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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
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Acute Effects of Three Cooked Non-Cereal Starchy Foods on Postprandial Glycemic Responses and in Vitro Carbohydrate Digestion in Comparison with Whole Grains: A Randomized Trial.
Zhu, R, Fan, Z, Han, Y, Li, S, Li, G, Wang, L, Ye, T, Zhao, W
Nutrients. 2019;11(3)
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The consumption of refined rice is associated with increased risk of type 2 diabetes (T2D) and is prone to cause hyperglycaemia after meals, even in healthy adults. Whereas whole grains and pulses were reported to reduce the risk of T2D and relatively mild postprandial (after a meal) glycaemic responses. The main aim of this study was to investigate the possibility of integrating the three non-cereal starchy food i.e. the lotus seed, adlay, and dried lily bulb into a glycaemic management diet, and compare their glycaemic characteristics with millet, waxy black rice and adzuki bean. The study is single-blind randomised crossover design study which recruited ten young women aged between 18 and 26 years. Sequentially numbered containers were used to implement the random allocation sequence. Results indicate that out of the 3 starchy foods tested in the study, only the lotus seed meals could be regarded as low-glycaemic index food compared to the adzuki bean meals. Furthermore, the cooked dried lily bulb, adlay, black rice and millet resulted as high-glycaemic index, regardless of the cooking duration. Authors conclude that careful choice of whole grain materials, minimized pre-soaking, and moderate cooking may be critical factors for successful glycaemic management for people of impaired glucose management.
Abstract
Plant origin, processing, and domestic preparation may affect the postprandial glycemic response (PGR) of starchy foods. The objective of this study was to examine the possibility of integrating domestically cooked non-cereal starchy foods commonly consumed in Northeast Asia into glycemic management diet, and compare their glycemic characteristics with those of waxy and non-waxy whole grains and starchy beans. In a randomized crossover trial, ten healthy subjects consumed dried lily bulb (LB), lotus seed (LS), adlay (AD), waxy black rice (BR), millet (MI), and adzuki bean (AB), pre-soaked and each cooked for two time durations. Acute PGR tests and in vitro carbohydrate digestion were carried out for each test food. Both the LS and AB meals achieved low glycemic index (GI 21⁻51), while the other starchy foods failed to show significant difference with rice (GI 83⁻109). The hydrolysis indexes of LS and AB were 37.7%⁻61.1%, significantly lower than other test foods. The in vitro tests indicated that pre-soaking resulted in high rapidly digestible starch (RDS) and low resistant starch (RS). Careful choice of whole grain materials, minimized pre-soaking, and moderate cooking may be critical factors for successful postprandial glycemic management for diabetic and pre-diabetic.
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Dietary Fiber Intake (Supplemental or Dietary Pattern Rich in Fiber) and Diabetic Kidney Disease: A Systematic Review of Clinical Trials.
Carvalho, CM, Gross, LA, de Azevedo, MJ, Viana, LV
Nutrients. 2019;11(2)
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Most of the financial burden of diabetes mellitus is related to management of its complications, and chronic kidney disease is the most expensive and debilitating. The aim of the study was to evaluate the effect of dietary fibre (supplemental or dietary pattern rich in fibre) on diabetic kidney disease. The study is a systemic review that included seven interventional clinical trials that comprised 161 patients with diabetes with an age range of 20 to 74 years. The mean fibre intake in the intervention was 24 g/day and 16 g/day in the control group. Results indicate that only the vegetarian dietary pattern was associated with beneficial kidney outcomes in both type 1 and type 2 diabetes mellitus. There were no other dietary patterns that had favourable effects on kidney outcomes. Authors conclude that a vegetarian dietary pattern may have a beneficial effects on renal outcomes.
Abstract
Fiber intake is associated with better glycemic control being an important nonpharmacologicaltreatment for diabetes (DM). We hypothesize that a dietary fiber intake can bringbenefits to diabetic kidney disease (DKD), improving renal outcomes. This systematic review aimedto evaluate the effect of dietary fiber (supplemental or dietary pattern rich in fiber) on DKD. Wesearched six databases to identify clinical trials that reported fiber intake and renal outcomes(albuminuria, proteinuria, estimated glomerular filtration rate (eGFR) dialysis) in patients with DM.From 1814 studies, 48 papers were fully evaluated. In the end, seven trials (161 patients, aged 58.3years, 49% females) were included. The studies were organized into three categories (vegetarian,Dietary Approaches to Stop Hypertension (DASH) diet, and fiber supplement), two evaluatedsupplements and five dietary patterns. Vegetarian diet reduced albuminuria in three trials, two inpatients with type 1 DM and one in patients with type 2 DM; and one study demonstrated a change inthe eGFR in type 1 DM. The individual quality of the studies was low/uncertain. A vegetarian dietarypattern may have a beneficial effect on these renal outcomes. However, the individual effect of theintake of fiber on DKD not was possible to be evaluated.
