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Background: Malignant tumors of the breast are the most diagnosed cancers in females globally. Recent evidence suggests that carbohydrate restriction (CR), especially ketogenic diets, has become a potential treatment approach for many malignancies, including breast cancer. Tamoxifen (TAX) is a selective estrogen receptor modulator (ERM) that can reduce the risk of cancer recurrence. The current work was designed to assess the impact of CR on the proliferation of breast adenocarcinoma cells and to compare this impact with that of TAX. Study groups included: group 1: vehicle-treated mice; group 2: the Ehrlich group: injected Ehrlich ascites carcinoma (EAC) cells (2.5 × 106) in 0.25 ml isotonic saline; group 3: CR group: mice were supplied with a diet regimen of severe CR throughout the study and injected EAC at week 7; group 4: hormonal therapy (HT) group: mice in this group injected with EAC at week 7 and then received TAX at a dose of 20 mg/kg 3 times/week orally for 3 weeks; and lastly group 5: the group of combined intervention. The mice in the CR, HT, and the combined groups received Ehrlich cancer cells at the same dose and route as the Ehrlich group. Results: CR and HT groups demonstrated a significant decrease in levels of insulin-like growth factor (IGF-1), carbohydrate antigen (CA 15–3), hexokinase 2 (HK2), hypoxia-inducible factor-1 (HIF-1) α, and malondialdehyde (MDA) compared to the Ehrlich group. Additionally, the mean area % of caspase-3 was significantly increased, and the mean area % of Ki67 and estrogen receptor (ER)α was significantly decreased. Conclusions: The combined treatment demonstrated the most advantageous outcome, as evidenced by reduced CA 15–3 levels, tumor size, and the mean area % of Ki67. This suggests that the addition of severe CR to the conventional therapy of breast cancer has a beneficial effect. [ABSTRACT FROM AUTHOR]

Ketogenic diets (KDs) are an alternative to improve strength performance and body composition in resistance training participants. The objective of this review and meta-analysis is to verify whether a ketogenic diet produces an increase in the strength of resistance-trained participants. We have evaluated the effect of the ketogenic diet in conjunction with resistance training on the strength levels in trained participants. Boolean algorithms from various databases (PubMed, Scopus, and Web of Science) were used. Meta-analyses were carried out, one on the 1-RM squat (SQ), with 106 trained participants or athletes, and another on the 1-RM on the bench press (BP), evaluating 119 participants. We did not find significant differences between the groups in the variables of SQ or BP, although the size of the effect was slightly higher in the ketogenic group. Conclusions: KDs do not appear to impair 1-RM performance; however, this test does not appear to be the most optimal tool for assessing hypertrophy-based strength session performance in resistance-trained participants. [ABSTRACT FROM AUTHOR]

This study investigates the effects of a ketogenic low-carbohydrate high-fat (LCHF) diet on body composition in healthy, young, normal-weight women. With the increasing interest in ketogenic diets for their various health benefits, this research aims to understand their impact on body composition, focusing on women who are often underrepresented in such studies. Conducting a randomized controlled feeding trial with a crossover design, this study compares a ketogenic LCHF diet to a Swedish National Food Agency (NFA)-recommended control diet over four weeks. Seventeen healthy, young, normal-weight women adhered strictly to the provided diets, with ketosis confirmed through blood β-hydroxybutyrate concentrations. Dual-energy X-ray absorptiometry (DXA) was utilized for precise body composition measurements. To avoid bias, all statistical analyses were performed blind. The findings reveal that the ketogenic LCHF diet led to a significant reduction in both lean mass (−1.45 kg 95% CI: [−1.90;−1.00]; p < 0.001) and fat mass (−0.66 kg 95% CI: [−1.00;−0.32]; p < 0.001) compared to the control diet, despite similar energy intake and physical activity levels. This study concludes that while the ketogenic LCHF diet is effective for weight loss, it disproportionately reduces lean mass over fat mass, suggesting the need for concurrent strength training to mitigate muscle loss in women following this diet. [ABSTRACT FROM AUTHOR]

Carbohydrate restriction is not typically recommended for children with type 1 diabetes mellitus (T1DM) because of concerns regarding growth retardation, ketoacidosis, severe hypoglycemia, and dyslipidemia. There is no consensus regarding the effects of carbohydrate restriction on the growth of children with T1DM. However, some previously reported cases of T1DM exhibited growth retardation during carbohydrate restriction, whereas others showed no obvious impairment. A female child with T1DM exhibited severe height growth velocity impairment during carbohydrate restriction in early childhood. Her height standard deviation score (SDS) was 1.12 at the initial T1DM diagnosis (2 yr and 11 mo of age) and -1.33 at 4 yr and 8 mo of age. Her height velocity was only 1.7 cm/yr (SDS -7.02). Discontinuing carbohydrate restriction substantially improved her height growth velocity. Implementing a carbohydrate-restricted diet in children with T1DM can negatively affect height growth velocity. [ABSTRACT FROM AUTHOR]

Introduction: Interventions which improve the body composition and metabolic health of women with breast cancer are essential because they can improve the prognosis of this disease. Ketogenic diets have been suggested as complementary nutritional treatments for cancer patients. This systematic review was conducted with aim to determine the effect of ketogenic diets on the therapeutic and metabolic outcomes of breast cancer. Methods: In this systematic review, in order to find the related articles, Medline, Embase, Google Scholar, ScienceDirect, Magiran, SID, ISC, and Cochrane databases were searched with the keywords of low carbohydrate, carbohydrate restriction, Ketogenic diet, breast cancer, breast tumor, and breast neoplasms in English and Persian languages until November 2022. Results: Five studies were reviewed. The results showed that breast cancer patients following a ketogenic diet had significant improvements in emotional and social functions, reduced disease symptoms, and improved metabolic health biomarkers (creatinine, triglycerides, insulin and free insulin-like growth factor I). Conclusion: Long-term adherence to a ketogenic diet can lead to weight loss, tumor size reduction, improved quality of life, improved inflammatory factors, body composition, insulin resistance, and serum lipid profile disorders in breast cancer patients. Clinical trials are suggested to evaluate the effects of ketogenic diets on these metabolic factors, treatment, and quality of life in women with breast cancer. [ABSTRACT FROM AUTHOR]

In glucose-deprived conditions, ketone bodies are produced by the liver mitochondria, through the catabolism of fatty acids, and are used peripherally, as an alternative energy source. Ketones are produced in the body under normal conditions, including during pregnancy and the neonatal period, when following a ketogenic diet (KD), fasting, or exercising. Additionally, ketone synthesis is also augmented under pathological conditions, including cases of diabetic ketoacidosis (DKA), alcoholism, and several metabolic disorders. Nonetheless, diet is the main regulator of total body ketone concentrations. The KDs are mimicking the fasting state, altering the default metabolism towards the use of ketones as the primary fuel source. Recently, KD has gained recognition as a medical nutrition therapy for a plethora of metabolic conditions, including obesity and diabetes mellitus (DM). The present review aims to discuss the role of ketones, KDs, ketonemia, and ketonuria in DM, presenting all the available new evidence in a comprehensive manner. [ABSTRACT FROM AUTHOR]

A pragmatic low carbohydrate diet intervention changes neither carbohydrate consumption nor glycemia in adolescents and young adults with type 1 diabetes in a randomized trial. Effects of a diet higher in carbohydrate/lower in fat versus lower in carbohydrate/higher in monounsaturated fat on post meal triglyceride concentrations and other cardiovascular risk factors in type 1 diabetes. Keywords: carbohydrate restriction; low-carbohydrate diet; meta-analysis; systematic review; type 1 diabetes EN carbohydrate restriction low-carbohydrate diet meta-analysis systematic review type 1 diabetes 2770 2773 4 08/03/23 20230901 NES 230901 BACKGROUND One of the most challenging parts in daily management of type 1 diabetes (T1D) is postprandial glucose excursions.[1] Based on the rationale that carbohydrates have the greatest impact on postprandial blood glucose, it has been suggested that decreasing carbohydrate consumption will improve postprandial glycaemic control.[1] However, the ideal dietary approach in T1D is ambiguous.[2] The American Diabetes Association suggests that medical nutrition therapy is fundamental for the management of diabetes, while arguing that there are no universal guidelines for the distribution of macronutrients for individuals with diabetes.[3] In contrast to type 2 diabetes (T2D),[4] randomized controlled trials (RCTs) assessing carbohydrate restriction in T1D have not been incorporated in a systematic review and meta-analysis. Carbohydrate restriction, low-carbohydrate diet, meta-analysis, systematic review, type 1 diabetes. [Extracted from the article]

