Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes

Abstract Background We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over 2 years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT). Methods Analyses were performed in patients with T2D who completed 2 years of this study (CCI; n = 194; usual care (UC): n = 68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 years and CIMT was measured at baseline and 2 years. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles. Results At 2 years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the principal component (PC) representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group. Conclusion Consumption of a very low carbohydrate diet with nutritional ketosis for 2 years in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.

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Impact of A Two-Year Trial of Nutritional Ketosis on Indices of Cardiovascular Disease Risk in Patients With Type 2 Diabetes

10.21203/rs.3.rs-78136/v1 ◽

2020 ◽

Author(s):

Shaminie J. Athinarayanan ◽

Sarah J. Hallberg ◽

Amy L. McKenzie ◽

Katharina Lechner ◽

Sarah King ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Supporting Evidence ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Ldl Particles ◽

Low Carbohydrate ◽

Lipoprotein Subfraction ◽

The Impact

Abstract Background: We have previously reported that in patients with type 2 diabetes (T2D) consumption of a very low carbohydrate diet capable of inducing nutritional ketosis over two years (continuous care intervention, CCI) resulted in improved body weight, glycemic control, and multiple risk factors for cardiovascular disease (CVD) with the exception of an increase in low density lipoprotein cholesterol (LDL-C). In the present study, we report the impact of this intervention on markers of risk for atherosclerotic cardiovascular disease (CVD), with a focus on lipoprotein subfraction particle concentrations as well as carotid-artery intima-media thickness (CIMT). Methods: Analyses were performed in patients with T2D who completed 2 yrs of this study (CCI; n=194; usual care (UC): n=68). Lipoprotein subfraction particle concentrations were measured by ion mobility at baseline, 1, and 2 yrs and CIMT was measured at baseline and 2 yrs. Principal component analysis (PCA) was used to assess changes in independent clusters of lipoprotein particles.Results: At two years, CCI resulted in a 23% decrease of small LDL IIIb and a 29% increase of large LDL I with no change in total LDL particle concentration or ApoB. The change in proportion of smaller and larger LDL was reflected by reversal of the small LDL subclass phenotype B in a high proportion of CCI participants (48.1%) and a shift in the PC representing the atherogenic lipoprotein phenotype characteristic of T2D from a major to a secondary component of the total variance. The increase in LDL-C in the CCI group was mainly attributed to larger cholesterol-enriched LDL particles. CIMT showed no change in either the CCI or UC group.Conclusion: Consumption of a very low carbohydrate diet with nutritional ketosis for 2 yrs in patients with type 2 diabetes lowered levels of small LDL particles that are commonly increased in diabetic dyslipidemia and are a marker for heightened CVD risk. A corresponding increase in concentrations of larger LDL particles was responsible for higher levels of plasma LDL-C. The lack of increase in total LDL particles, ApoB, and in progression of CIMT, provide supporting evidence that this dietary intervention did not adversely affect risk of CVD.

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Faculty Opinions recommendation of Comparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1164017.624674 ◽

2009 ◽

Author(s):

Marion Franz

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Comparative Study ◽

Dietary Intervention ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Fat Diet ◽

Low Carbohydrate ◽

Diet Versus

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Low-carbohydrate diet scores and risk of type 2 diabetes in men

American Journal of Clinical Nutrition ◽

10.3945/ajcn.110.004333 ◽

2011 ◽

Vol 93 (4) ◽

pp. 844-850 ◽

Cited By ~ 62

Author(s):

Lawrence de Koning ◽

Teresa T Fung ◽

Xiaomei Liao ◽

Stephanie E Chiuve ◽

Eric B Rimm ◽

...