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Vegetarian diets and risk of hospitalisation or death with diabetes in British adults: results from the EPIC-Oxford study.
Papier, K, Appleby, PN, Fensom, GK, Knuppel, A, Perez-Cornago, A, Schmidt, JA, Tong, TYN, Key, TJ
Nutrition & diabetes. 2019;9(1):7
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The identification of modifiable risk factors is vital for the reduction of the growing diabetes epidemic. Diet is one such lifestyle factor that might play a key role in the prevention of diabetes. The aim of the study was to investigate the association between vegetarianism and diabetes in a large, population-based study of British adults. The study is a prospective study of vegetarianism and diabetes risk in a cohort of 45,314 participants. Results indicate that the low meat eaters, fish eaters and vegetarians had a lower risk of developing diabetes compared to regular meat eaters. Authors conclude that people consuming a low or meat-free diet had a lower risk of hospitalisation or death with diabetes.
Abstract
BACKGROUND The global prevalence of diabetes is high and rapidly increasing. Some previous studies have found that vegetarians might have a lower risk of diabetes than non-vegetarians. OBJECTIVE We examined the association between vegetarianism and risk of hospitalisation or death with diabetes in a large, prospective cohort study of British adults. METHODS The analysed cohort included participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study who were diabetes free at recruitment (1993-2001), with available dietary intake data at baseline, and linked hospital admissions and death data for diabetes over follow-up (n = 45,314). Participants were categorised as regular meat eaters (≥50 g per day: n = 15,181); low meat eaters (<50 g of meat per day: n = 7615); fish eaters (ate no meat but consumed fish: n = 7092); and vegetarians (ate no meat or fish, including vegans: n = 15,426). We used multivariable Cox proportional hazards models to assess associations between diet group and risk of diabetes. RESULTS Over a mean of 17.6 years of follow-up, 1224 incident cases of diabetes were recorded. Compared with regular meat eaters, the low meat eaters, fish eaters, and vegetarians were less likely to develop diabetes (hazard ratio (HR) = 0.63, 95% confidence interval (CI) 0.54-0.75; HR = 0.47, 95% CI 0.38-0.59; and HR = 0.63, 95% CI 0.54-0.74, respectively). These associations were substantially attenuated after adjusting for body mass index (BMI) (low meat eaters: HR = 0.78, 95% CI 0.66-0.92; fish eaters: HR = 0.64, 95% CI 0.51-0.80; and vegetarians: HR = 0.89, 95% CI 0.76-1.05). CONCLUSIONS Low meat and non-meat eaters had a lower risk of diabetes, in part because of a lower BMI.
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The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial.
Myette-Côté, É, Durrer, C, Neudorf, H, Bammert, TD, Botezelli, JD, Johnson, JD, DeSouza, CA, Little, JP
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;315(6):R1210-R1219
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Inflammation is associated with the pathogenesis of insulin resistance, type 2 diabetes (T2D), and related complications. Lifestyle therapy is a frontline treatment for improving glucose control in people with T2D. The main aim of this study was to determine whether reducing hyperglycaemia with a low-carbohydrate high-fat (LC) diet could lower markers of innate immune cell activation and systemic inflammation in people with T2D. A secondary aim was to examine if the combination of an LCHF diet with strategically timed postmeal walking was superior to an LCHF diet alone. The study is a randomised cross over study which enrolled Individuals with physician-diagnosed T2D to complete three short-term controlled-intervention periods. Sixteen participants were enrolled (men = 8 and women = 8) who were aged between 48 and 72 years. Results indicate that while LC and LC together with exercise (LC+Ex) led to superior improvements in glucose control and fasting proinsulin (the pro-hormone precursor to insulin) levels as compared with low-fat low glycaemic index diet (GL), all three diets (GL, LC and LC+Ex), appeared to lower a particular marker of cellular inflammation over the short-term. Authors conclude that an LCHF diet with or without daily postmeal walks improved four-day glycaemic control and fasting proinsulin levels compared with a GL diet.
