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BackgroundWe 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).MethodsAnalyses 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.ResultsAt 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.ConclusionConsumption 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.

Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.

Despite major efforts to reduce atherosclerotic cardiovascular disease (ASCVD) burden with conventional risk factor control, significant residual risk remains. Recent evidence on non-traditional determinants of cardiometabolic health has advanced our understanding of lifestyle-disease interactions. Chronic exposure to environmental stressors like poor diet quality, sedentarism, ambient air pollution and noise, sleep deprivation and psychosocial stress affect numerous traditional and non-traditional intermediary pathways related to ASCVD. These include body composition, cardiorespiratory fitness, muscle strength and functionality and the intestinal microbiome, which are increasingly recognized as major determinants of cardiovascular health. Evidence points to partially overlapping mechanisms, including effects on inflammatory and nutrient sensing pathways, endocrine signalling, autonomic function and autophagy. Of particular relevance is the potential of low-risk lifestyle factors to impact on plaque vulnerability through altered adipose tissue and skeletal muscle phenotype and secretome. Collectively, low-risk lifestyle factors cause a set of phenotypic adaptations shifting tissue cross-talk from a proinflammatory milieu conducive for high-risk atherosclerosis to an anti-atherogenic milieu. The ketone body ß-hydroxybutyrate, through inhibition of the NLRP-3 inflammasome, is likely to be an intermediary for many of these observed benefits. Adhering to low-risk lifestyle factors adds to the prognostic value of optimal risk factor management, and benefit occurs even when the impact on conventional risk markers is discouragingly minimal or not present. The aims of this review are (a) to discuss novel lifestyle risk factors and their underlying biochemical principles and (b) to provide new perspectives on potentially more feasible recommendations to improve long-term adherence to low-risk lifestyle factors.

Depressive symptoms are prevalent among people with type 2 diabetes (T2D) and, even at low severity levels, are associated with worse diabetes outcomes. Carbohydrate restriction is an effective treatment for T2D but its long-term impacts on depressive symptoms are unclear. In the current study we explored changes in depressive symptoms over 2 years among 262 primarily non-depressed T2D patients participating in a continuous remote care intervention emphasizing carbohydrate restriction. Subclinical depressive symptoms decreased over the first 10 weeks and reductions were maintained out to 2 years. Increased frequency of blood ketone levels indicative of adherence to low carbohydrate eating predicted decreases in depressive symptoms. Concerns have been raised with recommending restrictive diets due to potential negative impacts on quality-of-life factors such as mood; however, results of the current study support positive rather than negative long-term impacts of closely monitored carbohydrate restriction on depressive symptoms., Author(s): Rebecca N. Adams [sup.1] , Shaminie J. Athinarayanan [sup.1] , Amy L. McKenzie [sup.1] , Sarah J. Hallberg [sup.1] [sup.2] , James P. McCarter [sup.3] [sup.4] , Stephen D. [...]

Urine color (Ucol) as a hydration assessment tool provides practicality, ease of use, and correlates moderately to strongly with urine specific gravity (Usg) and urine osmolality (Uosm). Indicative of daily fluid turnover, along with solute and urochrome excretion in 24-hr samples, Ucol may also reflect dietary composition. Thus, the purpose of this investigation was to determine the efficacy of Ucol as a hydration status biomarker after nutritional supplementation with beetroot (880 mg), vitamin C (1000 mg), and riboflavin (200 mg). Twenty males (Mean ± SD\ age, 21 ± 2 y; body mass, 82.12 ± 15.58 kg; height, 1.77 ± 0.06 m) consumed a standardized breakfast and collected all urine voids on one control day (CON) and 1 day after consuming a standardized breakfast and a randomized and double-blinded supplement (SUP) over 3 weeks. Participants replicated exercise and diet for one day before CON, and throughout CON and SUP. Ucol, Usg, Uosm, and urine volume were measured in all 24-hr samples, and Ucol and Usg were measured in all single samples. Ucol was a significant predictor of single sample Usg after all supplements (p < .05). Interestingly, 24-hr Ucol was not a significant predictor of 24-h Usg and Uosm after riboflavin supplementation (p = .20, p = .21). Further, there was a significant difference between CON and SUP 24-h Ucol only after riboflavin supplementation (p < .05). In conclusion, this investigation suggests that users of the UCC (urine color chart) should consider riboflavin supplementation when classifying hydration status and use a combination of urinary biomarkers (e.g., Usg and Ucol), both acutely and over 24 hr. [ABSTRACT FROM AUTHOR]

This field investigation assessed differences (e.g., drinking behavior, hydration status, perceptual ratings) between female and male endurance cyclists who completed a 164-km event in a hot environment (35 °C mean dry bulb) to inform rehydration recommendations for athletes. Three years of data were pooled to create 2 groups of cyclists: women (n = 15) and men (n = 88). Women were significantly smaller (p < .001) than men in height (166 ± 5 vs. 179 ± 7 cm), body mass (64.6 ± 7.3 vs. 86.4 ± 12.3 kg), and body mass index (BMI; 23.3 ±1.8 vs. 26.9 ± 3.4) and had lower preevent urinary indices of hydration status, but were similar to men in age (43 ± 7 years vs. 44 ± 9 years) and exercise time (7.77 ± 1.24 hr vs. 7.23 ± 1.75 hr). During the 164-km ride, women lost less body mass (-0.7 ± 1.0 vs. -1.7 ± 1.5 kg; -1.1 ± 1.6% vs. -1.9 ± 1.8% of body weight; p < .005) and consumed less fluid than men (4.80 ± 1.28 L vs. 5.59 ± 2.13 L; p < .005). Women consumed a similar volume of fluid as men, relative to body mass (milliliters/kilogram). To control for performance and anthropomorphic characteristics, 15 women were pair-matched with 15 men on the basis of exercise time on the course and BMI; urine-specific gravity, urine color, and body mass change (kilograms and percentage) were different (p < .05) in 4 of 6 comparisons. No gender differences were observed for ratings of thirst, thermal sensation, or perceived exertion. In conclusion, differences in relative fluid volume consumed and hydration indices suggest that professional sports medicine organizations should consider gender and individualized drinking plans when formulating pronouncements regarding rehydration during exercise. [ABSTRACT FROM AUTHOR]