Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Jones A.; *Wilkes V.; *Singh P.; *Moulik P.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2025. Glasgow . 42(Supplement 1) (no pagination), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background and Aims: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder causing hypothalamic-pituitary dysfunction, hyperphagia resulting in weight gain, short stature and mild cognitive impairment. We present two cases of PWS and role of GLP-1 analogues. Material(s) and Method(s): Retrospective review of two cases. Case 1: A 31-year-old female with PWS at the age of 7 years, learning difficulty, type 2 diabetes at 28 years, treated with metformin, linagliptin. She continued to gain weight despite calorie restriction, commenced on Semaglutide. Case 2: A 25-year-old female with PWS at age of 4 years, type 2 diabetes at 18 years, treated with metformin. Due to suboptimal glycaemic control, empagliflozin and liraglutide started. Result(s): Case 1: At initiation of Semaglutide, weight 93 kg, BMI 43.6 kg/m2, glycated haemoglobin (HbA1c) 106 mmol/mol (ref: 20-41). Twenty months on GLP-1 analogue, weight reduced by 21 kg, and HbA1c was 38 mmol/mol with reduction in appetite and positive change in eating habits. Case 2: At initiation of liraglutide, weight 91 kg, BMI 35 kg/ m2, HbA1c 72 mmol/mol. Six months later appetite, food cravings reduced; HbA1c 65 mmol/mol, weight stable. Conclusion(s): PWS is associated with high ghrelin, low insulin levels, visceral adiposity resulting in hyperphagia causing altered glucose metabolism predisposing to cardiovascular complications. Mainstay of treatment is behavioural modifications posing stress to patient and caregiver. There is no approved pharmacological management for this aspect of PWS. Systematic review on use of GLP-1 analogues with PWS showed improved glycaemic control, reduced appetite, without any significant side effects. Our patients showed improvements with metabolic control of type 2 diabetes, reducing food cravings. Further studies are required to explore exact mechanism of ghrelin suppression by GLP-1 analogues in PWS.

DOI: 10.1111/dme.15498

Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Jones A.; *Wilkes V.; *Singh P.; *Moulik P.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2025. Glasgow . 42(Supplement 1) (no pagination), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background: Hypobaric hypoxia and low temperatures at high altitude can cause hyperglycaemia or hypoglycaemia in people with diabetes, inaccuracy with capillary blood glucose monitoring and insulin freezing. At altitude, even mild neuroglycopaenia could have serious effects. Case: A 65-year-old lady with post-pancreatitis diabetes, treated with only basal insulin Glargine travelled on a skiing holiday 3000 feet above sea level. Continuous glucose monitoring (CGM) data 2 weeks before, 1 week during and 2 weeks after travel and ambulatory glucose profile (AGP) data were analysed. Mean glucose readings increased from 9.7 to 10.7 mmol/L with activity, level 2 time above range and level 1 time above range increased from 9% and 30% to 15% and 37%, respectively, time in range reduced from 61% to 48% post-high altitude travel. There was pronounced dawn phenomenon and postprandial glucose rise particularly after breakfast during high altitude travel. Glargine dose remained unchanged. These changes reverted back to baseline after descent. Discussion(s): Acute mountain sickness and hypoxia stimulates sympathoadrenergic activity and production of epinephrine, norepinephrine and cortisol. This inhibits skeletal muscle glucose uptake, stimulates muscle glycogenolysis and increases lactate production resulting in increased glucose production by liver. Increased insulin sensitivity at high altitude may be due to exercise induced upregulation of skeletal muscle GLUT4 receptor translocation. One study demonstrated high resting level of norepinephrine, glucose, c-peptide and cortisol levels on sudden ascent which normalised after acclimatisation. Cold temperature is more detrimental in accuracy of glucose measurement than hypoxia. One CGM study has shown similar increase in nocturnal glucose at high altitude. Literature on management of insulin-treated diabetes at high altitude is sparse and warrants further studies.

DOI: 10.1111/dme.15498

Type of publication:

Conference abstract

Author(s):

Beese S.E.; Narendran P.; Price M.J.; Tomlinson C.; Sharma P.; Harris I.M.; Adriano A.; Andrews R.C.; Moore D.J.; Quinn L.; Gada R.; *Horgan T.J.; Maggs F.; Burrows M.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2025. Glasgow . 42(Supplement 1) (no pagination), 2025. Date of Publication: 01 Feb 2025.

Abstract:

Background: Type 1 diabetes is characterised by destruction of pancreatic beta cells. We aimed to determine the effectiveness of immunotherapies for preserving residual beta cell function through c-peptide measurement in newly diagnosed type 1 diabetes. Method(s): A systematic review and network meta-analysis (NMA) was undertaken of RCTs of non-antigen-specific immunotherapies to preserve beta cells in newly diagnosed type 1 diabetes. Searches were carried out in MEDLINE, Embase, Cochrane CENTRAL and trial registries (31 July 2024). Risk of bias was assessed using Cochrane Risk of Bias Tool 1. A frequentist NMA was undertaken in R. The primary outcome was c-peptide and interventions were analysed by class. Result(s): Sixty trials were included (4597 patients, 32 classes) plus 43 ongoing/unpublished studies. Forty-one trials were eligible for the NMA. Eleven interventions demonstrated statistically significantly higher c-peptide at 12 months compared with placebo: MSC; both autologous and Wharton's jelly-derived cells, azathioprine, interferon alpha (5000 IU), dendritic cells, golimumab, low-dose ATG, 3 mg 1-course teplizumab, baricitinib, cyclosporin and 9/11 mg 2-course teplizumab (I2 = 66%). All these interventions, except for 9/11 mg 2-course teplizumab and cyclosporin, demonstrated >60% chance of being ranked first. Infusion of MSC (Wharton's jelly-derived) ranked highest (median rank 1, 95% CI 1-2). Few studies were considered high risk of bias overall. Conclusion(s): Whilst several interventions demonstrated statistically significantly better c-peptide levels at 12 months, the findings should be interpreted with caution. Heterogeneity was evident and some comparisons were based on limited data. However, these findings identify the most promising of therapies that should be studied further in head-to-head and combination RCTs.

DOI: 10.1111/dme.15498