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Competing Interests: GF is funded through grants from the UK Research and Innovation's Biotechnology and Biological Sciences Research Council, Medical Research Council, and the UK National Institute for Health and Care Research; has received educational funding for research from Nestle, Sosei Heptares, and Quorn Foods; and is director of two spin-out companies, Melico and Satisfed.

We examined the impact of APOE genotype on plasma lipids and glucose in a secondary analysis of data from a five-arm, randomised controlled, parallel dietary intervention trial ('RISCK' study), to investigate the impact of replacing saturated fatty acids (SFA) with either monounsaturated fat (MUFA) or carbohydrate of high or low glycaemic index (GI) on CVD risk factors and insulin sensitivity. We tested the impact of APOE genotype (carriage of E2 and E4 alleles versus E3/E3), determined retrospectively, on plasma lipids, lipoproteins and glucose homeostasis at baseline ( n = 469), and on the change in these variables after 24 weeks of dietary intervention ( n = 389). At baseline, carriers of E2 ( n = 70), E4 ( n = 125) and E3/E3 ( n = 274) expressed marked differences in total plasma cholesterol (TC, p = 0.001), low density lipoprotein cholesterol (LDL-C, p < 0.0001), apolipoprotein B (apo B, p < 0.0001) and total to high density lipoprotein cholesterol ratio (TC:HDL-C, p = 0.002), with plasma concentrations decreasing in the order E4 > E3/E3 > E2. Following intervention, there was evidence of a significant diet x genotype interaction with significantly greater decreases in TC ( p = 0.02) and apo B ( p = 0.006) among carriers of E4 when SFA was replaced with low GI carbohydrate on a lower fat diet (TC -0.28 mmol/L p = 0.03; apo B -0.1 g/L p = 0.02), and a relative increase in TC (in comparison to E3/E3) when SFA was replaced with MUFA and high GI carbohydrates (TC 0.3 mmol/L, p = 0.03). Among carriers of E2 (compared with E3/E3) there was an increase in triacylglycerol (TAG) when SFA was replaced with MUFA and low GI carbohydrates 0.46 mmol/L p = 0.001). There were no significant interactions between APOE genotype and diet for changes in indices of glucose homeostasis. In conclusion, variations in APOE genotype led to differential effects on the lipid response to the replacement of SFA with MUFA and low GI carbohydrates.

Background: The glycaemic index (GI) is a physiological measure of the ability of a carbohydrate to affect blood glucose. Interest is growing in this area for the clinical management of people at risk of, or with, established cardiovascular disease. There is a need to review the current evidence from randomised controlled trials (RCTs) in this area. This is an update of the original review published in 2008., Objectives: To assess the effect of the dietary GI on total mortality, cardiovascular events, and cardiovascular risk factors (blood lipids, blood pressure) in healthy people or people who have established cardiovascular disease or related risk factors, using all eligible randomised controlled trials., Search Methods: We searched CENTRAL, MEDLINE, Embase and CINAHL in July 2016. We also checked reference lists of relevant articles. No language restrictions were applied., Selection Criteria: We selected RCTs that assessed the effects of low GI diets compared to diets with a similar composition but a higher GI on cardiovascular disease and related risk factors. Minimum trial duration was 12 weeks. Participants included were healthy adults or those at increased risk of cardiovascular disease, or previously diagnosed with cardiovascular disease. Studies in people with diabetes mellitus were excluded., Data Collection and Analysis: Two reviewers independently screened and selected studies. Two review authors independently assessed risk of bias, evaluated the overall quality of the evidence using GRADE, and extracted data following the Cochrane Handbook for Systematic Reviews of Interventions. We contacted trial authors for additional information. Analyses were checked by a second reviewer. Continuous outcomes were synthesized using mean differences and adverse events were synthesized narratively., Main Results: Twenty-one RCTs were included, with a total of 2538 participants randomised to low GI intervention (1288) or high GI (1250). All 21 included studies reported the effect of low GI diets on risk factors for cardiovascular disease, including blood lipids and blood pressure.Twenty RCTs (18 of which were newly included in this version of the review) included primary prevention populations (healthy individuals or those at high risk of CVD, with mean age range from 19 to 69 years) and one RCT was in those diagnosed with pre-existing CVD (a secondary prevention population, with mean age 26.9 years). Most of the studies did not have an intervention duration of longer than six months. Difference in GI intake between comparison groups varied widely from 0.6 to 42.None of the included studies reported the effect of low GI dietary intake on cardiovascular mortality and cardiovascular events such as fatal and nonfatal myocardial infarction, unstable angina, coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, and stroke. The unclear risk of bias of most of the included studies makes overall interpretation of the data difficult. Only two of the included studies (38 participants) reported on adverse effects and did not observe any harms (low-quality evidence)., Authors' Conclusions: There is currently no evidence available regarding the effect of low GI diets on cardiovascular disease events. Moreover, there is currently no convincing evidence that low GI diets have a clear beneficial effect on blood lipids or blood pressure parameters.

