Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia.

BACKGROUND: Persons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non-high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)-mediated inhibition of lipoprotein lipase. METHODS: We carried out a 48-week, phase 2b, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of plozasiran, a hepatocyte-targeted APOC3 small interfering RNA, in patients with mixed hyperlipidemia (i.e., a triglyceride level of 150 to 499 mg per deciliter and either a low-density lipoprotein [LDL] cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). The participants were assigned in a 3:1 ratio to receive plozasiran or placebo within each of four cohorts. In the first three cohorts, the participants received a subcutaneous injection of plozasiran (10 mg, 25 mg, or 50 mg) or placebo on day 1 and at week 12 (quarterly doses). In the fourth cohort, participants received 50 mg of plozasiran or placebo on day 1 and at week 24 (half-yearly dose). The data from the participants who received placebo were pooled. The primary end point was the percent change in fasting triglyceride level at week 24. RESULTS: A total of 353 participants underwent randomization. At week 24, significant reductions in the fasting triglyceride level were observed with plozasiran, with differences, as compared with placebo, in the least-squares mean percent change from baseline of -49.8 percentage points (95% confidence interval [CI], -59.0 to -40.6) with the 10-mg-quarterly dose, -56.0 percentage points (95% CI, -65.1 to -46.8) with the 25-mg-quarterly dose, -62.4 percentage points (95% CI, -71.5 to -53.2) with the 50-mg-quarterly dose, and -44.2 percentage points (95% CI, -53.4 to -35.0) with the 50-mg-half-yearly dose (P<0.001 for all comparisons). Worsening glycemic control was observed in 10% of the participants receiving placebo, 12% of those receiving the 10-mg-quarterly dose, 7% of those receiving the 25-mg-quarterly dose, 20% of those receiving the 50-mg-quarterly dose, and 21% of those receiving the 50-mg-half-yearly dose. CONCLUSIONS: In this randomized, controlled trial involving participants with mixed hyperlipidemia, plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted. (Funded by Arrowhead Pharmaceuticals; MUIR ClinicalTrials.gov number NCT04998201.).

Barriers to and Facilitators of Implementing Guidelines for Detecting Familial Hypercholesterolaemia in Australia.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic condition that is a preventable cause of premature cardiovascular morbidity and mortality. High-level evidence and clinical practice guidelines support preventative care for people with FH. However, it is estimated that less than 10% of people at risk of FH have been detected using any approach across Australian health settings. The aim of this study was to identify the implementation barriers to and facilitators of the detection of FH in Australia. METHODS: Four, 2-hour virtual focus groups were facilitated by implementation scientists and a clinicians as part of the 2021 Australasian FH Summit. Template analysis was used to identify themes. RESULTS: There were 28 workshop attendees across four groups (n=6-8 each), yielding 13 barriers and 10 facilitators across three themes: (1) patient related, (2) provider related, and (3) system related. A "lack of care pathways" and "upskilling clinicians in identifying and diagnosing FH" were the most interconnected barriers and facilitators for the detection of FH. CONCLUSIONS: The relationships between barriers and facilitators across the patient, provider, and system themes indicates that a comprehensive implementation strategy is needed to address these different levels. Future research is underway to develop a model for implementing the Australian FH guidelines into practice.

Acute C-Terminal Crosslinking Telopeptide of Type I Collagen (CTX-1) Suppression with Milk Calcium or Calcium Carbonate Is Independent of Visceral Fat in a Randomized Crossover Study in Lean and Overweight Postmenopausal Women.

