High Glycemic Diet Research Articles

Aged Nrf2-Null Mice Develop All Major Types of Age-Related Cataracts

PurposeAge-related cataracts affect the majority of older adults and are a leading cause of blindness worldwide. Treatments that delay cataract onset or severity have the potential to delay cataract surgery, but require relevant animal models that recapitulate the major types of cataracts for their development. Unfortunately, few such models are available. Here, we report the lens phenotypes of aged mice lacking the critical antioxidant transcription factor Nfe2l2 (designated as Nrf2 −/−).MethodsThree independent cohorts of Nrf2 −/− and wild-type C57BL/6J mice were evaluated for cataracts using combinations of slit lamp imaging, photography of freshly dissected lenses, and histology. Mice were fed high glycemic diets, low glycemic diets, regular chow ad libitum, or regular chow with 30% caloric restriction.ResultsNrf2 −/− mice developed significant opacities between 11 and 15 months and developed advanced cortical, posterior subcapsular, anterior subcapsular, and nuclear cataracts. Cataracts occurred similarly in male mice fed high or low glycemic diets, and were also observed in 21-month male and female Nrf2 −/− mice fed ad libitum or 30% caloric restriction. Histological observation of 18-month cataractous lenses revealed significant disruption to fiber cell architecture and the retention of nuclei throughout the cortical region of the lens. However, fiber cell denucleation and initiation of lens differentiation was normal at birth, with the first abnormalities observed at 3 months.ConclusionsNrf2 −/− mice offer a tool to understand how defective antioxidant signaling causes multiple forms of cataract and may be useful for screening drugs to prevent or delay cataractogenesis in susceptible adults.

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

Diet is a modifiable risk factor for cardiovascular disease (CVD) and dementia, yet relatively little is known about the effect of a high glycemic diet (HGD) on the brain’s microvasculature. The objective of our study was to determine the molecular effects of an HGD on hippocampal microvessels and cognitive function and determine if a soluble epoxide hydrolase (sEH) inhibitor (sEHI), known to be vasculoprotective and anti-inflammatory, modulates these effects. Wild type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without the sEHI, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks. Brain hippocampal microvascular gene expression was assessed by microarray and data analyzed using a multi-omic approach for differential expression of protein and non-protein-coding genes, gene networks, functional pathways, and transcription factors. Global hippocampal microvascular gene expression was fundamentally different for mice fed the HGD vs. the LGD. The HGD response was characterized by differential expression of 608 genes involved in cell signaling, neurodegeneration, metabolism, and cell adhesion/inflammation/oxidation effects reversible by t-AUCB and hence sEH inhibitor correlated with protection against Alzheimer’s dementia. Ours is the first study to demonstrate that high dietary glycemia contributes to brain hippocampal microvascular inflammation through sEH.

High Glycemic Diet Is Related to Brain Amyloid Accumulation Over One Year in Preclinical Alzheimer's Disease.

Objective: To test the hypothesis that high glycemic diet is related to 1-year change in brain amyloid based on our prior cross-sectional evidence that high glycemic diet is associated with brain amyloid.Methods: This longitudinal, observational study assessed the relationship between reported habitual consumption of a high glycemic diet (HGDiet) pattern and 1-year brain amyloid change measured by Florbetapir F18 PET scans in 102 cognitively normal older adults with elevated or sub-threshold amyloid status that participated in a 1-year randomized, controlled exercise trial at the University of Kansas Medical Center in Kansas City.Results: Among all participants (n = 102), higher daily intake of the HGDiet pattern (β = 0.06, p = 0.04), sugar (β = 0.07, p = 0.01), and total carbohydrate (β = 0.06, p = 0.04) were related to more precuneal amyloid accumulation. These relationships in the precuneus were accentuated in participants with elevated amyloid at enrollment (n = 70) where higher intake of the HGDiet pattern, sugar, and carbohydrate were related to more precuneal amyloid accumulation (β = 0.11, p = 0.01 for all measures). In individuals with elevated amyloid, higher intake of the HGDiet pattern was also related to more amyloid accumulation in the lateral temporal lobe (β = 0.09, p < 0.05) and posterior cingulate gyrus (β = 0.09, p < 0.05) and higher sugar and carbohydrate intake were also related to more amyloid accumulation in the posterior cingulate gyrus (β = 0.10, p < 0.05 for both measures).Conclusion: This longitudinal observational analysis suggests that a high glycemic diet relates to higher brain amyloid accumulation over 1 year in regions of the temporoparietal cortex in cognitively normal adults, particularly in those with elevated amyloid status. Further studies are required to assess whether there is causal link between a high glycemic diet and brain amyloid.Clinical Trial Registration: ClinicalTrials.gov, Identifier (NCT02000583).

