Glucagon-like peptide-1 therapy in people with obesity restores natural killer cell metabolism and effector function.

OBJECTIVE: People with obesity (PWO) have functionally defective natural killer (NK) cells, with a decreased capacity to produce cytokines and kill target cells, underpinned by defective cellular metabolism. It is plausible that the changes in peripheral NK cell activity are contributing to the multimorbidity in PWO, which includes an increased risk of cancer. This study investigated whether therapy with long-acting glucagon-like peptide-1 (GLP-1) analogues, which are an effective treatment for obesity, could restore NK cell functionality in PWO. METHODS: In a cohort of 20 PWO, this study investigated whether 6 months of once weekly GLP-1 therapy (semaglutide) could restore human NK cell function and metabolism using multicolor flow cytometry, enzyme-linked immunosorbent assays, and cytotoxicity assays. RESULTS: These data demonstrate that PWO who received GLP-1 therapy have improved NK cell function, as measured by cytotoxicity and interferon-γ/granzyme B production. In addition, the study demonstrates increases in a CD98-mTOR-glycolysis metabolic axis, which is critical for NK cell cytokine production. Finally, it shows that the reported improvements in NK cell function appear to be independent of weight loss. CONCLUSIONS: The restoration, by GLP-1 therapy, of NK cell functionality in PWO may be contributing to the overall benefits being seen with this class of medication.

Retracing the tracks for SIAD: hyponatraemia due to post-traumatic brain injury hypopituitarism.

Hyponatraemia is common in hospital practice, with the syndrome of inappropriate antidiuresis (SIAD) being the most common underlying aetiology. A relatively less frequent but important cause is adrenal insufficiency (AI). We describe the case of a 63-year-old man who presented with symptomatic hyponatraemia and hypoglycaemia associated with abnormal body movements (ballism). The recent commencement of levothyroxine for newly diagnosed hypothyroidism, followed by fluid restriction for presumed SIAD, led to the worsening of a previously undiagnosed AI. His investigations confirmed central AI in association with thyroid and growth hormone deficiencies. The underlying cause of hypopituitarism, in this case, was a traumatic brain injury He responded well to steroid replacement and fluids. This case highlights that SIAD remains a diagnosis of exclusion, and other causes of hyponatraemia, including AI, should always be considered. Second, levothyroxine treatment without steroid replacement can lead to an adrenal crisis in patients with underlying AI.