BACKGROUND: Postmenopausal women with higher visceral adipose tissue (VAT) present with suppressed bone resorption (lower C-terminal crosslinking telopeptide of type I collagen; CTX-1) and turnover (lower osteocalcin) but whether this blunts the effect of calcium is unknown. OBJECTIVES: The primary outcome of this study was the effect of VAT on changes in CTX-1 after intake of 2 forms of calcium. Secondary outcomes included changes in parathyroid hormone (PTH), serum calcium, phosphorus, and alkaline phosphatase (ALP). METHODS: Randomized open three period crossover trial conducted between 2017 and 2019 at the University of South Australia among 77 lean and overweight postmenopausal women (53-79 y) with BMI <25 kg/m2 and >27 kg/m2, respectively. Participants received a single dose of milk (1000 mg calcium), calcium carbonate tablet (1000 mg calcium), and fruit juice (no calcium) in random order with a 7-d washout period. Blood samples were collected at baseline and hourly for 5 h. Data was analyzed by repeated measures ANOVA of log-transformed data. RESULTS: At baseline, women with higher VAT had significantly lower CTX-1 and higher PTH (44% lower and 30% higher, respectively, between Q4 and Q1, P < 0.0001). VAT had no influence on the acute changes in CTX-1 or PTH with calcium or juice. A suppression of 44% in CTX-1 was seen with calcium carbonate and milk and a suppression of 18% with juice. PTH was suppressed more with calcium carbonate (47%) compared to milk (22%). Milk calcium reduced PTH and CTX-1 at 2 h, whereas calcium carbonate reduced PTH in 1 h. The suppression in CTX-1 was slower with lowest concentrations at 4-5 h. CONCLUSIONS: Intake of 1000 mg calcium from milk or from calcium carbonate is effective in acutely suppressing bone resorption in postmenopausal women irrespective of visceral fat. This trial is registered at http://www.ANZCTR.org.au/ACTRN12617000779370.aspx as ACTRN 12617000779370).

Acute C-Terminal Crosslinking Telopeptide of Type I Collagen (CTX-1) Suppression with Milk Calcium or Calcium Carbonate Is Independent of Visceral Fat in a Randomized Crossover Study in Lean and Overweight Postmenopausal Women.

BACKGROUND: Postmenopausal women with higher visceral adipose tissue (VAT) present with suppressed bone resorption (lower C-terminal crosslinking telopeptide of type I collagen; CTX-1) and turnover (lower osteocalcin) but whether this blunts the effect of calcium is unknown. OBJECTIVES: The primary outcome of this study was the effect of VAT on changes in CTX-1 after intake of 2 forms of calcium. Secondary outcomes included changes in parathyroid hormone (PTH), serum calcium, phosphorus, and alkaline phosphatase (ALP). METHODS: Randomized open three period crossover trial conducted between 2017 and 2019 at the University of South Australia among 77 lean and overweight postmenopausal women (53-79 y) with BMI <25 kg/m2 and >27 kg/m2, respectively. Participants received a single dose of milk (1000 mg calcium), calcium carbonate tablet (1000 mg calcium), and fruit juice (no calcium) in random order with a 7-d washout period. Blood samples were collected at baseline and hourly for 5 h. Data was analyzed by repeated measures ANOVA of log-transformed data. RESULTS: At baseline, women with higher VAT had significantly lower CTX-1 and higher PTH (44% lower and 30% higher, respectively, between Q4 and Q1, P < 0.0001). VAT had no influence on the acute changes in CTX-1 or PTH with calcium or juice. A suppression of 44% in CTX-1 was seen with calcium carbonate and milk and a suppression of 18% with juice. PTH was suppressed more with calcium carbonate (47%) compared to milk (22%). Milk calcium reduced PTH and CTX-1 at 2 h, whereas calcium carbonate reduced PTH in 1 h. The suppression in CTX-1 was slower with lowest concentrations at 4-5 h. CONCLUSIONS: Intake of 1000 mg calcium from milk or from calcium carbonate is effective in acutely suppressing bone resorption in postmenopausal women irrespective of visceral fat. This trial is registered at http://www.ANZCTR.org.au/ACTRN12617000779370.aspx as ACTRN 12617000779370).

Effect of a moderate dose of fructose in solid foods on TAG, glucose and uric acid before and after a 1-month moderate sugar-feeding period.

There are few data on the effects on TAG, glucose and uric acid of chronic consumption of a moderate dose of fructose in solid foods. Twenty-eight participants with prediabetes and/or obesity and overweight commenced the study (BMI 32·3 kg/m2, age 44·7 years, fasting glucose 5·3 (sd 0·89) mmol/l and 2-h glucose 6·6 (sd 1·8) mmol/l). Twenty-four men and women who completed the study consumed, in random order, two acute test meals of muffins sweetened with either fructose or sucrose. This was followed by 4-week chronic consumption of 42 g/d of either fructose or sucrose in low-fat muffins after which the two meal tests were repeated. The sugar type in the chronic feeding period was also randomised. Fasting TAG increased after chronic consumption of fructose by 0·31 (sd 0·37) mmol/l compared with sucrose in those participants with impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) (P = 0·004). Total cholesterol (0·33 mmol/l), LDL-cholesterol (0·24 mmol/l) and HDL-cholesterol (0·08 mmol/l) increased significantly over the 1- month feeding period with no differences between muffin types. Fasting glucose was not different after 1 month of muffin consumption. Uric acid response was not different between the two sugar types either baseline or 1 month, and there were no differences between baseline and 1 month. The increase in fasting TAG in participants with IFG/IGT suggests the need for caution in people at increased risk of type 2 diabetes.