Background: The optimal nutritional treatment for gestational diabetes (GDM) is still a matter of debate. With increasing rates of GDM and potential negative consequences for the health of mother and child, the best treatment should be established. The Nordic diet with emphasis on plant-based protein show promising health outcomes in other populations but has yet to be investigated in GDM population. The aim of this study, which is part of the "Effect of plant-based Nordic diet versus carbohydrate-restricted diet on glucose levels in gestational diabetes" (eMOM) pilot study was to compare the short-term effects of healthy Nordic diet (HND) and the currently recommended moderate restriction of carbohydrates diet (MCRD) on glucose and lipid metabolism in women with GDM. Methods: This was a randomized crossover where each of the diet interventions (HND and MCRD) were consumed for 3 days with a 3-day wash-out period in between. In total, 42 pregnant women diagnosed with GDM (< 29 + 0 gestational week) were randomized. Glucose data was collected by continuous glucose monitors (CGM, Freestyle Libre®, Abbott, USA) worn for 14 days, and participants gave blood samples before and after diet interventions. The primary outcome was time spent in glucose target range (TIR, < 7.8 mmol/L). TIR, 3-day mean tissue glucose as well as changes in fasting glucose, homeostatic model of insulin resistance (HOMA-IR) and blood lipids were analyzed with paired samples statistical analyses. Results: Thirty-six women with complete 14 days CGM data were analyzed. Both diet interventions produced a high degree of TIR (99% SD 1.8), without a difference between the diets (p = 0.727). The 3-day mean glucose was significantly lower in HND than in MCRD (p = 0,049). Fasting insulin (p = 0,034), insulin resistance (p = 0,030), total and LDL cholesterol (p = 0,023 and 0,008) reduced more in the MCRD diet than the HND. NS differences in any other measure of CGM or blood tests. Conclusions: HND and MCRD did not differ in terms of their short-term effect on TIR. A larger study with sufficient power is needed to confirm the differences in short-term mean glucose, insulin resistance and lipid metabolism. Trial registration: Registered in clinicaltrials.gov (21/09/2018, NCT03681054). [ABSTRACT FROM AUTHOR]

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Although these diets may be viewed as an easy shortcut to lose weight rapidly and easily, subjects often use these diets without any medical counselling or nutritional rehabilitation for the long-term management of weight maintenance, which should represent the most important and ambitious goal of VLCKD nutritional therapy. Keywords: carbohydrate restriction; cardiometabolic risk; metabolic rehabilitation; precision nutrition; weight cycling; weight loss EN carbohydrate restriction cardiometabolic risk metabolic rehabilitation precision nutrition weight cycling weight loss 1 3 3 11/06/23 20231101 NES 231101 Very low-calorie ketogenic diets (VLCKDs) are nowadays considered a notable example of a dietary-based treatment with proven efficacy against a variety of conditions. Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission. [Extracted from the article]

A fully provided, hypocaloric, carbohydrate-reduced high-protein (CRHP) diet compared to a hypocaloric conventional diabetes (CD) diet for 6 weeks improved glycemic control to a greater extent in face of an intended 6% weight loss in individuals with type 2 diabetes mellitus (T2DM). The present 24-week extension of that study reports on the efficacy of CRHP and CD diets in a real-life setting. Sixty-five individuals with T2DM who completed the initial 6-week fully provided diet period (% energy from carbohydrate, protein, and fat was 30/30/40 in CRHP, and 50/17/33 in CD) continued a free-living, dietician guided 24-week period of which 59 individuals completed. The CRHP compared to CD group reported a 4% lower carbohydrate intake and had higher urea excretion by 22% (both p ≤ 0.05) at week 30, suggesting less difference in carbohydrate and protein intake between groups during the 24-week extension compared to week 6. The loss of body weight during the initial 6 weeks was maintained in both groups during the 24-week extension (−5.5 ± 4.5 and −4.6 ± 4.8 kg) as well as HbA1c (−8.4 ± 6.2 and −8.4 ± 6.9 mmol/mol) with no significant differences between groups. The additional benefits on glucoregulation harnessed by carbohydrate restriction under full diet provision for 6 weeks combined with titrated weight loss could not be maintained in a real-life setting of self-prepared diet aiming on similar diets for 6 months. [ABSTRACT FROM AUTHOR]

Objective: The cardio‐renal benefits of sodium glucose‐like transporter 2 inhibitor (SGLT2i) therapies have been demonstrated in patients with and without type 2 diabetes. However, no studies have explored the long‐term metabolic effects of SGLT2i, combined with dietary carbohydrate restriction. Our primary objective was to describe long‐term changes in weight, energy expenditure, appetite and body composition after 12 months of Dapagliflozin therapy, with carbohydrate restriction, in people with type 2 diabetes and obesity. Our secondary objective was to assess changes in adiponectin and leptin. Method: This was a 12‐month cohort study in a secondary care setting. Participants (n = 18) with type 2 diabetes (T2D) and class 3 obesity underwent baseline indirect calorimetry for determination of 24‐h energy expenditure, body composition, fasting serum leptin and adiponectin levels, and appetitive assessments. Following initiation of Dapagliflozin (and dietary carbohydrate restriction), measurements were repeated at monthly intervals up to 12 months. Results: Mean starting weight of participants was 129.4 kg (SD 25.9), mean BMI 46.1 kg/m2 (SD 8.3) and mean HbA1c 53.9 mmol/mol (14.1). Seventeen participants completed the study; after 12 months of Dapagliflozin and dietary carbohydrate restriction, mean weight loss was 8.1 kg (SD 11.3 kg; p =.009). This was mediated by reduced fat mass (mean loss, 9.9 kg; SD 10.4 kg; p =.002) associated with reduced serum leptin at 12 months (mean reduction 11,254 pg/ml; SD 16,075; p =.011). There were no significant changes in self‐reported appetite, 24‐h energy expenditure or serum adiponectin during follow‐up. Conclusion: In this study, combined Dapagliflozin therapy and carbohydrate restriction in patients with T2D and obesity resulted in a significant reduction of body weight and fat mass at 12 months without any discernible changes in energy expenditure or appetite. These results offer a scientific and clinical rationale to conduct an exploratory trial investigating the effects of a low carbohydrate diet combined with SGLT2 inhibitors in patients with T2D. [ABSTRACT FROM AUTHOR]

Purpose of Review: Very-low-carbohydrate (VLC) and ketogenic diets (KDs) have been used for weight loss and more recently in patients with insulin resistance and type 2 diabetes. The impact of VLC and KDs on lipids/lipoproteins is a concern. The purpose of this review is to discuss the impact of KDs on body weight and lipids/lipoproteins. Recent Findings: VLC/KDs contribute to greater weight loss in the short term (< 6 months) compared to higher carbohydrate diets, but there is typically no difference between the diets by 12 months. Triglyceride and high-density lipoprotein cholesterol levels generally improve, but there is a variable response in low-density lipoprotein cholesterol levels, with some individuals experiencing a dramatic increase, particularly those with latent genetic dyslipidemias. Summary: Healthcare professionals should educate patients on the risks and benefits of following VLC/KDs and encourage the consumption of carbohydrate-rich foods associated with positive health outcomes. [ABSTRACT FROM AUTHOR]