The effect of Vaccinium bracteatum Thunb. leaves addition on antioxidant capacity, physicochemical properties, and in vitro digestibility of rice extrudates.

Vaccinium bracteatum Thunb.leaves (VBTL) are a traditional Chinese herbal medicine with potential natural pigments and antioxidants. Its application information on extrusion is limited. In this study, to increase the usage of foods containing VBTL, rice-based extrudates with VBTL were investigated. The extrusion was performed at a wide temperature range (60-140°C) and with different VBTL supplementations (3%-10%). The extrudates with 10% VBTL showed a significant decrease in total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity upon extrusion. TPC and TFC increased with the rise of barrel temperature. The VBTL color was stable during the wide-temperature extrusion process. The bioactivities of the extrudates were positively correlated with the VBTLsupplement (R=0.943-0.989). In addition, different addition levels of VBTL significantly changed the water absorption index (WAI), water solubility index (WSI), pasting properties, and in vitro starch digestibility of the extrudates. Moreover, extrudates with 3% VBTL showed the highest WAI and peak viscosity but the lowest in vitro starch digestibility. These results may suggest that rice extrudates with a low supplement of VBTL have an acceptable color and may be used as functional additives for high antioxidant and low glycemic response diets. PRACTICAL APPLICATION: The results showed that the Vaccinium bracteatum Thunb. leaves (VBTL) color and antioxidation were stable during the wide-temperature extrusion process. Extrusion processing can be used to enlarge the usage of VBTL and simplify its traditional processing method. Applying VBTL to the process of extrusion appears to be a suitable method of producing value-added and low glycemic response extrudates.

The Glycemic Index, Postprandial Hypotension and Cardiovascular Disease

High glycemic index diets have been associated with an increased risk of cardiovascular disease events and all-cause mortality. We suggest that part of the reason for this association is through the effect of the rapidly digested high glycemic index carbohydrate diets in promoting the effects of postprandial hypotension in vulnerable individuals. Postprandial hypotension has been recognized as a problem especially affecting the frail elderly. The phenomenon occurs earlier in the day and includes syncope and falls acutely and more serious cardiovascular events and increased all-cause mortality in the longer-term. The mechanism appears to relate to the rapid digestion of carbohydrates foods. Strategies that reduce the amount of meal carbohydrates and their rate of absorption by enzyme inhibition or by delaying gastric emptying and have proved helpful as has increased fluid intake, presumably due to dilution of small intestinal contents and a reduction in the tonicity, so reducing the need for intestinal fluid secretion to dilute osmotically active sugars and products of digestion. In this way the need for increased blood flow to the gut can be reduced, that would otherwise steal blood from the systemic circulation resulting in a drop in blood pressure and an increase in heart rate. Slowly absorbed or low glycemic index carbohydrates would therefore appear potentially useful as part of the dietary strategy for the treatment of postprandial hypotension and conversely postprandial hypotension could be one of the reasons why high glycemic index diets have been associated with increased CVD risk.

Demographic Variables and Self-Management Practices as Correlates of Glycemic Control among Reproductive Age Diabetic Women in a Tertiary Hospital in Ile-Ife, Osun State, Nigeria

Glycemic Control Remains A Major Cornerstone In The Management Of Diabetes Mellitus. Despite Consistent Studies, The Incidence Of Both Short-And Long-Term Complications Of Diabetes Had Been Quite Alarming. This Study Employed A Descriptive Design. A Total Enumeration Of 185 Diabetic Women Of Reproductive Age Constituted The Sample Size. A Self-Structured Questionnaire With 40 Items Divided Into Five Sections And A Checklist For Recording Glycemic Control Were Used For Data Collection. The Data Analysis Involves The Use Of Statistical Package For Social Sciences (SPSS) Version 23. Results Were Presented As Frequencies, Mean And Standard Deviation, And Regression Analysis. The Findings From The Study Revealed That 112 (67.1%) Of The Women Had Normal Glycemic Status While 55 (32.9%) Had High Status. Furthermore, It Revealed A Significant Negative Correlation Between Educational Qualification And Glycemic Control (R = -.161, P= 0.049). The Study Revealed A Slight Significant Correlation Between Diet And Glycemic Control (R = -.148, P=0.052). Other Practices Did Not Share A Significant Correlation With Glycemic Control. The Study Concluded That An Appreciable Percentage Of The Respondents Had High Glycemic Control Status, Education And Diet Had A Significant Partial Correlation With Glycemic Control. Most Of The Women Had Good Practice Of Diet, Exercise, Medication, And Self-Monitoring Of Blood Glucose As Shown In Their Health Records. However, A Sharp Contrast Exists Between Their Record Of Glycemic Control, Which Was Good, And The Current Level, Which Revealed No Significant Correlations Between Self-Management Practices And Glycemic Control. Hence, The Need For More Patient Education On Self-Management Practices.

