SFEBES2021 Society for Endocrinology BES 2021 Clinical Endocrinology Trust Lecture (1 abstracts)
The balanced hormonal regulation of metabolism is the cornerstone of endocrinology. One of the most elegant aspects of our discipline is that increased or decreased hormone activities lead to predictable changes and diseases. We were surprised, therefore, to identify a novel disease where the same genetic alteration, a missense change in the beta-cell transcription factor MAFA, causes two very opposite conditions: life-threatening hypoglycaemia due to numerous small insulin-secreting tumours, or noninsulin-dependent diabetes resembling MODY. The altered MAFA protein, which normally would have a very short half-life and thus can dynamically respond to the demand / cessation of demand for insulin secretion, showed reduced activity but a significantly prolonged half-life. The resulting two phenotypes showed a strong gender imbalance, with females typically developing insulinomatosis while males rather demonstrate diabetes. While this disease, familial insulinomatosis and diabetes, is extremely rare, elucidating its mechanisms may help us to understand the complex regulation and tumorigenesis of beta cells. At the other end of the disease frequency spectrum are patients with iatrogenic Cushings syndrome due to corticosteroid treatment, some 3-11% of the general population. Based on our experimental data on the effect of cortisol on AMPK, the major metabolic enzyme influenced by metformin, we attempted to counteract the myriad of metabolic abnormalities associated with excess glucocorticoids using metformin. Our double-blind, randomised, placebo controlled trial on patients on steroid treatment, and no diabetes, receiving metformin or placebo resulted in better glucose, lipid, liver, thrombotic and bone parameters, and significantly reduced infections & hospital admissions. These data suggest the possibility, similar to bone and gastric protection, that we should consider the routine use of metformin for steroid-treated patients.
08 Nov 2021 - 10 Nov 2021