Efficacy and Findings of a Blinded Randomized Reintroduction Phase for the Low FODMAP Diet in Irritable Bowel Syndrome.

BACKGROUND & AIMS: The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities. METHODS: Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities. RESULTS: In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose. CONCLUSION: We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.

Association between low-carbohydrate-diet score, glycemia and cardiovascular risk factors in adults with type 1 diabetes.

BACKGROUND AND AIMS: Low-carbohydrate-diets (LCDs) are gaining popularity in individuals with type 1 diabetes (T1D). However, the impact of such diets on glycemia and cardiovascular risk factors is debated. This study aims to evaluate associations between low-carbohydrate intakes using LCD score with glycemia and cardiovascular risk factors (lipid profile) in adults with T1D or LADA in Québec, Canada. METHODS AND RESULTS: This is a cross-sectional study using data collected in the BETTER registry (02/2019 and 04/2021) including self-reported 24-h dietary recalls to calculate LCD scores, waist circumference, level-2 and level-3 hypoglycemic episodes and measured biochemical data (HbA1c, LDL-cholesterol and non-HDL-cholesterol). Participants were divided into quartiles (Q) based on LCD scores. Two hundred eighty-five adults (aged 48.2 ± 15.0 years; T1D duration 25.9 ± 16.2 years) were included. Categorical variables underwent Chi-squared/Fisher's Exact tests, while continuous variables underwent ANOVA tests. Mean carbohydrate intake ranged from 31.2 ± 6.9% (Q1) to 56.5 ± 6.8% (Q4) of total daily energy. Compared to Q4, more people in Q1 reported HbA1c ≤ 7% [≤53.0 mmol/mol] (Q1: 53.4% vs. Q4: 29.4%; P = 0.011). The same results were found in the models adjusted for age, sex and T1D duration. A greater proportion of participants in Q1 never experienced level-3 hypoglycemia compared to Q3 (Q1: 60.0% vs. Q3: 31.0%; P = 0.004). There were no differences across quartiles for frequency of level-2 hypoglycemia events and lipid profile (LDL-cholesterol and non-HDL-cholesterol). CONCLUSIONS: Low-carbohydrate intakes are associated with higher probabilities of reaching HbA1c target and of never having experienced level-3 hypoglycemia. No associations with level-2 hypoglycemia frequency, nor cardiovascular risk factors were observed.

[Gastrointestinal symptoms and dietary intake of patients with irritable bowel syndrome following a low FODMAP diet].

INTRODUCTION: High FODMAP (fermentable oligo-, di, monosaccharides and polyols) foods have been linked with worsening symptoms of IBS patients. The aim was to compare gastrointestinal symptoms and dietary intake of patients with irritable bowel syndrome following a low FODMAP diet, with or without individual nutrition therapy. MATERIALS AND METHODS: A total of 54 patients that met Rome IV criteria for IBS were randomized into two groups, guided group (individual nutrition therapy, n=28) and self-management group (learned about low FODMAP diet online, n=26). Both groups followed low FODMAP diet for 4 weeks. Four-day food records were used to assess dietary intake. Symptoms were assessed by the IBS-severity scoring system (ISB-SSS). RESULTS: The number of subjects who did not complete the study was 13, thereof five in the nutrition therapy and eight in the self-management group, leaving 23 and 18 subjects available for analysis, respectively. Symptoms declined from baseline to endpoint in both groups, by 183±101 points on average in the group receiving nutrition therapy (p< 0.001) and 132±110 points in the self-management group (p< 0.001), with no difference between groups. At baseline, about 80% of meals in both groups contained food high in FODMAP's. The corresponding proportion was 9% and 36% in week 3 in the nutrition therapy and self-management group, respectively (p< 0.001). CONCLUSION: Both groups experienced relieve of symptoms, but compliance to the low FODMAP diet was better in the group receiving individual nutrition therapy compared with the group who only received instructions on how to learn about low FODMAP diet online.

A six-month low-carbohydrate diet high in fat does not adversely affect endothelial function or markers of low-grade inflammation in patients with type 2 diabetes: an open-label randomized controlled trial.

