Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study

Area of Science:

• Endocrinology
• Metabolic Diseases
• Diabetes Research

Background:

• Insulin resistance and beta-cell dysfunction are critical in the progression from normal glucose tolerance (NGT) to Type 2 diabetes (T2DM).
• Understanding the threshold of glycemia at which beta-cell dysfunction manifests is crucial for early intervention.

Purpose of the Study:

• To determine the glycemic level at which beta-cell dysfunction becomes apparent in individuals with existing insulin resistance.
• To investigate the relationship between glucose tolerance, insulin resistance, and beta-cell function.

Main Methods:

• Evaluated insulin response (oral glucose tolerance test - OGTT) and insulin sensitivity (euglycemic insulin clamp) in 388 subjects (NGT, impaired glucose tolerance - IGT, T2DM).
• Calculated the insulin secretion/insulin resistance index (DeltaI/DeltaG/IR) to assess beta-cell function relative to insulin resistance and glycemic stimulus.

Main Results:

• A progressive decline in the insulin secretion/insulin resistance index (DeltaI/DeltaG/IR) was observed with increasing 2-hour plasma glucose (2-h PG) levels, starting in lean NGT individuals.
• This decline was more pronounced in IGT and T2DM groups, with similar patterns observed in both lean and obese subjects.

Conclusions:

• Beta-cell function, when assessed in relation to glycemic stimulus and insulin resistance, shows a progressive decline that initiates in individuals with normal glucose tolerance.
• These findings highlight that early signs of beta-cell impairment can be present before overt diabetes diagnosis.