Is Reduced First-Phase Insulin Release the Earliest Detectable
Abnormality in Individuals Destined to Develop Type 2 Diabetes?
Insulin is released from the pancreas in a biphasic manner in
response to a square-wave increase in arterial glucose
concentration. The first phase consists of a brief spike lasting
∼10 min followed by the second phase, which reaches a plateau at
2–3 h. It is widely thought that diminution of first-phase
insulin release is the earliest detectable defect of β-cell
function in individuals destined to develop type 2 diabetes and
that this defect largely represents β-cell exhaustion after
years of compensation for antecedent insulin resistance. In this
article, the origins of these concepts are reviewed and recent
evidence is presented suggesting that reductions in both phases
of insulin release are equally early, that they precede insulin
resistance other than that simply due to obesity, and that they
therefore may represent the primary genetic risk factor
predisposing individuals to typ