Effects of very low-carbohydrate vs. high-carbohydrate weight loss diets on psychological health in adults with obesity and type 2 diabetes: a 2-year randomized controlled trial.

AIMS: Very low-carbohydrate (LC) diets are popular for type 2 diabetes (T2DM) management; however, long-term effects on psychological health remain largely unknown. This study reports the effects of a LC diet on mood and cognitive function after 2 years and explores the potential predictors of changes in psychological health. METHODS: 115 adults (57% males; age: 58.5 ± 7.1 years) with obesity and T2DM were randomized to consume an energy reduced (~ 500 to 1000 kcal/day deficit), LC diet [14% energy as carbohydrate, 28% protein, 58% fat (< 10% saturated fat)] or an isocaloric high unrefined carbohydrate, low-fat diet [HC: 53% carbohydrate, 17% protein, 30% fat (< 10% saturated fat)] for 2 years. Both diets were combined with aerobic/resistance exercise (1 h, 3 days/week). Mood/well-being [Beck Depression Inventory (BDI), Spielberger State Anxiety Inventory (SAI), Profile of Mood States (POMS)], diabetes-related quality of life [Diabetes-39 (D-39)] and distress [Problem Areas in Diabetes (PAID) Questionnaire], and cognitive function were assessed during and post-intervention. RESULTS: 61 (LC: 33, HC: 28) participants completed the study. Weight loss was 9.1% after 12 months and 6.7% after 2 years with no difference between diet groups. There were no differences between the groups for the changes in any psychological health outcome (smallest p ≥ 0.19 for all time x diet interactions). Overtime, improvements in BDI, POMS [Total Mood Disturbance (TMD); four subscales], PAID, and D-39 (three subscales) scores occurred (p ≤ 0.05, time). Stepwise regression analysis showed improvements in BDI, POMS (TMD; two subscales), D-39, SAI, and PAID scores were significantly (p < 0.05) correlated with reductions in body weight and glycated hemoglobin. CONCLUSION: In adults with obesity and T2DM, energy-restricted LC and HC diets produced comparable long-term improvements on a comprehensive range of psychological health outcomes. The findings suggest both diets can be used as a diabetes management strategy as part of a holistic lifestyle modification program without concern of negative effects on mental well-being or cognition. TRIAL REGISTRATION: ACTRN12612000369820, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362168&isReview=true . Data described in the manuscript, code book, and analytic code will not be made available because approval has not been granted by participants.

Very Low and Higher Carbohydrate Diets Promote Differential Appetite Responses in Adults with Type 2 Diabetes: A Randomized Trial.

BACKGROUND: Effects of very low carbohydrate (VLC) diets on appetite response in individuals with type 2 diabetes remain unclear. OBJECTIVE: A secondary analysis was conducted to determine appetite responses to an energy-restricted [30% of energy (%E) deficit] very low carbohydrate (VLC) diet compared with a higher carbohydrate (HC) diet in adults who were overweight or obese with type 2 diabetes. METHODS: Forty-four men and 40 women (mean ± SD, age: 58.7 ± 6.6 y; weight: 100.4 ± 15.5 kg; BMI: 34.5 ± 4.1 kg/m2; glycated hemoglobin: 7.3 ± 1.0%; duration of diabetes: 6.7 ± 5.6 y) were randomly assigned to diets categorized as VLC [14%E carbohydrate (<50 g/d), 28%E protein, 58%E fat (<10%E saturated fat)], or energy-matched HC [53%E carbohydrate, 17%E protein, 30%E fat (<10%E saturated fat)] combined with progressive multicomponent exercise (60 min; 3 d/wk). Body weight, average weekly "daily fasting" and "daily overall" appetite perceptions (hunger, fullness, prospective consumption, and desire to eat-visual analog scales) were assessed at baseline and after 4 and 16 wk. Changes between diets over time were assessed using repeated measures ANOVA. RESULTS: Significant decreases in body weight did not differ between groups (VLC: -11.0 ± 5.4 kg/16 wk compared with HC: -10.1 ± 4.3 kg/16 wk, P = 0.40). Compared with HC, VLC had greater decreases in "daily overall" ratings of fullness (P time × diet < 0.01), such that scores were higher in HC at Week 4 (VLC:48 ± 3 vs HC:56 ± 3 mm, P = 0.001) and 16 (VLC:51 ± 2 vs HC:57 ± 3 mm, P = 0.019). Compared with HC, VLC had greater increases in prospective consumption ratings (P time × diet = 0.03), such that scores were lower in HC at Week 4 (VLC:33 ± 2 vs HC:28 ± 2 mm, P = 0.008), but not at Week 16 (VLC:33 ± 2 vs HC 31 ± 2 mm, P = 0.289). CONCLUSIONS: In the context of energy restriction, both HC and VLC energy-matched diets promoted comparable effects on fasting perceptions of appetite, but the HC diet resulted in greater "daily overall" fullness and reduced prospective consumption. Further research is required to evaluate the effects of ad libitum diets differing in amounts of carbohydrate on appetite response in populations with type 2 diabetes. This trial was registered at www.anzctr.org.au as ACTRN12612000369820.

Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial.

AIM: To examine whether a low-carbohydrate, high-unsaturated/low-saturated fat diet (LC) improves glycaemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D). METHODS: A total of 115 adults with T2D (mean [SD]; BMI, 34.6 [4.3] kg/m2 ; age, 58 [7] years; HbA1c, 7.3 [1.1]%) were randomized to 1 of 2 planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1 hour, 3 days/week) for 2 years: LC: 14% energy as carbohydrate, 28% as protein, 58% as fat (<10% saturated fat); or low-fat, high-carbohydrate, low-glycaemic index diet (HC): 53% as CHO, 17% as protein, 30% as fat (<10% saturated fat). HbA1c, glycaemic variability (GV), anti-glycaemic medication effect score (MES, calculated based on the potency and dosage of diabetes medication), weight, body composition, CVD and renal risk markers were assessed before and after intervention. RESULTS: A total of 61 (LC = 33, HC = 28) participants completed the study (trial registration: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820). Reductions in weight (estimated marginal mean [95% CI]; LC, -6.8 [-8.8,-4.7], HC, -6.6 [-8.8, -4.5] kg), body fat (LC, -4.3 [-6.2, -2.4], HC, -4.6 [-6.6, -2.7] kg), blood pressure (LC, -2.0 [-5.9, 1.8]/ -1.2 [-3.6, 1.2], HC, -3.2 [-7.3, 0.9]/ -2.0 [-4.5, 0.5] mmHg), HbA1c (LC, -0.6 [-0.9, -0.3], HC, -0.9 [-1.2, -0.5] %) and fasting glucose (LC, 0.3 [-0.4, 1.0], HC, -0.4 [-1.1, 0.4] mmol/L) were similar between groups (P ≥ 0.09). Compared to HC, the LC achieved greater reductions in diabetes medication use (MES; LC, -0.5 [-0.6, -0.3], HC, -0.2 [-0.4, -0.02] units; P = 0.03), GV (Continuous Overall Net Glycemic Action calculated every 1 hour (LC, -0.4 [-0.6, -0.3], HC, -0.1 [-0.1, 0.2] mmol/L; P = 0.001), and 4 hours (LC, -0.9 [-1.3, -0.6], HC, -0.2 [-0.6, 0.1] mmol/L; P = 0.02)); triglycerides (LC, -0.1 [-0.3, 0.2], HC, 0.1 [-0.2, 0.3] mmol/L; P = 0.001), and maintained HDL-C levels (LC, 0.02 [-0.05, 0.1], HC, -0.1 [-0.1, 0.01] mmol/L; P = 0.004), but had similar changes in LDL-C (LC, 0.2 [-0.1, 0.5], HC, 0.1 [-0.2, 0.4] mmol/L; P = 0.85), brachial artery flow mediated dilatation (LC, -0.5 [-1.5, 0.5], HC, -0.4 [-1.4, 0.7] %; P = 0.73), eGFR and albuminuria. CONCLUSIONS: Both diets achieved comparable weight loss and HbA1c reductions. The LC sustained greater reductions in diabetes medication requirements, and in improvements in diurnal blood glucose stability and blood lipid profile, with no adverse renal effects, suggesting greater optimization of T2D management.

A randomised-controlled trial of the effects of very low-carbohydrate and high-carbohydrate diets on cognitive performance in patients with type 2 diabetes.

This study compared the longer-term effects of a very low-carbohydrate, high-fat diet with a high-carbohydrate, low-fat diet on cognitive performance in individuals with type 2 diabetes (T2D). In total, 115 obese adults with T2D (sixty-six males, BMI: 34·6 (sd 4·3) kg/m2, age: 58 (sd 7) years, HbA1c: 7·3 (sd 1·1) %, diabetes duration: 8 (sd 6) years) were randomised to consume either an energy-restricted, very low-carbohydrate, low-saturated-fat (LC) diet or an energy-matched high unrefined carbohydrate, low-fat (HC) diet with supervised aerobic/resistance exercise (60 min, 3 d/week) for 52 weeks. Body weight, HbA1c and cognitive performance assessing perceptual speed, reasoning speed, reasoning ability, working memory, verbal fluency, processing speed, short-term memory, inhibition and memory scanning speed were assessed before and after intervention. No differences in the changes in cognitive test performance scores between the diet groups were observed for any of the cognitive function outcomes assessed (P≥0·24 time×diet). Percentage reduction in body weight correlated with improvements with perceptual speed performance. In obese adults with T2D, both LC and HC weight-loss diets combined with exercise training had similar effects on cognitive performance. This suggests that an LC diet integrated within a lifestyle modification programme can be used as a strategy for weight and diabetes management without the concern of negatively affecting cognitive function.

