Table 1.
A summary of human trials which have included direct measurements of β cell function following PPAR-γ agonist treatment in persons with IGT, IFG, T2DM or a history of gestational diabetes.
| Study | Patient population | Drug | Length of treatment | Measurements performed | Outcome(s) of improved β cell Function |
|---|---|---|---|---|---|
| Cavaghan et al. [38] | IGT | Tro | 12 weeks | 75 g OGTT IVGTT |
Improved insulin secretion rates adjusted for insulin sensitivity |
| Graded glucose infusion Spectral analysis for oscillatory glucose infusion |
Improved β cell sensing during oscillatory glucose infusion | ||||
| Prigeon et al. [138] | T2DM | Tro | 12 weeks | Acute insulin response to arginine IVGTT | Reduced proinsulin to insulin ratio |
| Miyazaki et al. [139] | T2DM | Pio | 26 weeks | 75 g OGTT | Increased plasma insulin response during OGTT |
| Increased insulinogenic index (AUC insulin/AUC glucose) | |||||
| Buchanan et al. (TRIPOD) [31] | History of GDM | Tro | 120 weeks | 75 g OGTT IVGTT |
Troglitazone-treated controls had a stable β cell compensation (DI) for insulin resistance, compared to placebo-treated controls who showed decreasing DI |
| Juhl et al. [34] | T2DM | Rosi | 13 weeks | IVGTT Hyperglycaemic clamp with arginine stimulation |
Improved glucose-entrained insulin secretion |
| Assessment of baseline high-frequency insulin pulsatility by spectral analysis | |||||
| Hyperinsulinaemic euglycaemic clamp | |||||
| Wallace et al. [35] | T2DM | Pio | 12 weeks | HOMA IVGTT and hyperglycaemic clamp Euglycaemic hyperinsulinaemic clamp |
Increased HOMA-%B Reduced proinsulin to insulin ratio |
| Xiang et al. (PIPOD) [32] | History of GDM | Pio | 36 weeks after TRIPOD study | 75 g OGTT IVGTT |
Stabilization of AIRg and DI, compared to placebo-treated controls who had worsening of AIRg and DI over the same time period |
| Kahn et al. (ADOPT) [33] | T2DM | Rosi | 48 weeks | HOMA | Slower rate of decline in HOMA-%B in rosiglitazone-treated subjects compared to those treated with either glyburide or metformin |
| Gastaldelli et al. [37] | T2DM | Pio or Rosi | 16 weeks | 75 g OGTT Two-step euglycaemia insulin clamp |
Increased insulin secretion/ insulin resistance index (ISR AUC/glucose AUC + IR) |
| Improved insulin secretory response per incremental plasma glucose response expressed in relationship to the severity of insulin resistance (ISR/G0–120 + IR) | |||||
| Hanley et al. (DREAM) [39] | IGT and IFG | Rosi | At least 24 months | 75 g OGTT | Increased insulinogenic index which was corrected for HOMA-IR |
| Decreased fasting proinsulin-to-C-peptide ratio |
ADOPT, A Diabetes Outcome Progression Trial; AIRg, acute insulin secretion during IVGTT; AUC, area under the curve; DI, disposition index; DREAM, Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication; GDM, gestational diabetes mellitus; HOMA, homeostasis model of assessment; HOMA-IR, homeostasis model of assessment of insulin resistance; HOMA-%B, homeostasis model of assessment of β cell function; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; ISR, insulin secretory response; IVGTT, intravenous glucose tolerance test; OGTT, oral glucose tolerance test; pio, pioglitazone; rosi, rosiglitazone; T2DM, type 2 diabetes mellitus; TRIPOD, TRoglitazone In the Prevention Of Diabetes; tro, troglitazone.