BACKGROUND: While a low-carbohydrate diet (LCD) reduces HbA1c in patients with type 2 diabetes (T2D), the associated high intake of fat may adversely affect cardiovascular risk factors. To address this, we examined the effect of a non-calorie-restricted LCD high in fat on endothelial function and markers of low-grade inflammation in T2D over 6 months. METHODS: In an open-label randomized controlled trial, 71 patients with T2D were randomized 2:1 to either a LCD (< 20 E% carbohydrates, 50-60 E% fat) or a control diet (50-60 E% carbohydrates, 20-30 E% fat) for six months. Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were assessed by ultrasound in the brachial artery together with plasma interleukin-6 (IL-6) and serum high-sensitivity C-reactive protein (hsCRP) in the participants at baseline (n = 70) and after six months (n = 64). RESULTS: The FMD and NID were unaltered in both groups after six months, and there were no between-group differences in change of either FMD (p = 0.34) or NID (p = 0.53) in response to the interventions. The circulating hsCRP and IL-6 levels decreased only in response to LCD (both p < 0.05). However, comparing changes over time with the control diet, the LCD did not reduce either IL-6 (p = 0.25) or hsCRP (p = 0.07) levels. The lack of changes in FMD and NID in response to LCD persisted after adjustment for cardiovascular risk factors. CONCLUSION: A LCD high in fat for six months does not adversely affect endothelial function or selected markers of low-grade inflammation, which suggests that this nutritional approach does not increase the risk of cardiovascular disease. Trial registration ClinicalTrials.gov (NCT03068078).

Type 1 diabetes and low carbohydrate diets-Defining the degree of nutritional ketosis.

AIMS: Adopting a low- or very low-carbohydrate (LCD or VLCD) diet in type 1 diabetes mellitus (T1D) is a controversial intervention. The main fear is that these diets may increase the risk of diabetic ketoacidosis. However, there is little data about the ketoacidosis risk and the level of physiological nutritional ketosis in individuals following these diets. We aimed to define the level of ketosis in those with T1D following carbohydrate restricted diets in a real-world observational study. METHODS: Patients with T1D who had self-selected dietary carbohydrate restriction were enrolled from local clinics and were compared to those following an unrestricted regular carbohydrate control diet (RCCD). Participants completed a 3-day diary, documenting food intake, ketones, and blood/interstitial glucose concentrations. RESULTS: Participants were divided into three groups according to mean carbohydrate intake: VLCD (<50 g carbohydrates/day) n = 6, LCD (50-130 g carbohydrates/day) n = 6, and RCCD (>130 g carbohydrates/day) n = 3. Mean beta-hydroxybutyrate (BOHB) concentrations were 1.2 mmol/l (SD 0.14), 0.3 mmol/l (SD 0.12) and 0.1mmol/l (SD 0.05) in the VLCD, LCD and RCCD groups, respectively (p = 0.02). Post hoc Dunn test demonstrated this reached statistical significance between the VLCD and RCCD groups (p = 0.02). CONCLUSION: Carbohydrate restricted diets, in particular VLCDs, are associated with a higher BOHB level. However, the degree of ketosis seen is much lower than we expected, and significantly lower than the level typically associated with diabetic ketoacidosis. This may suggest the risk of ketoacidosis is lower than feared, although safety will need to be evaluated further in large scale randomised trials.

Effects of a low carbohydrate diet on heart failure symptoms and quality of life in patients with diabetic cardiomyopathy: A randomised controlled trial pilot study.

BACKGROUND AND AIMS: Heart failure, insulin resistance and/or type 2 diabetes mellitus coexist in the syndrome that is diabetic cardiomyopathy. Patients with diabetic cardiomyopathy experience high symptom burden and poor quality of life. We tested the hypothesis that a low carbohydrate diet improves heart failure symptoms and quality of life in patients with diabetic cardiomyopathy. METHODS AND RESULTS: We conducted a 16-week randomised controlled pilot trial comparing the effects of a low carbohydrate diet (LC) to usual care (UC) in 17 adult patients with diabetic cardiomyopathy. New York Heart Association classification, weight, thirst distress and quality of life scores as well as blood pressure and biochemical data were assessed at baseline and at 16 weeks. Thirteen (n = 8 LC; n = 5 UC) patients completed the trial. The low carbohydrate diet induced significant weight loss in completers (p = 0.004). There was a large between-group difference in systolic blood pressure at the end of the study (Hedges's g 0.99[-014,2.08]). There were no significant differences in thirst or quality of life between groups. CONCLUSION: This is the first clinical trial utilising the low carbohydrate dietary approach in patients with diabetic cardiomyopathy in an outpatient setting. A low carbohydrate diet can lead to significant weight loss in patients with diabetic cardiomyopathy. Future clinical trials with larger samples and that focus on fluid and sodium requirements of patients with diabetic cardiomyopathy who engage in a low carbohydrate diet are warranted. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ANZCTR): ACTRN12620001278921. DATE OF REGISTRATION: 26th November 2020.