Comparative effects of intraduodenal protein and lipid on ghrelin, peptide YY, and leptin release in healthy men.

Intraduodenal infusion of lipid or protein potently reduces subsequent energy intake. There is evidence that the underlying mechanisms differ significantly between the two nutrients. While intraduodenal lipid stimulates glucagon-like peptide-1 and CCK much more than protein, the release of insulin and glucagon is substantially greater in response to protein. Ghrelin and PYY are both involved in short-term regulation, while leptin is a long-term regulator, of energy balance; the acute effects of nutrients on leptin release are unclear. We investigated the comparative effects of intraduodenal lipid and protein on plasma ghrelin, PYY, and leptin concentrations. Thirteen lean, young men received 90-min intraduodenal infusions of protein (whey hydrolysate) or lipid (long-chain triglyceride emulsion) at a rate of 3 kcal/min, or saline control, on three separate days. Blood samples were collected at baseline and regularly during infusions. Both lipid and protein potently suppressed plasma ghrelin compared with control (both P < 0.001), with no difference between them. While both lipid and protein stimulated plasma PYY (P < 0.001), the effect of lipid was substantially greater than that of protein (P < 0.001). Neither intraduodenal lipid nor protein affected plasma leptin. In conclusion, intraduodenal lipid and protein have discrepant effects on the release of PYY, but not ghrelin. When considered with our previous findings, it appears that, with the exception of ghrelin, the energy intake-suppressant effects of lipid and protein are mediated by different mechanisms.

Lesser suppression of energy intake by orally ingested whey protein in healthy older men compared with young controls.

Protein-rich supplements are used widely for the management of malnutrition in young and older people. Protein is the most satiating of the macronutrients in young. It is not known how the effects of oral protein ingestion on energy intake, appetite, and gastric emptying are modified by age. The aim of the study was to determine the suppression of energy intake by protein compared with control and underlying gastric-emptying and appetite responses of oral whey protein drinks in eight healthy older men (69-80 yr) compared with eight young male controls (18-34 yr). Subjects were studied on three occasions to determine the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a flavored water control-drink (0 g whey protein) on energy intake (ad libitum buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and appetite (0-180 min) in a randomized, double-blind, cross-over design. Energy intake was suppressed by the protein compared with control (P = 0.034). Suppression of energy intake by protein was less in older men (1 ± 5%) than in young controls (15 ± 2%; P = 0.008). Cumulative energy intake (meal+drink) on the protein drink days compared with the control day increased more in older (18 ± 6%) men than young (1 ± 3%) controls (P = 0.008). Gastric emptying of all three drinks was slower in older men (50% gastric-emptying time: 68 ± 5 min) than young controls (36 ± 5 min; P = 0.007). Appetite decreased in young, while it increased in older (P < 0.05). In summary, despite having slower gastric emptying, elderly men exhibited blunted protein-induced suppression of energy intake by whey protein compared with young controls, so that in the elderly men, protein ingestion increased overall energy intake more than in the young men.

Effects of fat, protein, and carbohydrate and protein load on appetite, plasma cholecystokinin, peptide YY, and ghrelin, and energy intake in lean and obese men.

While protein is regarded as the most satiating macronutrient, many studies have employed test meals that had very high and unsustainable protein contents. Furthermore, the comparative responses between lean and obese subjects and the relationships between energy intake suppression and gut hormone release remain unclear. We evaluated the acute effects of meals with modest variations in 1) fat, protein, and carbohydrate content and 2) protein load on gastrointestinal hormones, appetite, and subsequent energy intake in lean and obese subjects. Sixteen lean and sixteen obese men were studied on four occasions. Following a standardized breakfast, they received for lunch: 1) high-fat (HF), 2) high-protein (HP), 3) high-carbohydrate/low-protein (HC/LP), or 4) adequate-protein (AP) isocaloric test meals. Hunger, fullness, and gut hormones were measured throughout, and at t = 180 min energy intake at a buffet meal was quantified. In lean subjects, hunger was less and fullness greater following HF, HP, and AP compared with HC/LP meals, and energy intake was less following HF and HP compared with HC meals (P < 0.05). In the obese subjects, hunger was less following HP compared with HF, HC/LP, and AP meals, and energy intake was less following HP and AP compared with HF and HC meals (P < 0.05). There were no major differences in hormone responses to the meals among subject groups, but the CCK and ghrelin responses to HP and AP were sustained in both groups. In conclusion, HP meals suppress energy intake in lean and obese subjects, an effect potentially mediated by CCK and ghrelin, while obese individuals appear to be less sensitive to the satiating effects of fat.

Almond consumption affects fecal microbiota composition, stool pH, and stool moisture in overweight and obese adults with elevated fasting blood glucose: A randomized controlled trial.

