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 Clinicaltrials.gov: NCT02519309. Registered 10 August 2015.

Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects

High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity.
Obese subjects (29.0-44.6 kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12 weeks.
The age range of subjects was 21-62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2h oral glucose tolerance test did not differ (P>0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet.
Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets.

Limited Effect of Dietary Saturated Fat on Plasma Saturated Fat in the Context of a Low Carbohydrate Diet

Authors showed that a hypocaloric carbohydrate restricted diet (CRD) had two striking effects: (1) a reduction in plasma saturated fatty acids (SFA) despite higher intake than a low fat diet, and (2) a decrease in inflammation despite a significant increase in arachidonic acid (ARA). These findings are consistent with the concept that dietary saturated fat is efficiently metabolize in the presence of low carbohydrate, and that a CRD results in better preservation of plasma ARA.

Weight Loss Leads to Reductions in Inflammatory Biomarkers After a Very Low-carbohydrate and Low-fat Diet in Overweight Men

The primary purpose of this study was to compare a very low-carbohydrate and a low-fat weight loss diet on inflammatory biomarkers in overweight men. Both the low-fat and the very low-carbohydrate diet resulted in significant decreases in absolute concentrations of hsTNF-alpha, hsIL-6, hs-CRP and sICAM-1. There was no significant change in absolute sP-selectin concentrations after either diet. In summary, energy-restricted low-fat and very low-carbohydrate diets both significantly decreased several biomarkers of inflammation. These data suggest that in the short-term weight loss is primarily the driving force underlying the reductions in most of the inflammatory biomarkers.

Diet-Induced Weight Loss Is Associated with Decreases in Plasma Serum Amyloid A and C-Reactive Protein Independent of Dietary Macronutrient Composition in Obese Subjects

The very low-carbohydrate dieters had a significantly greater decrease in LogSAA, but their weight loss also was significantly greater. In this study, the decreases in inflammatory markers correlated significantly with weight loss. Also, change in LogSAA correlated with change in insulin resistance. Thus, in otherwise healthy, obese women, weight loss was associated with significant decreases in both SAA and CRP. These effects were proportional to the amount of weight lost but independent of dietary macronutrient composition.

Comparison of Low Fat and Low Carbohydrate Diets on Circulating Fatty Acid Composition and Markers of Inflammation

Overweight men and women with atherogenic dyslipidemia consumed ad libitum diets very low in carbohydrate (VLCKD) or low in fat (LFD) for 12 weeks. Both diets significantly decreased the concentration of several serum inflammatory markers, but there was an overall greater anti-inflammatory effect associated with the VLCKD. In summary, a very low carbohydrate diet resulted in profound alterations in fatty acid composition and reduced inflammation compared to a low fat diet.