In this study, both a low-glycemic index, reduced-calorie diet and a low-carbohydrate, ketogenic diet led to improvement in glycemic control, diabetic medication elimination/reduction, and weight loss in adherent overweight and obese individuals with type 2 diabetes over a 24-week period. The diet containing fewer carbohydrates, the LCKD, was most effective for improving glycemic control. In patients taking insulin, the effects were often quite powerful. For example, participants taking from 40 to 90 units of insulin before the study were able to eliminate their insulin use, while also improving glycemic control. Because this effect occurs immediately upon implementing the dietary changes, individuals with type 2 diabetes who are unable to adjust their own medication or self-monitor their blood glucose should not make these dietary changes unless under close medical supervision.
A low-carbohydrate, ketogenic diet combines two approaches that, on their own, improve blood glucose control: weight loss and a reduced-glycemic index diet. Weight loss via dietary modification has a beneficial effect on diabetes [27, 28]. A reduced-glycemic index diet without weight loss can also lead to improvement in diabetic control, with the magnitude of effect of a 0.43% reduction in hemoglobin A1c, when compared with higher-glycemic diets of similar carbohydrate content . The greater effect of the low-carbohydrate, ketogenic diet in this study appeared to be due to the lower carbohydrate intake, because statistical significance remained after adjustment for weight loss. Because "low-glycemic" diets in previous studies typically contain from 40–60% of calories from carbohydrate, it is possible that the beneficial effect of "low-glycemic" diets could be augmented by further reduction of the absolute amount of carbohydrate, or by a reduction in caloric content.
While this study was a treatment trial of individuals with type 2 diabetes, lifestyle modification has been shown to prevent type 2 diabetes in the Diabetes Prevention Program (DPP). The intensive lifestyle modification arm of the DPP included a calorie- and fat-restricted diet with an energy intake of 1380 kcal/day for women and 1583 kcal/day for men, and a percentage of energy from carbohydrate of 54% . While the effect was stronger than medication, the intensive lifestyle group developed diabetes at a rate of 20% after 4 years. Future research should include the use of lower-carbohydrate diets for the treatment and prevention of type 2 diabetes.
Like previous studies, we found that the LCKD led to weight reduction, improvement in glycemic control, and elevation in HDL-cholesterol, but no deterioration in fasting lipid parameters. Extending these findings, we observed that all metabolic syndrome components were improved by the LCKD . It is interesting to note that the LGID group reported consuming fewer calories than the LCKD group, yet had less weight loss. This may reflect problems with the diet data as collected, issues with differential physical activity, or metabolic inefficiency (leading to increased energy expenditure) which may occur during the consumption of a carbohydrate-restricted diet.
Limitations of this study include the lack of blinding of physicians and outcome assessors to treatment group, and the use of food records. The study participants were community volunteers, and predominantly women, which may limit generalization of these findings to clinical populations and men. The analysis and presentation of only detailed food records may bias the estimate of food intake. We chose the "completer analysis" as the primary outcome because we were interested in answering the question of what might be expected from patients who can adhere to the intervention. The LOCF analysis might generalize better to a population of patients who have different food preferences from their assigned diet, who lose/lack motivation, or who experience other barriers to dietary change. Another possible limitation is the baseline imbalance in the primary outcome, HgA1c, which occurred despite random allocation. The equation used to calculate energy requirements for the LGID participants may underestimate requirements, particularly in obese people. This would result in more severe energy restriction than the 500 kcal deficit as stated, which might bias the weight loss effects in favor of the LGID.
It is often presumed that obesity is the cause of type 2 diabetes, but there are clearly instances where obesity occurs without type 2 diabetes, and instances where type 2 diabetes occurs without obesity. In this study, the change in hemoglobin A1c was independent of the change in weight (Figure 2). This supports the concept that weight change and glycemic control are not serially linked but rather may be the result of the same pathophysiologic process, such as abnormal insulin metabolism.
The underlying principle of carbohydrate-restriction and the historic precedents of using the low-carbohydrate diet for type 2 diabetes suggest that the low-carbohydrate approach may be one of the most effective dietary treatments for diabetes. Our findings support this position, and it suggests that the burden of proof be placed upon alternative points of view. The dearth of randomized, controlled trials using the low-carbohydrate approach for type 2 diabetes, despite the historical and current clinical use of these approaches, challenges the idea that the randomized controlled trial should be the only guide of scientific inquiry and clinical practice.