Chronic diet-related metabolic diseases, including diabetes and obesity, impose enormous burdens on patient wellness, healthcare costs, and worker productivity. Given the interdependent nature of the human and economic costs of metabolic disease, companies should be incentivized to invest in the health of their workforce. We report data from an ongoing pilot program in which employees of a manufacturing company with obesity, prediabetes, or diabetes are being treated by a metabolic health clinic using a carbohydrate restriction, community-orientated telemedicine approach. 10 patients completed the first 6 months of the program, and all lost weight, with a mean weight reduction of 38.4 lbs (17.4 kg). Improvements in HbA1c, fasting glucose, HOMA-IR, triglycerides, C-reactive protein, and systolic blood pressure were also observed across the group. Furthermore, the 10-year risk of having a major cardiovascular event, as calculated by the American Heart Association risk calculator, decreased from a mean of 9.22 to 5.18%, representing a 44% relative risk reduction. As a result of improvements in their metabolic health, patients were able to discontinue medications, leading to an estimated annualized cost savings of USD 45,171.70. These preliminary data provide proof-of-principle that when companies invest in the metabolic health of their workers, both parties stand to gain. [ABSTRACT FROM AUTHOR]

Background Carbohydrate restriction is effective for type 2 diabetes management. Objectives We aimed to evaluate the dose-dependent effect of carbohydrate restriction in patients with type 2 diabetes. Methods We systematically searched PubMed, Scopus, and Web of Science to May 2021 for randomized controlled trials evaluating the effect of a carbohydrate-restricted diet (≤45% total calories) in patients with type 2 diabetes. The primary outcome was glycated hemoglobin (HbA1c). Secondary outcomes included fasting plasma glucose (FPG); body weight; serum total, LDL, and HDL cholesterol; triglyceride (TG); and systolic blood pressure (SBP). We performed random-effects dose-response meta-analyses to estimate mean differences (MDs) for a 10% decrease in carbohydrate intake. Results Fifty trials with 4291 patients were identified. At 6 months, compared with a carbohydrate intake between 55%–65% and through a maximum reduction down to 10%, each 10% reduction in carbohydrate intake reduced HbA1c (MD, −0.20%; 95% CI, −0.27% to −0.13%), FPG (MD, −0.34 mmol/L; 95% CI, −0.56 to −0.12 mmol/L), and body weight (MD, −1.44 kg; 95% CI, −1.82 to −1.06 kg). There were also reductions in total cholesterol, LDL cholesterol, TG, and SBP. Levels of HbA1c, FPG, body weight, TG, and SBP decreased linearly with the decrease in carbohydrate intake from 65% to 10%. A U-shaped effect was seen for total cholesterol and LDL cholesterol, with the greatest reduction at 40%. At 12 months, a linear reduction was seen for HbA1c and TG. A U-shaped effect was seen for body weight, with the greatest reduction at 35%. Conclusions Carbohydrate restriction can exert a significant and important reduction on levels of cardiometabolic risk factors in patients with type 2 diabetes. Levels of most cardiometabolic outcomes decreased linearly with the decrease in carbohydrate intake. U-shaped effects were seen for total cholesterol and LDL cholesterol at 6 months and for body weight at 12 months. [ABSTRACT FROM AUTHOR]

In sarcopenic obese subjects it is essential to reduce body weight and preserve lean mass, in order to avoid a worsening of muscle function. Several studies have shown that leucine supplementation can be useful to improve skeletal muscle mass in sarcopenic patients. The aim of our study was to evaluate the effectiveness of a short-term low-calorie diet (LCD) combined with supplementation with whey protein and leucine on weight loss, lean mass and muscle strength in sarcopenic, obese, hyperinsulinemic and post-menopausal women. Sixteen females with a mean age of 60 years (range: 50–70 years), BMI 37.6 kg/m2 (range: 31.7–44.1 Kg/m2), HOMA-index ≥ 2.5 (range: 2.9–12) were assigned to an LCD regimen (1000 kcal/day) with supplementation of 18 g whey proteins which 4.1 g of leucine for 45 days. Anthropometric indexes, blood and urine chemistry, body composition by DEXA, muscle strength by handgrip test and Short Physical Performance Battery (SPPB) were assessed at baseline and at the end of the treatment. A significant reduction in BMI (37.6 vs. 35.7 Kg/m2), waist circumference (107 vs. 102.4 cm), HOMA index (4.8 vs. 2.3) and fasting insulin (17.4 vs. 10.4 μIU/mL) was observed in all patients. Women preserved total lean body mass (55 vs. 5%) and significantly improved their muscle strength, as measured by handgrip (15.3 vs. 20.1 Kg), and their muscle function, as measured by SPPB (7.5 vs. 8.9). A significant increase in BUN was also observed (36.1 vs. 46.3). We conclude that LCD with adequate protein intake and supplementation with whey protein and leucine should be promoted to maintain muscle mass and improve muscle strength in post-menopausal women with sarcopenic obesity. [ABSTRACT FROM AUTHOR]

When lean people adopt carbohydrate-restricted diets (CRDs), they may develop a lipid profile consisting of elevated LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) with low triglycerides (TGs). The magnitude of this lipid profile correlates with BMI such that those with lower BMI exhibit larger increases in both LDL-C and HDL-C. The inverse association between BMI and LDL-C and HDL-C change on CRD contributed to the discovery of a subset of individuals—termed Lean Mass Hyper-Responders (LMHR)—who, despite normal pre-diet LDL-C, as compared to non-LMHR (mean levels of 148 and 145 mg/dL, respectively), exhibited a pronounced hyperlipidemic response to a CRD, with mean LDL-C and HDL-C levels increasing to 320 and 99 mg/dL, respectively, in the context of mean TG of 47 mg/dL. In some LMHR, LDL-C levels may be in excess of 500 mg/dL, again, with relatively normal pre-diet LDL-C and absent of genetic findings indicative of familial hypercholesterolemia in those who have been tested. The Lipid Energy Model (LEM) attempts to explain this metabolic phenomenon by positing that, with carbohydrate restriction in lean persons, the increased dependence on fat as a metabolic substrate drives increased hepatic secretion and peripheral uptake of TG contained within very low-density lipoproteins (VLDL) by lipoprotein lipase, resulting in marked elevations of LDL-C and HDL-C, and low TG. Herein, we review the core features of the LEM. We review several existing lines of evidence supporting the model and suggest ways to test the model's predictions. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests that "leanness" and good metabolic health markers may predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate restriction. Specifically, a recent cohort study demonstrated an inverse association between BMI and LDL-C change among individuals on carbohydrate-restricted diets and identified a subgroup of "Lean Mass Hyper-Responders" (LMHR) who exhibit exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We present the case of one subject, LM, who adopted a ketogenic diet for management of ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of the emergent LMHR phenotype. Assessments of LM's dietary intake, lipid panels, and BMI are consistent with prior data and suggest that the LMHR phenomenon is not dependent on saturated fat intake but inversely associates with BMI changes. Finally, computed tomography angiography conducted on LM after over 2 years of hypercholesterolemia revealed no evidence of calcified or non-calcified plaque. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Lifestyle modification and weight loss are cornerstones of type 2 diabetes management. However, carbohydrate restriction may have weight-independent beneficial effects on glycaemic control. This has been difficult to demonstrate because low-carbohydrate diets readily decrease body weight. We hypothesised that carbohydrate restriction enhances the beneficial metabolic effects of weight loss in type 2 diabetes. Methods: This open-label, parallel RCT included adults with type 2 diabetes, HbA1c 48–97 mmol/mol (6.5–11%), BMI >25 kg/m2, eGFR >30 ml min−1 [1.73 m]−2 and glucose-lowering therapy restricted to metformin or dipeptidyl peptidase-4 inhibitors. Participants were randomised by a third party and assigned to 6 weeks of energy restriction (all foods were provided) aiming at ~6% weight loss with either a carbohydrate-reduced high-protein diet (CRHP, percentage of total energy intake [E%]: CH30/P30/F40) or a conventional diabetes diet (CD, E%: CH50/P17/F33). Fasting blood samples, continuous glucose monitoring and magnetic resonance spectroscopy were used to assess glycaemic control, lipid metabolism and intrahepatic fat. Change in HbA1c was the primary outcome; changes in circulating and intrahepatic triacylglycerol were secondary outcomes. Data were collected at Copenhagen University Hospital (Bispebjerg and Herlev). Results: Seventy-two adults (CD 36, CRHP 36, all white, 38 male sex) with type 2 diabetes (mean duration 8 years, mean HbA1c 57 mmol/mol [7.4%]) and mean BMI of 33 kg/m2 were enrolled, of which 67 (CD 33, CRHP 34) completed the study. Body weight decreased by 5.8 kg (5.9%) in both groups after 6 weeks. Compared with the CD diet, the CRHP diet further reduced HbA1c (mean [95% CI] −1.9 [−3.5, −0.3] mmol/mol [−0.18 (−0.32, −0.03)%], p = 0.018) and diurnal mean glucose (mean [95% CI] −0.8 [−1.2, −0.4] mmol/l, p < 0.001), stabilised glucose excursions by reducing glucose CV (mean [95% CI] −4.1 [−5.9, −2.2]%, p < 0.001), and augmented the reductions in fasting triacylglycerol concentration (by mean [95% CI] −18 [−29, −6]%, p < 0.01) and liver fat content (by mean [95% CI] −26 [−45, 0]%, p = 0.051). However, pancreatic fat content was decreased to a lesser extent by the CRHP than the CD diet (mean [95% CI] 33 [7, 65]%, p = 0.010). Fasting glucose, insulin, HOMA2-IR and cholesterol concentrations (total, LDL and HDL) were reduced significantly and similarly by both diets. Conclusions/interpretation: Moderate carbohydrate restriction for 6 weeks modestly improved glycaemic control, and decreased circulating and intrahepatic triacylglycerol levels beyond the effects of weight loss itself compared with a CD diet in individuals with type 2 diabetes. Concurrent differences in protein and fat intakes, and the quality of dietary macronutrients, may have contributed to these results and should be explored in future studies. Trial registration: ClinicalTrials.gov NCT03814694. Funding: The study was funded by Arla Foods amba, The Danish Dairy Research Foundation, and Copenhagen University Hospital Bispebjerg Frederiksberg. [ABSTRACT FROM AUTHOR]