Shiftworkers have a higher risk of CHD and type 2 diabetes. They consume a large proportion of their daily energy and carbohydrate intake in the late evening or night-time, a factor which could be linked to their increase in disease risk. We compared the metabolic effects of varying both dietary glycaemic index (GI) and the time at which most daily energy intake was consumed. We hypothesised that glucose control would be optimal with a low-GI diet, consumed predominantly early in the day. A total of six healthy lean volunteers consumed isoenergetic meals on four occasions, comprising either high- or low-GI foods, with 60 % energy consumed predominantly early (breakfast) or late (supper). Interstitial glucose was measured continuously for 20 h. Insulin, TAG and non-esterified fatty acids were measured for 2 h following every meal. Highest glucose values were observed when large 5021 kJ (1200 kcal) high-GI suppers were consumed. Glucose levels were also significantly higher in predominantly late high- v. low-GI meals (P<0·01). Using an estimate of postprandial insulin sensitivity throughout the day, we demonstrate that this follows the same trend, with insulin sensitivity being significantly worse in high energy consumed in the evening meal pattern. Both meal timing and GI affected glucose tolerance and insulin secretion. Avoidance of large, high-GI meals in the evening may be particularly beneficial in improving postprandial glucose profiles and may play a role in reducing the risk of type 2 diabetes; however, longer-term studies are needed to confirm this.

Much interest has been focused on the relationship between glycaemic index and body-weight loss, some of which is fueled by popular media. However, there is a number of potential mechanisms that could be triggered by reducing the glycaemic index of the carbohydrate consumed in the diet. For example, the effect of foods on the gastrointestinal tract and the effect on blood glucose both could lead to potential appetite effects. Acute meal studies seem to point to an effect of glycaemic index on appetite regulation. However, the results of longer-term studies of weight loss are not as clear. In the present review a possible reason for this variation in outcome from the weight-loss studies will be discussed. The present review focuses on the possibility that the fermentable fibre content of the low-glycaemic-index diet may be important in weight-loss efficacy. A novel receptor that binds SCFA, the products of carbohydrate fermentation, has recently been described on the enteroendocrine L-cell in the colon. This cell releases a number of anorectic hormones and could offer an explanation of the appetite suppressant effects of fermentable carbohydrates. It could also explain the variability in the results of glycaemic-index weight-loss studies.

We aimed to determine whether altering dietary glycemic index (GI) in addition to healthy eating and weight loss advice affects arterial compliance and 24-hour blood pressure (BP), both coronary heart disease (CHD) risk factors. Middle-aged men with at least 1 CHD risk were randomized to a 6-month low-GI (LGI) or high-GI (HGI) diet. All were advised on healthy eating and weight loss. They were seen monthly to assess dietary compliance and anthropometrics. Carotid-femoral pulse wave velocity (PWV), fasting blood lipid profile, and glucose and insulin concentrations were measured at baseline and at months 3 and 6. Six-hour postprandial glucose and insulin responses and 24-hour ambulatory BP were also assessed at baseline and month 6. Thirty-eight subjects (HGI group, n = 16; LGI group, n = 22) completed the study. At month 6, groups differed in dietary GI, glycemic load, and carbohydrate intake (P < .001). Fasting insulin concentration and insulin resistance (calculated by homeostatic model assessment) were lower in the LGI than the HGI group (P < .01). The reduction in total cholesterol and 24-hour BP was bigger in the LGI than the HGI group (P < .05); and only the LGI group had significant reductions (P < .05) in PWV, low-density lipoprotein cholesterol, and triacylglycerol concentration. There were no differences in postprandial glucose or insulin responses between the groups. The results suggest that an LGI diet may be more beneficial in reducing CHD risk, including PWV and 24-hour BP, even in the setting of healthy eating and weight loss; and thus, further study is warranted.

