Paleo Nutritional Intervention for Type 2 Diabetes Mellitus: A Systematic Reevaluation and Consensus Report; Definition and Macronutrient Proposal for Trials

Background: Dietary interventions, including the Paleo diet (PD) play a crucial role in the treatment of patients with type 2 diabetes mellitus (T2DM). However, the clinical significance of them remains ambiguous due to limited conclusive studies. Objective: We conducted a systematic review to reevaluate existing research on the PD in individuals with T2DM, specifically focusing on whether this diet demonstrates a discernible improvement in metabolic biomarkers, further aiming to assess variables of interest (clinical definition, macronutrient ranges, and glycemic index of a PD) across trials. Methods: Online databases were searched for clinical trials and systematic reviews that included the PD as an intervention on patients with T2DM, from which 32 publications were selected. A random effects model was utilized to assess the difference in reported metabolic biomarkers from baseline to end-of-intervention time point. Variables of interest were analyzed across trials. Results: Four articles met inclusion criteria. The overall effect for the PD intervention across pooled studies was only significant for DBP (P<.001). Significant heterogeneity was found among pooled studies for the PD (FBG [P=0.03; I2=67%], glucose AUC0-120 [P=.002; I2=84%], SBP [P<.001; I2=93%], TC [P=.007; I2=80%], LDL [P < 0.001; I2=99%], and TG [P=0.04; I2=69%]) and the control diets (wt [P<.001; I2=99%], wc [P<.001; I2=99%], sodium:potassium ratio [P<.001; I2 = 96%], and HDL [P<.001; I2=87%]). A PD definition, macronutrient ranges, and glycemic index was proposed for conducting future trials. Conclusion: The inconclusiveness of the PD for T2DM was due to a number of inconsistencies across trials and systematic reviews. As a result, we propose consistency of PD definition (archeological definition and no modern-day interpretations, assumptions, or allowances of excluded foods), standardized macronutrient percentages, disease diagnosis, trial time length, and equal training across groups for all future trials. A standard control diet, such as the ADA diet, should be used as a comparison. The reduction in DBP across pooled results suggests that the PD may have a beneficial impact on metabolic markers related to T2DM.