Recently, the Japanese Diabetes Society relaxed their dietary approach, recommending a caloric restriction of 25–35 kcal/kg ideal body weight with carbohydrates composing 50–60% of total energy consumption. No other dietary approach is currently approved by the Japanese Diabetes Society guidelines [ 3 ]. In an endeavor to make dietary approaches more flexible and sustainable for diabetes patients in Japan, in August 2009 we adopted a non-calorie restricted, moderately low-carbohydrate diet (mLCD) with the approval of the Institutional Ethical Review Board of our hospital in Tokyo, Japan. In a randomized clinical trial, we found this mLCD to be more effective than caloric restriction for glycemic and lipid profile control in patients with type 2 diabetes [ 4 ]. However, this trial was limited to six months in duration. To evaluate the long-term efficacy and safety of mLCD as a sustainable dietary therapy and to check for rebound effects (which are common in dietary studies [ 5 ]), we conducted a 36-month observational study of patients with diabetes following our mLCD.

The most recent dietary guidelines of the American Diabetes Association (ADA) emphasize that no single diet is suitable for all people with diabetes, and likewise there is no ideal macronutrient balance [ 1 ]. Several dietary approaches have been proposed in Western countries for people with diabetes [ 1 2 ], with guidelines recommending that individuals discuss with health professionals (physicians and dietitians) which approach would be preferable, most effective, and sustainable for them.

2. Materials and Methods

We retrospectively enrolled 200 patients with type 2 diabetes who received outpatient treatment in Kitasato Institute Hospital, Tokyo, Japan between August 2009 and October 2016. Participants were instructed to restrict their carbohydrate intake to 20–40 g per meal and 70–130 g per day, with 10 g of carbohydrates consumed as a snack or drink at least once daily. Although we did not recommend any percentage of carbohydrate, fat, and protein to total caloric intake, it was 30:45:20 in our previous study [ 4 ]. A dietary salt restriction intervention was also performed on patients for whom it was deemed appropriate. Patients who injected insulin were recommended to monitor their capillary glucose levels frequently after mLCD was initiated.

At the first nutritional intervention and at six-month intervals thereafter, we measured the following: glycated hemoglobin (HbA1c), body weight, lipid profile (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG)), blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP)), liver enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT)), and renal function (urea nitrogen (UN), uric acid (UA), creatinine (Cr), estimated glomerular filtration rate (eGFR)). We also recorded the incidence of hypoglycemia (defined as self-monitored blood glucose levels less than 70 mg/dL, with or without hypoglycemic symptoms) for 2 months before the first intervention and for 2-month intervals during the intervention, and calculated the corresponding before/after ratios. Missing values were replaced with values obtained during the previous or following two months.

To investigate the interactions between response to the mLCD and participant baseline HbA1c level or body mass index (BMI, kg/m2), we conducted post hoc analyses. In one analysis, we classified participants according to their change in HbA1c during the 36 months of dietary intervention as follows: responder (decrease in HbA1c), unchanged (no change in HbA1c), or worsened (increase in HbA1c). In other analyses, we classified participants according to their baseline HbA1c (HbA1c < 7%, 7% ≤ HbA1c < 8%, 8% ≤ HbA1c < 9%, or 9% ≤ HbA1c) or BMI (BMI < 25, 25 ≤ BMI < 30, or 30 ≤ BMI).

Values are presented as the mean ± standard deviation (SD). Statistical analyses were performed using IBM SPSS 19 software (IBM Japan, Tokyo, Japan). We compared baseline and 36-month parameter values using the Wilcoxon signed-rank test. Multiple comparisons were made as appropriate using two-way analysis of variance (ANOVA).

This study was approved by the institutional review board of Kitasato Institution Hospital and performed in accordance with the Declaration of Helsinki. Informed consent was obtained in the form of an opt-out, by posting notices requesting that diabetes patients who had received guidance about low carbohydrate diets inform us if they did not want their records to be used for research purposes. This consent process was approved by the ethical review board at Kitasato Institution Hospital. All participants’ anonymity is preserved. This study was registered as clinical trial ID UMIN000022910.