Keyword(s):

Type 2 Diabetes ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Carbohydrate

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Effect of Low-Carbohydrate Diet on Metabolism in Type 2 Diabetes Patients with the Aid of Intelligent Administration of Insulin-Loaded Nanoparticle

Nanoscience and Nanotechnology Letters ◽

10.1166/nnl.2020.3255 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1445-1451

Author(s):

Xiaofan Zhang ◽

Youyou Zhang ◽

Lingjia Gu ◽

Haiying Tao ◽

Shuang Zhu

Keyword(s):

Type 2 Diabetes ◽

Glucose Solution ◽

Fasting Blood Glucose ◽

High Concentration ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Carbohydrate ◽

Hba1c Levels ◽

Diabetes Patients

Nanoparticles play a major role in drug delivery. We investigated the effects of the intelligent administration of insulin-loaded nanoparticles (ILNP) when combined with a low-carbohydrate diet (LCD) on the metabolism of patients with type 2 diabetes. ILNP and smart vesicle polymers were developed, and their properties were studied in vitro. Further clinical trials were performed, during which body mass index (BMI), fasting blood glucose (FBG) levels, and glycated hemoglobin (HbA1c) levels were compared between type 2 diabetes patients on LCDs those on normal diets. The results demonstrated that ILNP resisted protease degradation due to steric hindrance, and remained relatively stable at a pH range of 5.0 to 7.4. The nanoparticle enteric-coated capsules resisted the gastric juice acidity (pH = 2.5) and ensured the stable embedding of the insulin. The insulin was then released at a slightly higher pH (pH = 6.6), which mimicked the small intestine. Smart vesicle polymers further embedded the insulin and glucose oxidase simultaneously in nano polymer compounds, which allowed for a dose-dependent response to the concentration of glucose. Thus, the insulin was not released in a low-concentration glucose solution, but rather in a high-concentration glucose solution. Based on these results, we concluded that the clinical trial results showed that the intelligent administration of ILNP combined with a LCD reduced BMI, FBG, and HbA1c levels in patients with type 2 diabetes.

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Low-carbohydrate diet by staple change attenuates postprandial GIP and CPR levels in type 2 diabetes patients

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2019.107415 ◽

2019 ◽

Vol 33 (11) ◽

pp. 107415 ◽

Cited By ~ 1

Author(s):

Mizuho Kondo-Ando ◽

Yusuke Seino ◽

Risa Morikawa ◽

Kana Negi ◽

Hidechika Todoroki ◽

...

Keyword(s):

Type 2 Diabetes ◽

Carbohydrate Diet ◽

Low Carbohydrate Diet ◽

Low Carbohydrate ◽

Diabetes Patients

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Differential effects of sodium-glucose cotransporter 2 inhibitor and low-carbohydrate diet on body composition and metabolic profile in obese diabetic db/db mice

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001303 ◽

2020 ◽

Vol 8 (1) ◽

pp. e001303

Author(s):

Toru Kusakabe ◽

Shigefumi Yokota ◽

Mika Shimizu ◽

Takayuki Inoue ◽

Masashi Tanaka ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Composition ◽

Metabolic Profile ◽

The Body ◽

Carbohydrate Diet ◽

Glucose Levels ◽

Low Carbohydrate Diet ◽

Sodium Glucose Cotransporter ◽

Low Carbohydrate

IntroductionTreatment using sodium-glucose cotransporter (SGLT) 2 inhibitor and low-carbohydrate diet (LCD) for obesity and type 2 diabetes are similar in terms of carbohydrate limitation. However, their mechanisms of action differ, and the effects on the body remain unclear. We investigated the effects of SGLT2 inhibitor and LCD on body composition and metabolic profile using the db/db mouse model for obesity and type 2 diabetes.Research design and methodsEight-week-old male db/db mice were divided into four groups: mice receiving normal diet and vehicle or canagliflozin (Cana) administration and mice receiving LCD and vehicle or Cana administration for 8 weeks. Consumed calories were adjusted to be equal among the groups.ResultsBoth Cana administration and LCD feeding resulted in significant weight gain. Cana administration significantly decreased plasma glucose levels and increased plasma insulin levels with preservation of pancreatic β cells. However, LCD feeding did not improve plasma glucose levels but deteriorated insulin sensitivity. LCD feeding significantly reduced liver weight and hepatic triglyceride content; these effects were not observed with Cana administration. Combined treatment with LCD did not lead to an additive increase in blood β-ketone levels.ConclusionsSGLT2 inhibitors and LCD exert differential effects on the body. Their combined use may achieve better metabolic improvements in obesity and type 2 diabetes.

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