Regular almond consumption has been shown to improve body weight management, lipid profile and blood glucose control. We hypothesized that almond consumption would alter fecal microbiota composition, including increased abundance and activity of potentially beneficial bacterial taxa in adults who are overweight and obese with elevated fasting blood glucose. A total of 69 adults who were overweight or obese with an elevated plasma glucose (age: 60.8 ± 7.4, BMI ≥27 kg/m2, fasting plasma glucose ≥5.6 to <7.0 mmol/L) were randomized to daily consumption of either 2 servings of almonds (AS:56 g/day) or an isocaloric, high carbohydrate biscuit snack for 8 weeks. AS but not biscuit snack experienced significant changes in microbiota composition (P= .011) and increases in bacterial richness, evenness, and diversity (P< .01). Increases in both the relative and absolute abundance of operational taxonomic units in the Ruminococcaceae family, including Ruminiclostridium (false discovery rate P = .002), Ruminococcaceae NK4A214 (P = .002) and Ruminococcaceae UCG-003 (P = .002) were the principal drivers of microbiota-level changes. No changes in fecal short chain fatty acid levels, or in the carriage of the gene encoding butyryl-CoA:acetate CoA-transferase (an enzyme involved in butyrate synthesis) occurred. Almond consumption was not associated with reduced gut permeability, but fecal pH (P= .0006) and moisture content (P = .027) decreased significantly in AS when compared to BS. Regular almond consumption increased the abundance of potentially beneficial ruminococci in the fecal microbiota in individuals with elevated blood glucose. However, fecal short-chain fatty acid levels remained unaltered and the capacity for such microbiological effects to precipitate host benefit is not known.

Monosodium glutamate is not associated with obesity or a greater prevalence of weight gain over 5 years: findings from the Jiangsu Nutrition Study of Chinese adults.

Animal studies and one large cross-sectional study of 752 healthy Chinese men and women suggest that monosodium glutamate (MSG) may be associated with overweight/obesity, and these findings raise public concern over the use of MSG as a flavour enhancer in many commercial foods. The aim of this analysis was to investigate a possible association between MSG intake and obesity, and determine whether a greater MSG intake is associated with a clinically significant weight gain over 5 years. Data from 1282 Chinese men and women who participated in the Jiangsu Nutrition Study were analysed. In the present study, MSG intake and body weight were quantitatively assessed in 2002 and followed up in 2007. MSG intake was not associated with significant weight gain after adjusting for age, sex, multiple lifestyle factors and energy intake. When total glutamate intake was added to the model, an inverse association between MSG intake and 5 % weight gain was found (P = 0.028), but when the model was adjusted for either rice intake or food patterns, this association was abolished. These findings indicate that when other food items or dietary patterns are accounted for, no association exists between MSG intake and weight gain.

Nutritional adequacy of very low- and high-carbohydrate, low saturated fat diets in adults with type 2 diabetes: A secondary analysis of a 2-year randomised controlled trial.

BACKGROUND: Growing evidence supports use of very low-carbohydrate (LC) diets for glycaemic control in type 2 diabetes. However, limited data on the micronutrient adequacy of LC diets exist. OBJECTIVE: This study compared the long-term effects of a very low-carbohydrate, high unsaturated/low saturated fat (LC) diet to a high-carbohydrate, low-fat (HC) diet on micronutrient biomarkers in adults with obesity and type 2 diabetes. METHODS: 115 adults with type 2 diabetes (mean[SD]; BMI:34.6[4.3]kg/m2, age:58[7]yrs, HbA1c:7.3[1.1]%, 56[12]mmol/mol) were randomized to one of two planned, nutritionally-replete, energy-matched, hypocaloric diets (500-1000 kcal/day deficit): (1) LC:14% energy carbohydrate, 28%protein, 58%fat[<10% saturated fat]) or (2) HC:53%carbohydrate, 17%protein, 30%fat [<10%saturated fat]) for 2 years. Nutritional biomarkers- folate, ß-carotene, vitamin B12, D, E, copper, zinc, selenium, calcium, magnesium, sodium, potassium, iron, ferritin, transferrin and transferrin saturation were measured in fasting blood at baseline, 24, 52 and 104 weeks. RESULTS: 61 participants completed the study with similar dropouts in each group (P = 0.40). For all biomarkers assessed, there were no differential response between groups overtime (P ≥ 0.17 time × diet interaction). Mean vitamin and mineral levels remained within normal (laboratory-specific) reference ranges without any reported cases of clinical deficiencies. CONCLUSION: In free-living individuals with type 2 diabetes, nutrition biomarkers within normal ranges at baseline did not change significantly after 2 years on a prescribed LC or HC diet. These results demonstrate the feasibility of delivering a nutritionally replete LC diet and the importance of considering nutritional factors in planning LC diets that have strong public health relevance to the dietary management of type 2 diabetes. TRIAL REGISTRATION: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820.

