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. 2017 Jul 8;6(9):943–957. doi: 10.1016/j.molmet.2017.06.019

Figure 1.

Figure 1

Models of the contribution of beta cell mass and function to pathogenesis of type 1 diabetes (A) and type 2 diabetes (B). (A): Beta cell mass and function in the development of type 1 diabetes. Initiation of islet autoimmunity by genetic and environmental factors leads to a relapsing-remitting decline of beta cell function, continuously increasing beta cell workload, and stress in the asymptomatic prediabetes phase. Shortly before clinical manifestation of diabetes the prolonged intensified beta cell workload and autoimmunity results in total cellular exhaustion and enhanced cell death leading to a massive decrease in beta cell mass and the onset of hyperglycemia. In some patients, initial insulin treatment induces temporary remission called the “honeymoon phase,” which is attributed to a moderate reduction in beta cell workload and antigenicity, resulting in functional recovery of residual beta cells. However, ongoing autoimmunity and elevated workload lead to recurrence of cellular exhaustion, cell death, and the development of overt diabetes. Black line: beta cell mass; Blue line: beta cell function. The color-coded background indicates the intensity of beta cell workload and stress caused by immune infiltration, metabolic demand and hyperglycemia. (B): Beta cell mass and function in the development of type 2 diabetes. In many individuals, genetic predisposition and unhealthy lifestyle lead to an increased insulin resistance, which is typically met by massive functional and moderate morphological compensation to maintain normoglycemia, thus increasing the workload of each beta cell. In some of these individuals, functional compensation halts, despite prolonged insulin resistance and results in a further escalation of beta cell workload and glucose intolerance. In this prediabetic phase, chronic glucose intolerance and elevated blood glucose levels continuously exacerbate beta cell workload and stress, culminating in cellular exhaustion, cell death, and clinical manifestation of hyperglycemia. Thereafter, uncontrolled hyperglycemia, often in concert with other cytotoxic factors, leads to accelerated beta cell mass loss and functional deterioration in overt diabetic patients. Black line: beta cell mass; Blue line: beta cell function. The color-coded background indicates the intensity of beta cell workload and stress caused by insulin resistance, metabolic demand, hyperglycemia and additional cytotoxic factors.