Effect of diabetes-specific oral nutritional supplements with allulose on weight and glycemic profiles in overweight or obese type 2 diabetic patients

BACKGROUND/OBJECTIVES@#Diabetes-specific oral nutritional supplements (ONS) have anti-hyperglycemic effects, while D-allulose exerts anti-diabetic and anti-obesity effects.In this study, we investigated the efficacy and safety of diabetes-specific ONS, including allulose, on glycemic and weight changes in overweight or obese patients with type 2 diabetes mellitus (T2DM). @*SUBJECTS/METHODS@#A single-arm, historical-control pilot clinical trial was conducted on 26 overweight or obese patients with T2DM (age range: 30–70 yrs). The participants were administered 2 packs of diabetes-specific ONS, including allulose (200 kcal/200 mL), every morning for 8 weeks. The glycemic profiles, obesity-related parameters, and lipid profiles were assessed to evaluate the efficacy of ONS. @*RESULTS@#After 8 weeks, fasting blood glucose (FBG) level significantly decreased from 139.00 ± 29.66 mg/dL to 126.08 ± 32.00 mg/dL (P = 0.007) and glycosylated hemoglobin (HbA1c) improved (7.23 ± 0.82% vs. 7.03 ± 0.69%, P = 0.041). Moreover, the fasting insulin (δ: −1.81 ± 3.61 μU/mL, P = 0.017) and homeostasis model assessment for insulin resistance (HOMA-IR) (δ: −0.87 ± 1.57, P = 0.009) levels decreased at 8 weeks, and body weight significantly decreased from 67.20 ± 8.29 kg to 66.43 ± 8.12 kg (P = 0.008). Body mass index (BMI) also decreased in accordance with this (from 25.59 ± 1.82 kg/m2 to 25.30 ± 1.86 kg/m2 , P = 0.009), as did waist circumference (δ: −1.31 ± 2.04 cm, P = 0.003). @*CONCLUSIONS@#The consumption of diabetes-specific ONS with allulose in overweight or obese patients with T2DM improved glycemic profiles, such as FBG, HbA1c, and HOMA-IR, and reduced body weight and BMI.

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ≥ 250 mg/dL), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear factor-κB pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Daily walnut intake improves metabolic syndrome status and increases circulating adiponectin levels: randomized controlled crossover trial

BACKGROUND/OBJECTIVES: Several previous studies have investigated whether regular walnut consumption positively changes heart-health-related parameters. The aim of this study was to investigate the effects of daily walnut intake on metabolic syndrome (MetS) status and other metabolic parameters among subjects with MetS. SUBJECTS/METHODS: This study was a two-arm, randomized, controlled crossover study with 16 weeks of each intervention (45 g of walnuts or iso-caloric white bread) with a 6 week washout period between interventions. Korean adults with MetS (n = 119) were randomly assigned to one of two sequences; 84 subjects completed the trial. At each clinic visit (at 0, 16, 22, and 38 weeks), MetS components, metabolic parameters including lipid profile, hemoglobin A1c (HbA1c), adiponectin, leptin, and apolipoprotein B, as well as anthropometric and bioimpedance data were obtained. RESULTS: Daily walnut consumption for 16 weeks improved MetS status, resulting in 28.6%-52.8% reversion rates for individual MetS components and 51.2% of participants with MetS at baseline reverted to a normal status after the walnut intervention. Significant improvements after walnut intake, compared to control intervention, in high-density lipoprotein cholesterol (HDL-C) (P = 0.028), fasting glucose (P = 0.013), HbA1c (P = 0.021), and adiponectin (P = 0.019) were observed after adjustment for gender, age, body mass index, and sequence using a linear mixed model. CONCLUSION: A dietary supplement of 45 g of walnuts for 16 weeks favorably changed MetS status by increasing the concentration of HDL-C and decreasing fasting glucose level. Furthermore, consuming walnuts on a daily basis changed HbA1c and circulating adiponectin levels among the subjects with MetS. This trial is registered at ClinicalTrials.gov as NCT03267901.