Effects of intragastric tryptophan on acute changes in the plasma tryptophan/large neutral amino acids ratio and relationship with subsequent energy intake in lean and obese men.

Circulating tryptophan/large neutral amino acids (tryptophan/LNAA) ratio, an indicator of brain serotonin levels, may be important in appetite regulation, together with gastrointestinal (gastric emptying, plasma cholecystokinin) mechanisms. We have compared effects of intragastric tryptophan ('Trp') on the plasma tryptophan/LNAA ratio in lean and obese men, and the associations of the tryptophan/LNAA ratio, gastric emptying and CCK concentrations with energy intake. Lean and obese male participants (n = 16 each) received 3 g Trp or volume-matched control intragastrically, 15 min before a mixed-nutrient drink (300 mL, 400 kcal) (t = 0 min) in randomised, double-blind fashion. Plasma amino acid (for calculation of the plasma tryptophan/LNAA ratio) and CCK concentrations were measured from t = -20-60 min. Gastric emptying was assessed from t = 0-60 min, and ad-libitum energy intake from a standardised buffet-style meal from t = 60-90 min. The increase in the plasma tryptophan/LNAA ratio was less in obese, than lean, participants (P < 0.05), and greater in lean participants who reduced their energy intake (by >0 kcal) after Trp compared with those who did not (by ≤0 kcal) (P < 0.05). Moreover, in participants who reduced their energy intake, the ratio was lower in obese, than in lean (P < 0.05). There was a trend for an inverse correlation between energy intake with the plasma tryptophan/LNAA ratio in lean (r = -0.4, P = 0.08), but not in obese, participants. There was no significant difference in gastric emptying or CCK between participants who reduced their energy intake and those who did not. In conclusion, the plasma tryptophan/LNAA ratio appears to be a determinant of the suppression of energy intake in response to tryptophan in normal-weight people, but not in those with obesity. The role of the plasma tryptophan/LNAA ratio to regulate energy intake, and potential changes in obesity, warrant evaluation in prospective studies.

The addition of monosodium glutamate and inosine monophosphate-5 to high-protein meals: effects on satiety, and energy and macronutrient intakes.

In a fed and orally stimulated state, whether the addition of monosodium glutamate (MSG) (alone or in combination with inosine monophosphate-5 (IMP-5)) to a high-protein (HP) meal leads to early satiety and a difference in energy intake at a second course was investigated. Ten men and twelve women consumed, in random order, a first-course meal consisting of: (1) water (control); (2) a HP meal with 0.6% MSG and 0.25% IMP-5; (3) a HP meal with no additives; (4) a HP meal with MSG only; (5) a sham-fed meal 2 (oral-stimulation). Appetite perceptions, plasma concentrations of glucagon-like peptide 1 (GLP-1), glucose and insulin, and energy intake at a buffet (i.e. a second course) were measured before and after each condition. Changes in appetite, and in GLP-1, glucose and insulin, were similar for the three fed HP conditions and all were greater (post hoc all P < 0.01) than the control and sham conditions. Energy intake was not different following the HP+MSG+IMP (1.86 (SEM 0.3) MJ) as compared with the HP+MSG-only (2.24 (SEM 0.28) MJ) condition (P = 0.08), or for the HP+MSG+IMP compared with the HP no-additives condition (1.60 (SEM 0.29) MJ) (P = 0.21). Following the HP+MSG-only condition, 0.64 (SEM 0.20) MJ more energy was consumed compared with the HP no-additives condition (P = 0.005). We conclude that the addition of MSG to a HP meal does not influence perceptions of satiety and it may increase energy intake at a second course. Cephalic responses after the sham condition were of similar magnitude to the control and therefore just tasting food is not enough to influence appetite and energy intake.

Plasma Free Amino Acid Responses to Whey Protein and Their Relationships with Gastric Emptying, Blood Glucose- and Appetite-Regulatory Hormones and Energy Intake in Lean Healthy Men.

This study determined the effects of increasing loads of whey protein on plasma amino acid (AA) concentrations, and their relationships with gastric emptying, blood glucose- and appetite-regulatory hormones, blood glucose and energy intake. Eighteen healthy lean men participated in a double-blinded study, in which they consumed, on 3 separate occasions, in randomised order, 450-mL drinks containing either 30 g (L) or 70 g (H) of pure whey protein isolate, or control with 0 g of protein (C). Gastric emptying, serum concentrations of AAs, ghrelin, cholecystokinin (CCK), glucagon-like-peptide 1 (GLP-1), insulin, glucagon and blood glucose were measured before and after the drinks over 180 min. Then energy intake was quantified. All AAs were increased, and 7/20 AAs were increased more by H than L. Incremental areas under the curve (iAUC0-180 min) for CCK, GLP-1, insulin and glucagon were correlated positively with iAUCs of 19/20 AAs (p < 0.05). The strongest correlations were with the branched-chain AAs as well as lysine, tyrosine, methionine, tryptophan, and aspartic acid (all R2 > 0.52, p < 0.05). Blood glucose did not correlate with any AA (all p > 0.05). Ghrelin and energy intake correlated inversely, but only weakly, with 15/20 AAs (all R2 < 0.34, p < 0.05). There is a strong relationship between gluco-regulatory hormones with a number of (predominantly essential) AAs. However, the factors mediating the effects of protein on blood glucose and energy intake are likely to be multifactorial.