Modifying the Gut Microbiome Through Diet or Antibiotics Alters Bone Phenotypes in Older Mice

ObjectivesGut microbiota have been shown to influence bone quality and quantity, both risk determinants for osteoporosis. Previous research in young mice showed oral antibiotic treatment during rapid bone gain impaired bone tissue quality. We sought to determine if modifying the gut microbiome of aged mice through diet or antibiotic treatment affects bone geometry and/or strength. MethodsA high (HG) or low glycemic (LG) diet was fed in equal amounts to 12-mo. male mice. The diets differed only by starch composition, which was 100% rapidly digested amylopectin in the HG diet or 30% amylopectin/70% amylose in the LG diet. A third group received the LG diet containing antibiotics (ampicillin and neomycin; LGAbx). Feces were collected at baseline and after 10 months of treatment and 16s rRNA sequencing was performed followed by ecological diversity and differential abundance analysis. Femora were harvested after 12 months of treatment for analysis of bone geometry and strength via mechanical testing and imaging. ResultsAntibiotic treatment reduced alpha diversity, including an average 92% reduction in observed OTUs from baseline compared with 30% reduction in the other groups. Both diet and antibiotic treatment significantly altered taxonomic composition, including an expansion of Proteobacteria in response to antibiotics.Whole bone strength is determined by a combination of the section modulus (the measure of geometry most closely related to bending strength) and the mechanical properties of the bone tissue itself. In HG-fed mice the section modulus was greater than that of the other groups and the bone showed a correspondingly greater strength. However, in LGAbx-fed mice the whole bone strength was 22% lower than bones with similar section modulus in the LG and HG-fed groups, indicating impaired bone tissue material properties. ConclusionsAltering diet resulted in significant changes to bone geometry and strength, while changes in the gut microbiota associated with antibiotic treatment resulted in a reduction to bone strength which could not be explained by bone geometry. Our study indicates that dietary or antibiotics treatments applied to mice later in life can alter bone properties, which suggests that interventions to improve bone strength may be effective in older adults. Funding SourcesNIH/NIAMS, BrightFocus Foundation, Stanley N. Gershoff Scholarship.

Alterations to the gut microbiome impair bone tissue strength in aged mice

Whole bone strength and resistance to fracture are determined by a combination of bone quantity and bone quality – key factors in determining risk for osteoporosis and age-related fractures. Recent preclinical studies have shown that alterations to the gut microbiome can influence bone quantity as well as bone tissue quality. Prior work on the gut microbiome and bone has been limited to young animals, and it is unknown if the gut microbiome can alter bone tissue strength in aged animals. Here we ask if alterations to the constituents of the gut microbiome influence bone strength in older mice (12–24 months of age). Male C57BL/6J mice raised on a standard chow diet until 12 months of age were assigned to one of three diets: high glycemic, low glycemic, or low glycemic diet containing antibiotics (ampicillin and neomycin) to modify the constituents of the gut microbiome. The group fed the low glycemic diet containing antibiotics showed reductions in whole bone strength that could not be explained by geometry, indicating reduced bone tissue strength (p < 0.007). The high glycemic diet group had larger bone cross-sectional area and moment of inertia and a corresponding greater bone strength as compared to the low glycemic groups, however tissue strength did not noticeably differ from that of the low glycemic group. These findings demonstrate that modifying the gut microbiome in aged mice can alter bone tissue quality.

Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains.

Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer’s disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3β compared to healthy controls suggesting an impairment of metabolism in the AD patient’s brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment.