Practical Guidance for Food Consumption to Prevent Cardiovascular Disease.

This dietary guidance, informed by best contemporary evidence, aims to assist medical practitioners and allied health professionals in advising patients for the primary and secondary prevention of cardiovascular disease (CVD). While differing in some details from other current guidelines, the core messages accord with those published in 2019 by the American College of Cardiology/American Heart Association and the European Society of Cardiology/European Atherosclerosis Society; the National Lipid Association in 2014 and the NH&MRC Australian Dietary Guidelines in 2013. These were assessed through the Appraisal of Guidelines for Research and Evaluation (AGREE II) and the levels of evidence and classes of a recommendation developed using the GRADE system. Recommendations with high levels of evidence include increased consumption of plant based foods comprising mainly complex, fibre enriched carbohydrates (wholegrains, fruits and vegetables) while limiting intake of refined starches; partial replacement of saturated fats with monounsaturated or polyunsaturated fats and oils; reduced salt intake; achievement and maintenance of healthy weight; and low-to-moderate consumption of alcohol. Additional guidance but with moderate levels of evidence includes increased consumption of fish (and fish oils where indicated); reduction in sugar-sweetened beverages and added sugars; avoidance of butter and cream especially in those at increased CVD risk but encouragement of yoghurt; allow moderate consumption of lean meat but limit intake of processed meats; and limit cholesterol-rich foods such as eggs and crustaceans for those at increased CVD risk. Guidance has been formulated qualitatively on food categories of commonly eaten foods while avoiding prescriptive quantitative measures that are less readily translatable. This approach accords with current guidelines such as the American College of Cardiology/American Heart Association 2019 guidelines and is understandable and readily implemented.

Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry.

BACKGROUND: Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients. METHODS: The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia. We conducted a cross-sectional analysis of 1,528 FH adults enrolled in the registry from 28 lipid clinics. RESULTS: The mean age at enrolment was 53.4±15.1 years, 50.5% were male and 54.3% had undergone FH genetic testing, of which 61.8% had a pathogenic FH-causing gene variant. Only 14.0% of the cohort were family members identified through cascade testing. Coronary artery disease (CAD) was reported in 28.0% of patients (age of onset 49.0±10.5 years) and 64.9% had at least one modifiable cardiovascular risk factor. The mean untreated LDL-cholesterol was 7.4±2.5 mmol/L. 80.8% of patients were on lipid-lowering therapy with a mean treated LDL-cholesterol of 3.3±1.7 mmol/L. Among patients receiving lipid-lowering therapies, 25.6% achieved an LDL-cholesterol target of <2.5 mmol/L without CAD or <1.8 mmol/L with CAD. CONCLUSION: Patients in the national FH registry are detected later in life, have a high burden of CAD and risk factors, and do not achieve guideline-recommended LDL-cholesterol targets. Genetic and cascade testing are under-utilised. These deficiencies in care need to be addressed as a public health priority.

Impact of intermittent vs. continuous energy restriction on weight and cardiometabolic factors: a 12-month follow-up.

