fig3

Figure 3. A conceptual framework indicating the decline in beta-cell function due to natural aging, metabolic stress, and inflammation (e.g., obesity, use of tobacco, psychosocial stress, poor sleep, infection), which can influence the age of onset of diabetes. For a given trajectory of beta-cell function, those with reduced beta-cell capacity are more likely to decompensate early. With the onset of diabetes, ongoing lipoglucotoxicity and inflammation can further accelerate beta-cell loss, resulting in insulin requirement. Reducing metabolic stress, especially in people with vulnerable beta-cell function, may delay the onset of diabetes and insulin requirement^[128].