RESULTS  

The researchers included 230 participants in eight trials, including both trials that examined long-term changes (more than two months and less than two years) and short-term changes (in two-hour postprandial values). CL resulted in a slight to no difference in HbA1c (mean difference (MD), -0.21% in the intervention group; 95% CI -0.44% to+0.03%), plasma glucose (MD,+4.94mg/dL; 95% CI -8.34mg/dL to +18.22mg/dL), plasma insulin (MD, -3.63µIU/mL; 95% CI -11.88µIU/mL to +4.61µIU/mL), plasma GLP-1 (MD, +0.43pmol/L; 95% CI -0.69pmol/L to +1.56pmol/L), and plasma GIP (MD, -2.02pmol/L; 95% CI -12.34pmol/L to +8.31pmol/L). All these outcomes were of low-certainty evidence or very low-certainty evidence. None of the trials evaluated quality of life or adverse events. 

CONCLUSIONS  

There was no evidence for the potential efficacy of recommending CL beyond standard dietary advice on T2DM. 

DISCUSSION 

Regarding primary outcomes, carbohydrate-later meal patterns may result in a slight to no difference in HbA1c after two months to two years. Similarly, for secondary outcomes, carbohydrate-later meal patterns may result in a slight to no difference in plasma glucose, insulin and incretin 120 minutes after meals.  

Given the effect size of -0.21% in HbA1c (as an absolute value) over two months or longer, the meal sequence may not need to be positively taught in clinical practice. In the current diabetes guidelines, diet and exercise therapy are fundamental for the management of diabetes. A systematic review of obese patients with type 2 diabetes reported that a weight loss of 5% or more resulted in reduction of HbA1c by 0.91% after one year, and total energy intake and appropriate BMI were emphasised as the most important factors. Although there is no clear evidence on nutrient intake proportions, a RCT reported that a low-carbohydrate diet resulted in reduction of HbA1c by 0.6% after six months. Regarding lipids, a previous systematic review reported that a diet with increased monounsaturated fatty acids produced reduction of HbA1c by 0.21% after six months compared with a diet that decreased it. Furthermore, a systematic review on exercise therapy reported that exercise for more than 12 weeks lowered HbA1c by 0.67%. The reduction of HbA1c by 0.21% due to the meal sequence in the present study was not as large as those by diet and exercise in these studies. In addition, a previous systematic review found that HbA1c lowering <0.3% had no effect, whereas HbA1c lowering ≥0.5% had a -13% (95% CI -20% to -5%) effect on major cardiovascular events. Therefore, a reduction of HbA1c by 0.21% is not considered to be a value with a certain effect and, thus, the meal sequence may not need to be intensively taught in clinical practice. 

As a clinical implication, it may be better to prioritise conventional diet and exercise therapy. The clinical utility of the meal sequence remains unclear. In actual clinical practice, there are time and cost restrictions on dietary guidance. In the current dietary guidelines for diabetes care, dietitians and other healthcare providers initially prioritise the energy balance for patients with type 2 diabetes, particularly obese patients.  

In other words, they provide guidance to reduce total energy intake and increase physical activity. They then recommend an exercise strategy based on aerobic exercise, resistance exercise, or a combination. If more time is available or in consideration of other diseases, such as dyslipidaemia, hypertension, and renal disease, a change in nutrient intake proportions and food intake may also be advised. The results of the present study suggest that the efficacy of the meal sequence on diabetes do not outweigh the importance of a known total energy balance (including energy restrictions, appropriate BMI, and exercise regimens), nutrient intake and food content. Instructions by the meal sequence are not harmful. However, in consideration of the time and costs associated with counselling patients with diabetes, it may be more beneficial to prioritise conventional diet and exercise.   

SIGNIFICANCE OF THIS STUDY 

What is already known about this subject? 

• The number of patients with diabetes worldwide is expected to increase and those with type 2 diabetes always initially require lifestyle guidance, including diet and exercise
• Current dietary strategies to attenuate postprandial glucose are based on total energy intake and consumption and the amount or type of carbohydrate consumed despite the difficulties associated with adhering to a healthy diet by some patients
• A meal sequence, the carbohydrate-later meal pattern, was focused on as an easy and effective strategy to reduce postprandial glucose excursions in previous trials.

What are the new findings? 

• The authors conducted a systematic review and meta-analysis to confirm whether the meal sequence, the carbohydrate-later meal pattern, would affect outcomes of diabetes
• Carbohydrate-later meal patterns may result in a slight to no difference in HbA1c after two months to two years. Similarly, carbohydrate-later meal patterns may result in a slight to no difference in plasma glucose, insulin and incretin 120 min after meals
• There was no evidence for the potential efficacy of recommending carbohydrate-later meal patterns beyond standard dietary advice on type 2 diabetes.

How might these results change the focus of research or clinical practice? 

• These results suggest that the meal sequence will not be strongly prioritised in clinical practice
• Further large scale, well-designed randomised controlled trials (RCTs) of the meal sequence are warranted.

REFERENCES:  

Okami Y, Tsunoda H, Watanabe J, et al. Efficacy of a meal sequence in patients with type 2 diabetes: a systematic review and meta-analysis BMJ Open Diabetes Research and Care 2022;10: e002534. doi: 10.1136/bmjdrc-2021-002534.