(i) Reduced number of prediabetic individuals who progressed to type II DM [140]
(ii) Activates liver enzymes involved in glycolysis, gluconeogenesis, and lipid metabolism [141]
Bardoxolone methyl (CDDO-Me/RTA 402)
Synthetic (derivative of oleanolic acid)
Modification of Keap1 cysteine residues
(i) Efficacy in short-term clinical trials in patients with type II DM and CKD [107]
(ii) Did not reduce risk of end-stage renal disease (ESRD) or death from cardiovascular failure in patients with DM and stage IV CKD and was terminated early due to side effects [106]
Tert-butylhydroquinone (tBHQ)
Synthetic (preservative in unsaturated vegetable oils and edible animal fats)
Modification of Keap1 cysteine residues/activation of upstream kinases
(i) Prevented glucose-induced impairments in diabetic retinopathy [142]
Cinnamic aldehyde (CA)
Natural (found in bark of cinnamon tree)
Activation of upstream kinases
(i) Lowered blood glucose, total cholesterol, triglycerides, and increased HDL in diabetic rats and mice [143]
(ii) Prevented development of hypertension in conditions of insulin resistance [144]
(iii) Improved renal and glomerular function [110]
Resveratrol (RES)
Natural (polyphenol, found in the skin of red grapes, peanuts, and berries)