Low-carbohydrate diet and risk of cancer incidence: The Japan Public Health Center-based prospective study.

Epidemiological evidence on the effects of a long-term low-carbohydrate diet (LCD) on cancer incidence remains sparse. We investigate the association between LCD and the risk of overall and specific cancer site incidence in a Japanese population-based prospective cohort study among 90 171 participants aged 45-74. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a median 17.0 y of follow-up, we identified 15 203 cancer cases. A higher overall LCD score was associated with increased overall cancer risk (HR = 1.08 [CI: 1.02-1.14], P-trend = .012), while it was associated with decreased gastric cancer (GC) risk (0.81 [0.71-0.93], P-trend = .006). A higher animal-based LCD score was associated with higher risk of overall cancer (1.08 [1.02-1.14], P-trend = .003), colorectal cancer (CRC) (1.11 [0.98-1.25], P-trend = .018), rectal cancer (RC) (1.24 [1.00-1.54], P-trend = .025), lung cancer (LC) (1.16 [1.00-1.34], P-trend = .042), and lower risk of GC (0.90 [0.79-1.01], P-trend = .033). Furthermore, we found that plant-based LCD score was related to lower GC incidence (0.87 [0.77-0.99], P-trend = .031). Additionally, adjusted for plant fat intake amplified the adverse associations (overall cancer: 1.08 [1.02-1.14] vs. 1.11 [1.05-1.18]; CRC: 1.08 [0.95-1.22] vs. 1.13 [0.99-1.30]; LC: 1.14 [0.98-1.33] vs. 1.19 [1.01-1.41]). We conclude that LCD enriching with animal products was associated with increased overall cancer, CRC, and LC incidence. These adverse associations could be attenuated by plant fat consumption. LCD reduces the risk of developing GC. Long-term adherence to LCD without paying attention to the balance between animal and plant food source consumption might cause adverse overall cancer incidence consequences.

Gastrointestinal effects of diets low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols.

PURPOSE OF REVIEW: Food ingestion is an exacerbator of gastrointestinal symptoms, regardless of origin. Sufferers mistakenly assume that they have suffered an allergic reaction to a given food. Although classical IgE-mediated allergic reactions are rarely culpable, evidence for a role for intolerance to certain carbohydrates in irritable bowel syndrome (IBS) and related conditions increases. This review assesses the status of a commonly implicated group of poorly absorbed carbohydrates (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAPs) in gastrointestinal pathophysiology. RECENT FINDINGS: Although evidence of efficacy for low FODMAP diets in IBS accumulates, the magnitude of this effect has declined in recent studies. Comparisons to other dietary approaches have revealed conflicting results; some suggest superiority, others find parity. Concerns had been raised regarding long-term nutritional, psychological and microbiological impacts of FODMAP restriction; providing that the diet is administered in the recommended manner, these do not appear to be clinically important. The mechanisms whereby FODMAPs cause gastrointestinal symptoms continue to be explored. SUMMARY: FODMAPS induce gastrointestinal symptoms in susceptible individuals and their restriction provides clinical benefits. The magnitude of these benefits, the superiority of FODMAP restriction over other dietary approaches and the mechanisms of its effects continue to be defined.

Low-Carbohydrate Diet Score and Coronary Artery Calcium Progression: Results From the CARDIA Study.

OBJECTIVE: To investigate whether low-carbohydrate diets (LCDs) were associated with coronary artery calcium (CAC) progression. Approach and Results: We included the participants who completed computed tomography assessment of baseline CAC in 2000 to 2001 (year 15) and follow-up (year 20 or 25) and food frequency questionnaire (years 0, 7, and 20) in the CARDIA study (Coronary Artery Risk Development in Young Adults). CAC progression was defined as CAC >0 at follow-up among participants with baseline CAC of 0 and an annualized change of 10 or percent change of ≥10% for those with 0

Diet as a therapeutic tool in chronic gastrointestinal disorders: Lessons from the FODMAP journey.

