Effect of Oat ß-Glucan Supplementation on Chronic Kidney Disease: A Feasibility Study.

OBJECTIVE: Dietary supplementation with grains containing high ß-glucan fiber has been shown to attenuate the progression of chronic kidney disease (CKD) and vascular calcification in animal models. The aim of this study was to investigate the feasibility of consuming an oat ß-glucan supplement and to assess its effects on certain uremic toxins and markers of mineral metabolism in patients with CKD. DESIGN: This is a 20-week, nonrandomized, single-center, pretest-posttest study. Twenty-eight subjects with CKD stages 3-4 were enrolled. The mean age was 67.6 ± 8.9 years, and the mean estimated glomerular filtration rate was 35 ± 14 mL/min/1.73 m2. Subjects received a dietary supplement containing 3 g of oat ß-glucan per day for 12 weeks. The 4-week period before the start of the intervention was used as a baseline comparison for each subject. The primary outcome was pre-post supplement changes in plasma levels of two uremic toxins: trimethylamine N-oxide (TMAO) and asymmetric dimethylarginine. Secondary outcomes were pre-post supplement changes in serum calcium, phosphorus, and Klotho levels. Repeated-measures analysis of variance was used to test the differences in outcomes over the three-month-long intervention. RESULTS: Serum levels of TMAO decreased by a median of -17% (interquartile range: -46%, 7%) at the end of the intervention. A nonstatistically significant change was observed for asymmetric dimethylarginine (median -0.6% [-12%, 20%]) and serum Klotho (median -3% [-8%, 7%]). There were no changes in serum levels of calcium and phosphorus. One month after discontinuation of ß-glucan therapy, TMAO levels increased by a median of 16% (-12%, 36%) but remained slightly below the pretreatment levels. Eight subjects experienced side effects and discontinued the treatment. CONCLUSION: A diet supplemented with ß-glucan is safe and potentially efficacious in lowering serum concentrations of TMAO in patients with CKD. Larger trials with longer follow-up times are needed to determine whether such reductions translate into clinical benefits.

Brief Report: Zinc Supplementation and Inflammation in Treated HIV.

OBJECTIVE: In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy-treated HIV infection. METHODS: This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 mg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks. We assessed inflammatory and gut integrity biomarkers at baseline and 16 weeks. RESULTS: Overall, a total of 52 participants were enrolled (25 participants in the low-dose arm and 27 participants in the high-dose arm). Median (Interquartile range) age was 49 (38, 60) years, 77% were men and 73% were African Americans. At baseline, median zinc levels were 73 (64, 86) µg/dL. Median circulating zinc levels increased to 91 µg/dL in the low-dose arm and to 100 µg/dL in the high-dose arm. Overall, 48%-60% of participants experienced a reduction in biomarkers levels. The margin of reduction ranged between 8% and 21%. This change was meaningful with large effect size (Cohen D ranging from 5 to 19). CONCLUSIONS: In this pilot study, we found that zinc supplementation is effective at increasing circulating zinc levels. In addition, our findings provide novel data suggesting that zinc can affect a biological signature in people living with HIV and modulate biomarkers associated with clinical comorbidities.

Exercise-induced improvements in glucose effectiveness are blunted by a high glycemic diet in adults with prediabetes.

