Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus.

BACKGROUND & AIMS: Very-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes. METHODS: Thirty individuals with T2D (age 18-75 years, BMI 27-50  kg m-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR. RESULTS: Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01). CONCLUSION: VLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.

Cracking the combination: Gut hormones for the treatment of obesity and diabetes.

Obesity and type 2 diabetes are a veritable global pandemic. There is an imperative to develop new therapies for these conditions that can be delivered at scale to patients, which deliver effective and titratable weight loss, amelioration of diabetes, prevention of diabetic complications and improvements in cardiovascular health. Although agents based on glucagon-like peptide-1 (GLP-1) are now in routine use for diabetes and obesity, the limited efficacy of such drugs means that newer agents are required. By combining the effects of GLP-1 with other gut and metabolic hormones such as glucagon (GCG), oxyntomodulin, glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY), we may obtain improved weight loss, increased energy expenditure and improved metabolic profiles. Drugs based on dual agonism of GLP1R/GCGR and GLP1R/GIPR are being actively developed in clinical trials. Triple agonism, for example with GLPR1/GCGR/GIPR unimolecular agonists or using GLP-1/oxyntomodulin/PYY, is also being explored. Multi-agonist drugs seem set to deliver the next generation of therapies for diabetes and obesity soon.

A Complicated Pregnancy in an Adult with HNF4A p.R63W-Associated Fanconi Syndrome.

Renal Fanconi syndrome (RFS) is characterised by generalised dysfunction of the proximal renal tubules, resulting in excessive urinary loss of solutes, most notably bicarbonate, and type II (proximal) renal tubular acidosis. It is a rare condition, and literature around its management through pregnancy is limited. We present the management of a 37-year-old woman with RFS secondary to the HNF4A p.R63W mutation, through her third pregnancy. She presented at 28 + 5 weeks with dehydration, low serum bicarbonate, and profound metabolic acidosis. Daily infusions of sodium bicarbonate were necessary, and the requirements increased throughout the pregnancy. She also demonstrated both fasting hypoglycaemia and episodes of postprandial hyperglycaemia which required complex management. Due to concerns around fetal health, an elective caesarean section was performed at 34 weeks, delivering a healthy baby girl. This case highlights the potential complexity of pregnancy in patients with RFS and the need for a multidisciplinary approach to its management.

Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous infusion of these hormones ("GOP"), mimicking postprandial levels, reduces energy intake. Our objective was to study the effects of GOP on glycemia and body weight when given for 4 weeks to patients with diabetes and obesity. RESEARCH DESIGN AND METHODS: In this single-blinded mechanistic study, obese patients with prediabetes/diabetes were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also studied 21 patients who had undergone RYGB and 22 patients who followed a very low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and measures of glucose variability during continuous glucose monitoring. RESULTS: GOP infusion was well tolerated over the 4-week period. There was a greater weight loss (P = 0.025) with GOP (mean change -4.4 [95% CI -5.3, -3.5] kg) versus saline (-2.5 [-4.1, -0.9] kg). GOP led to a greater improvement (P = 0.0026) in fructosamine (-44.1 [-62.7, -25.5] µmol/L) versus saline (-11.7 [-18.9, -4.5] µmol/L). Despite a smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose tolerance after a mixed-meal stimulus and reduced glycemic variability compared with RYGB and VLCD. CONCLUSIONS: GOP infusion improves glycemia and reduces body weight. It achieves superior glucose tolerance and reduced glucose variability compared with RYGB and VLCD. GOP is a viable alternative for the treatment of diabetes with favorable effects on body weight.

Subclinical hypothyroidism or central hypothyroidism-The danger of thyroid function misinterpretation.

Correct interpretation of thyroid function tests is critical to providing appropriate care to patients with suspected thyroid disease. It is particularly important to distinguish central hypothyroidism from other types due to the potential of concurrent secondary adrenal insufficiency and thus the need for immediate steroid replacement prior to commencing thyroxine.

Junior doctor teaching delivered by near peers.

BACKGROUND: Near-peer teaching - trainees teaching more junior trainee colleagues - has been widely described in undergraduate medical education. Several benefits have been reported, including a more comfortable learning environment for learners and the development of tutors' teaching skills. Near-peer teaching programmes in postgraduate training are less commonly described in the existing literature, however. This article outlines a pilot study of a postgraduate near-peer teaching programme implemented at the Royal Victoria Infirmary, Newcastle, UK. METHODS: A 16-week teaching programme was developed in which core medical trainees delivered teaching sessions to their more junior Foundation Year-2 colleagues. The teaching was based on cases that the Foundation Year-2 doctors frequently manage during clinical practice. Evaluation questionnaires were completed and learners were asked to rate their confidence in managing the cases before and after each session. Furthermore, each tutor underwent a standardised teaching assessment during their first and final sessions. RESULTS: Fifteen sessions were delivered by four tutors. All sessions received positive feedback from learners with nine sessions receiving a five out of five rating. In addition, the confidence ratings of the learners increased following each session. The tutors improved in all items of the teaching assessments and the overall rating of their teaching. Near-peer teaching could enhance the training of junior doctors DISCUSSION: The results of this pilot study suggest that the benefits described in undergraduate near-peer teaching programmes may also be seen in postgraduate medical education. Thus near-peer teaching could enhance the training of junior doctors, and we encourage the proliferation of such programmes to further evaluate their benefits in this setting.

Participation in teaching opportunities during core medical training: barriers and enablers.

The development of teaching ability is an essential part of the core medical training curriculum. Delivering teaching for foundation trainees is one way to achieve this while also enhancing the training of junior colleagues, yet there is no current evidence that this occurs. This study describes the extent to which core medical trainees in a UK training region are teaching juniors and identifies potential influencing factors. Questionnaires were completed by 61 core medical trainees and 20 of these participated in five focus groups. Participants had delivered a median number of two training sessions; however, 36% had not delivered any. Focus group data suggested a clear interest in involvement, but barriers such as lack of time and lack of encouragement inhibited this. Although there is a wealth of potential opportunities to teach juniors, this study suggests these are not being fully utilised by core medical trainees. Measures have been proposed to help overcome the identified barriers.