Table 1.

Proposed stages of β-cell decompensation and dysregulation¹⁰

Stage	Ambient blood glucose value	Physiologic changes within islet/β-cell	Histologic changes noted within islet/β-cell
Stage 1	85–130 mg/dL	Lowered set-point for glucose-stimulated insulin secretion due to glucokinase activation	Normal gene expression profile β-cell hypertrophy β-cell hyperplasia
Stage 2	89–130 mg/dL	Loss of first-phase insulin response Near-normal insulin stores	Decreased expression of glucokinase, glucose transporter proteins, and transcription factors
Stage 3	130–285 mg/dL	Loss of second-phase insulin secretion Increased ratio of proinsulin: insulin, suggestive of β-cell injury Patient is maximally insulin resistant as 80% of the β-cell function is lost	Reduced insulin stores within β-cell Increased expression of genes which predispose to loss of β-cell mass and function In obese patients, up to 40% of the β-cell mass is lost
Stage 4	285–350 mg/dL	β-cell apoptosis and death	Amyloid and lipid deposits form within islets Islets become fibrosed
Stage 5	>350 mg/dL	Marked β-cell destruction Loss of signaling between the α- and β-cell can increase risk of hypoglycemia	Fibrosis