Evidence suggests that low carbohydrate eating patterns are effective for rapid weight loss 1, however, little is known about their long-term effects on the risk of chronic diseases. We assessed the association of a low carbohydrate diet score (LCD) with the incidence of type 2 diabetes using Melbourne Collaborative Cohort Study (MCCS) data. Between 1990 and 1994, the MCCS recruited 41,513 people aged 40 to 69 years. The first and second follow-ups were conducted in 1994-1998 and 2003-2007, respectively2. We analysed data from 39,185 participants. LCD at baseline was calculated as the percentage of energy from carbohydrate, fat, and protein. The higher the score the less carbohydrate contributed to energy intake. The association of LCD quintiles with the incidence of diabetes was assessed using modified Poisson regression, adjusted for lifestyle, obesity, socioeconomic and other confounders. LCD was positively associated with diabetes risk. Higher LCD score (p for trend = 0.001) was associated with increased risk of type 2 diabetes. Quintile 5 (38% energy from carbohydrates) versus quintile 1 (55% energy from carbohydrates) showed a 20% increased diabetes risk (incidence risk ratio (IRR) = 1.20 (95% CI: 1.05-1.37)). A further adjustment for BMI and WHR eliminated the association. Mediation analysis demonstrated that BMI attributed 76% of the LCD & diabetes association. Consuming a low carbohydrate diet, reflected as a high LCD score, may increase the risk of type 2 diabetes which is largely explained by obesity. Results imply the need for further studies, including clinical trials investigating the effects of a low carbohydrate diet in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Weight loss by ketogenic diet (KD) has gained popularity in management of nonalcoholic fatty liver disease (NAFLD). KD rapidly reverses NAFLD and insulin resistance despite increasing circulating nonesterified fatty acids (NEFA), the main substrate for synthesis of intrahepatic triglycerides (IHTG). To explore the underlying mechanism, we quantified hepatic mitochondrial fluxes and their regulators in humans by using positional isotopomer NMR tracer analysis. Ten overweight/obese subjects received stable isotope infusions of: [D7]glucose, [13C4]ß-hydroxybutyrate and [3-13C]lactate before and after a 6-d KD. IHTG was determined by proton magnetic resonance spectroscopy (1H-MRS). The KD diet decreased IHTG by 31% in the face of a 3% decrease in body weight and decreased hepatic insulin resistance (-58%) despite an increase in NEFA concentrations (+35%). These changes were attributed to increased net hydrolysis of IHTG and partitioning of the resulting fatty acids toward ketogenesis (+232%) due to reductions in serum insulin concentrations (-53%) and hepatic citrate synthase flux (-38%), respectively. The former was attributed to decreased hepatic insulin resistance and the latter to increased hepatic mitochondrial redox state (+167%) and decreased plasma leptin (-45%) and triiodothyronine (-21%) concentrations. These data demonstrate heretofore undescribed adaptations underlying the reversal of NAFLD by KD: That is, markedly altered hepatic mitochondrial fluxes and redox state to promote ketogenesis rather than synthesis of IHTG. [ABSTRACT FROM AUTHOR]

Intramuscular triglycerides (IMTG) are a key substrate during prolonged exercise, but little is known about the rate of IMTG resynthesis in the postexercise period. We investigated the hypothesis that the distribution of the lipid droplet (LD)-associated perilipin (PLIN) proteins is linked to IMTG storage following exercise. Fourteen elite male triathletes (27 ± 1 yr, 66.5 ± 1.3 mL·kg−1·min−1) completed 4 h of moderate-intensity cycling. During the first 4 h of recovery, subjects received either carbohydrate or H2O, after which both groups received carbohydrate. Muscle biopsies collected pre- and postexercise and 4 and 24 h postexercise were analyzed using confocal immunofluorescence microscopy for fiber type-specific IMTG content and PLIN distribution with LDs. Exercise reduced IMTG content in type I fibers (−53%, P = 0.002), with no change in type IIa fibers. During the first 4 h of recovery, IMTG content increased in type I fibers (P = 0.014), but was not increased more after 24 h, where it was similar to baseline levels in both conditions. During recovery the number of LDs labeled with PLIN2 (70%), PLIN3 (63%), and PLIN5 (62%; all P < 0.05) all increased in type I fibers. Importantly, the increase in LDs labeled with PLIN proteins only occurred at 24 h postexercise. In conclusion, IMTG resynthesis occurs rapidly in type I fibers following prolonged exercise in highly trained individuals. Furthermore, increases in IMTG content following exercise preceded an increase in the number of LDs labeled with PLIN proteins. These data, therefore, suggest that the PLIN proteins do not play a key role in postexercise IMTG resynthesis. [ABSTRACT FROM AUTHOR]

Background: Deliberately training with reduced carbohydrate availability, a paradigm coined training low, has shown to promote adaptations associated with improved aerobic capacity. In this context researchers have proposed that protein may be ingested prior to training as a means to enhance the protein balance during exercise without spoiling the effect of the low carbohydrate availability. Accordingly, this is being practiced by world class athletes. However, the effect of protein intake on muscle protein metabolism during training low has not been studied. This study aimed to examine if protein intake prior to exercise with reduced carbohydrate stores benefits muscle protein metabolism in exercising and non-exercising muscles. Methods: Nine well-trained subjects completed two trials in random order both of which included a high-intensity interval ergometer bike ride (day 1), a morning (day 2) steady state ride (90 min at 65% VO2peak, 90ss), and a 4-h recovery period. An experimental beverage was consumed before 90ss and contained either 0.5 g whey protein hydrolysate [WPH]/ kg lean body mass or flavored water [PLA]. A stable isotope infusion (L-[ring-13C6]-phenylalanine) combined with arterial-venous blood sampling, and plasma flow rate measurements were used to determine forearm protein turnover. Myofibrillar protein synthesis was determined from stable isotope incorporation into the vastus lateralis. Results: Forearm protein net balance was not different from zero during 90ss exercise (nmol/100 ml/min, PLA: 0.5 ± 2.6; WPH: 1.8, ± 3.3) but negative during the 4 h recovery (nmol/100 ml/min, PLA: − 9.7 ± 4.6; WPH: − 8.7 ± 6.5); no interaction (P = 0.5) or main effect of beverage (P = 0.11) was observed. Vastus lateralis myofibrillar protein synthesis rates were increased during 90ss exercise (+ 0.02 ± 0.02%/h) and recovery (+ 0.02 ± 0.02%/h); no interaction (P = 0.3) or main effect of beverage (P = 0.3) was observed. Conclusion: We conclude that protein ingestion prior to endurance exercise in the energy- and carbohydrate-restricted state does not increase myofibrillar protein synthesis or improve net protein balance in the exercising and non-exercising muscles, respectively, during and in the hours after exercise compared to ingestion of a non-caloric control. Trial registration: clinicaltrials.gov, NCT01320449. Registered 10 May 2017 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03147001 [ABSTRACT FROM AUTHOR]