BACKGROUND AND OBJECTIVE: Intermittent energy restriction continues to gain popularity as a weight loss strategy; however, data assessing it's long-term viability is limited. The objective of this study was to follow up with participants 12 months after they had completed a 12-month dietary intervention trial involving continuous energy restriction and two forms of intermittent energy restriction; a week-on-week-off energy restriction and a 5:2 programme, assessing long-term changes on weight, body composition, blood lipids and glucose. SUBJECTS AND METHODS: 109 overweight and obese adults, aged 18-72 years, attended a 12-month follow-up after completing a 12-month dietary intervention involving three groups: continuous energy restriction (1000 kcal/day for women and 1200 kcal/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (500 kcal/day on modified fast days each week for women and 600 kcal/day for men). The primary outcome was weight change at 24 months from baseline, with secondary outcomes of change in body composition, blood lipids and glucose. RESULTS: For the 109 individuals who completed the 12-month follow-up (82 female, 15 male, mean BMI 33 kg/m2), weight decreased over time with no differences between week-on and week-off and continuous energy restriction or 5:2 and continuous energy restriction with -4.5 ± 4.9 kg for continuous energy restriction, -2.8 ± 6.5 kg for week-on, week-off and -3.5 ± 5.1 kg for 5:2. Total cholesterol reduced over time and glucose, HDL, LDL and triglycerides were unchanged. DISCUSSION AND CONCLUSION: Intermittent energy restriction was as successful in achieving modest weight loss over a 24-month period as continuous energy restriction.

Correction to: Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men.

The original version of this article unfortunately contained a mistake.

Correction: Effect of intermittent compared to continuous energy restriction on weight loss and weight maintenance after 12 months in healthy overweight or obese adults.

Table 4 is still missing from both versions. It was labeled Table 3 in the first version but a reviewer wanted an extra table in the methods which became Table 1.

Effect of intermittent compared to continuous energy restriction on weight loss and weight maintenance after 12 months in healthy overweight or obese adults.

BACKGROUND AND OBJECTIVE: Intermittent energy restriction (IER) is an alternative to continuous energy restriction (CER) for weight loss. There are few long-term trials comparing efficacy of these methods. The objective was to compare the effects of CER to two forms of IER; a week-on-week-off energy restriction and a 5:2 program, during which participants restricted their energy intake severely for 2 days and ate as usual for 5 days, on weight loss, body composition, blood lipids, and glucose. SUBJECTS AND METHODS: A one-year randomized parallel trial was conducted at the University of South Australia, Adelaide, Australia. Participants were 332 overweight and obese adults, ages 18-72 years, who were randomized to 1 of 3 groups: CER (4200 kJ/day for women and 5040 kJ/day for men), week-on-week-off energy restriction (alternating between the same energy restriction as the continuous group for one week and one week of habitual diet), or 5:2 (2100 kJ/day on modified fast days each week for women and 2520 kJ/day for men, the 2 days of energy restriction could be consecutive or non-consecutive). Primary outcome was weight loss, and secondary outcomes were changes in body composition, blood lipids, and glucose. RESULTS: For the 146 individuals who completed the study (124 female, 22 male, mean BMI 33 kg/m2) mean weight loss, and body fat loss at 12 months was similar in the three intervention groups, -6.6 kg for CER, -5.1 kg for the week-on, week-off and -5.0 kg for 5:2 (p = 0.2 time by diet). Discontinuation rates were not different (p = 0.4). HDL-cholesterol rose (7%) and triglycerides decreased (13%) at 12 months with no differences between groups. No changes were seen for fasting glucose or LDL-cholesterol. DISCUSSION AND CONCLUSION: The two forms of IER were not statistically different for weight loss, body composition, and cardiometabolic risk factors compared to CER.

Non-nutritive Sweeteners and Glycaemic Control.

PURPOSE OF REVIEW: The consumption of foods and beverages containing non-nutritive sweeteners (NNS) has increased worldwide over the last three decades. Consumers' choice of NNS rather than sugar or other nutritive sweeteners may be attributable to their potential to reduce weight gain. RECENT FINDINGS: It is not clear what the effects of NNS consumption are on glycaemic control and the incidence of type 2 diabetes. This review aims to examine this question in epidemiological, human intervention and animal studies. It is not clear that NNS consumption has an effect on the incidence of type 2 diabetes or on glycaemic control even though there is some evidence for the modification of the microbiome and for interaction with sweet taste receptors in the oral cavity and the intestines' modification of secretion of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), ghrelin and glucose-dependent insulinotropic polypeptide (GIP), which may affect glycaemia following consumption of NNS. In conclusion, long-term studies of NNS consumption are required to draw a firm conclusion about the role of NNS consumption on glycaemic control.

A whey/guar "preload" improves postprandial glycaemia and glycated haemoglobin levels in type 2 diabetes: A 12-week, single-blind, randomized, placebo-controlled trial.