BACKGROUND AND AIM: Diet is a powerful tool in the management of gastrointestinal disorders, but developing diet therapies is fraught with challenge. This review discusses key lessons from the FODMAP diet journey. METHODS: Published literature and clinical experience were reviewed. RESULTS: Key to designing a varied, nutritionally adequate low-FODMAP diet was our accurate and comprehensive database of FODMAP composition, made universally accessible via our user-friendly, digital application. Our discovery that FODMAPs coexist with gluten in cereal products and subsequent gluten/fructan challenge studies in nonceliac gluten-sensitive populations highlighted issues of collinearity in the nutrient composition of food and confirmation bias in the interpretation of dietary studies. Despite numerous challenges in designing, funding, and executing dietary randomized controlled trials, efficacy of the low-FODMAP diet has been repeatedly demonstrated, and confirmed by real-world experience, giving this therapy credibility in the eyes of clinicians and researchers. Furthermore, real-world application of this diet saw the evolution of a safe and effective three-phased approach. Specialist dietitians must deliver this diet to optimize outcomes as they can target and tailor the therapy and to mitigate the key risks of compromising nutritional adequacy and precipitating disordered eating behaviors, skills outside the gastroenterologist's standard tool kit. While concurrent probiotics are ineffective, specific fiber supplements may improve short-term and long-term outcomes. CONCLUSIONS: The FODMAP diet is highly effective, but optimal outcomes are contingent on the involvement of a gastroenterological dietitian who can assess, educate, and monitor patients and manage risks associated with implementation of this restrictive diet.

Low-carbohydrate diets and the risk of pancreatic cancer: a large prospective cohort study.

Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1: 0.61; 95% confidence interval: 0.45, 0.82; Ptrend < 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged <65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.

Effects of carbohydrate restriction on postprandial glucose metabolism, ß-cell function, gut hormone secretion, and satiety in patients with Type 2 diabetes.

Dietary carbohydrate restriction may improve the phenotype of Type 2 diabetes (T2D) patients. We aimed to investigate 6 wk of carbohydrate restriction on postprandial glucose metabolism, pancreatic α- and ß-cell function, gut hormone secretion, and satiety in T2D patients. Methods In a crossover design, 28 T2D patients (mean HbA1c: 60 mmol/mol) were randomized to 6 wk of carbohydrate-reduced high-protein (CRHP) diet and 6 wk of conventional diabetes (CD) diet (energy-percentage carbohydrate/protein/fat: 30/30/40 vs. 50/17/33). Twenty-four-hour continuous glucose monitoring (CGM) and mixed-meal tests were undertaken and fasting intact proinsulin (IP), 32,33 split proinsulin concentrations (SP), and postprandial insulin secretion rates (ISR), insulinogenic index (IGI), ß-cell sensitivity to glucose (Bup), glucagon, and gut hormones were measured. Gastric emptying was evaluated by postprandial paracetamol concentrations and satiety by visual analog scale ratings. A CRHP diet reduced postprandial glucose area under curve (net AUC) by 60% (P < 0.001), 24 h glucose by 13% (P < 0.001), fasting IP and SP concentrations (both absolute and relative to C-peptide, P < 0.05), and postprandial ISR (24%, P = 0.015), while IGI and Bup improved by 31% and 45% (both P < 0.001). The CRHP diet increased postprandial glucagon net AUC by 235% (P < 0.001), subjective satiety by 18% (P = 0.03), delayed gastric emptying by 15 min (P < 0.001), decreased gastric inhibitory polypeptide net AUC by 29% (P < 0.001), but had no significant effect on glucagon-like-peptide-1, total peptide YY, and cholecystokinin responses. A CRHP diet reduced glucose excursions and improved ß-cell function, including proinsulin processing, and increased subjective satiety in patients with T2D.

Effects of Low FODMAP Diet on Symptoms, Fecal Microbiome, and Markers of Inflammation in Patients With Quiescent Inflammatory Bowel Disease in a Randomized Trial.

