Background: The appearance of hyperglycemia is due to insulin resistance, functional deficits in the
secretion of insulin and a reduction of β-cell mass. There is a long-standing debate as to the relative
contribution of these factors to clinically manifest β-cell dysfunction. The aim of this study was to
verify the acute effect of one of these factors, the reduction of β-cell mass, on the subsequent
development of hyperglycemia.
Methods: To pursue this aim, non-diabetic patients, scheduled for identical pancreaticoduodenectomy
surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamps (HC), followed
by arginine stimulation before and after surgery. Based on post-surgery OGTT, subjects were divided
into 3 groups depending on glucose tolerance: normal (post-NGT), impaired (post-IGT) or diabetic
Results: At baseline, the three groups showed similar fasting glucose and insulin levels, however,
examining the various parameters, we found that reduced first phase insulin secretion and reduced
glucose sensitivity and rate sensitivity were predictors of eventual post-surgery development of
impaired glucose tolerance and diabetes.
Conclusion: Despite comparable functional mass and fasting glucose and insulin levels at baseline,
and the very same 50% mass reduction, only reduced first phase insulin secretion and glucose
sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal
to the pathogenesis of type 2 diabetes (T2DM).
- Beta cells