AIMS: To evaluate the effects of 12 weeks of treatment with a whey/guar preload on gastric emptying, postprandial glycaemia and glycated haemoglobin (HbA1c) levels in people with type 2 diabetes (T2DM). MATERIALS AND METHODS: A total of 79 people with T2DM, managed on diet or metformin (HbA1c 49 ± 0.7 mmol/mol [6.6 ± 0.1%]), were randomized, in single-blind fashion, to receive 150 mL flavoured preloads, containing either 17 g whey protein plus 5 g guar (n = 37) or flavoured placebo (n = 42), 15 minutes before two meals, each day for 12 weeks. Blood glucose and gastric emptying (breath test) were measured before and after a mashed potato meal at baseline (without preload), and after the preload at the beginning (week 1) and end (week 12) of treatment. HbA1c levels, energy intake, weight and body composition were also evaluated. RESULTS: Gastric emptying was slower (P < 0.01) and postprandial blood glucose levels lower (P < 0.05) with the whey/guar preload compared to placebo preload, and the magnitude of reduction in glycaemia was related to the rate of gastric emptying at both week 1 (r = -0.54, P < 0.001) and week 12 (r = -0.54, P < 0.0001). At the end of treatment, there was a 1 mmol/mol [0.1%] reduction in HbA1c in the whey/guar group compared to the placebo group (49 ± 1.0 mmol/mol [6.6 ± 0.05%] vs. 50 ± 0.8 mmol/mol [6.7 ± 0.05%]; P < 0.05). There were no differences in energy intake, body weight, or lean or fat mass between the groups. CONCLUSIONS: In patients with well-controlled T2DM, 12 weeks' treatment with a low-dose whey/guar preload, taken twice daily before meals, had sustained effects of slowing gastric emptying and reducing postprandial blood glucose, which were associated with a modest reduction in HbA1c, without causing weight gain.

Longitudinal nutritional changes in aging Australian women.

BACKGROUND AND OBJECTIVES: The importance of diet for the maintenance of health during aging is attracting a growing body of research interest. Given dietary intakes, along with BMI, are substantial contributors to disease burden, this study aimed to investigate prospective changes in dietary patterns and nutrient intakes in a sample of mid to late-life women over 14 years. METHODS AND STUDY DESIGN: Participants were from the Women's Healthy Ageing Project (WHAP); a longitudinal cohort of Australian-born women within the Melbourne metropolitan area. 173 participants were included in this analysis, their mean age in 1998 was 55 years (range 51-62) and in 2012 was 70 years (range 66-76). Diet was assessed using the Dietary Questionnaire for Epidemiological Studies Version 2 in 1998 and 2012. Nutritional intakes, Dietary Inflammatory Index (DII®) scores, Mediterranean Diet (MD) scores, sociodemographic and physical measures were calculated for all participants at both time points. RESULTS: Energy intake was found to significantly decrease over time (p<0.005). Energy-adjusted (i.e., energy density) total fat, saturated fat, monounsaturated fat and cholesterol intakes increased over time (all p<0.002), while energy-adjusted and absolute carbohydrate intake decreased (p<0.002). Adherence to the MD decreased over time (p<0.001) whilst DII scores increased slightly over time, although this result was not significant. CONCLUSIONS: This study shows significant changes in the intake of energy and several nutrients in a cohort of aging Australian women in the Melbourne metropolitan area over a period of 14 years. Between 1998 and 2012, changes in indices reflecting overall diet were consistently in the direction of a poorer diet.

Effects of Different Weight Loss Approaches on CVD Risk.

PURPOSE OF REVIEW: In this review, we aimed to answer the question as to whether deliberate weight loss can reduce cardiovascular events or improve cardiovascular risk factors and whether different methods of weight loss can have a differential effect on risk factor improvement. RECENT FINDINGS: It would appear that deliberate weight loss reduces total mortality by 16% in obese people with risk factors including type 2 diabetes. People with type 2 diabetes who lose at least 10% of their initial body weight reduce CVD end points by 21% with dietary weight loss while the effect is greater with the greater weight loss induced by bariatric surgery with a 32% reduction in events. Mortality reduction may vary from 29 to up to 79%. Replacing some carbohydrate with protein appears to enhance weight maintenance over 12 months and in addition lowers serum triglyceride and blood pressure. A very-low-carbohydrate diet elevates LDL cholesterol when a high saturated fat "Atkins" style approach is used, but a high unsaturated fat version is safe and effective over a 12-month period and reduces medication requirements in people with type 2 diabetes. A very-low-calorie liquid diet produces excellent weight loss in the short-term, but long-term weight loss is no different to less restrictive dieting. Weight loss lowers CVD events and total mortality and a higher protein (18-25% of energy), lower carbohydrate (< 45% of energy) diet may be superior for weight maintenance and risk factor improvement, but there are no data on event reduction.

