Section 3 How Can We Assess  -Cell Health and Function?

 -Cell Adaptation and Failure: Opportunities for Prevention and Treatment of Type 2 Diabetes

Disclosure This slide kit is intended to provide current information on issues concerning  -cells in patients with type 2 diabetes. Some of the information and agents mentioned may include discussions of off-label, non–FDA-approved, or investigational uses. Please refer to each manufacturer’s full prescribing information before prescribing any of the agents mentioned in this program. Slides that include discussion of off-label uses are identified with the symbol .

This slide kit is intended to provide current information on issues concerning  -cells in patients with type 2 diabetes.

Some of the information and agents mentioned may include discussions of off-label, non–FDA-approved, or investigational uses. Please refer to each manufacturer’s full prescribing information before prescribing any of the agents mentioned in this program.

Slides that include discussion of off-label uses are identified with the symbol .

Tools to Assess  -Cell Health and Function Research Tools Acute insulin response to glucose (usually IV administration)* can be used to calculate the Disposition Index Insulin secretion during hyperglycemia (fixed or increasing)* Maximum insulin response to arginine during hyperglycemia* Oscillatory insulin secretion patterns Glucose-insulin relationships (fasting and during OGTT) Proinsulin:insulin ratios Clinical Tools Glucose levels (reflect  -cell compensation for insulin resistance) *Should be expressed relative to degree of insulin resistance

Research Tools

Acute insulin response to glucose (usually IV administration)*

can be used to calculate the Disposition Index

Insulin secretion during hyperglycemia (fixed or increasing)*

Maximum insulin response to arginine during hyperglycemia*

Oscillatory insulin secretion patterns

Glucose-insulin relationships (fasting and during OGTT)

Proinsulin:insulin ratios

Clinical Tools

Glucose levels (reflect  -cell compensation for insulin resistance)

Clinical Assessment of  -Cell Function Why not just measure insulin? Fasting and stimulated insulin levels determined by  -cell function and insulin resistance No practical way to determine  -cell compensation for insulin resistance from serum insulin values Insulin assays are not standardized; cannot establish normal or at-risk values

Why not just measure insulin?

Fasting and stimulated insulin levels determined by  -cell function and insulin resistance

No practical way to determine  -cell compensation for insulin resistance from serum insulin values

Insulin assays are not standardized; cannot establish normal or at-risk values

Clinical Assessment of  -Cell Function: Why Not Just Measure Insulin? Same β -cell function, different insulin levels Same insulin levels, different function Insulin sensitivity Insulin level Normal Patient #2 Patient #1 Insulin sensitivity Insulin level Normal Impaired Patient #4 Patient #3

Clinical Assessment of  -Cell Function: Why Measure Glucose? Glucose levels are determined by the interaction between insulin sensitivity (demand) and insulin secretion (supply) Normally, supply changes to meet demand if insulin sensitivity falls, insulin secretion rises reciprocally and vice versa Failure to compensate results in elevated glucose levels. Thus, glucose levels reflect  -cell compensation elevated glucose = inadequate  -cell compensation rising glucose = falling  -cell compensation

Glucose levels are determined by the interaction between insulin sensitivity (demand) and insulin secretion (supply)

Normally, supply changes to meet demand

if insulin sensitivity falls, insulin secretion rises reciprocally and vice versa

Failure to compensate results in elevated glucose levels. Thus, glucose levels reflect  -cell compensation

elevated glucose = inadequate  -cell compensation

rising glucose = falling  -cell compensation

Falling  -Cell Function and Rising Glucose Levels Baseline Posttrial testing TRIPOD Study – Incident Diabetes Cases Minutes Plasma glucose (mg/dL) Acute insulin response IV glucose (  U/mL x min) Insulin sensitivity ( S i ) Xiang AH et al. J Clin Endocrinol Metab. 2004;89:2846-2851. 0 40 80 120 0 100 200 300 Buchanan TA et al. Diabetes . 2002;51:2796-2803. Baseline Posttrial 1,000 800 600 400 200 0 0 2 4 6