A small trial indicates that men with type 2 diabetes may have a blunted physiological response to oral sodium intake, highlighting potential disruptions in gut-kidney communication and implications for blood pressure management.
A small crossover trial in men with type 2 diabetes suggests that the body’s normal response to sodium taken by mouth may be blunted in the setting of diabetes, pointing to a possible disturbance in gut-kidney signalling. In the study, published online on 12 September 2026 in Clinical Kidney Journal and led by Charlotte Mosterd at Amsterdam University Medical Centre, oral sodium loading prompted less sodium excretion than intravenous loading in the diabetes group, unlike in healthy volunteers. The finding adds to a long line of research indicating that the digestive tract helps the body detect sodium intake and communicate that information to the kidneys.
Mosterd and colleagues studied 11 men with type 2 diabetes, all with preserved kidney function and no albumin in the urine, and compared three interventions given in random order a week apart: intravenous sodium, oral sodium with placebo infusion, and oral sodium with a short exenatide infusion. The oral and intravenous sodium loads were almost equivalent. The main outcome was urinary sodium excretion over 24 hours, with blood pressure, sodium handling and measured glomerular filtration rate also tracked. A separate comparison group of 10 healthy people received the oral and intravenous sodium loads to test whether the expected early natriuretic response, meaning increased sodium loss in the urine, was present.
In healthy participants, oral sodium produced a faster rise in sodium excretion than intravenous sodium at two hours, which fits with earlier studies in the 1970s and 1990s suggesting that the gut or portal circulation acts as a monitor of salt intake. But in the men with type 2 diabetes, that early advantage was absent, and the researchers found no meaningful differences in total 24-hour urinary sodium excretion, urine volume, fractional sodium excretion, blood pressure or measured kidney filtration across the three interventions. A short exenatide infusion did not restore the response.
The result does not prove that gut-kidney signalling is broken in all people with diabetes, and the study was small, mechanistic and limited to a brief exposure to exenatide. Still, it fits with prior work showing that GLP-1 receptor agonists such as exenatide can affect gut function and renal sodium handling, even when they do not acutely change kidney haemodynamics. The authors said that understanding this pathway better could eventually help explain salt sensitivity in metabolic disease and point towards new approaches for blood pressure and cardiorenal protection.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