Effect of weight loss on pulse wave velocity: systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of clinical trials involving adults, to determine the effect of weight loss induced by energy restriction with or without exercise, antiobesity drugs or bariatric surgery on pulse wave velocity (PWV) measured at all arterial segments. APPROACH AND RESULTS: A systematic search of Pubmed (1966 to 2014), EMBASE (1947 to 2014), MEDLINE (1946 to 2014), and the Cochrane Library (1951 to 2014) was conducted and the reference lists of identified articles were searched to find intervention trials (randomized/nonrandomized) that aimed to achieve weight loss and included PWV as an outcome. The search was restricted to human studies. Two independent researchers extracted the data. Data were analyzed using Comprehensive Meta Analysis version 2 using random effects analysis. A total of 22 studies were included in the qualitative synthesis and 20 studies (3 randomized controlled trials), involving 1259 participants, were included in the meta-analysis. The standardized mean difference for the overall effect of weight loss on PWV measured at all sites was -0.32 (95% confidence interval, -0.41, -0.24; P=0.0001). Carotid femoral pulse wave velocity (standardized mean difference, -0.35; 95% confidence interval, -0.44, -0.26; P=0.0001; 16 studies) and brachial ankle PWV (standardized mean difference, -0.48; 95% confidence interval, -0.78, -0.18; P=0.002; 5 studies) were improved with weight loss. Meta-regression showed that change in blood pressure was a predictor of change in PWV (P<0.01). CONCLUSION: Modest weight loss (mean 8% of initial body weight) achieved with diet and lifestyle measures improved PWV. The results of this meta-analysis suggest that weight loss may reduce PWV, although future research is required.

Postprandial insulin and glucose levels are reduced in healthy subjects when a standardised breakfast meal is supplemented with a filtered sugarcane molasses concentrate.

PURPOSE: A phytochemical- and mineral-rich filtered sugarcane molasses concentrate (FMC), when added to carbohydrate-containing foods as a functional ingredient, lowers postprandial blood glucose and insulin responses. We hypothesised that this beneficial effect would also occur if FMC was administered as an oral supplement taken before a meal. METHODS: This study measured the postprandial glucose and insulin responses elicited by different doses of FMC administered immediately prior to a standard breakfast to healthy subjects. Each subject was given three or five breakfast meals once, on different days. The composition of the meals was identical, except for the addition of either placebo syrup (test meal 1) or increasing doses of FMC (test meals 2-5). RESULTS: The plasma glucose concentration curves were similar for the five test meals. Plasma insulin curves were lowered in a dose-dependent manner. Stratifying subjects based on age, BMI and insulin resistance showed greater effects of low doses of FMC on lowering insulin responses in those subjects with potentially greater insulin resistance. When insulin response is standardised to amount of carbohydrate in the meal/dose combination, the reduction in response is linear and inversely proportional to the FMC dose. CONCLUSIONS: FMC shows promise as an agent that can reduce insulin responses and lessen the load on the pancreatic beta cells.

Salt Restriction in Diabetes.

There are no long-term interventions examining the effects of salt reduction in people with diabetes, and these are urgently required. Sodium reduction is controversial as it appears that an intake below 2.5 g and above 6 g/day of salt is associated with increased cardiovascular disease risk. However, pre-existing illness leading to a lower salt intake may confound the findings. Only a few studies have prospectively collected data on the sodium intake and excretion of people with diabetes and examined hard end points. In addition, future studies need to collect more data on food intake as well as coexistent illnesses to address potential confounding. The World Health Organization recommends a reduction to less than 5 g/day salt in adults. Given that the available evidence suggests that the salt intake of people with type 2 diabetes is generally well above 6 g/day it seems reasonable to ensure individuals with diabetes have an intake below 6 g/day. However, such recommendations need to be individualized.