Clinico-epidemiological profile of acne vulgaris and its relationship with insulin resistance in males vs females: A comparative study

Aim: To analyse the clinico-epidemiological profile of acne vulgaris and its relationship with insulin resistance among males and females. Material and Method: The present cross sectional observational study was conducted in the department of Dermatology, Venereology and Leprosy at Chattrapati Shivaji Subharti Hospital from November 2018 to April 2020 for 1 and a half among 500 clinically diagnosed patients of acne vulgaris attending the out-patient department. General physical examination including BMI, anthropometry which includes height, weight, triceps skin thickness and waist/hip ratio was done. Investigations comprised of fasting blood sugar and fasting insulin levels. These assess the insulin resistance based on HOMA-IR. Results: Out of 500 subjects, 262 (52.4%) were males and 238 (47.6%) were females. The mean age of the study group was 21.63 years. Males with BMI>25 kg/m2 reported more acne vulgaris as compared to females with statistically significant difference. Overall, males underwent more stress than females. 53.84% of the patients consuming High Glycemic diet were males and rest females. Mean HOMA-IR was found more in grade IV acne among males as well as females. A positive correlation was seen as the fasting insulin levels and the HOMA-IR values were more in subjects with more severe acne. Conclusion: Education about acne is necessary in schools and among the public, so that one knows where to seek appropriate advice and receive early effective treatment so as to prevent complications, both transient and permanent.

Reported chronic high glycemic diet intake predicts amyloid deposition in the precuneus of cognitively normal older adults over one year

AbstractBackgroundWe previously reported that high glycemic diet (HGD) was related to cerebral amyloid deposits, a pathologic hallmark of Alzheimer’s disease (AD), in multiple highly metabolic regions of interest (ROI). The purpose of this study was to test high glycemic diet’s relationship with longitudinal change in cerebral amyloid deposition in older adults.MethodsThis longitudinal study included 106 cognitively normal older adults with elevated (n=72) and non‐elevated (n=34) amyloid participating in a one‐year exercise intervention trial. Habitual dietary intake was collected at baseline using the National Cancer Institute’s Diet History Questionnaire (DHQ II) and intake was quantified using Diet*Calc software. We derived a HGD pattern using principal covariates regression (PCovR). Amyloid PET (Florbetapir F18) scans were obtained on a GE Discovery ST‐16PET/CT scanner at baseline and 52‐weeks. MIMNuero software was used to standardize the PET images to the whole cerebellum and calculate tracer standard uptake value ratios (SUVR) in 6 ROIs. One‐year regional SUVR delta scores were calculated. We constructed ordinary least squares regression models to assess HGD’s relationship with continuous regional delta SUVR scores controlling for age, sex, and intervention group assignment. Statistical analyses were performed using R (v. 3.6.2; R Foundation, Vienna, Austria). Statistical significance was set at p &lt; 0.05.ResultsThe participants were 68% female with a mean age of 71.1 ± 5.2 years. In the precuneus, higher intake of the derived HGD pattern (β=0.23, p=0.02), sugar (β=0.24, p=0.01), and total carbohydrate (β=0.22, p=0.03) correlated with more amyloid accumulation. Higher reported intake of carbohydrate as a percentage of total energy was related to more amyloid accumulation in the inferior medial frontal gyrus (β=0.20, p=0.04), posterior cingulate gyrus (β=0.20, p=0.04), precuneus (β=0.21, p=0.04), and superior parietal lobule (β=0.21, p=0.03).ConclusionThe results of this study corroborate our previous findings and suggest a physiological role for HGD in amyloid pathology prior to onset of AD‐related symptoms.

Acne in Indian population: An epidemiological study evaluating multiple factors

Acne is one of the most common skin diseases seen in clinical practice and is caused by multiple factors. Epidemiological data on acne are limited from developing countries. Using a questionnaire survey, the epidemiological data of acne were evaluated with a view to establishing possible contributing etiological factors in dermatology practice in India. Out of 6409 patients included in the study 45% were male and 55% were female. The mean age of the patients was 24.64 years. Smoking habit was reported in 14% of the patients while high glycemic diet (HGD) was seen in half of the cases. Of respondents, 41% knew that acne was due to increased sebum production and blockade of pilosebaceous units whereas 35% had due to excessive cosmetic use. Grade II acne was predominant (47%) and majority of the patients had inflammatory papular acne (51%). The presence of hyperpigmentation (35%) and scarring (29%) was considered to be a reflection of the severity of the acne. Moisturizers and cleansers were one of the most common supportive measure of acne management. Cleansers were prescribed for 53% of the patients whereas 43% of the patients were prescribed moisturizers. Amongst topical treatment, adapalene and BPO combination (34%) was the most commonly prescribed combination followed by adapalene &amp; clindamycin combination (29%). Monotherapy was not commonly prescribed. Most of the patients were managed with combination therapy. Isotretinoin was most commonly prescribed medication in all grades of acne comprising of 40% of the patients. This study presents the demographic features and clinical characteristics of acne in dermatology office practice in India.