Abstract
Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.
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Circulating bile acids in healthy adults respond differently to a dietary pattern characterized by whole grains, legumes and fruits and vegetables compared to a diet high in refined grains and added sugars: A randomized, controlled, crossover feeding study.
Ginos, BNR, Navarro, SL, Schwarz, Y, Gu, H, Wang, D, Randolph, TW, Shojaie, A, Hullar, MAJ, Lampe, PD, Kratz, M, et al
Metabolism: clinical and experimental. 2018;83:197-204
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Bile acids are produced in the liver and are important for the absorption of fat and fat-soluble vitamins. About 95% of bile acids are reabsorbed. Circulating plasma bile acids can affect glucose metabolism and inflammation, and are thought to play a role in the development of metabolic syndrome. The aim of this study was to evaluate how plasma bile acid levels are influenced by a diet rich in whole grains, legumes, fruit and vegetables (low glycaemic load, GL) compared to a diet high in refined grains and sugar (high GL). The study evaluated data from a previous double-blind randomised, cross over feeding trial. 80 healthy adults had the low or high GL diet for four weeks, and after a four-week washout period, received the other diet for four weeks. Three specific plasma bile acids, which are thought to have a positive impact on glucose metabolism, were higher in the low GL group compared to the high GL group. Some individual plasma bile acids were positively associated with HOMA-IR (a measure of glucose metabolism/insulin resistance). There was no significant association between bile acid concentrations and C-reactive protein (a marker of inflammation). The authors conclude that the increase in certain bile acids on the low GL diet may be beneficial and that this effect may be to some extent mediated by the impact of the higher fibre content of the low GL diet on the gut microbial metabolism, which affects plasma bile acid levels.
Abstract
OBJECTIVE The effects of diets high in refined grains on biliary and colonic bile acids have been investigated extensively. However, the effects of diets high in whole versus refined grains on circulating bile acids, which can influence glucose homeostasis and inflammation through activation of farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5), have not been studied. MATERIALS AND METHODS We conducted a secondary analysis from a randomized controlled crossover feeding trial (NCT00622661) in 80 healthy adults (40 women/40 men, age 18-45 years) from the greater Seattle Area, half of which were normal weight (BMI 18.5-25.0 kg/m2) and half overweight to obese (BMI 28.0-39.9 kg/m2). Participants consumed two four-week controlled diets in randomized order: 1) a whole grain diet (WG diet), designed to be low in glycemic load (GL), high in whole grains, legumes, and fruits and vegetables, and 2) a refined grain diet (RG diet), designed to be high GL, high in refined grains and added sugars, separated by a four-week washout period. Quantitative targeted analysis of 55 bile acid species in fasting plasma was performed using liquid chromatography tandem mass spectrometry. Concentrations of glucose, insulin, and CRP were measured in fasting serum. Linear mixed models were used to test the effects of diet on bile acid concentrations, and determine the association between plasma bile acid concentrations and HOMA-IR and CRP. Benjamini-Hochberg false discovery rate (FDR) < 0.05 was used to control for multiple testing. RESULTS A total of 29 plasma bile acids were reliably detected and retained for analysis. Taurolithocholic acid (TLCA), taurocholic acid (TCA) and glycocholic acid (GCA) were statistically significantly higher after the WG compared to the RG diet (FDR < 0.05). There were no significant differences by BMI or sex. When evaluating the association of bile acids and HOMA-IR, GCA, taurochenodeoxycholic acid, ursodeoxycholic acid (UDCA), 5β‑cholanic acid‑3β,12α‑diol, 5‑cholanic acid‑3β‑ol, and glycodeoxycholic acid (GDCA) were statistically significantly positively associated with HOMA-IR individually, and as a group, total, 12α‑hydroxylated, primary and secondary bile acids were also significant (FDR < 0.05). When stratifying by BMI, chenodeoxycholic acid (CDCA), cholic acid (CA), UDCA, 5β-cholanic acid-3β, deoxycholic acid, and total, 12α-hydroxylated, primary and secondary bile acid groups were significantly positively associated with HOMA-IR among overweight to obese individuals (FDR < 0.05). When stratifying by sex, GCA, CDCA, TCA, CA, UDCA, GDCA, glycolithocholic acid (GLCA), total, primary, 12α‑hydroxylated, and glycine-conjugated bile acids were significantly associated with HOMA-IR among women, and CDCA, GDCA, and GLCA were significantly associated among men (FDR < 0.05). There were no significant associations between bile acids and CRP. CONCLUSIONS Diets with comparable macronutrient and energy composition, but differing in carbohydrate source, affected fasting plasma bile acids differently. Specifically, a diet characterized by whole grains, legumes, and fruits and vegetables compared to a diet high in refined grains and added sugars led to modest increases in concentrations of TLCA, TCA and GCA, ligands for FXR and TGR5, which may have beneficial effects on glucose homeostasis.