AIMS: Glucose effectiveness (GE) refers to the ability of glucose to influence its own metabolism through insulin-independent mechanisms. Diminished GE is a predictor of progression to type 2 diabetes. Exercise training improves GE, however, little is known about how dietary interventions, such as manipulating the glycemic index of diets, interact with exercise-induced improvements in GE in at-risk populations. METHODS: We enrolled 33 adults with obesity and pre-diabetes (17 males, 65.7 ± 4.3 years, 34.9 ± 4.2 kg m-2) into a 12-week exercise training program (1 h day-1 and 5 day week-1 at ~ 85% of maximum heart rate) while being randomized to concurrently receive either a low (EX-LOG: 40 ± 0.3 au) or high (EX-HIG: 80 ± 0.6 au) glycemic index diet. A 75-g oral-glucose-tolerance test (OGTT) was performed before and after the intervention and GE was calculated using the Nagasaka equation. Insulin resistance was estimated using a hyperinsulinemic-euglycemic clamp and cardiorespiratory fitness using a VO2max test. RESULTS: Both EX-LOG and EX-HIG groups had similar improvements in weight (8.6 ± 5.1 kg, P < 0.001), VO2max (6 ± 3.5 mL kg-1 min-1, P < 0.001) and clamp-measured peripheral insulin resistance (1.7 ± 0.9 mg kg-1 min-1, P < 0.001), relative to baseline data. GE in EX-LOG and EX-HIG was similar at baseline (1.9 ± 0.38 vs. 1.85 ± 0.3 mg dL-1 min-1, respectively; P > 0.05) and increased by ~ 20% post-intervention in the EX-LOG arm (∆GE: 0.07-0.57 mg dL-1 min-1, P < 0.05). Plasma free fatty acid (FFA) concentrations also decreased only in the EX-LOG arm (∆FFA: 0.13 ± 0.23 mmol L-1, P < 0.05). CONCLUSIONS: Our data suggest that a high glycemic index diet may suppress exercise-induced enhancement of GE, and this may be mediated through plasma FFAs.

Trends and determinants of stunting among under-5s: evidence from the 1995, 2001, 2006 and 2011 Uganda Demographic and Health Surveys.

OBJECTIVE: To describe trends of childhood stunting among under-5s in Uganda and to assess the impact of maternal education, wealth and residence on stunting. DESIGN: Serial and pooled cross-sectional analyses of data from Uganda Demographic and Health Surveys (UDHS) of 1995, 2001, 2006 and 2011. Prevalence of stunting and mean height-for-age Z-score were computed by maternal education, wealth index, region and other sociodemographic characteristics. Multivariable logistic and linear regression models were fitted to survey-specific and pooled data to estimate independent associations between covariates and stunting or Z-score. Sampling weights were applied in all analyses. SETTING: Uganda. SUBJECTS: Children aged <5 years. RESULTS: Weighted sample size was 14 747 children. Stunting prevalence decreased from 44·8% in 1995 to 33·2% in 2011. UDHS reported stunting as 38% in 1995, underestimating the decline because of transitioning from National Center for Health Statistics/Centers for Disease Control and Prevention standards to WHO standards. Nevertheless, one in three Ugandan children was still stunted by 2011. South Western, Mid Western, Kampala and East Central regions had highest odds of stunting. Being born in a poor or middle-income household, of a teen mother, without secondary education were associated with stunting. Other persistent stunting predictors included small birth size, male gender and age 2-3 years. CONCLUSIONS: Sustained decrease in stunting suggests that child nutrition interventions have been successful; however, current prevalence does not meet Millennium Development Goals. Stunting remains a public health concern and must be addressed. Customizing established measures such as female education and wealth creation while targeting the most vulnerable groups may further reduce childhood stunting.

Exercise training-induced improvement in skeletal muscle PGC-1α-mediated fat metabolism is independent of dietary glycemic index.