Similarities and differences between alpha-tocopherol and gamma-tocopherol in amelioration of inflammation, oxidative stress and pre-fibrosis in hyperglycemia induced acute kidney inflammation

BACKGROUND/OBJECTIVES: Diabetes mellitus (DM) is a major chronic disease which increases global health problems. Diabetes-induced renal damage is associated with inflammation and fibrosis. Alpha (AT) and gamma-tocopherols (GT) have shown antioxidant and anti-inflammatory effects in inflammation-mediated injuries. The primary aim of this study was to investigate effects of AT and GT supplementations on hyperglycemia induced acute kidney inflammation in alloxan induced diabetic mice with different levels of fasting blood glucose (FBG). MATERIALS/METHODS: Diabetes was induced by injection of alloxan monohydrate (150 mg/kg, i.p) in ICR mice (5.5-week-old, male) and mice were subdivided according to their FBG levels and treated with different diets for 2 weeks; CON: non-diabetic mice, m-DMC: diabetic control mice with mild FBG levels (250 mg/dl < or = FBG < or = 450 mg/dl), m-AT: m-DM mice fed AT supplementation (35 mg/kg diet), m-GT: m-DM mice with GT supplementation (35 mg/kg diet), s-DMC: diabetic control mice with severe FBG levels (450 mg/dl < FBG), s-AT: s-DM mice with AT supplementation, s-GT: s-DM mice with GT supplementation. RESULTS: Both AT and GT supplementations showed similar beneficial effects on NFkappaB associated inflammatory response (phosphorylated inhibitory kappa B-alpha, interleukin-1beta, C-reactive protein, monocyte chemotactic protein-1) and pre-fibrosis (tumor growth factor beta-1 and protein kinase C-II) as well as an antioxidant emzyme, heme oxygenase-1 (HO-1) in diabetic mice. On the other hands, AT and GT showed different beneficial effects on kidney weight, FBG, and oxidative stress associated makers (malondialdehyde, glutathione peroxidase, and catalase) except HO-1. In particular, GT significantly preserved kidney weight in m-DM and improved FBG levels in s-DM and malondialdehyde and catalase in m- and s-DM, while AT significantly attenuated FBG levels in m-DM and improved glutathione peroxidase in m- and s-DM. CONCLUSIONS: The results suggest that AT and GT with similarities and differences would be considered as beneficial nutrients to modulate hyperglycemia induced acute renal inflammation. Further research with careful approach is needed to confirm beneficial effects of tocopherols in diabetes with different FBG levels for clinical applications.

Anti-adipogenic effect of mulberry leaf ethanol extract in 3T3-L1 adipocytes

BACKGROUND/OBJECTIVES: Adipogenesis is part of the cell differentiation process in which undifferentiated fibroblasts (pre-adipocytes) become mature adipocytes with the accumulation of lipid droplets and subsequent cell morphological changes. Several transcription factors and food components have been suggested to be involved in adipogenesis. The aim of this study was to determine whether mulberry leaf ethanol extract (MLEE) affects adipogenesis in 3T3-L1 adipocytes. MATERIALS/METHODS: The 3T3-L1 adipocytes were treated with different doses of MLEE for 8 days starting 2 days post-confluence. Cell viability, fat accumulation, and adipogenesis-related factors including CCAAT-enhancer-binding protein alpha (C/EBPalpha), peroxisome proliferator-activated receptor gamma (PPARgamma), PPARgamma coactivator 1 alpha (PGC-1alpha), fatty acid synthase (FAS), and adiponectin were analyzed. RESULTS: Results showed that MLEE treatments at 10, 25, 50, and 100 microg/ml had no effect on cell morphology and viability. Without evident toxicity, all MLEE treated cells had lower fat accumulation compared with control as shown by lower absorbances of Oil Red O stain. MLEE at 50 and 100 microg/ml significantly reduced protein levels of PPARgamma, PGC-1alpha, FAS, and adiponectin in differentiated adipocytes. Furthermore, protein level of C/EBPalpha was significantly decreased by the treatment of 100 microg/ml MLEE. CONCLUSION: These results demonstrate that MLEE treatment has an anti-adipogenic effect in differentiated adipocytes without toxicity, suggesting its potential as an anti-obesity therapeutic.

Effect of combined mulberry leaf and fruit extract on liver and skin cholesterol transporters in high fat diet-induced obese mice

Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications.

Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic mice

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.

Effect of Hominis Placenta on cutaneous wound healing in normal and diabetic mice

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.

Dietary Habits and Nutrition Knowledge of Children Using Community Food Service Centers according to Family Type

The objective of this study was to assess dietary habits and nutrition knowledge of elementary school students who use community food-service centers according to family type. The subjects were comprised of 147 individuals in low-income households, aged from 7 to 12 years, and who consumed free meals at community welfare centers or at local children's centers in Seoul and Kyunggi-do, Korea. Dietary habits and dietary intake were obtained using 24-hr recall. Children in low-income single parent families skipped breakfast more frequently than children in low-income married parent families. No difference in nutrition intake or dietary habits was observed between children in low-income single parent families and children in low-income married parent families. More interest and financial support of the government are required to develop nutrition education and food assistance programs for children in low-income single parent families.

Effects of Occasional Mid-Morning Snacks on Dietary Behaviors and School Life in Elementary School Students / 대한지역사회영양학회지

The objective of this study was to investigate the effect of occasional mid-morning snacks (MMS) on dietary behaviors and school life among elementary students. The students, mothers, and teachers from two elementary schools in Seoul were selected. The schools have been provided a steamed sweet-potato or potato, or a piece of ricecake or cake with a pack of milk as MMS 3-4 times a month for more than 3 years. Most students were satisfied with the MMS. Mothers and teachers reported that their children or students were happier, more active, and more energetic in school with MMS. Furthermore, the students answered that they could drink milk better on the day when the school provided MMS. Many students felt that it was relevant to serve a simple menu at lunch time if they were served MMS. Also, students became more interested in school meals or foods with MMS. In addition, mothers who had jobs wanted more frequent MMS. The degree of satisfaction about MMS of the teachers was higher than that of students or mothers. Many teachers thought that their students drank milk better with MMS and further, that it made students to drink more milk on other days. In conclusion, MMS had positive effects on the dietary behavior and school life of elementary students. Therefore, it can be a good option for eliminating skipping breakfast because it provides more nutrition, makes students drink more milk, and allows students to enjoy school activities more.

Dietary intake based on physical activity level in Korean elementary school students

Prevalence of childhood obesity is increasing significantly worldwide due to energy imbalance perhaps stemming from undesirable dietary behavior and physical activity level. The objective of the study was to examine the effects of physical activity level on nutritional status in elementary school students. The subjects were comprised of 287 elementary school students between 4th and 6th grades in Seoul, Korea. The level of physical activity was scored with a modified Godin leisure-time exercise questionnaire and was categorized as active, moderately active, and sedentary. Dietary intakes were obtained using a 24-hour food recall method. An analysis of variance (ANOVA) was conducted to test for global significant differences of nutrient intakes by physical activity level. Boys were more active than girls. Daily intakes of energy in moderately active boys were significantly higher than in the sedentary group, but intakes of calcium and iron in moderately active boys were lower than active boys. For girls, physical activity level did not affect nutrient density at all. Intakes of calcium, vitamin C, and folate for both boys and girls were below 50% of recommended intake. Physical activity did not affect nutrient density and our participants were exposed to nutritional imbalance. Therefore, the results suggest that nutrition education regarding balanced diet and optimum physical activity is required for children's health and growth.

Effects of Short Term Antioxidant Cocktail Supplementation on the Oxidative Stress and Inflammatory Response of Renal Inflammation in Diabetic Mice

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-kappaB activation was indirectly demonstrated by pIkappaB-alpha and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-kappaB activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-1beta and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

Effects of Gamma-Tocopherol (GT) Supplementation on Vitamin E Concentration in Cigarette Smoke (CS) Exposed Mice

