Type of publication:

Conference abstract

Author(s):

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

Aims: In newly diagnosed type 1 diabetes, residual beta cell function (indicated by c-peptide) is associated with improved glucose control and reduced long-term complications. We assessed time trends in RCTs of categories of interventions for beta cell preservation in newly diagnosed type 1 diabetes. Method(s): RCTs of any intervention for newly diagnosed type 1 diabetes measuring c-peptide were identified in Cochrane CENTRAL, MEDLINE, Embase and trials registries (to July 2024). Trends in trial characteristics were assessed, focusing on types of intervention. Result(s): The 171 completed published trials were distributed across non-antigen-specific (NAS) immunomodulatory therapies (n = 60, 33%), vitamins (n = 23, 13%), antigen-specific immunotherapies (n = 20, 11%), interventions to maintain glucose control (n = 38, 21%) and 'other' interventions (n = 39, 22%). A further 102 ongoing/ unpublished trials were included. Over 40 years, RCT frequency has increased, with 54 trials published between 2011 and 2020 and 39 since 2021. Twenty-four ongoing trials of 'other' interventions and 19 NAS trials have been initiated since 2021. Average sample size per trial has increased from 63 (SD 66) prior to 2014 to 83 (SD 110) in the last 10 years. Taking the NAS group as an example, time from completion of data collection to publication has increased. Trials with significant primary endpoint results are published 6 months quicker than non-significant findings (mean 17.6 vs 23 months). The number of NAS trials with significant results has risen from 40% (13/33) to 61% (16/26). Conclusion(s): RCTs of therapies to preserve beta cells are increasing in frequency with greater focus on NAS interventions and therapies not easily fitting standard categories. Significant findings may be published sooner.

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 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

Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Al-Samaraaie E.; *Cane C.; *Beard N.; *Moulik P.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2024. London . 41(Supplement 1) (no pagination), 2024. Date of Publication: 01 Apr 2024

Abstract:

Aims: Shropshire and Telford have significantly higher minor and major non-traumatic diabetic lower-limb amputations. We analysed data on risk factors leading to major amputation. Method(s): Data on all 48 major non-traumatic lower-limb amputation in diabetes between April 2022 and March 2023 were analysed. Result(s): 90% type 2 diabetes with 32 (67%) diabetes duration >10 years, 11 (23%) <10 years, 1 was diagnosed at admission. 17 (35%) were female. 38 (80%) were between 50 and 80, 9 (18%) over 80 years age. 26 (54%) had below knee and 22 (46%) above knee amputation. Postcode-based assessment of deprivation indices revealed amputations were higher in patients from most deprived (29%) compared to deprived (25%), average (21%), affluent (20%) and very affluent (4%) areas. 20 (41%) were considered concordant, 18 (37%) non-concordant by the assessing clinician. 21 (42%) were overweight or obese. Half were current or ex-smokers, 58% hypertensive, 79% hyperlipidaemic or on statins, 83% on antiplatelet/anticoagulants. Sixteen (44%) had eGFR >60 mL/min, 17 (35%) 30-60 mL/min, 4 (8%) eGFR 15-30mL/min and none with eGFR <15mL/min. HbA1c was <48 mmol/mol in 10%, 48-68 mmol/mol in 35%, 69-99 mmol/mol in 37% and >100 mmol/mol in 17%. 37% had pre-proliferative/proliferative retinopathy or maculopathy. 80% had high risk feet, 28 (58%) previous foot ulcers and 19 (40%) previous amputation. 80% had neuropathy and peripheral arterial disease and 10% had Charcot. Final cause of amputation was critical ischaemia in 27 (56%), infection/osteomyelitis/sepsis in 7 (15%), spreading gangrene in 10 (21%) and Charcot in 4 (8%). Conclusion(s): Long-standing diabetes with multiple chronic complications and social deprivation were associated with major amputations. Cardiovascular risk factors were generally well managed. Preventive strategies must focus on improving metabolic and risk factor management early in disease.

DOI: 10.1111/dme.15295

Link to full-text [NHS OpenAthens account required]

Type of publication:

Conference abstract

Author(s):

*Cane C.L.; *Jones A.M.; *Moulik P.K.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2024. London . 41(Supplement 1) (no pagination), 2024. Date of Publication: 01 Apr 2024.