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Glycemic index, glycemic load, and risk of type 2 diabetes: results from 3 large US cohorts and an updated meta-analysis.
Bhupathiraju, SN, Tobias, DK, Malik, VS, Pan, A, Hruby, A, Manson, JE, Willett, WC, Hu, FB
The American journal of clinical nutrition. 2014;100(1):218-32
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Carbohydrates are the principle dietary components that effect blood glucose concentrations. The association between Type 2 diabetes (T2D) and diets with different levels of sugars and carbohydrates has been controversial in the prevention of T2D. Foods can be measured for their impact on blood glucose concentration using the Glycaemic Index (GI) and the Glycaemic Load (GL). The objective of this meta-analysis was to update previous studies and evaluate the association between the GI and GL of dietary intake and the risk of T2D. The authors found a significant association between the GI and GL of food intake and T2D risk and conclude that high GI and GL foods increase the risk of T2D. However, GI is more strongly associated to T2D than GL.
Abstract
BACKGROUND Epidemiologic evidence for the relation between carbohydrate quality and risk of type 2 diabetes (T2D) has been mixed. OBJECTIVE We prospectively examined the association of dietary glycemic index (GI) and glycemic load (GL) with T2D risk. DESIGN We prospectively followed 74,248 women from the Nurses' Health Study (1984-2008), 90,411 women from the Nurses' Health Study II (1991-2009), and 40,498 men from the Health Professionals Follow-Up Study (1986-2008) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed by using a validated questionnaire and updated every 4 y. We also conducted an updated meta-analysis, including results from our 3 cohorts and other studies. RESULTS During 3,800,618 person-years of follow-up, we documented 15,027 cases of incident T2D. In pooled multivariable analyses, those in the highest quintile of energy-adjusted GI had a 33% higher risk (95% CI: 26%, 41%) of T2D than those in the lowest quintile. Participants in the highest quintile of energy-adjusted GL had a 10% higher risk (95% CI: 2%, 18%) of T2D. Participants who consumed a combination diet that was high in GI or GL and low in cereal fiber had an ~50% higher risk of T2D. In the updated meta-analysis, the summary RRs (95% CIs) comparing the highest with the lowest categories of GI and GL were 1.19 (1.14, 1.24) and 1.13 (1.08, 1.17), respectively. CONCLUSION The updated analyses from our 3 cohorts and meta-analyses provide further evidence that higher dietary GI and GL are associated with increased risk of T2D.
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Sucralose affects glycemic and hormonal responses to an oral glucose load.
Pepino, MY, Tiemann, CD, Patterson, BW, Wice, BM, Klein, S
Diabetes care. 2013;36(9):2530-5
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Non-nutritive sweeteners (NNS) are food additives that provide a sweet taste to food but have few, if any, calories. Currently, seven NNS (sucralose, saccharin, aspartame, acesulfame potassium, neotame, stevia, and Luo han guo extract) are approved by the U.S. Food and Drug Administration and are widely used in thousands of food products. The aim of this study was to analyse whether sucralose ingestion alters the glycaemic and hormonal responses to glucose ingestion in obese subjects who are not regular users of NNS. Seventeen participants who were obese but not insulin resistant participated in the study. They were studied on two separate occasions, 7 days apart, in a crossover design. Sucralose was used as it matches the sweetness of a typical diet soda and also stimulates glucagon-like peptide 1 [a type of peptide hormone] secretion. Results demonstrate that: - the ingestion of sucralose alters the metabolic response to an oral glucose load in obese people who are not regular consumers of NNS. - insulin clearance from plasma was slower after sucralose than after water ingestion. - glucose-induced glucagon [hormone that helps control blood sugar levels] suppression was the same after both sucralose and water ingestion Authors conclude that sucralose is not metabolically inert but has physiologic effects.
