Efficacy of a Moderately Low Carbohydrate Diet in a 36-Month Observational Study of Japanese Patients with Type 2 Diabetes

AUTHOR’S ABSTRACT: We previously showed that a non-calorie-restricted, moderately low-carbohydrate diet (mLCD) is more effective than caloric restriction for glycemic and lipid profile control in patients with type 2 diabetes. To determine whether mLCD intervention is sustainable, effective, and safe over a long period, we performed a 36-month observational study. We sequentially enrolled 200 patients with type 2 diabetes and taught them how to follow the mLCD. We compared the following parameters pre- and post-dietary intervention in an outpatient setting: glycated hemoglobin (HbA1c), body weight, lipid profile (total cholesterol, low and high-density lipoprotein cholesterol, triglycerides), systolic and diastolic blood pressure, liver enzymes (aspartate aminotransferase, alanine aminotransferase), and renal function (urea nitrogen, creatinine, estimated glomerular filtration rate). Data from 157 participants were analyzed (43 were lost to follow-up). The following parameters decreased over the period of study: HbA1c (from 8.0 ± 1.5% to 7.5 ± 1.3%, p < 0.0001) and alanine aminotransferase (from 29.9 ± 23.6 to 26.2 ± 18.4 IL/L, p = 0.009). Parameters that increased were high-density lipoprotein cholesterol (from 58.9 ± 15.9 to 61.2 ± 17.4 mg/dL, p = 0.001) and urea nitrogen (from 15.9 ± 5.2 to 17.0 ± 5.4 mg/dL, p = 0.003). Over 36 months, the mLCD intervention showed sustained effectiveness (without safety concerns) in improving HbA1c, lipid profile, and liver enzymes in Japanese patients with type 2 diabetes.

Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.


Carbohydrate restriction markedly improves glycemic control in patients with type 2 diabetes (T2D) but necessitates prompt medication changes. Therefore, we assessed the effectiveness and safety of a novel care model providing continuous remote care with medication management based on biometric feedback combined with the metabolic approach of nutritional ketosis for T2D management.


We conducted an open-label, non-randomized, controlled, before-and-after 1-year study of this continuous care intervention (CCI) and usual care (UC). Primary outcomes were glycosylated hemoglobin (HbA1c), weight, and medication use. Secondary outcomes included fasting serum glucose and insulin, HOMA-IR, blood lipids and lipoproteins, liver and kidney function markers, and high-sensitivity C-reactive protein (hsCRP).


349 adults with T2D enrolled: CCI: n = 262 [mean (SD); 54 (8) years, 116.5 (25.9) kg, 40.4 (8.8) kg m2, 92% obese, 88% prescribed T2D medication]; UC: n = 87 (52 (10) years, 105.6 (22.15) kg, 36.72 (7.26) kg m2, 82% obese, 87% prescribed T2D medication]. 218 participants (83%) remained enrolled in the CCI at 1 year. Intention-to-treat analysis of the CCI (mean ± SE) revealed HbA1c declined from 59.6 ± 1.0 to 45.2 ± 0.8 mmol mol-1 (7.6 ± 0.09% to 6.3 ± 0.07%, P < 1.0 × 10-16), weight declined 13.8 ± 0.71 kg (P < 1.0 × 10-16), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 × 10-16). Insulin therapy was reduced or eliminated in 94% of users; sulfonylureas were entirely eliminated in the CCI. No adverse events were attributed to the CCI. Additional CCI 1-year effects were HOMA-IR – 55% (P = 3.2 × 10-5), hsCRP – 39% (P < 1.0 × 10-16), triglycerides – 24% (P < 1.0 × 10-16), HDL-cholesterol + 18% (P < 1.0 × 10-16), and LDL-cholesterol + 10% (P = 5.1 × 10-5); serum creatinine and liver enzymes (ALT, AST, and ALP) declined (P ≤ 0.0001), and apolipoprotein B was unchanged (P = 0.37). UC participants had no significant changes in biomarkers or T2D medication prescription at 1 year.


These results demonstrate that a novel metabolic and continuous remote care model can support adults with T2D to safely improve HbA1c, weight, and other biomarkers while reducing diabetes medication use. 

Renal Function Following Three Distinct Weight Loss Dietary Strategies During 2Years of a Randomized Controlled Trial

This study addressed the long-term effect of various diets, particularly low-carbohydrate high-protein, on renal function on participants with or without type 2 diabetes.
In the 2-year Dietary Intervention Randomized Controlled Trial (DIRECT), 318 participants (age, 51 years; 86% men; BMI, 31 kg/m(2); mean estimated glomerular filtration rate [eGFR], 70.5 mL/min/1.73 m(2); mean urine microalbumin-to-creatinine ratio, 12:12) with serum creatinine <176 μmol/L (eGFR ≥ 30 mL/min/1.73 m(2)) were randomized to low-fat, Mediterranean, or low-carbohydrate diets. The 2-year compliance was 85%, and the proportion of protein intake significantly increased to 22% of energy only in the low-carbohydrate diet (P < 0.05 vs. low-fat and Mediterranean). We examined changes in urinary microalbumin and eGFR, estimated by Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration formulas.
Significant (P < 0.05 within groups) improvements in eGFR were achieved in low-carbohydrate (+5.3% [95% CI 2.1-8.5]), Mediterranean (+5.2% [3.0-7.4]), and low-fat diets (+4.0% [0.9-7.1]) with similar magnitude (P > 0.05) across diet groups. The increased eGFR was at least as prominent in participants with (+6.7%) or without (+4.5%) type 2 diabetes or those with lower baseline renal function of eGFR <60 mL/min/1.73 m(2) (+7.1%) versus eGFR ≥ 60 mL/min/1.73 m(2) (+3.7%). In a multivariable model adjusted for age, sex, diet group, type 2 diabetes, use of ACE inhibitors, 2-year weight loss, and change in protein intake (confounders and univariate predictors), only a decrease in fasting insulin (β = -0.211; P = 0.004) and systolic blood pressure (β = -0.25; P < 0.001) were independently associated with increased eGFR. The urine microalbumin-to-creatinine ratio improved similarly across the diets, particularly among participants with baseline sex-adjusted microalbuminuria, with a mean change of -24.8 (P < 0.05).
A low-carbohydrate diet is as safe as Mediterranean or low-fat diets in preserving/improving renal function among moderately obese participants with or without type 2 diabetes, with baseline serum creatinine <176 μmol/L. Potential improvement is likely to be mediated by weight loss-induced improvements in insulin sensitivity and blood pressure.