Efficacy of Real-Time Continuous Glucose Monitoring to Improve Effects of a Prescriptive Lifestyle Intervention in Type 2 Diabetes: A Pilot Study.

INTRODUCTION: Optimising patient adherence to prescribed lifestyle interventions to achieve improved blood glucose control remains a challenge. Combined use of real-time continuous glucose monitoring systems (RT-CGM) may promote improved glycaemic control. This pilot study examines the effects of a prescriptive lifestyle modification programme when combined with RT-CGM on blood glucose control and cardiovascular disease risk markers. METHODS: Twenty adults (10 men, 10 women) with obesity and type-2 diabetes (T2D) (age 60.55 ± 8.38 years, BMI 34.22 ± 4.67 kg/m2) were randomised to a prescriptive low-carbohydrate diet and lifestyle plan whilst continuously wearing either an RT-CGM or an 'offline-blinded' monitor (control) for 12 weeks. Outcomes were glycaemic control (HbA1c, fasting glucose, glycaemic variability [GV]), diabetes medication (MeS), weight, blood pressure and lipids assessed pre- and post-intervention. RESULTS: Both groups experienced reductions in body weight (RT-CGM - 7.4 ± 4.5 kg vs. control - 5.5 ± 4.0 kg), HbA1c (- 0.67 ± 0.82% vs. - 0.68 ± 0.74%), fasting blood glucose (- 1.2 ± 1.9 mmol/L vs. - 1.0 ± 2.2 mmol/L), LDL-C (- 0.07 ± 0.34 mmol/L vs. - 0.26 ± 0.42 mmol/L) and triglycerides (- 0.32 ± 0.46 mmol/L vs. - 0.36 ± 0.53 mmol/L); with no differential effect between groups (P ≥ 0.10). At week 12, GV indices were consistently lower by at least sixfold in RT-CGM compared to control (CONGA-1 - 0.27 ± 0.36 mmol/L vs. 0.06 ± 0.19 mmol/L; CONGA-2 - 0.36 ± 0.54 mmol/L vs. 0.05 ± 2.88 mmol/L; CONGA-4 - 0.44 ± 0.67 mmol/L vs. - 0.02 ± 0.42 mmol/L; CONGA-8 - 0.36 ± 0.61 vs. 0.02 ± 0.52 mmol/L; MAGE - 0.69 ± 1.14 vs. - 0.09 ± 0.08 mmol/L, although there was insufficient power to achieve statistical significance (P ≥ 0.11). Overall, there was an approximately 40% greater reduction in blood glucose-lowering medication (MeS) in RT-CGM (- 0.30 ± 0.59) compared to control (0.02 ± 0.23). CONCLUSION: This study provides preliminary evidence that RT-CGM may be an effective strategy to optimise glucose control whilst following a low-carbohydrate lifestyle programme that targets improved glycaemic control, with minimal professional support. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry identifier, ANZTR: 372898. FUNDING: Grant funding was received for the delivery of the clinical trial only, by the Diabetes Australia Research Trust (DART).

Effects of almond consumption on metabolic function and liver fat in overweight and obese adults with elevated fasting blood glucose: A randomised controlled trial.

BACKGROUND: Almonds are a rich source of bioactive components. This study examined the effects of daily almond consumption on glycaemic regulation, liver fat concentration and function, adiposity, systemic inflammation and cardiometabolic health. METHODS: 76 adults with elevated risk of type 2 diabetes (T2D) or T2D (age: 60.7 ± 7.7 years, body mass index: 33.8 ± 5.6 kg/m2) were randomly assigned to daily consumption of either 2 servings of almonds (AS:56 g/day) or an isocaloric, higher carbohydrate biscuit snack (BS) for 8 weeks. Glycosylated haemoglobin (HbA1c), glycaemic variability (GV), liver fat, serum aminotransferases, body weight and composition, markers of cardio-metabolic risk and systemic inflammation were assessed at baseline and week 8. RESULTS: No group differential effects were observed on HbA1c, GV, body weight and composition, liver fat and aminotransferases, cardio-metabolic health and inflammatory markers (all P > 0.05). For serum TC/HDL-C ratio a significant gender × treatment × time interaction occurred (P < 0.01), such that in women TC/HDL-C ratio was significantly reduced after AS compared to BS (-0.36 [0.26] mmol/L [n = 14] vs. -0.14 [0.32] mmol/L [n = 17]; P = 0.05), but not in men (P = 0.52). CONCLUSIONS: Compared to BS, AS consumed between meals did not substantially alter glycaemic regulation, liver fat or function, adiposity, and metabolic health and inflammatory markers. Serum TC/HDL-C ratio improved in women, but not in men with AS; but as this sub-analysis was not defined a priori the results should be interpreted with caution. Further research should examine the longer-term health effects of regular almond consumption and differential gender responses. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: Australia New Zealand Clinical Trial Registry: ACTRN12616000571471 (https://www.anzctr.org.au).

