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

Additional file 1: Table S1. Detailed baseline characteristics for participants in the continuous care intervention (CCI) and usual care (UC) groups

Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: An open-label, non-randomised controlled study

OBJECTIVE: One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS: This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS: At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). CONCLUSIONS: One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D

Raisins and additional walking have distinct effects on plasma lipids and inflammatory cytokines

<p>Abstract</p> <p>Background</p> <p>Raisins are a significant source of dietary fiber and polyphenols, which may reduce cardiovascular disease (CVD) risk by affecting lipoprotein metabolism and inflammation. Walking represents a low intensity exercise intervention that may also reduce CVD risk. The purpose of this study was to determine the effects of consuming raisins, increasing steps walked, or a combination of these interventions on blood pressure, plasma lipids, glucose, insulin and inflammatory cytokines.</p> <p>Results</p> <p>Thirty-four men and postmenopausal women were matched for weight and gender and randomly assigned to consume 1 cup raisins/d (RAISIN), increase the amount of steps walked/d (WALK) or a combination of both interventions (RAISINS + WALK). The subjects completed a 2 wk run-in period, followed by a 6 wk intervention. Systolic blood pressure was reduced for all subjects (P = 0.008). Plasma total cholesterol was decreased by 9.4% for all subjects (P < 0.005), which was explained by a 13.7% reduction in plasma LDL cholesterol (LDL-C) (P < 0.001). Plasma triglycerides (TG) concentrations were decreased by 19.5% for WALK (P < 0.05 for group effect). Plasma TNF-α was decreased from 3.5 ng/L to 2.1 ng/L for RAISIN (P < 0.025 for time and group × time effect). All subjects had a reduction in plasma sICAM-1 (P < 0.01).</p> <p>Conclusion</p> <p>This research shows that simple lifestyle modifications such as adding raisins to the diet or increasing steps walked have distinct beneficial effects on CVD risk.</p

Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations

Reproducibility of ambulatory blood pressure changes from the initial values on two different days

OBJECTIVE: We tested the reproducibility of changes in the ambulatory blood pressure (BP) from the initial values, an indicator of BP reactivity and cardiovascular health outcomes, in young, healthy adults. METHOD: The subjects wore an ambulatory BP monitor attached by the same investigator at the same time of day until the next morning on two different days (day 1 and day 2) separated by a week. We compared the ambulatory BP change from the initial values at hourly intervals over 24 waking and sleeping hours on days 1 and 2 using linear regression and repeated measures analysis of covariance. RESULTS: The subjects comprised 88 men and 57 women (mean age±SE 22.4±0.3 years) with normal BP (118.3±0.9/69.7±0.6 mmHg). For the total sample, the correlation between the ambulatory BP change on day 1 vs. day 2 over 24, waking, and sleeping hours ranged from 0.37-0.61; among women, the correlation was 0.38-0.71, and among men, it was 0.24-0.52. Among women, the ambulatory systolic/diastolic BP change was greater by 3.1±1.0/2.4±0.8 mmHg over 24 hours and by 3.0±1.1/2.4±0.8 mmHg over waking hours on day 1 than on day 2. The diastolic ambulatory BP change during sleeping hours was greater by 2.2±0.9 mmHg on day 1 than on day 2, but the systolic ambulatory BP change during sleeping hours on days 1 and 2 did not differ. Among men, the ambulatory BP change on days 1 and 2 did not differ. CONCLUSION: Our primary findings were that the ambulatory BP change from the initial values was moderately reproducible; however, it was more reproducible in men than in women. These results suggest that women, but not men, may experience an alerting reaction to initially wearing the ambulatory BP monitor

Effects of a carbohydrate-restricted diet on emerging plasma markers for cardiovascular disease

BACKGROUND: Increasing evidence supports carbohydrate restricted diets (CRD) for weight loss and improvement in traditional markers for cardiovascular disease (CVD); less is known regarding emerging CVD risk factors. We previously reported that a weight loss intervention based on a CRD (% carbohydrate:fat:protein = 13:60:27) led to a mean weight loss of 7.5 kg and a 20% reduction of abdominal fat in 29 overweight men. This group showed reduction in plasma LDL-cholesterol and triglycerides and elevations in HDL-cholesterol as well as reductions in large and medium VLDL particles and increases in LDL particle size. In this study we report on the effect of this intervention with and without fiber supplementation on plasma homocysteine, lipoprotein (a) [Lp(a)], C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). METHODS: Twenty nine overweight men [body mass index (BMI) 25–35 kg/m(2)] aged 20–69 years consumed an ad libitum CRD (% carbohydrate:fat:protein = 13:60:27) including a standard multivitamin every other day for 12 wk. Subjects were matched by age and BMI and randomly assigned to consume 3 g/d of either a soluble fiber supplement (n = 14) or placebo (n = 15). RESULTS: There were no group or interaction (fiber × time) main effects, but significant time effects were observed for several variables. Energy intake was spontaneously reduced (-30.5%). This was accompanied by an increase in protein intake (96.2 ± 29.8 g/d to 107.3 ± 29.7 g/d) and methionine intake (2.25 ± 0.7 g/d, to 2.71 ± 0.78 g/d; P < 0.001). Trans fatty acid intake was significantly reduced (-38.6%) while dietary folate was unchanged, as was plasma homocysteine. Bodyweight (-7.5 ± 2.5 kg) was reduced as was plasma Lp(a) (-11.3%). Changes in plasma Lp(a) correlated with reductions in LDL-cholesterol (r = .436, P < 0.05) and fat loss (r = .385, P < 0,05). At wk 12, both CRP (-8.1%) and TNF-α (-9.3%) were reduced (P < 0.05) independently of weight loss. IL-6 concentrations were unchanged. CONCLUSION: A diet based on restricting carbohydrates leads to spontaneous caloric reduction and subsequent improvement in emerging markers of CVD in overweight/obese men who are otherwise healthy

Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction

BACKGROUND: Diets that restrict carbohydrate (CHO) have proven to be a successful dietary treatment of obesity for many people, but the degree of weight loss varies across individuals. The extent to which genetic factors associate with the magnitude of weight loss induced by CHO restriction is unknown. We examined associations among polymorphisms in candidate genes and weight loss in order to understand the physiological factors influencing body weight responses to CHO restriction. METHODS: We screened for genetic associations with weight loss in 86 healthy adults who were instructed to restrict CHO to a level that induced a small level of ketosis (CHO ~10% of total energy). A total of 27 single nucleotide polymorphisms (SNPs) were selected from 15 candidate genes involved in fat digestion/metabolism, intracellular glucose metabolism, lipoprotein remodeling, and appetite regulation. Multiple linear regression was used to rank the SNPs according to probability of association, and the most significant associations were analyzed in greater detail. RESULTS: Mean weight loss was 6.4 kg. SNPs in the gastric lipase (LIPF), hepatic glycogen synthase (GYS2), cholesteryl ester transfer protein (CETP) and galanin (GAL) genes were significantly associated with weight loss. CONCLUSION: A strong association between weight loss induced by dietary CHO restriction and variability in genes regulating fat digestion, hepatic glucose metabolism, intravascular lipoprotein remodeling, and appetite were detected. These discoveries could provide clues to important physiologic adaptations underlying the body mass response to CHO restriction

Type 2 diabetes prevention focused on normalization of glycemia: A two-year pilot study

The purpose of this study is to assess the effects of an alternative approach to type 2 diabetes prevention. Ninety-six patients with prediabetes (age 52 (10) years; 80% female; BMI 39.2 (7.1) kg/