Insulin antibodies are prevalent in adults with type 1 diabetes referred for islet cell transplantation and are modified by islet transplantation and immunosuppression: an Australian experience.

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody-negative post islet cell transplantation.

Adapting Protocols or Models for Use in Insulin-Requiring Diabetes and Islet Transplant Recipients.

The authors' perspective is described regarding modifications made in their clinic to glucose challenge protocols and mathematical models in order to estimate insulin secretion, insulin sensitivity and glucose effectiveness in patients living with Insulin-Requiring Diabetes and patients who received Pancreatic Islet Transplants to treat Type I diabetes (T1D) with Impaired Awareness of Hypoglycemia. The evolutions are described of protocols and models for use in T1D, and Insulin-Requiring Type 2 Diabetes (T2D) that were the basis for studies in the Islet Recipients. In each group, the need for modifications, and how the protocols and models were adapted is discussed. How the ongoing application of the adaptations is clarifying the Islet pathophysiology in the Islet Transplant Recipients is outlined.

Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of exercise, vs rest, on circulating insulin and glucose, following pre-exercise insulin pump basal rate reduction. METHODS: This was an open-label, two-stage randomised crossover study of 14 adults (seven women, seven men) with type 1 diabetes established on insulin pump therapy. In each stage, participants fasted and insulin delivery was halved following a single insulin basal rate overnight. Exercise (30 min moderate-intensity stationary bicycle exercise, starting 60 min post-basal reduction) and rest stages were undertaken in random order at a university hospital. Randomisation was computer-generated, and allocation concealed via sequentially numbered sealed opaque envelopes. Venous blood was collected at 15 min intervals from 60 min pre- until 210 min post-basal rate reduction. Changes in plasma free insulin (the primary outcome), and changes in plasma glucose, with exercise were compared with changes when resting. Outcomes were assessed blinded to group assignment. RESULTS: Following basal rate reduction when rested, mean (± SE) free insulin decreased by 4.9 ± 2.9%, 16.2 ± 2.6% and 18.6 ± 3.2% at 1, 2 and 3 h, respectively (p < 0.05 after 75 min). With exercise, relative to rest, mean free insulin increased by 6 ± 2 pmol/l after 15 min and 5 ± 2 pmol/l after 30 min (p < 0.001), then declined post-exercise (p < 0.001). Three participants (mean baseline glucose 5.0 ± 0.1 mmol/l) required glucose supplementation to prevent or treat exercise-related hypoglycaemia. In the other 11 participants (mean baseline glucose 8.4 ± 0.5 mmol/l), glucose increased by 0.8 ± 0.3 mmol/l with exercise (p = 0.028). CONCLUSIONS/INTERPRETATION: Halving the basal insulin rate 1 h prior to exercise did not significantly reduce circulating free insulin by exercise commencement. Exercise itself transiently increased insulin levels. In participants with low-normal glucose pre-exercise, hypoglycaemia was not prevented by insulin basal rate reduction alone. Greater insulin basal rate reduction and supplemental carbohydrate may be required to prevent exercise-induced hypoglycaemia. TRIAL REGISTRATION: ANZCTR.org.au ACTRN12613000581763 FUNDING: Australian Diabetes Society, Hugh DT Williamson Foundation, Lynne Quayle Charitable Trust Fund.

The minimal model of glucose disposal in the analysis of glucose effectiveness: importance of early insulin data.

BACKGROUND: Glucose effectiveness (S(g)) is an important component in glucose tolerance. Values of S(g) using "open loop" glucose kinetic computer programs are usually higher compared to closed loop method (CLM) programs that incorporate insulin secretion modeling. We aimed to test whether these differences are caused by (1) inclusion of insulin secretion modeling or (2) the method of representing plasma insulin values in the first few minutes of the frequently sampled intravenous glucose tolerance test (FSIGT). METHODS: FSIGTs without insulin supplementation were performed in six healthy volunteers, and the Bergman minimal model was fitted to the data using the simulation and modeling program SAAM. RESULTS: The CLM, which represents the insulin data in the first few minutes by a best-fit curve extrapolated to the y-axis, yielded a significantly lower S(g) than the approach similar to the computer program MINMOD, where the first few minutes of insulin data are represented by a line joining the basal to the peak values (1.55 +/- 0.28 vs. 1.97 +/- 0.27 [SE] x 10(-2)/min, P < 0.05). This second analysis was then repeated while forcing the program to represent the insulin data after the insulin peak in the same way as in the CLM, obtaining an almost identical result for S(g) (1.99 +/- 0.29). Insulin sensitivity was not significantly affected. CONCLUSIONS: The higher S(g) estimates are caused by the method of representing the first few minutes of insulin data rather than by the incorporation of insulin secretion modeling. It is, therefore, important to know how the early insulin data are represented when comparing results from different computer modeling programs.