Glucose metabolism is normally regulated by a feedback loop including islet β cells
and insulin-sensitive tissues, in which tissue sensitivity to insulin affects magnitude
of β-cell response. If insulin resistance is present, β cells maintain normal glucose
tolerance by increasing insulin output. Only when β cells cannot release sufficient
insulin in the presence of insulin resistance do glucose concentrations rise. Although
β-cell dysfunction has a clear genetic component, environmental changes play an essential
part. Modern research approaches have helped to establish the important role that
hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction,
and the potential role of changes in the microbiome. Several new approaches for treatment
have been developed, but more effective therapies to slow progressive loss of β-cell
function are needed. Recent findings from clinical trials provide important information
about methods to prevent and treat type 2 diabetes and some of the adverse effects
of these interventions. However, additional long-term studies of drugs and bariatric
surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby
reduce the harmful effects of this disease.
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