Cigarette smoke (CS) induces oxidative and nitrosative stress to the respiratory tract (RT) via both oxidants contained in CS and by CS-induced activation of RT inflammatory-immune pro-oxidant processes. CS exposure has been associated with reduced levels of plasma micronutrient antioxidants, in part due to an increased utilization and turnover of alpha-tocopherol (AT). It has been suggested that gamma-tocopherol (GT) may have an expanded spectrum of antioxidant activation compared to alpha-tocopherol (AT). In order to investigate effects of high GT supplementation as compared to AT, C57 BL/6 mice were fed control AT (35 mg/kg diet) or high GT (1,000 mg/kg diet) diet for 8-10 weeks and then exposed to 60 mg/m3 CS, 6 hr/day for 3 days. AT and GT levels and their metabolites were measured at endpoints. High GT supplementation significantly reduced AT levels in plasma, liver and lung compared to AT. CS increased levels of AT and GT in plasma and lung of control AT group but decreased GT levels in lung of high GT supplemented group. Moreover, CS significantly decreased GT metabolite, gamma-CEHC. The results suggest that high GT supplementation have selective modulation of concentrations of vitamin E and its metabolite in plasma and lung but not in liver against in vivo CS exposure.

Apo E4 Genotype as the Alzheimer Indictor in Korean Senior Subjects Aged 50 to 64 Years Old

Recent studies described the epsilon 4 allele of apoE confers a two-to fourfold increased risk for late-onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly around apo E. Therefore, the goal of this study was to find the association between Alzheimer and apo E4 genotype in the 107 elderly between 50 to 64 years old who visited to FHWC of Sungshin Women's University. We conducted the questionnaire survey (general & 24 hr dietary recall), anthropometerics (BP, waist & BMI) and blood biochemistry (FBS & lipid profiles). LDL-c and HOMA-IR were calculated by Friedwald's and Matthew's formulas. The apo E genotyping was performed by PCR-RFLP method and subjects were divided into three allele groups (epsilon 3; wild, epsilon 2 & epsilon 4; mutants). The apo E allele frequencies were 7.0% for the epsilon 2, 83.6% for the epsilon 3 and 9.3% for the epsilon 4. In comparison with biochemistry characteristics by apo E genotype, FBS was significantly higher in epsilon 4 (129.2 +/- 6.8) than that in the others (epsilon 2: 117 +/- 7.4, epsilon 3: 107.3 +/- 2.2)(p 150 mg/dl) & low HDL (< 40 mg/dl: male symbol or < 50 mg/dl: female symbol )]. The cytokines levels such as IL-1beta, IL-6 and TNF-alpha were not different among three apoE alleles. After the adjusting sex, age & dietary fiber, LDL-c level was significantly higher in epsilon 4 (108.3 +/- 7.7) than that in epsilon 2 (100.4 +/- 8.4)(p < 0.05). According to food intake and the recipe on the basis of 24 hr dietary recall, the elderly with epsilon 4 allele took higher intake frequency of the light -colored vegetable (radish, onion & cabbage) and pan-fried foods (sauteed beef and vegetables, stir-fried vienna with vegetables) than the others. We knew that the elderly with epsilon 4 allele had been restricted the calories intakes with high dietary fiber (33.6 + 2.5 g/d) to maintain the normal level of FBS and LDL-c. On next study, the prevalence of Alzheimer's disease in this population who has epsilon 4 allele on the condition of calories restriction will be continually follow-up.

Alpha-Tocopherol Transfer Protein (alpha-TTP): Insights from Alpha-Tocopherol Transfer Protein Knockout Mice

Alpha-tocopherol transfer protein (alpha-TTP) is a liver cytosolic transport protein that faciliates alpha-tocopherol (alpha-T) transfer into liver secreted plasma lipoproteins. Genetic defects in alpha-TTP, like dietary vitamin E deficiency, are associated with infertility, muscular weakness and neurological disorders. Both human and alpha-TTP deficient (alpha-TTP-/-) mice exhibit severe plasma and tissue vitamin E deficiency that can be attenuated by sufficient dietary alpha-T supplementations. In this review, we summarize the literature concerning studies utilizing the alpha-TTP-/- mice. Levels of vitamin E in the alpha-TTP-/- mice do not appear to be directly related to the amounts of dietary alpha-T or to the levels of alpha-TTP protein in tissues. The alpha-TTP-/- mice appear to present a good model for investigating the specific role of alpha-T in tissue vitamin E metabolism. Furthermore, alpha-TTP-/- mice appear to be useful to elucidate functions of alpha-TTP beyond its well recognized functions of transferring alpha-T from liver to plasma lipoprotein fractions.