Evidence suggests that a low-glycemic index (LGI) diet has a satiating effect and thus may enhance weight maintenance following weight loss. This study was conducted at Hammersmith Hospital, London, UK, and assessed the effect of altering diet GI on weight-loss maintenance. It consisted of a weight-loss phase and a 4-month randomized weight maintenance phase. Subjects were seen monthly to assess dietary compliance and anthropometrics. Appetite was assessed bimonthly by visual analogue scales while meal challenge postprandial insulin and glucose concentrations were assessed before and after the intervention. Following a median weight loss of 6.1 (interquartile range: 5.2-7.1) % body weight, subjects were randomized to a high-glycemic index (HGI) (n = 19) or LGI (n = 23) diet. Dietary composition differed only in GI (HGI group: 63.7 +/- 9.4; LGI group: 49.7 +/- 5.7, P < 0.001) and glycemic load (HGI group: 136.8 +/- 56.3; LGI group: 89.7 +/- 27.5, P < 0.001). Groups did not differ in body weight (weight change over 4 months, HGI group: 0.3 +/- 1.9 kg; LGI group: -0.7 +/- 2.9 kg, P = 0.3) or other anthropometric measurements. This pilot study suggests that in the setting of healthy eating, changing the diet GI does not appear to significantly affect weight maintenance.

Background: Many laboratories offer glycemic index (GI) services., Objective: We assessed the performance of the method used to measure GI., Design: The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally., Results: Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model)., Conclusions: The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.

Objective: To identify associations between dietary glycaemic index (GI) and weight, body mass index and other risk factors for cardiovascular disease (CVD) - waist-to-hip ratio (WHR), lipoprotein fractions, triacylglycerols (TAG) and blood pressure (BP) - in an older British population., Design: Cross-sectional dietary, anthropometric and biochemical data from the National Diet and Nutritional Survey for adults aged over 65 years were reanalysed using a hierarchical regression model. Associations between body weight, CVD risk factors, and dietary factors including GI and fibre intakes were explored among 1152 healthy older people living in the UK between 1994 and 1995., Results: In the unadjusted model, GI was significantly and directly associated with TAG (beta = 0.008 +/- 0.003) and diastolic BP (beta = 0.325 +/- 0.164) in males. These relationships were attenuated and non-significant after adjustment for potential confounding factors. WHR (beta = 0.003 +/- 0.001) and TAG (beta = 0.005 +/- 0.002) were significantly predicted by GI in males and females combined. The association with WHR was attenuated by adjustment for sex, age, region and social class; the relationship with TAG was non-significant after adjustment for other potential dietary confounders., Conclusion: After controlling for potential confounders, no clear links were detected between GI and body weight or other CVD risk factors. This study provides little evidence for advising the consumption of a low-GI diet in the elderly to prevent weight gain or improve other CVD risk factors.