Abstract:

A 26-year-old nulliparous female presented with a 2-week history of a right breast lump. She had type 1 diabetes for 17 years and polycystic ovaries. Her diabetes distress led to suboptimal glycaemic control. There was firm tissue under the right nipple-areola complex, and ultrasound (US) demonstrated a suspicious 43-mm mixed echogenic lesion with posterior shadowing (U4). Core biopsy revealed marked fibrosis with fibroblasts and entrapped benign breast ducts and adipose tissue. Breast ducts were highlighted by epithelial markers (AE1/3 and small P63), blood vessels by CD34, and fibroblasts and myoepithelial layers by smooth muscle actin (SMA). She was reassured; 2 years later she developed a left breast lump and 26-mm focal hypoechoic glandular lesion on US, right breast lesion unchanged. A diagnosis of DMP was made. DMP occurs in 20- to 40 year-old women with long duration of type 1 diabetes. It can occur in men rarely. It presents with a painless, hard, mobile breast lesions which are irregular. Bilateral lesions develop in 50% patients. Axillary lymphadenopathy is absent. Mammography reveals dense glandular tissue and US shows acoustic shadows behind the lesion. Core biopsy is recommended. DMP is a benign condition which may raise concerns of breast cancer. It may be associated with autoimmunity and occasionally seen in insulin treated type 2 diabetes, systemic lupus erythematosus and Hashimoto's. Microscopy shows periductal, perilobular and perivascular B-lymphocytic infiltrates with some T cells, fibroblast proliferation and collagen. Management is conservative unless a larger lesion requires excision. To date, only one case report has been published on breast cancer in a patient with DMP.

DOI: 10.1111/dme.15295

Link to full-text [no password required]

Type of publication:

Conference abstract

Author(s):

*Jones A.M.; *Basavaraju N.; *Moulik P.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2024. London . 41(Supplement 1) (no pagination), 2024. Date of Publication: 01 Apr 2024.

Abstract:

A 42-year-old lady with complex diabetes was diagnosed age 19 years. She went on an insulin pump (Medtronic Minimed), Hba1c was 56 mmol/mol which crept up to 72 mmol/mol. She developed hypertension, nephropathy and laser treated retinopathy. Starting Freestyle Libre with Medtronic640 improved Hba1c down to 52 mmol/mol. Her social and financial circumstances, including being a single mum, deteriorated leading to diabetes distress and burnout. Healthcare and diabetes management became a burden. Ambulatory glucose profile (AGP) showed time in range (TIR) 28%, high (H) 23%, very high (VH) 42% and Hba1c71 mmol/mol. Counselling and motivational interviewing with regular support was provided. She had stopped all medications and insisted on a pump break. Hba1c increased to 118 mmol/mol, TIR14%, H5%, VH81%, mean glucose (MG) 23.3 mmol/L. She wanted to restart the pump and it was felt on previous pump therapy she had safer glucose levels and no ketoacidosis. AGP improved with TIR29%, H18%, VH52%, MG15.4 mmol/L in 2 weeks. After 3 months, TIR was 33%, H20% VH42%, Hba1c76 mmol/mol. Weight was increasing with associated diabulimia. Dulaglutide was started after counselling. TIR51%, H16%, VH9%, level 1 hypoglycaemia11%, level 2 hypoglycaemia13%. She started HCL (Medtronic 780G with Guardian G4) and Hba1c was 45 mmol/mol, TIR66%, H18%, VH15%, level 1 hypoglycaemia1%, level 2 hypoglycaemia0%. Her weight has come down from 99 to 82 kg with BMI 31.4 kg/m². Renal function has improved (eGFR 33 to 42 mL/min). Quality of life (QOL) assessments show great improvement. This case highlights a life plan is as important as a health plan. A motivational and supportive approach, advanced technologies and some off-license medication reduced diabetes burden and improved patient engagement.

DOI: 10.1111/dme.15296

Link to full-text [no password required]

Type of publication:

Conference abstract

Author(s):

*Basavaraju N.; *Al-Samaraaie E.; *Moulik P.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2024. London . 41(Supplement 1) (no pagination), 2024. Date of Publication: 01 Apr 2024.