Added sugar and sugar-sweetened beverages are associated with increased postpartum weight gain and soluble fiber intake is associated with postpartum weight loss in Hispanic women from Southern California

Obesity prevalence remains high in the United States, and there is an increased risk among women who do not lose their gestational weight gain during the postpartum period. Indicators of dietary carbohydrate quality including added sugar consumption, glycemic load, and glycemic index have been linked with weight gain, whereas fiber may protect against obesity. However, these dietary factors have not been examined during the postpartum period. The aim of this study was to determine whether dietary sugars and fiber intake were associated with changes in postpartum weight. We examined Hispanic women from the longitudinal Southern California Mother's Milk Study (n=99) at 1 and 6 mo postpartum. Maternal assessments included height, weight, and dietary intake based on 24-h diet recalls. We used multivariable linear regression to examine the relation between maternal diet and change in postpartum weight after adjusting for maternal age, height, and energy intake. Higher intake of added sugar was associated with postpartum weight gain (β: 0.05; 95% CI: 0.004, 0.10; P=0.05). In addition, a half 8-ounce (8 fluid ounces=236.6 mL) serving per day increase in soft drinks was associated with a 1.52-kg increase in weight (95% CI: 0.70, 2.34 kg; P<0.001). A high glycemic index (β: 0.25; 95% CI: 0.07, 0.42; P=0.006) and glycemic load (β: 0.04; 95% CI: 0.002, 0.08; P=0.04) were associated with postpartum weight gain. Higher soluble fiber was associated with a decrease in postpartum weight (β: -0.82 kg; 95% CI: -1.35, -0.29 kg; P=0.003) and the negative effects of added sugar, sugary beverages, and high-glycemic-index and -load diets were partially attenuated after adjusting for soluble fiber intake. Increased consumption of added sugar, sugar-sweetened beverages, and high-glycemic diets were associated with greater weight gain in the first 6 mo postpartum. In addition, increased consumption of soluble fiber was associated with postpartum weight loss, which may partially offset the obesogenic effects of some dietary sugars.

Obesity in African-Americans: The role of physiology.

The disproportionate obesity in African American (AA) women has a physiologic basis and can be explained by the interactive effects of insulin secretion, insulin clearance, insulin sensitivity and the glycaemic load of the diet. This review will present data supporting a physiologic basis for obesity propensity in obesity-prone AA women that resides in their unique metabolic/endocrine phenotype: high beta-cell responsiveness, low hepatic insulin extraction and relatively high insulin sensitivity, which together result in a high exposure of tissues and organs to insulin. When combined with a high-glycaemic (HG) diet (that stimulates insulin secretion), this underlying propensity to obesity becomes manifest, as ingested calories are diverted from energy production to storage. Our data indicate that both weight loss and weight loss maintenance are optimized with low-glycaemic (LG) vs HG diet in AA. Whether greater obesity in AA is mechanistically related to their greater prevalence of type 2 diabetes is debatable. This review provides data indicating that obesity is not strongly related to insulin resistance in AA. Rather, insulin resistance in AA is associated with relatively low adipose tissue in the leg, consistent with a genetic predisposition to impaired lipid storage. Greater bioenergetic efficiency has been reported in AA and, via resultant oxidative damage, could plausibly contribute to insulin resistance. In summary, it is proposed here that a subset of AA women are predisposed to obesity due to a specific metabolic/endocrine phenotype. However, greater diabetes risk in AA has an independent aetiology based on impaired lipid storage and mitochondrial efficiency/oxidative stress.