OBJECTIVE: This study hypothesized that a low-glycemic diet combined with exercise would increase expression of nuclear regulators of fat transport and oxidation in insulin-resistant skeletal muscle. METHOD: Nineteen subjects (64 ± 1 y; 34 ± 1 kg/m2 ) were randomized to receive isocaloric high-glycemic-index (HiGIX; 80 ± 0.6 units, n = 10) or low-glycemic-index (LoGIX; 40 ± 0.3 units, n = 9) diets combined with supervised exercise (1 h/d, 5 d/wk at ∼85% HRmax ) for 12 weeks. Insulin sensitivity was determined by hyperinsulinemic-euglycemic clamp. Skeletal muscle biopsies were obtained before and after the intervention to assess fasting gene and protein expression. RESULTS: Weight loss was similar for both groups (9.5 ± 1.3 kg). Likewise, improvements in insulin sensitivity (P < 0.002) and PPARγ (P < 0.002), PGC-1α (P = 0.003), CD36 (P = 0.003), FABP3 (mRNA, P = 0.01 and protein, P = 0.02), and CPT1B (mRNA, P = 0.03 and protein, P = 0.008) expression were similar for both interventions. Increased insulin sensitivity correlated with increased PGC-1α expression (P = 0.04), and increased fasting fat oxidation correlated with increased FABP3 (P = 0.04) and CPT1B (P = 0.05) expression. CONCLUSIONS: An exercise/diet program resulting in 8% to 10% weight loss improved insulin sensitivity and key molecular mechanisms in skeletal muscle that are controlled by PGC-1α. These effects were independent of the glycemic index of the diets.

Nutrition Recommendations in Elderly and Aging.

Maintaining optimal health and well-being in the older adult requires understanding of how physiologic changes influence nutritional status, familiarity with the available validated tools to assess status, identification of factors predisposing older adults to malnutrition, and evidence-based practice regarding the nutritional needs of this age group. Evidence-based guidance on these core practice components is provided to the clinician in this article.

Lifestyle-induced decrease in fat mass improves adiponectin secretion in obese adults.

PURPOSE: Several studies have identified relationships between weight loss and adipokine levels; however, none have looked at the combined effect of aerobic exercise training with the consumption of a low- or a high-glycemic diet. We examined the effects of 12 wk of aerobic exercise combined with either a low-glycemic index diet (∼40 U) plus exercise (LoGIX) or a high-glycemic index diet (∼80 U) diet plus exercise (HiGIX) on plasma leptin and adiponectin (total and high molecular weight [HMW]) in 27 older obese adults (age = 65 ± 0.5 yr, body mass index = 34.5 ± 0.7 kg·m). METHODS: Insulin sensitivity was calculated from an oral glucose tolerance test. Fasting HMW adiponectin and leptin were quantified from plasma samples obtained before the insulin sensitivity index obtained from the oral glucose tolerance test. Glucose and insulin measures were obtained before and every 30 min during the test. Dual-energy x-ray absorptiometry and computerized tomography were used to determine body composition and to quantify subcutaneous and visceral abdominal adiposity, respectively. RESULTS: Fasting leptin was significantly decreased in both groups (LoGIX: preintervention = 33.8 ± 4.7, postintervention = 19.2 ± 4.5; HiGIX: preintervention = 27.9 ± 4.2, postintervention = 11.9 ± 2.2 ng·mL; P = 0.004), and HMW adiponectin was significantly increased (LoGIX: preintervention = 1606.9 ± 34.6, postintervention = 3502.3 ± 57; HiGIX: preintervention = 3704.8 ± 38.1, postintervention = 4284.3 ± 52.8 pg·mL; P = 0.003) after the 12-wk intervention. Total body fat was reduced after both interventions. Visceral fat mass was inversely correlated with HMW adiponectin, whereas subcutaneous fat correlated with leptin. CONCLUSIONS: The data suggest that exercise training, independent of dietary glycemic index, favorably alters HMW adiponectin and leptin secretion and that a reduction in visceral fat mass is a key factor regulating HMW adiponectin in older obese persons.

Exercise training with weight loss and either a high- or low-glycemic index diet reduces metabolic syndrome severity in older adults.

