The GH-IGF-I axis is disturbed in patients with type 1 diabetes. Our aim was to investigate whether abnormalities are found in patients in very good glycemic control and, if so, to estimate the role of residual beta-cell function. Patients with hemoglobin A1c (HbA1c) less than 6% (reference range, 3.6-5.4%) were selected for the study. Twenty-two men and 24 women, aged 41.3 +/- 13.8 yr (mean +/- SD), with a diabetes duration of 17.8 +/- 14.6 yr participated. Healthy controls (15 women and nine men), aged 41.3 +/- 13.0 yr, were also studied. Overnight fasting serum samples were analyzed for HbA1c, C peptide, free and total IGFs, IGF-binding proteins (IGFBPs), GH-binding protein, and IGFBP-3 proteolysis. HbA1c was 5.6 +/- 0.5% in patients and 4.4 +/- 0.3% in controls. Total IGF-I was 148 +/- 7 microg/liter in patients and 178 +/- 9 microg/liter in controls (P < 0.001). Free IGF-I, total IGF-II, IGFBP-3, and GH-binding protein were lower, whereas IGFBP-1, IGFBP-1-bound IGF-I, and IGFBP-2 were elevated compared with control values. Patients with detectable C peptide (> or =100 pmol/liter) had higher levels of total IGF-I, free IGF-I, and total IGF-II and lower levels of IGFBP-1 and IGFBP-2 than those with an undetectable C peptide level despite having identical average HbA1c. IGFBP-3 proteolysis did not differ between patients and controls. Despite very good glycemic control, patients with type 1 diabetes and no endogenous insulin production have low free and total IGF-I. Residual beta-cell function, therefore, seems more important for the disturbances in the IGF system than good metabolic control per se, suggesting that portal insulin delivery is needed to normalize the IGF system.

No abstract

The increase in circulating adiponectin concentrations in patients with type 1 diabetes appears to be strongly associated with long diabetes duration, irrespective of the metabolic control. Among other factors, a putative role for residual beta-cell function in the regulation of circulating adiponectin levels can be considered but we did not find sufficient evidence for this in the present study.

Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

OBJECTIVE -To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes.RESEARCH DESIGN AND METHODS -A total of 14 patients with type 1 diabetes, aged 35 Ϯ 13 years (mean Ϯ SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs.RESULTS -The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 Ϯ 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 Ϯ 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 Ϯ 3 min and aspart at 55 Ϯ 6 min after injection (P ϭ 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs.CONCLUSIONS -The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediateacting insulin given at bedtime. Diabetes Care 25:1049 -1054, 2002T wo rapid-acting insulin analogs are now available for treatment of patients with diabetes. Insulin lispro has an inversion of the amino acids proline and lysine at positions 28 and 29 in the B-chain of the insulin molecule (1), and insulin aspart has a single amino acid substitution in position 28 of the B-chain (2). Lispro has a slightly increased affinity for the IGF-I receptor, but regarding metabolic and mitogenic effects, lispro and aspart are similar to human insulin (3). Both analogs form less stable hexamers than human regular insulin and, owing to this, have a faster absorption, more rapid action, and shorter duration after subcutaneous injection (1,3-13). The short duration of these insulin analogs affects the need for basal insulin substitution.We have recently reported a comparison of the morning insulin profiles of insulin aspart and lispro after subcutaneous injection in patients with type 1 diabetes treated with preprandial insulin injections during the day and human intermediate-acting insulin at bedtime (14). The insulin profiles of these anal...

The in vitro IGF-I bioactivity was higher in patients treated with CIPII compared with CSII supporting the theory that the route of insulin administration is of importance for the activity of the IGF system. Intraperitoneal insulin administration may therefore be beneficial by correcting the alterations of the IGF system in T1D.

The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

No abstract