. 2014 Jan;10(1):2–42. doi: 10.2174/1573399810666140214093600

Table 4.

Selected Applications of BCF Tests that Include Physiological Assessments of Hormone and Glucose Changes in Subjects with Different Degrees of Glucose Intolerance and Under Different Treatment Regimens.

Subjects and Glucose Status	Treatment	Key Findings
FASTING HOMEOSTASIS BETWEEN GLUCOSE AND INSULIN (HOMA)
T2DM [152]	ALO±PIO on MET background for 26 wk	Proinsulin/insulin and HOMA-B improved more with ALO+PIO than with PIO alone (P<0.01) ALO had no additional effect on HOMA-IR over PIO alone
DYNAMIC RELATIONSHIP BETWEEN GLUCOSE AND INSULIN AFTER NUTRIENT LOAD
T2DM, drug naïve [170]	SITA+MET for 52 wk	HOMA-B increased from 50.3±33.5 to 75.1±32.8 (P<0.01) OGTT IGI increased from 11.3±1.3 to 35.0±6.3 (P<0.01) Multivariate regression analysis: HbA_1c reduction significantly associated with high baseline HbA_1c, low IGI, and short duration of diabetes after adjusting for age, sex, BMI, blood pressure, triglycerides, creatinine, hsCRP, glucagon, C-peptide, HOMA-B, and HOMA-IR
T2DM [173]	ROSI or 70/30 insulin esc for 6 mo	Proinsulin-to-insulin ratio decreased with ROSI by 36% (P=0.03); no change with insulin IVGTT AIR_g improved with ROSI (P<0.001) IVGTT S_I (ISI) improved by 92.3% with ROSI; no improvement with insulin ROSI: IVGTT DI increased from 0.18 at BL to 4.18 (P=0.02); no change with insulin
T2DM [154]	LINA or PBO for 24 wk	Tests: HOMA-B, HOMA-IR, MTT, DI LINA improved HOMA-B (P=0.049 vs. PBO) and proinsulin/insulin ratio (P=0.025 vs. PBO); no change in HOMA-IR LINA: MTT 2-h PPG reduction from BL of -3.2±0.7 mmol/L (P<0.0001 vs. PBO) LINA: MTT DI improved (P=0.0005 vs. PBO)
T2DM [139]	VILDA or PBO on MET background for 52 wk	MTT insulin secretion increased with VILDA; reduced with PBO (P=0.018 between groups) MTT insulin sensitivity improved with VILDA; no change with PBO (P=0.036 between groups) Adaptation index (pre-hepatic insulin secretion x oral glucose insulin sensitivity) increased with VILDA; decreased with PBO (P=0.04) Change in adaptation index correlated with change in HbA_1c (r=-0.39; P=0.004)
T2DM, drug naïve [174]	VILDA or PBO for 24 wk	VILDA increased HOMA-B vs. BL (+10.3±1.5) and vs. PBO (P=0.01); decreased proinsulin-to-insulin ratio vs. BL (-0.05±0.01) and PBO (P<0.001) VILDA improved all MTT-derived parameters (P<0.05 vs. BL) VILDA improved MTT ISR/G (P<0.001) and IGI vs. PBO (P=0.045)
HYPERGLYCEMIC CLAMP WITH/WITHOUT ARGININE STIMULATION
T2DM, drug naïve [155]	SITA or PBO on MET background for 12 mo	SITA: Increased in HOMA-B and reduced HOMA-IR more than PBO (P<0.05) SITA, but not PBO, decreased proinsulin-to-insulin ratio (P<0.01 vs. BL) Clamp: SITA had greater improvements in first- and second-phase insulin response, M value, AIR_arg, and DI (P<0.05 vs. PBO) Regression analysis: Correlation between HbA_1c reduction and M value increase (P<0.034), greater first-phase insulin response (P<0.022), greater second-phase insulin response (P<0.025), AIR_arg (P<0.031), and DI (P<0.043)
T2DM, drug naïve [156]	VILDA or PBO on MET background for 12 mo	VILDA: Improved HOMA-B and HOMA-IR vs. PBO (P<0.05) Clamp: VILDA improved first- and second-phase insulin response, M value, AIR_arg, and DI vs. PBO (P<0.05)
T2DM, drug naïve [157]	ExBID or PBO on MET background for 12 mo	Tests: HOMA-B, HOMA-IR, proinsulin-to-insulin ratio, combined euglycemic-hyperinsulinemic and hyperglycemic clamp with arginine stimulation, first- and second-phase insulin secretion, M value, DI ExBID improved HOMA-B and HOMA-IR vs. PBO (P<0.05). No change in proinsulin-to-insulin ratio vs. PBO Clamp: ExBID improved M value (+34%) and DI (+55%) vs. PBO (P<0.05) Clamp: ExBID improved first- (+21%) and second-phase (+34%) insulin response, and AIR_arg (+25%) vs. PBO (P<0.05)
T2DM [151]	ExBID or ROSI on MET background for 20 wk	MTT PPG, PP insulin, and PP C-peptide decreased in all groups vs. BL (P<0.05) MTT: ExBID and ExBID+ROSI improved Matsuda index and DI vs. BL (P<0.05). For ROSI, Matsuda index improved vs. BL (P<0.05), but no change in DI vs. BL MTT: ExBID had a greater first-phase insulin response than ROSI (P=0.018) MTT: ExBID and ExBID+ROSI: Greater second-phase insulin response than ROSI (P<0.05) Clamp: ROSI and ExBID+ROSI: Improved M value vs. BL (P<0.05). No change with ExBID

Abbreviations: ALO, alogliptin; BCF, β-cell function; BID, twice daily; BL, baseline; BMI, body mass index; d, day(s); DI, disposition index; Esc, dose escalation allowed; Ex, exenatide; FPG, fasting plasma glucose; HbA_1c, glycated hemoglobin A_1c; HOMA, homeostasis model assessment; IGI, insulinogenic index; IGT, impaired glucose tolerance; IR, insulin resistance; ISI, insulin sensitivity index; ISR, insulin secretion rate; IVGTT, intravenous glucose tolerance test; LINA, linagliptin; mo, month(s); MET, metformin; MTT, mixed-meal tolerance test; OGTT, oral glucose tolerance test; PBO, placebo; PIO, pioglitazone; PP, postprandial; PPG, postprandial glucose; QD, once daily; QW, once weekly; ROSI, rosiglitazone; SAXA, saxagliptin; SITA, sitagliptin; T2DM, type 2 diabetes mellitus; VILDA, vildagliptin; vs., versus; wk, week(s); y, year(s).