Dietary Starch Composition Effects on Cx43-intercellular Communication Channels and Short-Term Memory

Abstract Objectives Intercellular communication mediated by gap junctions is critical for cognitive and sensory functions and is disturbed with age and age-related diseases. We analyzed the impact of consuming a high glycemic diet or a low glycemic dietary intervention on Cx43, a component of gap junction intercellular communication channels associated with spatial short-term memory, in different age groups of mice. Methods Male C57Bl6/J mice (n = 12–13) aged 7 months were fed equal amounts of either a high glycemic (HG) diet or a low glycemic (LG) diet for 1 month or 9 months. Within the 9-month feeding trial, half of the HG-fed animals were switched to the LG diet (HGxLG) at 4.5 months. The diets are isocaloric, but the HG starch is 100% composed of amylopectin, and the LG diet contains a 30% amylopectin/70% amylose mixture of starch and is digested much slower. We also analyzed tissues from a previous feeding trial where 12-month aged animals were fed these same diets over 12 months. The animals were weighed weekly, underwent intraperitoneal glucose tolerance tests to evaluate glycemic response, were tested for cognition using a novel object recognition test, and tissues were collected. Tissues including brain and eye samples were evaluated for Cx43, a component of gap junction intercellular communication channels, using immunohistochemistry and western blotting. Results At both time points, compared to the LG-fed controls, the HG-fed animals had significantly increased (&amp;gt;10%) body weight, while the HGxLG crossover animals’ body weight did not differ significantly from the LG-fed controls at 15 months. At 14 months, there was no significant difference in novel object recognition, although there was a trend of improved novel object recognition in the HGxLG crossover group. Cx43 gap junction protein accumulated in eye tissues of the HG-fed animals, and this accumulation was attenuated in the HGxLG group. Conclusions These results suggest that detrimental consequences of a high glycemic diet during aging on cognitive function may be reversible, supporting that a switch in dietary habits may be an effective nutritional intervention in older adults. Funding Sources USDA JM HNRCA Pilot Grant Program, NIH, USDA NIFA, USDA, Thome Memorial Foundation, and the BrightFocus Foundation.

The Interaction of Gut Microbiota Composition and Dietary Starch Form on Gut Health in Aged Mice

Abstract Objectives A high glycemic diet has been shown to increase gut permeability, which is associated with increased disease risk. Our objective was to evaluate the role of gut microbiota in mediating the relationship between dietary starch composition and gut health. Methods A high (HG) or low glycemic (LG) diet was fed in equal amounts to male mice from 12 to 24 months of age. The diets differed only by starch composition, which was 100% rapidly-digested amylopectin in the HG diet or 30% amylopectin/70% amylose in the LG diet. Within each diet, mice were assigned to one of three treatment conditions: continuous broad-spectrum antibiotic treatment (ampicillin and neomycin; HGabx or LGabx), weekly fecal microbiota transplants (FMT) from donor control mice fed the alternate diet (HG[tLG] or LG[tHG]), or a control group receiving no additional treatment. Feces were collected for microbiome analysis. Colon sections were collected for histology. Results The diet affected gut microbiota composition, with significantly greater abundance of Clostridium, Ruminococcus, and Coprobacillus in the HG-fed control animals compared with LG-fed controls. Antibiotic treatment in HG-fed animals resulted in elimination of Bacteroidetes and most Firmicutes and a proliferation of Proteobacteria, whereas LG-fed animals were able to maintain Bacteroidetes and a lower abundance of Proteobacteria. Fecal microbiota transplants altered the gut microbiome and recipients differed from their donors. Histological evaluation of colons showed increased intestinal disease in HG-fed animals across all treatments, including increased inflammatory cell infiltration and abnormal villi. Antibiotic treatment in HG-fed animals resulted in the most severe disease phenotype, and most animals died within 4–6 months on treatment and presented with an enlarged and hemorrhagic cecum upon necropsy. Conclusions The high glycemic diet altered the gut microbiome and increased the prevalence of pathological intestinal morphology, which was further exacerbated with antibiotic treatment. Our work suggests that dietary starch form has a substantial effect on the gut health outcomes, particularly in the context of antibiotic treatment or fecal microbiota transplants. Funding Sources BrightFocus Foundation, USDA/NIFA AFRI, USDA, Stanley N. Gershoff Scholarship, NIH RO1, Thome Memorial Foundation.

