The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial

Abstract

Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.

Keywords: cytokines; exercise; glucose; ketogenic diet.

Fig. 1.

Consolidated standards of reporting trials flow diagram. CVD, cardiovascular disease.

Fig. 2.

Mean glucose and mean amplitude of glycemic excursions (MAGEs) from continuous glucose monitoring during each 4-day diet intervention. Mean glucose (A) and MAGE (B) calculated from continuous glucose monitoring throughout each intervention. Fisher least-significant difference post hoc tests following significant one-way repeated-measures ANOVA; GL, low-fat low-glycemic index guidelines diet; LC, low-carbohydrate high-fat diet; LC+Ex, low-carbohydrate high-fat diet and exercise. †P ≤ 0.001 vs. CON. ‡P < 0.05 vs. LC.

Fig. 3.

Changes in (Δ) fasting glucose, C-peptide, insulin, and proinsulin following each 4-day diet intervention. Fasting glucose (A), fasting C-peptide (B), fasting insulin (C), and fasting proinsulin (D) presented as change scores (post − pre within each condition). Linear mixed models revealed a significant main effect of time for fasting glucose (P < 0.001) and a significant condition × time interaction for proinsulin (P < 0.001). GL, low-fat low-glycemic index guidelines diet; LC, low-carbohydrate high-fat diet; LC+Ex, low-carbohydrate high-fat diet and exercise. †P ≤ 0.01 and ‡P = 0.001 for preplanned contrast of post vs. pre within condition.

Fig. 4.

Changes in (Δ) peripheral blood mononuclear cells (PBMCs) phosphorylated c-Jun NH₂-terminal kinase (p-JNK) following each 4-day diet intervention. A: representative Western blot image showing total and p-JNK before (pre) and after (post) each intervention. Band intensities were expressed relative to a pooled sample of human PBMCs included in every blot (pool). B: data for p-JNK/total JNK presented as change scores (post − pre within each condition). Linear mixed models revealed a significant main effect of time for p-JNK (P < 0.05). GL, low-fat low-glycemic index guidelines diet; LC, low-carbohydrate high-fat diet; LC+Ex, low-carbohydrate high-fat diet and exercise. ‡P < 0.05 for preplanned contrast of post vs. pre within condition.

Fig. 5.

Changes in (Δ) monocyte-derived microparticles (MMPs) and leukocyte-derived microparticles (LMPs) following each 4-day diet intervention. MMPs (A) and LMPs (B) presented as change scores (post − pre within each condition). Linear mixed models revealed a significant condition × time interaction for MMPs (P < 0.05). GL, low-fat low-glycemic index guidelines diet; LC, low-carbohydrate high-fat diet; LC+Ex, low-carbohydrate high-fat diet and exercise. ‡P < 0.05 for preplanned contrast of post vs. pre within condition.