Endocrine Abstracts

The discovery of insulin and its subsequent mass manufacture transformed the lives of people with type 1 diabetes. Insulin replacement is not, however, without risk and it soon emerged that many individuals with type 1 diabetes experienced iatrogenic hypoglycaemia. Hypoglycaemia in type 1 diabetes has both immediate (cognitive impairment) and longer-term consequences. In this presentation I will focus on the longer-term consequences of recurrent hypoglycaemia and in particular...

The fundamental importance of insulin to glucose homeostasis is well recognized and most evident in type 1 diabetes where β-cell destruction and loss of endogenous insulin secretion lead to marked hyperglycaemia and ketosis. The pancreatic α-cell product, glucagon, has garnered less scientific attention. However, the demonstration that glucagon receptor null mice did not develop diabetes following near-complete chemical destruction of the pancreatic β-cell renew...

Background: Hypoglycaemia in Type 1 diabetes (T1D) and type 2 diabetes is associated with long-term cognitive dysfunction. We have previously demonstrated that recurrent hypoglycaemia (RH) in a rodent model of T1D induces oxidative stress and inflammation in the hippocampus, associated with impaired cognitive function. This study sought to investigate whether pre-treatment with a potent inducer of the antioxidant response would ameliorate these cognitive deficits.<p class=...

Hypoglycaemia is an almost unavoidable consequence of iatrogenic insulin therapy in type 1 diabetes. Recurrent hypoglycaemia (RH) results in suppression of normal counter-regulatory hormonal and physiological responses (CRR) to future episodes increasing the risk of severe hypoglycaemia. The mechanisms responsible for this phenomenon remain unclear but may reflect changes in critical hypothalamic glucose sensing neurons (GSN). We set out to indirectly test the hypothesis that ...

Background: In diabetes, exposure to frequent episodes of hypoglycaemia diminishes a persons awareness of hypoglycaemia, by poorly defined mechanisms. Evidence suggests that, at least in part, changes in cell behaviour within the ventromedial hypothalamus may contribute to this defect and that changes in AMP-activated protein kinase (AMPK), a key glucose-sensing enzyme are involved. Evidence suggests there are (mal)adaptations within neurons, however, little is known about cha...

In population studies, premature cardiovascular disease is associated with cortisol dysregulation. Recently, recurrent hypoglycaemia in individuals with type 1 diabetes (T1D) was reported to be associated with increase carotid intima–media thickness. Hypoglycaemia is a potent activator of the hypothalamo-pituitary–adrenal axis (HPA axis) with eventual release of cortisol. We hypothesized that individuals with T1D who experience recurrent hypoglycaemia might demonstra...

Vascular disease is a major cause of morbidity and mortality in people who have diabetes. Hyperglycaemia is associated with increased transcriptional activity of nuclear factor of activated T cells (NFAT) in the vasculature. NFAT activation enhances expression of pro-inflammatory mediators including osteopontin, COX2 and IL6, implicated in the development of vascular disease. This study investigated the therapeutic potential of NFAT inhibition on the progression of microvascul...