Background: Findings of the effect of dietary glycemic index (GI) and glycemic load (GL) on the risk of incident diabetes are inconsistent., Objective: We examined the associations of dietary GI and GL with clinical variables at baseline and the incidence of diabetes., Design: The 7321 white Whitehall II participants (71% men) attending screening in 1991-1993, free of diabetes at baseline, and with food-frequency questionnaire data were followed for 13 y., Results: At baseline, dietary GI and GL were associated inversely with HDL cholesterol, and GI was associated directly with triacylglycerols. Dietary GI and GL were related inversely to fasting glucose and directly to 2-h postload glucose, but only the association between GI and 2-h postload glucose was robust to statistical adjustments for employment grade, physical activity, smoking status, and intakes of alcohol, fiber, and carbohydrates. High-dietary GI was not associated with increased risk of incident diabetes. Hazard ratios (HRs) across sex-specific tertiles of dietary GI were 1.00, 0.95 (95% CI: 0.73, 1.24), and 0.94 (95% CI: 0.72, 1.22) (adjusted for sex, age, and energy misreporting; P for trend = 0.64). Corresponding HRs across tertiles of dietary GL were 1.00, 0.92 (95% CI: 0.71, 1.19), and 0.70 (95% CI: 0.54, 0.92) (P for trend = 0.01). The protective effect on diabetes risk remained significant after adjustment for employment grade, smoking, and alcohol intake but not after further adjustment for carbohydrate and fiber intakes., Conclusion: The proposed protective effect of low-dietary GI and GL diets on diabetes risk could not be confirmed in this study.

Elevated postprandial glycaemia has been linked to CVD in a number of different epidemiological studies involving predominantly non-diabetic volunteers. The MiniMed continuous glucose monitor, which measures blood glucose every 5 min, over a 24 h period, was used to investigate changes in blood glucose readings before and after instigating a diet with low glycaemic index (GI) for 1 week in free-living healthy individuals. Nine healthy people (age 27 (SEM 1.3) years, BMI 23.7 (SEM 0.7) kg/m2, one male, eight females) completed the study. A reduction in GI (59.7 (SEM 2) v. 52.1 (SEM 2), P<0.01) occurred in all nine subjects while energy and other macronutrients remained constant. A significant reduction was also observed in fasting glucose at 06.00 hours (5.4 (SEM 0.2) v. 4.4 (SEM 0.3) mmol/l, P<0.001), mean glucose (5.6 (SEM 0.2) v. 5.1 (SEM 0.2) mmol/l, P=0.004), area under the 24 h glucose curve (8102 (SEM 243) v. 750 (SEM 235) mmol/l per min, P=0.004) and area under the overnight, 8 h glucose curve (2677 (SEM 92) v. 2223 (SEM 121) mmol/l per min, P=0.01). The present study provides important data on how a simple adjustment to the diet can improve glucose profiles that, if sustained in the long term, would be predicted from epidemiological studies to have a favourable influence on CVD.

