) of obesity and obese children (OB) to assess the relationship between their energy (EI) and fat intake and adiposity. DESIGN: Cross-sectional study of energy and fat intake in children, using 7-day weighed intakes validated by doubly labelled water (DLW) energy expenditure. SUBJECTS: A total of 114 pre-pubertal children, 50 HR (mean AE s.d., 6.7 AE 0.6 y, 25.7 AE 4.8 kg, 21.3 AE 6.6% body fat), 50 LR (mean AE s.d., 6.6 AE 0.8 y, 23.6 AE 3.7 kg, 18.9 AE 5.7% body fat) and 14 OB (mean AE s.d., 6.8 AE 1.0 y, 37.7 AE 5.3 kg, 34.8 AE 5.6% body fat). MEASUREMENTS: Body fatness was measured using deuterium dilution, total energy expenditure (TEE) by DLW and dietary intake using 7-day weighed records. RESULTS: EI was 98% of TEE in LR children, 95% in HR children and 86% in OB children. Although EI was similar in each group (LR, 7.03 AE 1.26 MJ=day; HR, 7.30 AE 1.46 MJ=day; OB, 7.55 AE 1.67 MJ=day), obese children consumed more fat in absolute (g) and relative (percentage energy) terms than LR children (LR, 68 AE 13 g, 36.4 AE 4.2%; OB, 80 AE 25 g, 39.5 AE 4.6%; P < 0.05). There was a significant linear trend towards increasing fat intake (percentage energy) with increasing risk of obesity (P < 0.05). While HR children were heavier and fatter than LR children (P < 0.05), their EI and fat intake were not significantly greater (HR, 73 AE 17 g, 37.3 AE 4.4%). Dietary fat intake (percentage energy) was weakly but significantly related to body fatness (r 2 ¼ 0.05, P ¼ 0.02) by step-wise regression. Since energy from fat was the only macronutrient that was a significant predictor of body fatness, results were therefore analysed using quartiles of fat intake (percentage energy) as cut-offs. When grouped in this way children with the lowest intakes were leaner than those with the highest intakes (19.5 AE 7.5 vs 24.9 AE 9.4% body fatness; P < 0.05). There was a significant trend for increasing fatness as fat intake increased (P < 0.05). CONCLUSION: Fat intake is related to body fatness in childhood.
Type 2 diabetes is associated with biochemical evidence of low-grade inflammation, and experimental studies have suggested that both insulin and glucose affect inflammatory responses. To determine the effect of in vivo changes in glucose availability and plasma insulin concentrations in humans, we administered 20 U/kg Escherichia coli lipopolysaccharide (LPS) or saline (control) to 14 subjects during a euglycemic hyperinsulinemic clamp (n = 6) or an infusion of sterile saline (n = 8). Parallel in vitro studies on human whole blood were undertaken to determine whether there was a direct effect of glucose, insulin, and leptin on proinflammatory cytokine production. Infusion of glucose and insulin significantly amplified and/or prolonged the cardiovascular, plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and counterregulatory hormone responses to LPS, whereas the effects on fever, plasma norepinephrine concentrations, and oxygen consumption were unaffected. In vitro studies showed no modulation of LPS-stimulated IL-6 or TNF-alpha production by glucose, insulin, or leptin at physiologically relevant concentrations. Hyperinsulinemia indirectly enhances key components of the systemic inflammatory and stress responses in this human model of infection.
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