BACKGROUND: The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low (LoGIx)- or high (HiGIx)-glycemic index diet on the severity of the metabolic syndrome (Z-score). METHODS: Twenty-one adults (66.2±1.1 years; BMI=35.3±0.9 kg/m2) with the metabolic syndrome were randomized to 12 weeks of exercise (60 min/day for 5 days/week at about 85% HRmax) and provided a LoGIx (n=11) or HiGIx (n=10) diet. Z-scores were determined from: blood pressure, triglycerides (TGs), high-density lipoproteins (HDLs), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and nonesterfied fatty acid (NEFA) suppression were also assessed. RESULTS: LoGIx and HiGIx diets decreased body mass and insulin resistance and increased aerobic fitness comparably (p<0.05). LoGIx and HiGIx diets decreased the Z-score similarly as each intervention decreased blood pressure, TGs, FPG and WC (p<0.05). The HiGIx diet tended to suppress NEFA during insulin stimulation compared with the LoGIx diet (p=0.06). CONCLUSIONS: Our findings highlight that exercise with weight loss reduces the severity of the metabolic syndrome whether individuals were randomized to a HiGIx or a LoGIx diet.

Intramyocellular lipid content and insulin sensitivity are increased following a short-term low-glycemic index diet and exercise intervention.

The relationship between intramyocellular (IMCL) and extramyocellular lipid (EMCL) accumulation and skeletal muscle insulin resistance is complex and dynamic. We examined the effect of a short-term (7-day) low-glycemic index (LGI) diet and aerobic exercise training intervention (EX) on IMCL and insulin sensitivity in older, insulin-resistant humans. Participants (66 ± 1 yr, BMI 33 ± 1 kg/m(2)) were randomly assigned to a parallel, controlled feeding trial [either an LGI (LGI/EX, n = 7) or high GI (HGI/EX, n = 8) eucaloric diet] combined with supervised exercise (60 min/day, 85% HR(max)). Insulin sensitivity was determined via 40 mU·m(-2)·min(-1) hyperinsulinemic euglycemic clamp and soleus IMCL and EMCL content was assessed by (1)H-MR spectroscopy with correction for fiber orientation. BMI decreased (kg/m(2) -0.6 ± 0.2, LGI/EX; -0.7 ± 0.2, HGI/EX P < 0.0004) after both interventions with no interaction effect of diet composition. Clamp-derived insulin sensitivity increased by 0.91 ± 0.21 (LGI/EX) and 0.17 ± 0.55 mg·kg(-1)·min(-1) (HGI/EX), P = 0.04 (effect of time). HOMA-IR was reduced by -1.1 ± 0.4 (LGI/EX) and -0.1 ± 0.2 (HGI/EX), P = 0.007 (effect of time), P = 0.02 (time × trial). Although both interventions increased IMCL content, (Δ: 2.3 ± 1.3, LGI/EX; 1.4 ± 0.9, HGI/EX, P = 0.03), diet composition did not significantly effect the increase. However, the LGI/EX group showed a robust increase in the [IMCL]/[EMCL] ratio compared with the HGI/EX group (Δ: 0.5 ± 0.2 LGI/EX vs. 0.07 ± 0.1, P = 0.03). The LGI/EX group also demonstrated greater reductions in [EMCL] than the HGI/EX group (Δ: -5.8 ± 3.4, LGI/EX; 2.3 ± 1.1, HGI/EX, P = 0.03). Changes in muscle lipids and insulin sensitivity were not correlated; however, the change in [IMCL]/[EMCL] was negatively associated with the change in FPI (r = -0.78, P = 0.002) and HOMA-IR (r = -0.61, P = 0.03). These data suggest that increases in the IMCL pool following a low glycemic diet and exercise intervention may represent lipid repartitioning from EMCL. The lower systemic glucose levels that prevail while eating a low glycemic diet may promote redistribution of lipid stores in the muscle.

A low-glycemic index diet and exercise intervention reduces TNF(alpha) in isolated mononuclear cells of older, obese adults.

