High glycemic variability has been associated with increased oxidative stress and β-cell dysfunction. To test whether changes in glycemic variability impact β-cell function and oxidative stress markers in adults with prediabetes, we conducted an RCT where we provided study subjects controlled diets varying in glycemic index (GI) to experimentally manipulate post-prandial glucose excursions. After 2 weeks on a control diet (mean GI= 55-58), subjects were randomized to 1 of 3 groups for 4 weeks: low (LGI <35) GI diet, high (HGI >70) GI diet plus the anti-oxidant N-acetylcysteine (HGI/NAC) 600 mg BID or HGI diet plus placebo (HGI/PLAC). Subjects underwent CGMS (iPro), fasting markers of oxidative stress (GSH/GSSG and TBARS) and an IVGTT at the end of each diet. Independent t-test was used to test the intervention effect on the change in disposition index (DI), a marker of β-cell function. Fifty-two subjects (26M/26F, age 53±10 y, BMI 32.1±6.2 kg/m2) with IFG and/or IGT completed the study (18 LGI, 17 HGI/NAC, 17 HGI/PLAC). The 3 groups did not differ by sex, age, BMI, A1c, fasting or 2 h glucose (ANOVA). On the control diet, DI was inversely correlated with CGMS mean daily glucose (r=-0.33, p=0.02) and daily SD glucose (r=-0.31, p=0.03) and the GSH/GSSG ratio (r=-0.35, p=0.01), but not TBARS (r=0.13, p=0.4). Compared to LGI, HGI/PLAC increased mean CGMS glucose (change -1.4±1.9 LGI vs. 4.6±2.4 HGI/PLAC mg/dl, p=0.05) and SD (change -2.6±1.3 vs. 5.0±2.2, p=0.005). Results did not differ between HGI/PLAC and HGI/NAC. There were no significant intervention effects on DI, TBARS or GSH/GSSG ratio. Changes in CGMS mean glucose and SD and oxidative stress markers did not correlate with changes in DI.
In conclusion, GI diet-induced changes in glucose concentrations and variability did not impact β-cell function or oxidative stress markers. These results suggest that glucose variability may be a consequence of β-cell dysfunction rather than a cause.
K. Utzschneider: Consultant; Self; Novo Nordisk Inc.. T.N. Johnson: None. K. Breymeyer: None. M.L. Neuhouser: None.