Abstract:

Introduction: HbA1c is a useful measure of glycaemic control over the preceding 3 months with an emphasis on preceding 30 days. We present four clinical scenarios that affect its reliability. Case 1: Twenty-nine-year-old female started on Dapsone for hidradenitis suppurativa. Pre-dapsone HbA1c was 38 mmol/mol and 2 years post-dapsone HbA1c <18 mmol/mol, normal fructosamine 272 mumol/L (211-328), glucose-6-phosphate dehydrogenase (G6PD) activity 12.9 IU/gHb (8.8-12.8), methaemoglobin 8.6% (0-1.5) and reticulocyte 6.5% (0.5-2.5) indicating haemolysis. Case 2: Forty-nine-year-old female with type 1 diabetes and rheumatoid arthritis started on sulfasalazine. HbA1c dropped from 65 to 30 mmol/mol, fructosamine 415 mumol/L (211-328), mildly raised reticulocyte 2.6%, haemoglobin 128 g/L (115-165) indicating mild haemolysis. Case 3: Fifty-nine-year-old male with type 2 diabetes and genetic haemochromatosis (C282Y homozygous) started venesection. HbA1c prior was 63 mmol/mol reduced to 29 mmol/mol, fructosamine 262 mumol/L and c-peptide 2760 pmol/L indicate good beta cell reserve. Case 4: Seventy-year-old female with Graves' disease, post-radioiodine hypothyroidism, HbA1c <20 mmol/mol (was 41 mmol/mol 2 years ago) as part of annual hypertension screen. Fasting glucose 6.0 mmol/L, low haemoglobin 102 g/L, high reticulocytes 9.5%, direct antiglobulin Coombs test positive indicating low HbA1c due to autoimmune haemolytic anaemia. Discussion(s): HbA1c depends on glycation of red blood cells (RBC) and is proportional to ambient glucose concentrations. Conditions that affect RBC lifespan and turnover can alter HbA1c values. Dapsone causes oxidative haemolysis as can sulfasalazine. Venesection and haemolytic anaemia shorten life span of red blood cells and duration of haemoglobin exposed to glucose in the bloodstream resulting in falsely lower HbA1c. Conclusion(s): Clinicians must be aware of conditions affecting accuracy of HbA1c and consider alternate tests including venous glucose, fructosamine, capillary glucose or continuous glucose monitoring.

DOI: 10.1111/dme.15296

Link to full-text [no password required]

Type of publication:

Conference abstract

Author(s):

*Cane C.; *Beard N.; *Al-Samaraaie E.; *Basavaraju N.; *Moulik P.

Citation:

Diabetic Medicine. Conference: Diabetes UK Professional Conference 2024. London . 41(Supplement 1) (no pagination), 2024. Date of Publication: 01 Apr 2024.

Abstract:

Aims: Mortality following major diabetic amputation is high. We analysed data on factors leading to mortality following major amputation. Method(s): Data on all 48 major non-traumatic diabetic lower-limb amputation between April 2022 and March 2023 were analysed in September 2023. 33 (69%) were alive and 15 (31%) had died. Result(s): 90% patients had type 2 diabetes and 67% had diabetes duration>10 years. 17 (35%) were female. 38 (80%) were between 50 and 80, 9 (18%) over 80 years old. 21 (42%) were overweight or obese. 26 (54%) had below knee amputation (BKA) and 22 (46%) above knee amputation (AKA). Half were current or ex-smokers, 58% hypertensive, 79% hyperlipidaemic or on statins, 83% on antiplatelet/anticoagulants. 27 (57%) had eGFR >60 mL/min, 17 (35%) eGFR 30-60 mL/min, 4 (8%) eGFR 15-30 mL/min and none with eGFR <15 mL/min. 37% had pre-proliferative/proliferative retinopathy or maculopathy, 28 (58%) previous foot ulcers and 19 (40%) previous amputation. 80% had neuropathy and 80% peripheral arterial disease. Cause of amputation was critical ischaemia in 27 (56%), sepsis/spreading gangrene in 17 (36%). 10 patients died in hospital and 5 in the community. Cause of death was cardiorespiratory in 6 (40%), sepsis related to DFU in 2 (13%), sepsis unrelated to DFU in 3 (20%), old age/dementia in 2 (13%) and unknown in 2 (13%). Mortality was similar in BKA and AKA. Mann-Whitney test with Monte Carlo correction suggested age >40 at diagnosis of diabetes, advanced nephropathy and retinopathy additionally predicted mortality. Conclusion(s): A third of patients had died within a year following major amputation. Majority were older patients with multiple risk factors contributing both to amputation and mortality, but additional predictors of mortality were nephropathy and retinopathy.

DOI: 10.1111/dme.15296

Link to full-text [no password required]