An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial.

A greater percentage of participants lost at least 5% of their body weight in the LC intervention versus the control group. Participants in the intervention group lowered their triglyceride levels more than participants in the control group  Dropout was 8% (1/12) and 46% (6/13) for the intervention and control groups, respectively (P=.07). The online delivery of this approach gives it the potential to have wider impact in the  treatment of type 2 diabetes.

A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes

Background: Type 2 diabetes (T2D) is typically managed with a reduced fat diet plus glucose-lowering medications, the latter often promoting weight gain.

Objective: We evaluated whether individuals with T2D could be taught by either on-site group or remote means to sustain adequate carbohydrate restriction to achieve nutritional ketosis as part of a comprehensive intervention, thereby improving glycemic control, decreasing medication use, and allowing clinically relevant weight loss.

Methods: This study was a nonrandomized, parallel arm, outpatient intervention. Adults with T2D (N=262; mean age 54, SD 8, years; mean body mass index 41, SD 8, kg·m−2; 66.8% (175/262) women) were enrolled in an outpatient protocol providing intensive nutrition and behavioral counseling, digital coaching and education platform, and physician-guided medication management. A total of 238 participants completed the first 10 weeks. Body weight, capillary blood glucose, and beta-hydroxybutyrate (BOHB) levels were recorded daily using a mobile interface. Hemoglobin A1c(HbA1c) and related biomarkers of T2D were evaluated at baseline and 10-week follow-up.

Results: Baseline HbA1c level was 7.6% (SD 1.5%) and only 52/262 (19.8%) participants had an HbA1c level of <6.5%. After 10 weeks, HbA1c level was reduced by 1.0% (SD 1.1%; 95% CI 0.9% to 1.1%, P<.001), and the percentage of individuals with an HbA1c level of <6.5% increased to 56.1% (147/262). The majority of participants (234/262, 89.3%) were taking at least one diabetes medication at baseline. By 10 weeks, 133/234 (56.8%) individuals had one or more diabetes medications reduced or eliminated. At follow-up, 47.7% of participants (125/262) achieved an HbA1c level of <6.5% while taking metformin only (n=86) or no diabetes medications (n=39). Mean body mass reduction was 7.2% (SD 3.7%; 95% CI 5.8% to 7.7%, P<.001) from baseline (117, SD 26, kg). Mean BOHB over 10 weeks was 0.6 (SD 0.6) mmol·L−1 indicating consistent carbohydrate restriction. Post hoc comparison of the remote versus on-site means of education revealed no effect of delivery method on change in HbA1c (F1,260=1.503, P=.22).

Conclusions: These initial results indicate that an individualized program delivered and supported remotely that incorporates nutritional ketosis can be highly effective in improving glycemic control and weight loss in adults with T2D while significantly decreasing medication use.

Implementing a low-carbohydrate, ketogenic diet to manage type 2 diabetes mellitus.

Abstract: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the modern world. For individuals affected by obesity-related T2DM, clinical studies have shown that carbohydrate restriction and weight loss can improve hyperglycemia, obesity, and T2DM. Areas covered: Reducing carbohydrate intake to a certain level, typically below 50 g per day, leads to increased ketogenesis in order to provide fuel for the body. Such low-carbohydrate, ketogenic diets were employed to treat obesity and diabetes in the 19th and early 20th centuries. Recent clinical research has reinvigorated the use of the ketogenic diet for individuals with obesity and diabetes. Although characterized by chronic hyperglycemia, the underlying cause of T2DM is hyperinsulinemia and insulin resistance, typically as a result of increased energy intake leading to obesity. The ketogenic diet substantially reduces the glycemic response that results from dietary carbohydrate as well as improves the underlying insulin resistance. This review combines a literature search of the published science and practical guidance based on clinical experience. Expert commentary: While the current treatment of T2DM emphasizes drug treatment and a higher carbohydrate diet, the ketogenic diet is an effective alternative that relies less on medication, and may even be a preferable option when medications are not available.

Effects of low-carbohydrate- compared with low-fat-diet interventions on metabolic control in people with type 2 diabetes: a systematic review including GRADE assessments.

Glycated hemoglobin declined more in people who consumed low carbohydrate food than in those who consumed low-fat food in the short term. There is low to high (majority moderate) certainty for small improvements of unclear clinical importance in plasma glucose, triglycerides, and HDL concentrations favoring low carbohydrate food at half of the prespecified time points. Currently available data provide low- to moderate certainty evidence that dietary carbohydrate restriction to a maximum of 40% yields slightly better metabolic control of uncertain clinical importance than reduction in fat to a maximum of 30% in people with T2D.

Outcomes of a Digitally Delivered Low-Carbohydrate Type 2 Diabetes Self-Management Program: 1-Year Results of a Single-Arm Longitudinal Study

Of the 743 participants with a starting HbA1c at or above the type 2 diabetes threshold of 6.5%, 195 (26.2%) reduced their HbA1c to below the threshold while taking no glucose-lowering medications or just metformin. Of the participants who were taking at least one hypoglycemic medication at baseline, 40.4% (289/714) reduced one or more of these medications. Almost half (46.40%, 464/1000) of all participants lost at least 5% of their body weight. Overall, glycemic control and weight loss improved, especially for participants who completed all 10 modules of the program. For example, participants with elevated baseline HbA1c (≥7.5%) who engaged with all 10 weekly modules reduced their HbA1c from 9.2% to 7.1% (P<.001) and lost an average of 6.9% of their body weight (P<.001).

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.

Effect of dietary carbohydrate restriction on glycemic control in adults with diabetes: A systematic review and meta-analysis.

Carbohydrate-restricted diets, in particular those that restrict carbohydrate to < 26% of total energy, produced greater reductions in HbA1c at 3 months (WMD -0.47%, 95% CI: -0.71, -0.23) and 6 months (WMD -0.36%, 95% CI: -0.62, -0.09), with no significant difference at 12 or 24 months. There was no difference between moderately restricted (26-45% of total energy) and high carbohydrate diets at any time point. Although there are issues with the quality of the evidence, this review suggests that carbohydrate-restricted diets could be offered to people living with diabetes as part of an individualised management plan.

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. 

Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study.


Cardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.


We investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons.


The CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m-2). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (- 4.9%, P = 0.02), small LDL-P (- 20.8%, P = 1.2 × 10-12), LDL-P size (+ 1.1%, P = 6.0 × 10-10), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10-16), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 × 10-7), triglyceride/HDL-C ratio (- 29.1%, P < 10-16), large VLDL-P (- 38.9%, P = 4.2 × 10-15), and LDL-C (+ 9.9%, P = 4.9 × 10-5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10-7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 × 10-5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10-5). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m-2] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C.


A continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased. Trial registration NCT02519309. Registered 10 August 2015.

Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance

Author’s abstract:


Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states.


Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR).


The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia.


Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to 30% compared to no such changes after three 60%-carbohydrate meals, an effect that was independent of pre-meal exercise. The parallel timing and magnitude of postprandial insulin and GIP changes suggest their dependence on a delayed intestinal adaptation to a low-carbohydrate diet. Pre-meal exercise exacerbated glucose intolerance with both diets most likely due to impairment of insulin signaling by pre-meal elevation of FFAs.