Background: Low carbohydrate high fat (LCHF) diets are increasing in popularity amongst patients with type 2 diabetes (T2D), however it is unclear what constitutes a sustainable LCHF diet in a real-world setting. Methods: This descriptive multi-method study characterized the diets, T2D status, and personal experiences of individuals with T2D who claimed to have followed an LCHF diet for at least 6 months. Participants completed a medications history, mixed-method dietary assessment, provided a blood sample, and were interviewed in-depth about their experiences with the diet (First-Assessment). Past medical records were obtained corresponding to T2D diagnosis and prior to starting their LCHF diets. Additionally, participants were followed up 15 months later to assess T2D remission (Follow-Up). Results: Twenty-eight participants completed First-Assessment and 24 completed Follow-Up. Habitual carbohydrate intake was 20 to 50 g/d for 10 participants and 50 to 115 g/d for 17 participants. Commonly reported foods were full-fat dairy, non-starchy vegetables, coconut oil, eggs, nuts, olives and avocados, olive oil, and red meat and poultry with fat. Median (interquartile range) for HbA1c was 7.5 (6.5–9.5) % prior to starting their diets, 5.8 (5.4–6.2) % at First-Assessment and 5.9 (5.3–6.6) % at Follow-Up. Reported body weight and glucose-lowering medication requirements were considerably lower at both assessments than when starting the diet. At Follow-Up, 24 participants had been following their LCHF diets for 35 (26–53) months, the majority of which were in full or partial T2D remission. Participants perceived reduced hunger and cravings as one of the most important aspects of their diets. Of concern, many participants felt unsupported by their doctors. Conclusion: This study described the foods and characteristics of an LCHF "lifestyle" that was sustainable and effective for certain T2D patients in a real-world setting. [ABSTRACT FROM AUTHOR]

Aim: To identify core diet and delivery components of low‐carbohydrate (CHO) diets that have demonstrated efficacy for type 2 diabetes (T2D) management. Materials and methods: MEDLINE, Pre‐MEDLINE, EMBASE, CINAHL and the Cochrane Library of Controlled Trials databases were systematically searched from inception until August 18, 2018. Primary intervention studies of low‐CHO diets (≤130 g/d or 26% total energy intake [TEI]) were included. Content analysis was performed on the low‐CHO diet protocols classified as safe and effective for T2D management. Results: A total of 41 studies published between 1963 and 2018 were included, of which 40 were classified as safe and effective for inclusion in the primary analysis. Thirteen studies (13/40) were on very‐low‐CHO diets (<50 g/d), 14/40 included low‐CHO diets (≤130 g/d or 26% TEI), and 13/40 were adapted according to participant progress. Thirty‐one studies reported a total energy prescription, of which 18/31 encouraged ad libitum intakes. Twenty studies reported a prescribed dietary fat amount, of which 18/20 were unrestricted or high‐fat (>35% TEI). Twenty‐six studies reported a prescribed dietary protein amount, of which 22 were unrestricted or were high‐protein (>25% TEI). The types of dietary CHO, fat and protein recommended were predominantly whole foods. Common delivery methods reported were dietician and/or physician involvement, moderate to high frequency of contact (≥1 session/month) and use of participant self‐monitoring. Conclusions: Multiple approaches for developing and delivering a low‐CHO diet intervention for T2D management are safe and effective. A comprehensive set of core dietary components to consider in the formulation of low‐CHO diet protocols were identified for use in clinical practice and to inform evidence‐based guidelines for T2D management. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Dietary recommendations for treating type 2 diabetes are unclear but a trend towards recommending a diet reduced in carbohydrate content is acknowledged. We compared a carbohydrate-reduced high-protein (CRHP) diet with an iso-energetic conventional diabetes (CD) diet to elucidate the effects on glycaemic control and selected cardiovascular risk markers during 6 weeks of full food provision of each diet. Methods: The primary outcome of the study was change in HbA1c. Secondary outcomes reported in the present paper include glycaemic variables, ectopic fat content and 24 h blood pressure. Eligibility criteria were: men and women with type 2 diabetes, HbA1c 48–97 mmol/mol (6.5–11%), age >18 years, haemoglobin >6/>7 mmol/l (women/men) and eGFR >30 ml min−1 (1.73 m)−2. Participants were randomised by drawing blinded ballots to 6 + 6 weeks of an iso-energetic CRHP vs CD diet in an open label, crossover design aiming at body weight stability. The CRHP/CD diets contained carbohydrate 30/50 energy per cent (E%), protein 30/17E% and fat 40/33E%, respectively. Participants underwent a meal test at the end of each diet period and glycaemic variables, lipid profiles, 24 h blood pressure and ectopic fat including liver and pancreatic fat content were assessed at baseline and at the end of each diet period. Data were collected at Copenhagen University Hospital, Bispebjerg and Copenhagen University Hospital, Herlev. Results: Twenty-eight participants completed the study. Fourteen participants carried out 6 weeks of the CRHP intervention followed by 6 weeks of the CD intervention, and 14 participants received the dietary interventions in the reverse order. Compared with a CD diet, a CRHP diet reduced the primary outcome of HbA1c (mean ± SEM: −6.2 ± 0.8 mmol/mol (−0.6 ± 0.1%) vs −0.75 ± 1.0 mmol/mol (−0.1 ± 0.1%); p < 0.001). Nine (out of 37) pre-specified secondary outcomes are reported in the present paper, of which five were significantly different between the diets, (p < 0.05); compared with a CD diet, a CRHP diet reduced the secondary outcomes (mean ± SEM or medians [interquartile range]) of fasting plasma glucose (−0.71 ± 0.20 mmol/l vs 0.03 ± 0.23 mmol/l; p < 0.05), postprandial plasma glucose AUC (9.58 ± 0.29 mmol/l × 240 min vs 11.89 ± 0.43 mmol/l × 240 min; p < 0.001) and net AUC (1.25 ± 0.20 mmol/l × 240 min vs 3.10 ± 0.25 mmol/l × 240 min; p < 0.001), hepatic fat content (−2.4% [−7.8% to −1.0%] vs 0.2% [−2.3% to 0.9%]; p < 0.01) and pancreatic fat content (−1.7% [−3.5% to 0.6%] vs 0.5% [−1.0% to 2.0%]; p < 0.05). Changes in other secondary outcomes, i.e. 24 h blood pressure and muscle-, visceral- or subcutaneous adipose tissue, did not differ between diets. Conclusions/interpretation: A moderate macronutrient shift by substituting carbohydrates with protein and fat for 6 weeks reduced HbA1c and hepatic fat content in weight stable individuals with type 2 diabetes. Trial registration: ClinicalTrials.gov NCT02764021. Funding: The study was funded by grants from Arla Food for Health; the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; the Department of Clinical Medicine, Aarhus University; the Department of Nutrition, Exercise and Sports, University of Copenhagen; and Copenhagen University Hospital, Bispebjerg. [ABSTRACT FROM AUTHOR]