Abstract
OBJECTIVE Nonnutritive sweeteners (NNS), such as sucralose, have been reported to have metabolic effects in animal models. However, the relevance of these findings to human subjects is not clear. We evaluated the acute effects of sucralose ingestion on the metabolic response to an oral glucose load in obese subjects. RESEARCH DESIGN AND METHODS Seventeen obese subjects (BMI 42.3 ± 1.6 kg/m(2)) who did not use NNS and were insulin sensitive (based on a homeostasis model assessment of insulin resistance score ≤ 2.6) underwent a 5-h modified oral glucose tolerance test on two separate occasions preceded by consuming either sucralose (experimental condition) or water (control condition) 10 min before the glucose load in a randomized crossover design. Indices of β-cell function, insulin sensitivity (SI), and insulin clearance rates were estimated by using minimal models of glucose, insulin, and C-peptide kinetics. RESULTS Compared with the control condition, sucralose ingestion caused 1) a greater incremental increase in peak plasma glucose concentrations (4.2 ± 0.2 vs. 4.8 ± 0.3 mmol/L; P = 0.03), 2) a 20 ± 8% greater incremental increase in insulin area under the curve (AUC) (P < 0.03), 3) a 22 ± 7% greater peak insulin secretion rate (P < 0.02), 4) a 7 ± 4% decrease in insulin clearance (P = 0.04), and 5) a 23 ± 20% decrease in SI (P = 0.01). There were no significant differences between conditions in active glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide, glucagon incremental AUC, or indices of the sensitivity of the β-cell response to glucose. CONCLUSIONS These data demonstrate that sucralose affects the glycemic and insulin responses to an oral glucose load in obese people who do not normally consume NNS.
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Effects of dietary composition on energy expenditure during weight-loss maintenance.
Ebbeling, CB, Swain, JF, Feldman, HA, Wong, WW, Hachey, DL, Garcia-Lago, E, Ludwig, DS
JAMA. 2012;307(24):2627-34
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Many diets can produce weight loss over the short term, but most people struggle to maintain this loss over the long term. One explanation is that weight loss results in biological effects, such as a decline in energy expenditure and an increase in hunger, that promote weight regain. The aim of the study was to examine the effects of three different diets on energy expenditure, hormones (including leptin, insulin, cortisol and thyroid hormones) and metabolic indicators following a 10-15% weight loss. The three diets differed widely in macronutrient composition and were: low-fat/high glycaemic load (60% energy from carbohydrates, 20%, 20% protein) LF; low glycaemic index (40%-40%-20%) LGI; and very low carbohydrate/low glycaemic load (10%-60%-30%) VLC. Participants were assigned to one of the three diets for four weeks. Participants on the VLC diet had a resting energy expenditure (REE) of 67kcal/day greater than the LF diet, as well as a total energy expenditure (TEE) of 300kcal/day greater. The physiological basis for these differences is unclear. Although the VLC diet produced the greatest improvements in most metabolic syndrome markers, it also resulted in increased cortisol and inflammation markers. These could be deleterious to health in the long term.
Abstract
CONTEXT Reduced energy expenditure following weight loss is thought to contribute to weight gain. However, the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied. OBJECTIVE To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss. DESIGN, SETTING, AND PARTICIPANTS A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children's Hospital Boston and Brigham and Women's Hospital, Boston, Massachusetts, between June 16, 2006, and June 21, 2010, with recruitment by newspaper advertisements and postings. INTERVENTION After achieving 10% to 15% weight loss while consuming a run-in diet, participants consumed an isocaloric low-fat diet (60% of energy from carbohydrate, 20% from fat, 20% from protein; high glycemic load), low-glycemic index diet (40% from carbohydrate, 40% from fat, and 20% from protein; moderate glycemic load), and very low-carbohydrate diet (10% from carbohydrate, 60% from fat, and 30% from protein; low glycemic load) in random order, each for 4 weeks. MAIN OUTCOME MEASURES Primary outcome was resting energy expenditure (REE), with secondary outcomes of total energy expenditure (TEE), hormone levels, and metabolic syndrome components. RESULTS Compared with the pre-weight-loss baseline, the decrease in REE was greatest with the low-fat diet (mean [95% CI], -205 [-265 to -144] kcal/d), intermediate with the low-glycemic index diet (-166 [-227 to -106] kcal/d), and least with the very low-carbohydrate diet (-138 [-198 to -77] kcal/d; overall P = .03; P for trend by glycemic load = .009). The decrease in TEE showed a similar pattern (mean [95% CI], -423 [-606 to -239] kcal/d; -297 [-479 to -115] kcal/d; and -97 [-281 to 86] kcal/d, respectively; overall P = .003; P for trend by glycemic load < .001). Hormone levels and metabolic syndrome components also varied during weight maintenance by diet (leptin, P < .001; 24-hour urinary cortisol, P = .005; indexes of peripheral [P = .02] and hepatic [P = .03] insulin sensitivity; high-density lipoprotein [HDL] cholesterol, P < .001; non-HDL cholesterol, P < .001; triglycerides, P < .001; plasminogen activator inhibitor 1, P for trend = .04; and C-reactive protein, P for trend = .05), but no consistent favorable pattern emerged. CONCLUSION Among overweight and obese young adults compared with pre-weight-loss energy expenditure, isocaloric feeding following 10% to 15% weight loss resulted in decreases in REE and TEE that were greatest with the low-fat diet, intermediate with the low-glycemic index diet, and least with the very low-carbohydrate diet. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00315354.
