Aileen King, Amazon Austin, Manasi Nandi, James Bowe
Poster 403, European Association for the Study of Diabetes Annual Meeting, Munich, Germany, September 2016
Background and aims
Rodent models of diabetes are often used in pre-clinical islet transplantation studies. In most studies, blood glucose is measured daily and often the time-point is not reported. The aim of this study was to measure blood glucose continuously in a rat model of islet transplantation to assess blood glucose excursions in the night when the rats are active and are feeding.
Materials and methods
Three male Lewis rats were implanted intraperitoneally with continuous glucose telemetry devices with blood glucose measured in the descending aorta in accordance with manufacturer’s instructions. Following complete recovery from surgery blood glucose monitoring started, with recordings taken every 10 seconds. After five days of baseline measurements the rats were injected with 65mg/kg streptozotocin (STZ) to induce diabetes. Five days later, 2000-3000 Lewis rat islets were implanted under the kidney capsule and animals were maintained for a further 14 days. Each rat generated 207355 individual blood glucose measurements, and as such for purposes of statistical analysis mean blood glucose concentrations for each day (7am-7pm) and night cycle (7pm-7am) were calculated.
In the non-diabetic state, the mean difference in blood glucose concentrations between day and night was minimal (day: 6.9±0.6 mmol/l vs night: 7.2±0.7 mmol/l, p=0.764, t-test. Mean day-night difference: 0.42±0.1mM). After STZ injection, rats became hyperglycaemic (>20 mmol/l) within 13-22h and day to night blood glucose excursions increased (day: 24.7±2.8 mmol/l vs night: 33.0±4.8 mmol/l; mean excursion: 8.3±1.2 mmol/l, p<0.0001 vs pre-STZ, t-test. Data within 5 hours of an insulin injection were excluded). After transplantation, two rats showed improved blood glucose concentrations but day vs night glucose excursions were still significant (day time mean of 10.5 mmol/l and 11.0 mmol/l vs night mean of 14.6 mmol/l and 14.8 mmol/l respectively, p<0.0001 vs respective mean day glucose concentrations, t-test. Mean excursion: 3.8 mmol/l and 4.2 mmol/l respectively). The graph below shows the trace of one of these rats. The third rat remained hyperglycaemic and showed substantial day vs night glucose excursions, similar to that seen after STZ-treatment (mean day blood glucose: 25.2 mmol/l vs night blood glucose 38.1 mmol/l, p<0.0001, t-test. Mean excursion 12.0 mmol/l).
During basal conditions, differences in mean blood glucose concentrations between the night and day are minimal in Lewis rats. In an islet transplantation model, blood glucose excursions during the night are significantly pronounced after STZ administration. Despite the improvement in glycaemic control following transplantation, the significant night time glucose excursions persist. This may lead to an over-estimation of the efficacy of an intervention, as most researchers measure blood glucose during the day. The data also highlights the importance of consistent glucose monitoring time-points both within a study and when comparing studies.