Objective: Type I diabetes is a disease characterised by an extreme reduction in serum insulin levels. Diet and exercise have gained considerable attention in the treatment of diabetes. Therefore, this study was carried out to investigate the effect of diet with carbohydrate but without daily energy restriction on various metabolites (glucose, triglycerides, cholesterol, lactate), some electrolytes (Ca, Mg, Na, K, P, Cl) and essential metals (Mn, Co, Cu, Se, Zn, Fe) in the blood of rats with streptozotocin-induced diabetes. Materials and methods: Thirty-three male rats were divided into four groups of standard rat diet (SR)-fed control, SR-diet fed diabetics, low carbohydrate-standard protein-high fat (LCSPHF) diet-fed diabetics, and very low carbohydrate-high protein-high fat (VLCHPHF) diet-fed diabetics. Diabetes was induced by an i.p. injection of 50 mg/kg streptozotocin. The rats were fed with the specially prepared diets for 28 days. Results: The decreased-serum Cl and the increased-serum glucose levels were only the difference between the controls and SR diet-fed diabetic rats regarding to measured parameters. Lowering carbohydrate and increasing fat ratio in diet caused an increase in serum cholesterol and triglyceride levels leading to an increased-serum Fe and Ca, and decreased-serum Na and Cu levels in diabetic rats. Conclusion: The serum mineral changes should be taken into consideration together with the changes in serum glucose, cholesterol, and triglyceride levels for the secondary complications of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus is a serious autoimmune disease for which no cure is available. The treatment includes insulin therapy, carbohydrate counting, eating healthy foods, exercising regularly, and maintaining a healthy weight. The goal is to keep blood glucose levels close to normal most of the time to delay or prevent complications. Despite the increase in the use of insulin pumps and continuous glucose monitors in recent years, the management of type 1 diabetes remains suboptimal in terms of glycaemic control and normal glycated haemoglobin (HbA1c) level. This article discusses the case of a child with type 1 diabetes who was successfully treated with a very low-carbohydrate diet, resulting in normal levels of HbA1c and normal blood glucose 95% of the time in a range of 70–180 mg/dL (4.0 mmol/L−10 mmol/L). Therefore, further studies are needed to verify how a very low carbohydrate diet impacts child development. [ABSTRACT FROM AUTHOR]

Background: Low-carbohydrate, high-fat (LCHF) diets are useful for treating a range of health conditions, but there is little research evaluating the degree of carbohydrate restriction on outcome measures. This study compares anthropometric and cardiometabolic outcomes between differing carbohydrate-restricted diets. Objective: Our hypothesis was that moderate carbohydrate restriction is easier to maintain and more effective for improving cardiometabolic health markers than greater restriction. Design: A total of 77 healthy participants were randomised to a very low-carbohydrate ketogenic diet (VLCKD), low-carbohydrate diet (LCD), or moderate-low carbohydrate diet (MCD), containing 5%, 15% and 25% total energy from carbohydrate, respectively, for 12-weeks. Anthropometric and metabolic health measures were taken at baseline and at 12 weeks. Using ANOVA, both within and between-group outcomes were analysed. Results: Of 77 participants, 39 (51%) completed the study. In these completers overall, significant reductions in weight and body mass index occurred ((mean change) 3.7 kg/m2; 95% confidence limits (CL): 3.8, 1.8), along with increases in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, (0.49 mmol/L; 95% CL; 0.06, 0.92; p = 0.03), and total cholesterol concentrations (0.11 mmol/L; 95% CL; 0.00, 0.23; p = 0.05). Triglyceride (TG) levels were reduced by 0.12 mmol/L (95% CL; -0.20, 0.02; p = 0.02). No significant changes occurred between groups. The largest improvements in high density lipoprotein cholesterol (HDL-c) and TG and anthropometric changes occurred for the VLCKD group. Conclusions: Low-carbohydrate, high-fat diets have a positive effect on markers of health. Adherence to the allocation of carbohydrate was more easily achieved in MCD, and LCD groups compared to VLCKD and there were comparable improvements in weight loss and waist circumference and greater improvements in HDL-c and TG with greater carbohydrate restriction. [ABSTRACT FROM AUTHOR]

Weight class athletes use weight-making strategies to compete in specific weight categories with an optimum power-to-weight ratio. There is evidence that low carbohydrate diets might offer specific advantages for weight reduction without the negative impact on strength and power previously hypothesized to accompany carbohydrate restriction. Therefore, the purpose of this study was to determine whether a low-carbohydrate ketogenic diet (LCKD) could be used as a weight reduction strategy for athletes competing in the weight class sports of powerlifting and Olympic weightlifting. Fourteen intermediate to elite competitive lifting athletes (age 34 ± 10.5, n = 5 female) consumed an ad libitum usual diet (UD) (>250 g daily intake of carbohydrates) and an ad libitum LCKD (≤50 g or ≤10% daily intake of carbohydrates) in random order, each for 3 months in a crossover design. Lifting performance, body composition, resting metabolic rate, blood glucose, and blood electrolytes were measured at baseline, 3 months, and 6 months. The LCKD phase resulted in significantly lower body mass (-3.26 kg, p = 0.038) and lean mass (-2.26 kg, p = 0.016) compared with the UD phase. Lean mass losses were not reflected in lifting performances that were not different between dietary phases. No other differences in primary or secondary outcome measures were found between dietary phases. Weight class athletes consuming an ad libitum LCKD decreased body mass and achieved lifting performances that were comparable with their UD. Coaches and athletes should consider using an LCKD to achieve targeted weight reduction goals for weight class sports. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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 x 10-12), LDL-P size (+ 1.1%, P = 6.0 x 10-10), ApoB (- 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10-16), ApoB/ApoA1 ratio (- 9.5%, P = 1.9 x 10-7), triglyceride/HDL-C ratio (- 29.1%, P < 10-16), large VLDL-P (- 38.9%, P = 4.2 x 10-15), and LDL-C (+ 9.9%, P = 4.9 x 10-5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 x 10-7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased - 11.9% (P = 4.9 x 10-5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 x 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. Conclusions: 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 [ABSTRACT FROM AUTHOR]

Introduction 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. Methods 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). Results 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 x 10-16), weight declined 13.8 ± 0.71 kg (P < 1.0 x 10-16), and T2D medication prescription other than metformin declined from 56.9 ± 3.1% to 29.7 ± 3.0% (P < 1.0 x 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 x 10-5), hsCRP - 39% (P < 1.0 x 10-16), triglycerides - 24% (P < 1.0 x 10-16), HDL-cholesterol + 18% (P < 1.0 x 10-16), and LDL-cholesterol + 10% (P = 5.1 x 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. Conclusions 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. [ABSTRACT FROM AUTHOR]

Background: Carbohydrate restricted diet regimen is widely accepted as therapeutic approach for the treatment of kidney disease associated with type-2 diabetes, obesity and hypertensive disorders. The present study tested the influence of carbohydrate-energy restricted diet (CR) on type-1 diabetes induced renal dysfunction, hypoxia and structural alterations against diabetic rat group fed control diet (ad libitium). Methods: Male wistar rats weighing between 180 and 190 g were subjected to 30% carbohydrate energy restricted diet (CR) and diabetes was induced by administration of streptozotocin (45 mg/kg., i.p). Assessment of renal function was done after 4 weeks by determining the serum levels of creatinine, BUN, proteinuria. Oxidative stress was determined by estimating the reduced glutathione, malonaldehyde levels, catalase activity and extent of renal hypoxia by estimating the HIF-1α levels in kidney tissue homogenates. Histological studies were conducted on kidney sections using hematoxylin and eosin, periodic acid-schiff staining. Results: Diabetic rats exhibited marked hyperglycemia and renal dysfunction developed in diabetic rats fed control diet (ad libitium) as shown by significantly elevated levels of serum creatinine, BUN and massive proteinuria after 4 weeks period. CR diet treatment in diabetic rats significantly lowered hyperglycemia, reversed the above renal functional abnormalities, reduced oxidative stress and enhanced HIF-1α levels. Furthermore histological examination of kidney sections from CR diet treated diabetic rat group showed absence of glomerular hypertrophy, mesangial expansion and tubular vacoulations. Conclusion: Our results demonstrated that CR diet treatment in diabetic rats attenuated renal damage by reducing oxidative stress and preventing the development of hypoxia by up-regulating HIF-1α levels. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study was conducted to establish the comparative effects of carbohydrate versus fat restriction on metabolic indices in Type 2 diabetic (T2D) patients with coronary heart disease (CHD). METHODS: This randomized, clinical trial was done among 56 overweight persons with T2D and CHD aged 40-85 years old. The patients were randomly allocated to take either a highcarbohydrate (HC) diet (60-65% carbohydrates and 20-25% fats) (n = 28) or a restricted carbohydrate (RC) diet (43-49% carbohydrate and 36-40% fats) (n = 28) for 8 weeks to determine metabolic status. RESULTS: After 8 weeks of treatment, RC diet decreased fasting plasma glucose (FPG) (-11.5 ± 28.3 vs. +7.0 ± 26.9 mg/dl, P = 0.010) and high-sensitivity C-reactive protein (hs-CRP) (-564.3 ± 1280.1 vs. +286.1 ± 1789.2 ng/ml, P = 0.040) compared with a HC diet. Moreover, compared with a HC diet, RC diet increased total antioxidant capacity (TAC) (+274.8 ± 111.5 vs. +20.2 ± 82.5 mmol/l, P < 0.001) and glutathione (GSH) levels (+51.6 ± 111.5 vs. -32.6 ± 88.5 µmol/l, P = 0.003). No significant alterations between the two groups were found in terms of their effect on other metabolic profiles. CONCLUSION: RC diet in overweight T2D with CHD had beneficial effects on FPG, hs-CRP, TAC, and GSH values. [ABSTRACT FROM AUTHOR]

