Acute metabolic responses to a high-carbohydrate meal in outpatients with type 2 diabetes treated with a low-carbohydrate diet: a crossover meal tolerance study

Abstract

Background: A low-carbohydrate diet (LCD) achieves good glycemic control in type 2 diabetes (T2DM) compared with a high-carbohydrate diet. With respect to energy metabolism, acute metabolic responses to high-carbohydrate meals (HCMs) have not been determined in LCD patients with T2DM.

Subjects and methods: We enrolled 31 subjects with T2DM (mean age: 62 yrs, mean hemoglobin A1c level: 6.9%), of whom 13 were on a strict LCD (26% carbohydrate diet), and 18 a moderate one (44% carbohydrate diet). Two isocaloric meals were administered to all subjects in a randomized crossover design. The carbohydrate:protein:fat ratios of HCMs and low-carbohydrate meals (LCMs) were 59:20:21 and 7:20:73, respectively. Serum beta-hydroxybutyrate, acetoacetate, free fatty acids (FFAs), triglyceride and insulin, and plasma glucose concentrations were measured for 120 minutes after the intake of each meal.

Results: HCMs rapidly decreased postprandial beta-hydroxybutyrate, acetoacetate and FFA concentrations within 2 hours in all patients in combination with rapid increases in serum insulin and plasma glucose, while LCMs increased or did not change beta-hydroxybutyrate, acetoacetate and FFAs (P < 0.001 for all). HCMs did not change postprandial triglyceride concentrations over 2 hours, while LCMs gradually increased them (P < 0.001). HCMs sharply and rapidly decreased postprandial beta-hydroxybutyrate and acetoacetate concentrations in strict LCD subjects over 2 hours, but only slightly decreased them in moderate LCD subjects (P < 0.001, difference between strict and moderate LCD subjects). The parameter Deltaketone bodies (level at 120 minutes - level at baseline) was significantly correlated with the insulinogenic index (Spearman's r = 0.503 for beta-hydroxybutyrate and 0.509 for acetoacetate), but not with total insulin secretory capacity. Moreover, HCMs slightly decreased postprandial triglyceride levels in strict LCD subjects but somewhat increased them in the moderate LCD subjects (P = 0.002). The parameter Deltatriglyceride was significantly correlated with background dietary %carbohydrate (Spearman's r = 0.484).

Conclusion: HCMs rapidly decreased postprandial ketone body concentrations in T2DM patients treated with a LCD. The decreases were more remarkable in strict than in moderate LCD subjects. HCMs slightly decreased postprandial triglyceride levels in strict LCD subjects. The parameter Deltaketone bodies was significantly correlated with the insulinogenic index, as was Deltatriglyceride with background dietary %carbohydrate.

Figure 1

Postprandial glucose and insulin concentrations under HCM (green) and LCM (orange) in all individual subjects. HCMs caused postprandial glucose and insulin concentrations to increase rapidly, while LCMs increased them only slightly (P < 0.001 for the difference between the two meals for both glucose and insulin).

Figure 2

Postprandial β-hydroxybutyrate, acetoacetate and FFA concentrations under HCM and LCM in all subjects. Vertical lines show means ± SD. HCMs (black square) rapidly decreased postprandial β-hydroxybutyrate, acetoacetate and FFA concentrations, while LCMs (white square) increased or did not change them (P < 0.001 for the difference between the two meals for β-hydroxybutyrate, acetoacetate and FFAs).

Figure 3

Postprandial triglyceride concentrations under HCM and LCM in all subjects. Vertical lines show means ± SD. LCMs (white square) increased postprandial triglyceride concentrations, while HCMs (black square) induced little change (P < 0.001 for the difference between the two meals).

Figure 4

Individual changes in postprandial β-hydroxybutyrate levels in the moderate (orange) and strict (blue) CARD subjects after the intake of HCM and LCM.

Figure 5

Individual changes in postprandial acetoacetate levels in the moderate (orange) and strict (blue) CARD subjects after the intake of HCM and LCM.

Figure 6

Individual changes in postprandial triglyceride levels in the moderate (orange) and strict (blue) CARD subjects after the intake of HCM and LCM.

Figure 7

The relationship between Δketone bodies (level at 120 minutes - level at baseline) and the insulinogenic index after the intake of HCM. Closed and open circles indicate subjects in the strict and moderate CARD groups, respectively. The parameter Δketone bodies was significantly correlated with the insulinogenic index (β-hydroxybutyrate: Spearman's r = 0.503, P = 0.004; acetoacetate: Spearman's r = 0.509, P = 0.003).

Figure 8

The relationship between Δtriglyceride or Δβ-hydroxybutyrate (level at 120 minutes - level at baseline) and background dietary %carbohydrate after the intake of HCM. Closed and open circles indicate subjects in the strict and moderate CARD groups, respectively. Background dietary %carbohydrate was strongly correlated with Δtriglyceride (Spearman's r = 0.484, P = 0.006) and was moderately correlated with Δβ-hydroxybutyrate (Spearman's r = 0.380, P = 0.035). Excluding the two subjects with a greatest decrease of serum triglycerides did not materially alter the association between Δtriglyceride and dietary %carbohydrate (Spearman's r = 0.487 [P = 0.007]).