Basic and clinical science posters: New insulins, technology, therapies and treatment

Continuous glucose monitoring profiles in people living with HIV without diabetes

H Daultrey^1,3, T Levett¹, J Wright², K Davies¹, N Oliver⁴, AJ Chakera^1,3

¹Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK, ²Department of Medical Education, Brighton and Sussex Medical School, Brighton, UK, ³Department of Diabetes and Endocrinology, Brighton and Sussex University Hospital Trust, Brighton, UK, ⁴Department of Metabolism, Digestion and Reproduction, Imperial College Healthcare NHS Trust, London, UK

Aims People living with HIV (PLHIV) have a higher risk of developing type 2 diabetes. At present, there is no agreed screening test for diabetes as studies have found HbA1c to be falsely low in PLHIV. The British HIV Association advises an annual HbA1c in those aged 40 years and over, while the American Diabetes Association and European AIDS society advise a fasting glucose. The aim here was to assess the glucose profile in PLHIV without diabetes.

Methods Each participant wore a Dexcom G6 continuous glucose monitor (CGM) for up to 10 days. An oral glucose tolerance test (OGTT) was performed to confirm the absence of diabetes.

Results A total of 17 participants mean age 51.2 years (±8.5), 16 males and 1 female were included in the analysis. Mean 0min glucose on OGTT was 5.6mmol/l. Median number of CGM readings was 2,850 (interquartile range, 2,791–2,856). The mean average glucose was 6.2mmol/l (±0.5). Median % time between 3.9mmol/l and 7.8mmol/l was 94% (interquartile range, 90–95). Mean within individual coefficient of variation was 15.64% (±2.4).

Conclusions This is the first study using CGM to assess a normal reference sensor glucose range in PLHIV. The values presented here are similar to recent studies assessing sensor glucose profiles in individuals without diabetes. These glucose ranges can help inform future studies exploring glucose thresholds in screening for diabetes in PLHIV and enable a comparison to glucose values in individuals without diabetes or HIV.

Evaluation of the effects of the selective serotonin reuptake inhibitor paroxetine on mouse beta cell function

K Toczyska, B Liu, SJ Persaud

Diabetes, King's College London, London, UK

Aims Selective serotonin reuptake inhibitors (SSRIs), a widely used type of antidepressant, can improve glycaemic control in depressed diabetic patients by unknown mechanisms. Therefore, this study aimed to investigate the direct effects of paroxetine (Paxil), a commonly prescribed SSRI, on beta cell function.

Methods Beta cell proliferation (BrdU incorporation), ATP generation (CellTiter-Glo), viability (Trypan blue exclusion) and apoptosis (Caspase-Glo caspase3/7 activities) were quantified after 48 h exposure to paroxetine. The acute effects of paroxetine on insulin secretion from mouse islets were determined by perifusion and radioimmunoassay.

Results Paroxetine significantly increased MIN6 beta cell proliferation (OD 450nm: control: 0.102 ± 0.004; 0.01μM: 0.142 ± 0.013; 0.1μM: 0.147 ± 0.015, n=8, p < 0.05) and ATP generation (luminescence units, control: 3,798,491 ± 365,772; 0.01μM: 4,767,906 ± 1,802,099; 0.1μM: 5,749,196 ± 93,685, n=7, p < 0.01), without having any effect on Trypan blue dye uptake by beta cells. Paroxetine did not affect basal mouse islet apoptosis (luminescence units, control: 39,206 ± 6,694; 0.01μM: 39,969 ± 6,691; 0.1μM: 38,408 ± 8,062, n=8, p > 0.2), but at 0.01μM it decreased cytokine-induced apoptosis by 26.3%. Paroxetine also increased insulin secretion from perifused mouse islets (AUC, control: 406.8 ± 44.0; 0.1μM paroxetine: 648.7 ± 65.9, n=4, p < 0.05).

Conclusions These data indicate that paroxetine, at low therapeutic concentrations, induces beta cell proliferation, increases ATP generation, protects against cytokine-induced apoptosis and potentiates glucose-induced insulin secretion. It is therefore possible that this SSRI improves glycaemic control in vivo, at least in part, through direct effects on beta cells.

Acknowledgement Diabetes Research Group