BACKGROUND & AIMS: There is limited evidence that a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) reduces gut symptoms in quiescent inflammatory bowel disease (IBD). We performed a randomized, controlled trial to investigate the effects of a low FODMAP diet on persistent gut symptoms, the intestinal microbiome, and circulating markers of inflammation in patients with quiescent IBD. METHODS: We performed a single-blind trial of 52 patients with quiescent Crohn's disease or ulcerative colitis and persistent gut symptoms at 2 large gastroenterology clinics in the United Kingdom. Patients were randomly assigned to groups that followed a diet low in FODMAPs (n = 27) or a control diet (n = 25), with dietary advice, for 4 weeks. Gut symptoms and health-related quality of life were measured using validated questionnaires. Stool and blood samples were collected at baseline and end of trial. We assessed fecal microbiome composition and function using shotgun metagenomic sequencing and phenotypes of T cells in blood using flow cytometry. RESULTS: A higher proportion of patients reported adequate relief of gut symptoms following the low FODMAP diet (14/27, 52%) than the control diet (4/25, 16%, P=.007). Patients had a greater reduction in irritable bowel syndrome severity scores following the low FODMAP diet (mean reduction of 67; standard error, 78) than the control diet (mean reduction of 34; standard error, 50), although this difference was not statistically significant (P = .075). Following the low FODMAP diet, patients had higher health-related quality of life scores (81.9 ± 1.2) than patients on the control diet (78.3 ± 1.2, P = .042). A targeted analysis revealed that in stool samples collected at the end of the study period, patients on the low FODMAP diet had significantly lower abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Faecalibacterium prausnitzii than patients on control diet. However, microbiome diversity and markers of inflammation did not differ significantly between groups. CONCLUSIONS: In a trial of the low FODMAP diet vs a control diet in patients with quiescent IBD, we found no significant difference after 4 weeks in change in irritable bowel syndrome severity scores, but significant improvements in specific symptom scores and numbers reporting adequate symptom relief. The low FODMAP diet reduced fecal abundance of microbes believed to regulate the immune response, compared with the control diet, but had no significant effect on markers of inflammation. We conclude that a 4-week diet low in FODMAPs is safe and effective for managing persistent gut symptoms in patients with quiescent IBD. www.isrctn.com no.: ISRCTN17061468.

Low Carbohydrate Diets and Estimated Cardiovascular and Metabolic Syndrome Risk in Prostate Cancer.

PURPOSE: A low carbohydrate diet (LCD) was shown to suggestively slow prostate cancer (PC) growth. In noncancer patients, LCDs improve metabolic syndrome (MetS) without weight loss. However, concerns about negative impact on cardiovascular disease (CVD) risk remain. The objective of this secondary analysis is to determine the impact of an LCD on risk of MetS and estimated CVD risk in patients with PC. MATERIALS AND METHODS: Pooled data were analyzed from 2 randomized trials testing LCD vs control on 1) preventing insulin resistance after starting hormone therapy (CAPS1) and 2) slowing PC growth in recurrent PC after failed primary treatment (CAPS2). Both trials included a usual care control vs LCD intervention in which patients were instructed to limit carbohydrate intake to ≤20 gm/day, and in CAPS1 only, to walk for ≥30 minutes/day for ≥5 days/week. MetS components (hypertension, high triglycerides, low high-density lipoprotein cholesterol, central obesity and diabetes), 10-year CVD risk estimated using the Framingham Score with either body mass index (BMI) or lipids, and remnant cholesterol were compared between arms using mixed models adjusting for trial. RESULTS: LCD resulted in a significantly reduced risk of MetS (p=0.004) and remnant cholesterol (p <0.001). Moreover, LCD resulted in significantly lower estimated CVD risk using BMI (p=0.002) over the study with no difference in estimated CVD risk using lipids (p=0.14). CONCLUSIONS: LCD resulted in a significantly reduced risk of MetS and remnant cholesterol, and a significantly lower estimated CVD risk using BMI. By comparison, there was no difference in estimated CVD risk using lipids. Study limitations include small sample size, short followup, and inability to distinguish effects of carbohydrate restriction and weight loss. Long-term studies are needed to confirm this finding.

A low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of gestational diabetes mellitus in Chinese women: a prospective cohort study.

We aimed to examine the association between low-carbohydrate diet (LCD) scores during the first trimester and gestational diabetes mellitus (GDM) risk in a Chinese population. A total of 1455 women were included in 2017. Dietary information during the first trimester was collected by 24-h dietary recalls for 3 d. The overall, animal and plant LCD scores, which indicated adherence to different low-carbohydrate dietary patterns, were calculated. GDM was diagnosed based on the results of a 75-g, 2-h oral glucose tolerance test at 24-28 weeks gestation. Log-binomial models were used to estimate relative risks (RR) and 95 % CI. The results showed that the multivariable-adjusted RR of GDM from the lowest to the highest quartiles of the overall LCD score were 1·00 (reference), 1·15 (95 % CI 0·92, 1·42), 1·30 (95 % CI 1·06, 1·60) and 1·24 (95 % CI 1·01, 1·52) (P = 0·026 for trend). Multivariable-adjusted RR (95 % CI) of GDM from the lowest to the highest quartiles of the animal LCD score were 1·00 (reference), 1·20 (95 % CI 0·96, 1·50), 1·41 (95 % CI 1·14, 1·73) and 1·29 (95 % CI 1·04, 1·59) (P = 0·002 for trend). After additional adjustment for gestational weight gain before GDM diagnosis, the association of the overall LCD score with GDM risk was non-significant, while the association of animal LCD score with GDM risk remained significant. In conclusion, a low-carbohydrate dietary pattern characterised by high animal fat and protein during the first trimester is associated with an increased risk of GDM in Chinese women.