Approximately 50 % of patients with heart failure have diastolic heart failure (HFPEF) with the major predisposing risk factors age, inactivity, obesity, insulin resistance (IR), type-2 diabetes, and hypertension. The prognosis of HFPEF is comparable to that of systolic heart failure, but without any specific or effective treatment. This review presents a biomathematically corrected diagnostic approach for quantification of diastolic dysfunction (DD) via the age dependency of diastolic function. Pathophysiological mechanisms for DD in the cardiometabolic syndrome (CMS) are mainly based on downstream effects of IR including insufficient myocardial energy supply. The second section discusses therapeutic strategies for the control and therapy of CMS, IR, and the associated DD/HFPEF with a focus on dietary therapy that is independent of weight loss but improves all manifestations of the CMS and reduces cardiovascular risk. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper was to investigate the impact of specific carbohydrate restriction (polysaccharides and disaccharides) in the form of the specific carbohydrate diet (SCD) in treating irritable bowel syndrome (IBS). Design/methodology/approach – A female patient diagnosed with diarrhea predominant IBS was assigned to the SCD for six months. The diet occurred in phases and was advanced based on the individual’s tolerance level under the guidance of a registered dietitian. Quality of life was measured by a pre- and post-IBS severity score questionnaire. Gastrointestinal symptoms were measured by self-assessment of IBS symptoms using a seven-point Likert-like scale, with −3 = substantially worse to +3 = substantially better. Probiotics were consumed throughout the duration of the study. Findings – The quality of life severity score significantly improved from a severity of 315 (with 500 being the most severe) to 15. The initial symptoms from the first day on the diet compared to the total period for bloating, abdominal pain/discomfort, flatulence/wind, diarrhea, bowel urgency, stool consistency, stool frequency, energy levels, incomplete evacuation and abdominal rumbling were improved significantly (p < 0.0005). The SCD diet significantly improved the quality of life and IBS symptoms in a female patient with IBS-diarrhea. Originality/value – This study is the first of its kind to evaluate the efficacy of the SCD to treat IBS. The SCD should be considered a therapeutic option to treating IBS after fermentable carbohydrate restriction. [ABSTRACT FROM AUTHOR]

Background: Hyperinsulinemic hypoglycemia is a rare complication of Roux-en-Y gastric bypass (RYGB) surgery. Meals with a high carbohydrate (carb) content and high glycemic index (GI) may provoke these hypoglycemic attacks. The aim of this study is to assess the effects of reducing meal carb content and GI on glycemic responses in patients with post-RYGB hypoglycemia. Methods: Fourteen patients with post-RYGB hypoglycemia underwent two meal tests: a mixed meal test (MMT) with a carb content of 30 g and a meal test with the low GI supplement, Glucerna SR 1.5® (Glucerna meal test (GMT)). Plasma glucose and serum insulin levels were measured for a period of 6 h. Results: Peak glucose levels were reached at T during GMT and at T during MMT, and they were 1.5 ± 0.3 mmol/L lower during GMT than during MMT (7.5 ± 0.4 vs 9.0 ± 0.4 mmol/L, P < 0.005). GMT induced the most rapid rise in plasma insulin: at T plasma, insulin was 30.7 ± 8.5 mU/L higher during GMT than during MMT ( P < 0.005). None of the carb-restricted meals induced post-prandial hypoglycemia. Conclusion: A 30-g carb-restricted meal may help to prevent post-prandial hypoglycemia in patients with post-RYGB hypoglycemia. The use of a liquid, low GI, supplement offers no additional advantage. [ABSTRACT FROM AUTHOR]

High-fat versus high-carbohydrate diets for optimal higher intensity endurance exercise performance: and the winner is... Keywords: carbohydrate restriction; exercise performance; glycogen; ketogenic diet EN carbohydrate restriction exercise performance glycogen ketogenic diet 727 728 2 02/02/21 20210201 NES 210201 In the past 50 years, the question of what the optimal dietary macronutrient composition for human health is has resulted in a perpetual merry-go-round of responses from health practitioners and scientists, often leaving the public dizzy with confusion. Low carbohydrate, high fat diet impairs exercise economy and negates the performance benefit from intensified training in elite race walkers. [Extracted from the article]

The influence of restricting available carbohydrates (CHOs) on shoot growth was studied by cane girdling field grown Vitis vinifera L. Sauvignon Blanc grapevines before budbreak. Canes were girdled 5, 10 or 20 cm from the terminal bud of the cane, and the shoot growth of the terminal bud was monitored over the course of a single growing season. A linear relationship was found between the initial rate of shoot growth and the amount of cane isolated by the girdle. A decrease in available CHOs during initial shoot growth appeared to inhibit the shoot's ability to produce new vegetative nodes past the point of discontinuity, resulting in a decrease in total leaf area due to incomplete leaf expansion. The transition from the vine's dependence on reserve CHOs to a net positive state appeared to occur when shoot growth reached a steady state. In the case of severe CHO restriction, no lateral growth occurred, suggesting the CHO status in the vine may play a role in lateral bud growth. The cross-sectional area of canes or shoots were shown to have a linear relationship to their CHO content, which allows for an estimation of the amount of CHOs required to obtain growth similar to the control treatment. Additionally, main shoot leaf area can be used to predict total CHO content in the shoot at harvest. The carbohydrate availability of a developing grapevine shoot has a direct influence on shoot architecture and leaf development. The initial rate of shoot growth will determine its ability to develop adequate leaf area, which is required for growth. An estimation of the carbohydrates present in a cane or shoot can be determined by using the shoot's or cane's cross-sectional area, or by using the total leaf area of the shoot. [ABSTRACT FROM AUTHOR]

Recent studies suggest that carbohydrate restriction can improve the training-induced adaptation of muscle oxidative capacity. However, the importance of low muscle glycogen on the molecular signaling of mitochondrial biogenesis remains unclear. Here, we compare the effects of exercise with low (LG) and normal (NG) glycogen on different molecular factors involved in the regulation of mitochondrial biogenesis. Ten highly trained cyclists ( VO 65 ± 1 ml/kg/min, W 387 ± 8 W) exercised for 60 min at approximately 64 % VO with either low [166 ± 21 mmol/kg dry weight (dw)] or normal (478 ± 33 mmol/kg dw) muscle glycogen levels achieved by prior exercise/diet intervention. Muscle biopsies were taken before, and 3 h after, exercise. The mRNA of peroxisome proliferator-activated receptor-γ coactivator-1 was enhanced to a greater extent when exercise was performed with low compared with normal glycogen levels (8.1-fold vs. 2.5-fold increase). Cytochrome c oxidase subunit I and pyruvate dehydrogenase kinase isozyme 4 mRNA were increased after LG (1.3- and 114-fold increase, respectively), but not after NG. Phosphorylation of AMP-activated protein kinase, p38 mitogen-activated protein kinases and acetyl-CoA carboxylase was not changed 3 h post-exercise. Mitochondrial reactive oxygen species production and glutathione oxidative status tended to be reduced 3 h post-exercise. We conclude that exercise with low glycogen levels amplifies the expression of the major genetic marker for mitochondrial biogenesis in highly trained cyclists. The results suggest that low glycogen exercise may be beneficial for improving muscle oxidative capacity. [ABSTRACT FROM AUTHOR]