The Short-Term Effect of a High-Glycemic Diet on Mouse Obesity and Intestinal Microbiota Composition

Abstract Objectives High glycemic index diet has been demonstrated to induce obesity and insulin resistance. The role of gut microbiota, as a key mediator of several metabolic syndromes, has not been elucidated. The objective of this project is to understand the effect of gut microbiota in a high-glycemic diet-induced obesity and associated metabolic complications. Methods Male C57Bl6/J mice aged 8–9 weeks were fed with a high-glycemic diet (HG, amylopectin-based) or low-glycemic diet (LG, amylose-based) ad libitum for 8 weeks. Body composition was determined by MRIs. Intraperitoneal glucose tolerance tests were performed after 6 weeks on diet. Mice were euthanized after 8 weeks on diet. Results After two weeks on diet, the HG group (n = 12) mice had a significantly higher body fat mass by MRI analysis, as compared to the LG group (n = 12) despite having similar body weight and equal food consumption. After 6 weeks, mice in the HG group had a significantly higher fasting glucose level compared to the LG group. There was no difference in fasting triglyceride level. Gonadal, subcutaneous and brown fat adipose tissue weight were significantly higher in the HG group after 8 weeks on diet. 16S rDNA sequencing on feces showed that the HG mice have a significantly higher Shannon diversity and different overall microbiome structure compared to the LG mice. The microbial community in the LG group was predominated by Bacteroidetes, particularly by Bacteroides thetaiotaomicron (Relative abundance 48.65 ± 12.88% versus HG 14.69 ± 0.07%), while the HG group was predominated by Firmicutes. Ongoing analysis will investigate the relative role of key microbial taxa on obesity and glucose homeostasis. Conclusions Consuming two weeks of a high-glycemic index diet induced adiposity and hyperglycemia along with a shift of the overall gut microbiota composition compared to a low-glycemic index diet. Funding Sources NIH, USDA, Robert C and Veronica Atkins Foundation

SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma

Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N<95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.1, 2 Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD3. Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention4,5. This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters.

A low glycemic diet protects disease-prone Nrf2-deficient mice against age-related macular degeneration

Age-related macular degeneration (AMD) is a major blinding disease, affecting over 14% of the elderly. Risk for AMD is related to age, diet, environment, and genetics. Dietary modulation of AMD risk is a promising treatment modality, but requires appropriate animal models to demonstrate advantages of diet. Mice lacking the antioxidant transcription factor Nrf2 (Nfe2l2) develop age-related retinopathy relevant to human AMD. Here we evaluated the effect of consuming high glycemic (HG) or low glycemic (LG) diets until 18-months of age on development of features relevant to AMD in Nrf2-null mice. Nrf2-null mice that consumed HG diets developed atrophic AMD, characterized by photoreceptor degeneration, retinal pigment epithelium (RPE) atrophy and pigmentary abnormalities, basal laminar deposits, and loss of the choriocapillaris. In contrast, Nrf2-null-mice that consumed LG diets did not develop retinal disease phenotypes. Consumption of HG diets was associated with accumulation of advanced glycation end-products in the RPE and systemically, whereas consumption of the LG diet was associated with increased levels of anti-glycative and anti-oxidative detoxification machinery. Together our data indicate that the Nrf2-null HG mouse is a good model for atrophic AMD studies and that the LG diet can activate protective pathways to prevent AMD, even in a genetically predisposed animal.

Dietary pattern in relation to the risk of Alzheimer's disease: a systematic review.

Alzheimer's disease (AD) is a progressive neurodegenerative disease leading to a gradual and irreversible loss of memory, linguistic skills, and perception of time and space, thinking, and behavior. Dietary pattern has been presented as a contributor to the incidence of Alzheimer's. This study aimed at reviewing the evidence on the relation between dietary pattern and AD. This systematic search was performed on the articles available in PubMed, Scopus, and Web of Sciences databases until May 2019 using keywords, including (diet, food, dietary pattern, food pattern) and (Alzheimer's disease) among observational studies. After excluding duplicated, and irrelevant studies, 26 studies were eligible for this review study. We categorized the studied dietary patterns into two groups: healthy and unhealthy diet. This study reviewed two case-control, five cross-sectional, and 19 prospective studies. Eight studies assessed unhealthy diet (high-fat diet, high-glycemic diet, sweetened sugary beverage, etc.) and the risk of AD. In addition, the other studies considered the effect of healthy diet such as Mediterranean diet, dietary approaches to stop hypertension (DASH), Mediterranean-DASH intervention for neurodegenerative delay, and seafood-rich diet on AD. This literature review indicated that adherence to a healthy dietary pattern has neuroprotective effects on AD prevention, while unhealthy diet can cause neurodegenerative effects in AD etiology. In conclusion, our findings showed that adherence to healthy diet can decrease oxidative stress and inflammation and accumulation of amyloid-β and consequently can decrease the risk of AD.