Carbohydrate restriction following strenuous glycogen-depleting exercise does not potentiate the acute molecular response associated with mitochondrial biogenesis in human skeletal muscle.

PURPOSE: Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle. METHODS: In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise. RESULTS: Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption. CONCLUSION: CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.

Marked Hypertriglyceridemia in a Patient with type 2 Diabetes Receiving SGLT2 Inhibitors.

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis.

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

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

In contrast to Western diet, a plant-based, high-fat, low-sugar diet does not exacerbate retinal endothelial injury in streptozotocin-induced diabetes.

Controversy remains about how diet affects the vascular endothelial dysfunction associated with disordered insulin-glucose homeostasis. It is postulated that the type and level of certain macronutrients contribute to endothelial dysfunction in vascular diabetes complications. However, it is not well understood how specific macronutrients affect the molecular inflammatory response under conditions of hyperglycemia. Here, we examined retinal microvascular endothelial injury in streptozotocin (STZ)-diabetic rats fed a laboratory Western diet (WD). WD, characterized by its high content of saturated fat, cholesterol, and sugar, significantly increased retinal leukocyte accumulation and endothelial injury in the STZ-diabetic rats. Suppression of endothelial NF-κB signaling in the STZ model reduced the WD-induced increase in leukocyte accumulation. To isolate the effect of dietary fat, we generated high-fat diets with varying fatty acid balance and type. These diets contained moderate amounts of carbohydrates but no sugar. We found that neither high levels of saturated or unsaturated fats per se increased retinal leukocyte accumulation and endothelial injury in the STZ-diabetic rat model but that the combination of high levels of dietary cholesterol with specific saturated fatty acids that are abundant in WD exacerbated leukocyte accumulation and endothelial injury in the retinas of STZ-diabetic rats.-Barakat, A., Nakao, S., Zandi, S., Sun, D., Schmidt-Ullrich, R., Hayes, K. C., Hafezi-Moghadam, A. In contrast to Western diet, a plant-based, high-fat, low-sugar diet does not exacerbate retinal endothelial injury in streptozotocin-induced diabetes.

Ketogenic and low-sugar diets for patients with cancer: perceptions and practices of medical oncologists in Canada.

PURPOSE: Many patients with cancer are interested in complementary therapies, including strategies such as reduced carbohydrate diets. Guidelines regarding the use of these diets during cancer treatment are lacking; therefore, we aimed to explore the perceptions and practices of medical oncologists in Canada regarding low-sugar and ketogenic diets. METHOD: A cross-sectional, online multiple-choice survey was distributed to 206 Canadian medical oncologists. Questions explored frequency of patient interactions, oncologist perceptions of efficacy, advice given to patients, and concerns about side effects related to reduced carbohydrate diets. RESULTS: Responses were received from 57 medical oncologists in seven of thirteen provinces and territories, with an overall response rate of 28%. Forty-nine percent of respondents were asked at least weekly about a low-sugar diet, and 9% about the ketogenic diet. Eighty-five percent supported the use of a low-added sugar diet in patients with diabetes or hyperglycemia, while conversely 87% did not support the use of a ketogenic diet for any of their patients undergoing active cancer treatment. Respondents felt either that a ketogenic diet was not effective (31%) or that the effect on cancer outcomes was unknown (69%). Ninety-six percent of respondents had concerns about a ketogenic diet for patients receiving active cancer treatment. CONCLUSION: The role of reduced carbohydrate diets during cancer treatment is topical. Canadian oncologists are particularly reluctant to support a ketogenic diet for patients on active cancer treatment, with concerns about side effects and unknown efficacy. There may be a role for continuing medical education and institutional guidelines to inform these discussions with patients.