Distribution of viable Candidatus Liberibacter asiaticus (CaLas) in sweet orange fruit and leaves (‘Hamlin’ and ‘Valencia’) and transcriptomic changes associated with huanglongbing (HLB) infection in fruit tissues are reported. Viable CaLas was present in most fruit tissues tested in HLB trees, with the highest titre detected in vascular tissue near the calyx abscission zone. Transcriptomic changes associated with HLB infection were analysed in flavedo (FF), vascular tissue (VT), and juice vesicles (JV) from symptomatic (SY), asymptomatic (AS), and healthy (H) fruit. In SY ‘Hamlin’, HLB altered the expression of more genes in FF and VT than in JV, whereas in SY ‘Valencia’, the number of genes whose expression was changed by HLB was similar in these tissues. The expression of more genes was altered in SY ‘Valencia’ JV than in SY ‘Hamlin’ JV. More genes were also affected in AS ‘Valencia’ FF and VT than in AS ‘Valencia’ JV. Most genes whose expression was changed by HLB were classified as transporters or involved in carbohydrate metabolism. Physiological characteristics of HLB-infected and girdled fruit were compared to differentiate between HLB-specific and carbohydrate metabolism-related symptoms. SY and girdled fruit were smaller than H and ungirdled fruit, respectively, with poor juice quality. However, girdling did not cause misshapen fruit or differential peel coloration. Quantitative PCR analysis indicated that many selected genes changed their expression significantly in SY flavedo but not in girdled flavedo. Mechanisms regulating development of HLB symptoms may lie in the host disease response rather than being a direct consequence of carbohydrate starvation. [ABSTRACT FROM PUBLISHER]

The adoption of carbohydrate-restrictive diets to improve health is increasing in popularity, but there is a dearth of research on individuals who choose to severely restrict or entirely exclude carbohydrates. The present study investigated the beliefs and experiences of individuals following a diet that severely limits, or entirely excludes, dietary carbohydrates, colloquially known as a 'zero-carb' diet, for at least 6 months. Zero-carb dieters (n = 170) recruited via a social networking site completed an online qualitative survey prompting them to discuss their motives, rationale, and experiences of following a low-carb diet. Transcripts of participants' responses were analyzed using inductive thematic analysis. Results revealed that participants' decision to follow a zero-carb diet was driven by health concerns and benefits. Participants expressed a strong social identity and belongingness to online zero-carb communities. Participants reported strong intentions to follow the diet indefinitely. Shortcomings of the diet centered on experienced stigma; lack of support from healthcare providers and significant others; limited access to, and high cost of, foods; and limited scientific data on the diet. Further research into the benefits and shortcomings of zero-carb diets across settings and populations is warranted, and guidelines for healthcare professionals on how to support individuals following a zero-carb diet are needed. [ABSTRACT FROM AUTHOR]

Dietary carbohydrate restriction in the treatment of diabetes and metabolic syndrome is based on an underlying principle of control of insulin secretion and the theory that insulin resistance is a response to chronic hyperglycemia and hyperinsulinemia. As such, the theory is intuitive and has substantial experimental support. It has generally been opposed by health agencies because of concern that carbohydrate will be replaced by fat, particularly saturated fat, thereby increasing the risk of cardiovascular disease as dictated by the so-called diet-heart hypothesis. Here we summarize recent data showing that, in fact, substitution of fat for carbohydrate generally improves cardiovascular risk factors. Removing the barrier of concern about dietary fat makes carbohydrate restriction a reasonable, if not the preferred method for treating type 2 diabetes and metabolic syndrome. We emphasize the ability of low carbohydrate diets to improve glycemic control, hemoglobin A1C and to reduce medication. We review evidence that such diets are effective even in the absence of weight loss. [ABSTRACT FROM AUTHOR]

The metabolic syndrome is a cluster of symptoms associated with insulin resistance and known to precede the onset of type 2 diabetes. Overweight and obesity contribute significantly to the development of the metabolic syndrome. In fact, weight loss has a huge impact in decreasing the symptoms associated with the metabolic syndrome. Several studies have demonstrated that just by losing 7% to 10% of initial body weight is sufficient to have improvement in waist circumference, dyslipidemias (elevated triglycerides and low high-density-lipoprotein cholesterol), trunk fat, and plasma glucose. This paper underlines the importance of weight loss and type of diet in reversing the symptoms of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests a role for carbohydrate restriction in the dietary treatment of atherogenic dyslipidemia. The effects of carbohydrate restriction on the specific aspects of lipoprotein metabolism affected by atherogenic dyslipidemia under weight-stable and weight-loss conditions are reviewed here. [ABSTRACT FROM AUTHOR]

To determine the effects of carbohydrate restriction (CR) with and without soluble fiber on lipoprotein metabolism, 29 men participated in a 12-wk weight loss intervention. 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) with a macronutrient energy distribution of approximately 10% carbohydrate, approximately 65% fat, and approximately 25% protein. Because the groups did not differ in any of the variables measured, all data were pooled and comparisons were made between baseline and 12 wk. After 12 wk, subjects had a mean weight loss of 7.5 kg (P<0.001), and abdominal fat was reduced by 20% (P<0.001). Plasma LDL cholesterol and triglycerides (TG) were significantly reduced by 8.9 and 38.6%, respectively. Similarly, apolipoproteins C-I (-13.8%), C-III (-21.2%) and E (-12.5%) were significantly lower after the intervention. In contrast plasma HDL-cholesterol concentrations were increased by 12% (P<0.05). Changes in plasma TG were positively correlated with reductions in large (r=0.615, P<0.01) and medium VLDL particles (r=0.432, P<0.05) and negatively correlated with LDL diameter (r=-0.489, P<0.01). Changes in trunk fat were positively correlated with medium VLDL (r=0.474, P<0.0) and small LDL (r=0.405, P<0.05) and negatively correlated with large HDL (r=-0.556, P<0.01). We conclude that weight loss induced by CR favorably alters the secretion and processing of plasma lipoproteins, rendering VLDL, LDL, and HDL particles associated with decreased risk for atherosclerosis and coronary heart disease. [ABSTRACT FROM AUTHOR]

Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45–40 E%, n = 13), (2) low CHO diets (<40–30 E%, n = 16), and (3) very-low CHO diets (<30–3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs. [ABSTRACT FROM AUTHOR]

Compared to low-fat diets, low-carbohydrate (CHO) diets cause weight loss (WL) over a faster time frame; however, it is unknown how changes in food cravings and eating behavior contribute to this more rapid WL in the early phases of dieting. We hypothesized that reductions in food cravings and improved eating behaviors would be evident even after a relatively short (4-week) duration of CHO-restriction, and that these changes would be associated with WL. Adult participants (n = 19, 53% males, mean ± SD: BMI = 34.1 ± 0.8 kg/m2; age 40.6 ± 1.9 years) consumed a CHO-restricted diet (14% CHO, 58% fat, 28% protein) for 4 weeks. Before and after the intervention, specific and total cravings were measured with the Food Craving Inventory (FCI) and eating behaviors assessed with the Three-Factor Eating questionnaire. Food cravings were significantly reduced at week 4, while women had significantly greater reductions in sweet cravings than men. Dietary restraint was significantly increased by 102%, while disinhibiton and hunger scores were reduced (17% and 22%, respectively, p < 0.05). Changes in cravings were unrelated to changes in body weight except for the change in high-fat cravings where those who lost the most weight experienced the least reductions in fat cravings (r = −0.458, p = 0.049). Changes in dietary restraint were inversely related to several FCI subscales. A short-term, low-CHO diet was effective in reducing food cravings. These data suggest that in subjects that have successfully lost weight on a low-CHO diet, those who craved high-fat foods at the onset were able to satisfy their cravings—potentially due to the high-fat nature of this restricted diet. [ABSTRACT FROM AUTHOR]