Energy expenditure, satiety, and plasma ghrelin, glucagon-like peptide 1, and peptide tyrosine-tyrosine concentrations following a single high-protein lunch.

High-protein (HP) foods are more satiating and have a higher thermogenic effect than normal protein foods over the short-term as well as the long-term. We hypothesized that acute effects of higher protein intake on satiety may be related to acute metabolic and hormonal responses. The study was a single-blind, randomized, crossover design. Subjects underwent 2 indirect calorimetry tests for measurement of energy expenditure (EE) and substrate oxidation. After a standard subject-specific breakfast, subjects received 1 of 2 randomly assigned treatments: an appropriate protein (AP) lunch (10% energy (E) protein, 60%E carbohydrate, 30%E fat), or a HP lunch (25%E protein, 45%E carbohydrate, 30%E fat). The increase in postlunch EE tended to be greater after the HP lunch (0.85 +/- 0.32 kJ/min) than after the AP lunch (0.73 +/- 0.22 kJ/min) (P = 0.07). The respiratory quotient did not differ between the HP (0.84 +/- 0.04) and the AP (0.86 +/- 0.04) treatments. Satiety visual analogue scales (VAS) scores were significantly higher 30 and 120 min after the HP lunch than after the AP lunch. The area under the curve of the VAS score for satiety was higher after the HP lunch (263 +/- 61 mm/h) than after the AP lunch (AP 236 +/- 76 mm/h) (P < 0.02). Effects of the meals on satiety and diet-induced thermogenesis did not occur simultaneously with changes in plasma ghrelin, glucagon-like peptide 1, and peptide tyrosine-tyrosine concentrations. A single HP lunch, therefore, does not exert its acute effect on satiety through increased concentrations of satiety-related hormones. Other factors, which may explain the HP effect on satiety, may be metabolites or amino acids.

Serve Size and Estimated Energy and Protein Contents of Meals Prepared by 'Meals on Wheels' South Australia Inc.: Findings from a Meal Audit Study.

An audit of 'standard' (STD) and 'energy and protein fortified' (HEHP) meals from Meals on Wheels (MOW) South Australia's summer menu was conducted to evaluate the consistency, and serve size and nutrient contents, of their menu items. Twenty soups, 20 mains and 20 desserts from each of the STD and HEHP menus were prepared at the MOW South Australia's kitchen and delivered to three 'sham(dummy)-clients' over a 5-week period. Each meal component was weighed in triplicate, to the nearest gram, the variation within the serve weight was calculated, and the overall energy and protein content of each meal was determined using FoodWorks (Xyris Software, Highgate Hill, Queensland, Australia). On average, the variability for soups and mains was ≤6% and for desserts was ≤10% and although the measured serve sizes of the MOW meals were consistently smaller than prescribed serve size, the differences were minor. As a percentage of recommended daily intakes (RDIs) for adults aged over 60 years, we calculated that the STD meals contained 21-39% for energy and 42-63% for protein while the HEHP meals contained 29-55% for energy and 46-69% for protein. These findings demonstrate that MOW meals currently meet the voluntary meal guidelines for energy and protein.

Effect of gender on the acute effects of whey protein ingestion on energy intake, appetite, gastric emptying and gut hormone responses in healthy young adults.

