After type 2 diabetes patients initially respond to diet and oral hypoglycemic agents, why do they usually relapse into hyperglycemia, despite dietary compliance and maximal drug dosages? Is this a case of β-cell desensitization to the drugs, or is it something more sinister happening to the β-cell over time? Is there ongoing apoptosis of β-cells, and, if so, is this caused by aberrant genetic programming or something bad that invades the β-cell’s microenvironment? Type 2 diabetes is characterized as a polygenic disorder and generally thought of as a syndrome, rather than a single specific entity. This suggests that a common adverse force is exerted on β-cells in all patients, regardless of the initial specific pathogenesis. One such force all patients experience in common is the chronic tendency toward developing abnormally high glucose levels on a daily basis. Even though fasting glucose and HbA1c levels might be within the normal range, postprandial levels of glucose are often abnormal. The glucose toxicity theory proposes that continual exposure to modest increases in blood glucose over a long period of time could have adverse effects on β-cells. In essence, the consequence of type 2 diabetes, hyperglycemia, is proposed as a secondary cause of continued β-cell deterioration.