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Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study.
Runchey, SS, Pollak, MN, Valsta, LM, Coronado, GD, Schwarz, Y, Breymeyer, KL, Wang, C, Wang, CY, Lampe, JW, Neuhouser, ML
European journal of clinical nutrition. 2012;66(10):1146-52
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Dietary intervention studies have shown detrimental metabolic effects of high-glycaemic load diets. The glycaemic index (GI) is the numerical classification of a particular food’s blood glucose-raising effect. The aim of this study was to evaluate the effect of a high-glycaemic load diet on circulating levels of insulin-like growth factor-1 (IGF-1) [hormone] and insulin-like growth factor-binding protein 3 (IGFBP-3) [protein] compared to a low-glycaemic load diet. The study is a randomised controlled crossover study which enrolled 84 normal weight and overweight-obese healthy individuals. The study included two 28-day weight-maintaining high- and low-glycaemic load diets. Results indicate that consumption of a low-glycaemic load diet resulted in lower post-prandial [after a meal] insulin and glucose responses and modestly lower fasting IGF-1 and IGF-1/IGFBP-3 concentrations. However, there were no observable effects of glycaemic load on insulin resistance or glucose-adjusted post-prandial insulin responses in these healthy participants. Authors conclude that further intervention studies are required in order to weigh the impact of dietary glycaemic load on risk for chronic disease.
Abstract
BACKGROUND/OBJECTIVES The effect of a low glycemic load (GL) diet on insulin-like growth factor-1 (IGF-1) concentration is still unknown but may contribute to lower chronic disease risk. We aimed to assess the impact of GL on concentrations of IGF-1 and IGF-binding protein-3 (IGFBP-3). SUBJECTS/METHODS We conducted a randomized, controlled crossover feeding trial in 84 overweight obese and normal weight healthy individuals using two 28-day weight-maintaining high- and low-GL diets. Measures were fasting and post-prandial concentrations of insulin, glucose, IGF-1 and IGFBP-3. In all 80 participants completed the study and 20 participants completed post-prandial testing by consuming a test breakfast at the end of each feeding period. We used paired t-tests for diet component and linear mixed models for biomarker analyses. RESULTS The 28-day low-GL diet led to 4% lower fasting concentrations of IGF-1 (10.6 ng/ml, P=0.04) and a 4% lower ratio of IGF-1/IGFBP-3 (0.24, P=0.01) compared with the high-GL diet. The low-GL test breakfast led to 43% and 27% lower mean post-prandial glucose and insulin responses, respectively; mean incremental areas under the curve for glucose and insulin, respectively, were 64.3±21.8 (mmol/l/240 min; P<0.01) and 2253±539 (μU/ml/240 min; P<0.01) lower following the low- compared with the high-GL test meal. There was no effect of GL on mean homeostasis model assessment for insulin resistance or on mean integrated post-prandial concentrations of glucose-adjusted insulin, IGF-1 or IGFBP-3. We did not observe modification of the dietary effect by adiposity. CONCLUSIONS Low-GL diets resulted in 43% and 27% lower post-prandial responses of glucose and insulin, respectively, and modestly lower fasting IGF-1 concentrations. Further intervention studies are needed to weigh the impact of dietary GL on risk for chronic disease.