BACKGROUND/OBJECTIVES: Protein supplements, usually drinks rich in whey protein, are used widely for weight loss purposes in overweight adults. Information comparing the effects of whey protein on appetite and energy intake in men and women is limited. The objective was to compare the acute effects of whey-protein intake on energy intake, appetite, gastric emptying and gut hormones in healthy young men and women. SUBJECTS/METHODS: Gastric emptying (3D-ultrasonography), blood glucose and plasma insulin, glucagon, ghrelin, cholecystokinin (CCK), gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) concentrations (0-180 min), appetite (visual analogue scales), and ad libitum energy intake from a buffet meal (180-210 min) were determined after ingestion of 30 g (120 kcal) or 70 g (280 kcal) whey protein, or a flavoured-water control drink (~2 kcal) in 8 healthy young men (25 ± 2 y, 72 ± 3 kg, 23 ± 1 kg/m2) and 8 women (23 ± 1 y, 64 ± 2 kg, 24 ± 0.4 kg/m2). RESULTS: There was a protein-load effect on gastric emptying, blood glucose, plasma insulin, glucagon, ghrelin, CCK, GIP and GLP-1 concentrations, and perceptions of hunger, desire to eat and prospective food consumption (P < 0.05). Ad libitum energy intake (average decrease of 206 ± 39 kcal (15 ± 2%) for men and of 46 ± 54 kcal (0 ± 26%) for women for the mean of the intakes after the 30 and 70 g whey-protein loads) and hunger were suppressed more by whey-protein ingestion in men than women (P = 0.046). There was no difference in suppression of energy intake between the 30 and 70 g protein loads (P = 0.75, interaction effect P = 0.19). Consequently, total energy intake (protein drink plus buffet meal) increased more compared to control in women than men (P = 0.010). The drinks emptied more slowly, and plasma glucagon, CCK and GLP-1 increased less after the protein drinks, in women than men (P < 0.05). CONCLUSION: The acute effects of whey protein ingestion on appetite, energy intake, gastric emptying and gut hormone responses are influenced by gender in healthy young adults.

Dose-Dependent Effects of Randomized Intraduodenal Whey-Protein Loads on Glucose, Gut Hormone, and Amino Acid Concentrations in Healthy Older and Younger Men.

Protein-rich supplements are used widely for the prevention and management of malnutrition in older people. We have reported that healthy older, compared to younger, adults have less suppression of energy intake by whey-protein-effects on appetite-related hormones are unknown. The objective was to determine the effects of intraduodenally administered whey-protein on glucose, gut hormone, and amino acid concentrations, and their relation to subsequent ad libitum energy intake at a buffet meal, in healthy older and younger men. Hydrolyzed whey-protein (30 kcal, 90 kcal, and 180 kcal) and a saline control (~0 kcal) were infused intraduodenally for 60 min in 10 younger (19-29 years, 73 ± 2 kg, 22 ± 1 kg/m²) and 10 older (68-81 years, 79 ± 2 kg, 26 ± 1 kg/m²) healthy men in a randomized, double-blind fashion. Plasma insulin, glucagon, gastric inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), and amino acid concentrations, but not blood glucose, increased, while ghrelin decreased during the whey-protein infusions. Plasma GIP concentrations were greater in older than younger men. Energy intake correlated positively with plasma ghrelin and negatively with insulin, glucagon, GIP, GLP-1, PYY, and amino acids concentrations (p < 0.05). In conclusion, intraduodenal whey-protein infusions resulted in increased GIP and comparable ghrelin, insulin, glucagon, GIP, GLP-1, PYY, and amino acid responses in healthy older and younger men, which correlated to subsequent energy intake.

Plant sterols lower LDL-cholesterol and triglycerides in dyslipidemic individuals with or at risk of developing type 2 diabetes; a randomized, double-blind, placebo-controlled study.

BACKGROUND: Managing cardiovascular disease (CVD) risk factors, e.g., dyslipidemia in type-2 diabetes mellitus (T2DM) is critically important as CVD is the most common cause of death in T2DM patients. This study aimed to investigate the effect of plant sterols (PS) on lowering both elevated low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). METHODS: In a double-blind, randomized, placebo-controlled, parallel study, 161 individuals at increased risk of and with established T2DM, consumed low-fat spreads without or with added PS (2 g/d) for 6 weeks after a 2-week run-in period. Increased risk of developing T2DM was defined by the Australian T2DM Risk Assessment Tool (AUSDRISK). Fasting serum/plasma total cholesterol (TC), LDL-C, TG, high-density lipoprotein cholesterol (HDL-C), glucose and insulin were measured at baseline and after 6 weeks. Effects on acute and chronic postprandial blood lipids, glucose and insulin were measured over 4-h in 39 individuals with T2DM following a mixed meal challenge without and with added 2 g/d PS at week 6. The study was registered at clinicaltrials.gov (NCT02288585). RESULTS: Hundred fifty-one individuals completed the study and 138 (57% men, 43% women; 44 with and 94 at risk of T2DM) were included in per protocol analysis. Baseline LDL-C and TG were 3.8 ± 1.0 and 2.5 ± 0.8 mmol/l, respectively. PS intake significantly lowered fasting LDL-C (-4.6%, 95%CI -1.2; -8.0; p = 0.009), TC (-4.2%, 95%CI -1.2; -7.1; p = 0.006) and TG (-8.3%, 95% -1.1, -15.0; p = 0.024) with no significant changes in HDL-C, glucose or insulin. Postprandial lipid (TG, TC, LDL-C, HDL-C, remnant cholesterol), glucose and insulin responses did not differ. CONCLUSIONS: In individuals at risk of and with established T2DM and with elevated TG and LDL-C, 2 g/d of PS results in dual LDL-C plus TG lowering. Postprandial lipid or glycemic responses did not differ between PS and control treatment.