Table 2.

Studies on ALA’s effect on insulin sensitivity (M and insulin sensitivity indexes) **.

[72] Jacob et al., 1996	Germany/T2D	ALA 100 mg/500 NaCl (intravenous infusion) or placebo	During glucose clamp study	Oral antihyperglycemic therapy	Mean insulin-mediated glucose disposal increased by about 50% in ALA group (from 3.76 mL/kg/min to 5.82 mL/kg/min, p < 0.05), no significant change in control group (from 3.57 mL/kg/min to 3.91 mL/kg/min)
[73] Jacob et al., 1999	Germany/T2D (About 20% of the patients exhibited diabetic complications)	ALA 600 mg, 1200 mg, 1800 mg or placebo (oral administration) per day	1 month	Oral antihyperglycemic therapy	No insulin-mediated glucose disposal differences between placebo and other groups. Insulin sensitivity significantly increased in all the active groups pooled together (+27%, p < 0.01) compared to placebo
[74] Kamenova et al., 2006	Greece/T2D	ALA 1200 mg (oral administration) per day. A group of normo-tolerant subjects served as control	One month	Metformin (850 mg once daily to three times daily)	Mean insulin-mediated glucose disposal significantly increased in ALA group (from 3.202 to 5.951 mg/kg/min, p < 0.01). and after treatment was not statistically different from control group.
[83] Masharani et al., 2010	USA/PCOS with oligomenorrhoea without hyperandrogenism	Controlled-release ALA 1200 mg per day (No control groups)	4 months	Oral contraceptives and/or spironolactone	Mean insulin-mediated glucose disposal significantly increased (from 9.7 ± 1.3 mg/min/kg/mU to 11.1 ± 1.7 mg/min/kg/mU after treatment). Two subjects not on oral contraceptives experienced a doubling of periods respect to four months prior to study entry.
[84] Xiao et al., 2011	Canada/Overweight and obese patients without history of diabetes	Patients were treated in random order with oral placebo followed by NaCl infusion (SAL), oral placebo followed by intralipid infusion (IH), oral ALA 1800 mg per day followed by NaCl infusion (ALA) and oral ALA 1800 mg per day followed by intralipid infusion (ALA + IH)	2 weeks each phase	No medications	Insulin sensitivity index and disposition were 19 and 25% lower in IH and IH + ALA, respectively, vs. SAL (p < 0.05), indicating lipid-inducedinsulin resistance. Insulin sensitivity in ALA was similar to SAL.

** Insulin-mediated glucose disposal (M) (mg/kg/min), insulin sensitivity index (l² × kg⁻¹ × min ⁻¹ × pmol⁻¹) and disposition index (l²× kg⁻¹ x min⁻²) are obtained from height, weight and glucose infusion rate (GIR) during the last 30–60 min of euglycemic hyper-insulinemic clamp.