Previous reports of the effect of dietary carbohydrate restriction on glucose excursion were limited to evaluation by the glucose tolerance test (Himsworth 1940; Wang et al. 1999; Numao et al. 2012). There were unclear points on the influence on glucose metabolism in actual dietary life. The present study by CGM showed that after extreme restriction of carbohydrate, an influence on the blood glucose variability persisted for at least 24 hours in healthy subjects. After dietary carbohydrate restriction for one day, the glucose fluctuation on the following day after the LC/HF diet increased significantly, compared with the fluctuations on days after the ingestion of an NC diet. In particular, the postprandial glucose levels were elevated after breakfast and dinner.
Some researchers have examined glucose loading as a possible cause of the blood glucose fluctuations (Randle et al. 1963; Anderson and Herman 1975; Wang et al. 1999; Numao et al. 2012). Numao et al. (2012) observed that early insulin secretion was lower and post-load blood glucose levels and plasma glucagon-like peptide 1 (GLP-1) levels were higher after the consumption of a low-carbohydrate/high-fat diet for 3 days, compared with those after the consumption of a normal carbohydrate/fat diet for 3 days. Previous studies have indicated that the plasma FFA levels also increase after dietary carbohydrate restriction and that this increase in the FFA levels might be associated with exaggerated post-load blood glucose excursions (Randle et al. 1963; Wang et al. 1999). Anderson and Herman (1975) have suggested that the high fat content associated with low-carbohydrate diets is responsible for the deterioration in the post-load blood glucose levels, rather than the low-carbohydrate content of these diets. Considering these prior studies, both insulin resistance caused by a high FFA plasma level and a decrease in first-phase insulin secretion after a LC/HF diet might have induced the glucose fluctuations observed in this study.
In our results, the AUC/4h/140 after lunch was equivalent on D2 and D4, unlike after breakfast and dinner. According to studies using CGM in patients with type 2 diabetes, exercise significantly decreases the postprandial glucose level, but not the fasting glucose level (MacLeod et al. 2013). Although we did not evaluate the subjects’ activity levels, glucose fluctuations after lunch might be more strongly affected by daytime activity.
Postprandial hyperglycemia has been reported to be a risk factor for cardiovascular events in non-diabetic patients (Tominaga et al. 1999) as well as diabetic patients (Ceriello et al. 2004). Hyperglycemia after glucose loading has been reported to inhibit endothelial flow-mediated dilatation (FMD), which is a measure of the endothelial function that is used to evaluate the cardiovascular risk. Suppression of FMD has been reported by oral glucose loading in subjects with impaired glucose tolerance or diabetes (Kawano et al. 1999) and normal glucose tolerance (Title et al. 2000). In this study, a diet with extreme change in dietary carbohydrate and fat content induced greater blood glucose excursions than a balanced-nutrient diet. These findings suggest that extreme changes in the dietary nutrient balance could induce higher blood glucose fluctuation and have adverse effects in daily life. It also suggests that if an extremely low-carbohydrate diet is stopped abruptly, it could cause a larger degree of postprandial hyperglycemia than an ordinary diet. A gradual re-increase in glucose would probably prevent postprandial hyperglycemia after an extremely low-carbohydrate diet.
This study had several limitations. First, we did not observe the changes in the levels of the insulin, C-peptide, GLP-1, and FFA, and could not assess whether the increase in the postprandial blood glucose levels on the day after carbohydrate restriction was caused by a decrease in insulin secretion or increase in insulin resistance. However, considering the previous studies mentioned above, both elements would affect this result. Second, we did not conduct a glucose tolerance test in the subjects before they were enrolled in this study. Although none of the subjects had a history of diabetes and all of them had HbA1c levels within the normal range (Table 1), we could not distinguish whether the glucose tolerance of the participants was normal or impaired. Third, the observation period was relatively short. An appropriate observation period should include the term during which the influence of the glucose fluctuation recovers after an LC/HF diet. Finally the number of subjects was also small. A larger sample size is needed to compare differences between the sexes. However, we are the first to precisely investigate, by CGM, the around 24-hours effect of a LC/HF diet on the blood glucose profile.
In conclusion, low-carbohydrate/high-fat diets, even for a short duration, can induce increasing blood glucose fluctuations that lasted for at least all of the following day in actual dietary life. Specifically, we found significant increases in the 24-hour SD, MAGE, AUC/4h/140 after breakfast and dinner, and the AUC above the mean blood glucose level plus one SD on the following day after the ingestion of an LC/HF diet, compared with those values on the day after the ingestion of an NC diet.
Further studies on a larger number of subjects and precise glucose and hormonal investigations with varying carbohydrate contents in the test meals are required to confirm the influence of low-carbohydrate/high-fat diets on the blood glucose fluctuation.