Background Starchy foods can have a profound effect on metabolism. The structural properties of starchy foods can affect their digestibility and postprandial metabolic responses, which in the long term may be associated with the risk of type 2 diabetes and obesity. Objectives This systematic review sought to evaluate the clinical evidence regarding the impact of the microstructures within starchy foods on postprandial glucose and insulin responses alongside appetite regulation. Methods A systematic search was performed in the PUBMED, Ovid Medicine, EMBASE, and Google Scholar databases for data published up to 18 January 2021. Data were extracted by 3 independent reviewers from randomized crossover trials (RCTs) that investigated the effect of microstructural factors on postprandial glucose, insulin, appetite-regulating hormone responses, and subjective satiety scores in healthy participants. Results We identified 745 potential articles, and 25 RCTs (n  = 369 participants) met our inclusion criteria: 6 evaluated the amylose-to-amylopectin ratio, 6 evaluated the degree of starch gelatinization, 2 evaluated the degree of starch retrogradation, 1 studied starch–protein interactions, and 12 investigated cell and tissue structures. Meta-analyses showed that significant reductions in postprandial glucose and insulin levels was caused by starch with a high amylose content [standardized mean difference (SMD) = −0.64 mmol/L*min (95% CI: −0.83 to −0.46) and SMD = −0.81 pmol/L*min (95% CI: −1.07 to −0.55), respectively], less-gelatinized starch [SMD = −0.54 mmol/L*min (95% CI: −0.75 to −0.34) and SMD = −0.48 pmol/L*min (95% CI: −0.75 to −0.21), respectively], retrograded starch (for glucose incremental AUC; SMD = −0.46 pmol/L*min; 95% CI: −0.80 to −0.12), and intact and large particles [SMD = −0.43 mmol/L*min (95% CI: −0.58 to −0.28) and SMD = −0.63 pmol/L*min (95% CI: −0.86 to −0.40), respectively]. All analyses showed minor or moderate heterogeneity (I2 < 50%). Sufficient evidence was not found to suggest how these structural factors influence appetite. Conclusions The manipulation of microstructures in starchy food may be an effective way to improve postprandial glycemia and insulinemia in the healthy population. The protocol for this systematic review and meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) as CRD42020190873. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- Optimizing glycemic control in diabetic patients undergoing maintenance hemodialysis requires accurate assessment. We hypothesize that 1) 48-h continuous glucose monitoring (CGM) provides additional, clinically relevant, information to that provided by the A1C measurement and 2) glycemic profiles differ significantly between day on and day off dialysis. RESEARCH DESIGN AND METHODS -- With the use of GlucoDay S, 48-h CGM was performed in 19 type 2 diabetic subjects undergoing hemodialysis to capture consecutive 24-h periods on and off dialysis. Energy intake was calculated using food diaries. A1C was assayed by a high-performance liquid chromatography method. RESULTS-- CGM data were available for 17 subjects (13 male) with a mean (range) age of 61.5 years (42-79 years) and diabetes duration of 18.8 years (4-30 years). The 24-h CGM area under the glucose curve and 24-h mean glucose values were significantly higher during the day off dialysis than on dialysis (5,932.1 ± 2,673.6 vs. 4,694 ± 1,988.0 mmol ⋅ 3 min[sup -1] ⋅ l[sup -l], P = 0.022, and 12.6 ± 5.6 vs. 9.8 ± 3.8 mmol/l, P = 0.013, respectively), independent of energy intake. Asymptomatic hypoglycemia occurred in 4 subjects, 3 within 24 b of dialysis, and the glucose nadir in 14 subjects occurred within 24 h of dialysis. CONCLUSIONS- Glucose values are significantly lower on dialysis days than on nondialysis days despite similar energy intake. The risk of asymptomatic hypoglycemia was highest within 24 h of dialysis. Physicians caring for patients undergoing hemodialysis need to be aware of this phenomenon and consider enhanced glycemic monitoring after a hemodialysis session. CGM provides glycemic information in addition to A1C, which is potentially relevant to clinical management. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding how diets with a low glycemic index have been shown to improve glucose tolerance in clinical studies.

Highlights: [•] Naked (hull-less) barley lines with lower GI values than oats were selected for UK agronomy from large segregating bulks. [•] The naked lines are a valuable resource for breeding and product testing for commercial supply chain development for food barley. [•] A QTL for β glucan content associated with the CslF6 gene (but not associated with nud) can be targeted in marker assisted selection. [Copyright &y& Elsevier]

Abstract: Aims: Study the effect of several boluses of a new diabetes-specific formula (DSF) during the day on 24h glucose profile. Methods: In this randomized, controlled, double-blind, cross-over study 12 ambulatory type 2 diabetic patients were included. Subjects received a new DSF and an isocaloric standard fibre-containing formula (SF) while continuing their anti-diabetic medication. Subjects received 100% of their calculated daily energy requirements as bolus feeding every 3h (5 times/day, starting at 8.00a.m.±1h). Results: Glucose profiles were significantly better after administration of DSF compared with SF determined as mean glucose concentration (±SEM) (8.7±0.5 versus 9.6±0.6mmol/L, p <0.05 during 24h; 9.4±0.6 versus 10.7±0.6mmol/L, p <0.001 during daytime) or as incremental area under the curve during daytime (−44%; p <0.05). Subjects receiving DSF experienced less hyperglycaemic time over 24h (−26%; p <0.05) and during daytime (−30%; p <0.05). Furthermore, lower individual and mean (delta) peak glucose levels were found (p <0.05). No clinically relevant differences in gastrointestinal tolerance were observed. Conclusions: Using DSF resulted in significantly better 24h and postprandial glucose profiles than fibre-containing SF after bolus administration and may therefore help to improve glycaemic control in diabetic patients. [Copyright &y& Elsevier]