Low-glycemic index diets and exercise independently improve glucose tolerance and reduce diabetes risk. However, the combined effect of a low-glycemic index diet and exercise on inflammation and glucose metabolism is not known. Therefore, we randomized 28 insulin-resistant adults (age: 66 ± 1 y; BMI: 34.2 ± 0.7 kg · m(-2)) to a 12-wk, low (LGI = 40) or high- (HGI = 80) glycemic index diet plus aerobic exercise (5 d · wk(-1), 60 min · d(-1), 80-85% heart rate(max)) intervention. All food and fluids were provided during the study. Inflammation was assessed from cytokine (TNFα and IL-6) secretion using peripheral blood mononuclear cells (MNC) stimulated overnight with LPS. Glycemic response was determined following ingestion of a 75-g glucose solution. Fasting blood samples were collected for additional cytokine [TNFα, IL-6, and monocyte chemoattractant protein 1 (MCP-1)] analysis. Both interventions decreased BMI (P < 0.001), fasting plasma glucose (P = 0.01), and insulin (P = 0.02). The glycemic response was reduced only in the LGI group (P = 0.04). Plasma and MNC-derived TNFα secretion were reduced in the LGI group (P = 0.02) but increased in the HGI group (P = 0.02). Secretion of IL-6 from MNC and plasma IL-6 and MCP-1 concentrations were reduced in the LGI group. The change in MNC-derived TNFα (r = 0.43; P = 0.04) and plasma MCP-1 (r = 0.44; P = 0.04) correlated with decreases in the glycemic response. These data highlight the importance of diet composition in the treatment and prevention of inflammation and hyperglycemia. A low-glycemic index diet has antiinflammatory and antidiabetogenic effects when combined with exercise in older, obese prediabetics.

A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans.

BACKGROUND: The optimal lifestyle intervention that reverses diabetes risk factors is not known. OBJECTIVE: We examined the effect of a low-glycemic index (GI) diet and exercise intervention on glucose metabolism and insulin secretion in obese, prediabetic individuals. DESIGN: Twenty-two participants [mean ± SEM age: 66 ± 1 y; body mass index (in kg/m(2)): 34.4 ± 0.8] underwent a 12-wk exercise-training intervention (1 h/d for 5 d/wk at ≈ 85% of maximum heart rate) while randomly assigned to receive either a low-GI diet (LoGIX; 40 ± 0.3 units) or a high-GI diet (HiGIX; 80 ± 0.6 units). Body composition (measured by using dual-energy X-ray absorptiometry and computed tomography), insulin sensitivity (measured with a hyperinsulinemic euglycemic clamp with [6,6-(2)H(2)]-glucose), and oral glucose-induced insulin and incretin hormone secretion were examined. RESULTS: Both groups lost equal amounts of body weight (-8.8 ± 0.9%) and adiposity and showed similar improvements in peripheral tissue (+76.2 ± 14.9%) and hepatic insulin sensitivity (+27.1 ± 7.1%) (all P < 0.05). However, oral glucose-induced insulin secretion was reduced only in the LoGIX group (6.59 ± 0.86 nmol in the prestudy compared with 4.70 ± 0.67 nmol in the poststudy, P < 0.05), which was a change related to the suppressed postprandial response of glucose-dependent insulinotropic polypeptide. When corrected for changes in ß cell glucose exposure, changes in insulin secretion were attenuated in the LoGIX group but became significantly elevated in the HiGIX group. CONCLUSIONS: Although lifestyle-induced weight loss improves insulin resistance in prediabetic individuals, postprandial hyperinsulinemia is reduced only when a low-GI diet is consumed. In contrast, a high-GI diet impairs pancreatic ß cell and intestinal K cell function despite significant weight loss. These findings highlight the important role of the gut in mediating the effects of a low-GI diet on type 2 diabetes risk reduction.

Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humans.

BACKGROUND: The optimal combination of diet and exercise that produces the greatest reversal of obesity-related insulin resistance is unknown. OBJECTIVES: We examined the effects of a combined 7-d low-glycemic index (low-GI) diet and exercise training intervention on insulin sensitivity in older obese humans. DESIGN: Participants [n = 32; mean (+/-SEM) age: 66 +/- 1 y; body mass index (in kg/m(2)): 33.8 +/- 0.7] were randomly assigned to a parallel, double-blind, controlled-feeding trial and underwent supervised aerobic exercise (EX; 60 min/d at 80-85% maximum heart rate) in combination with either a low-GI (LoGI + EX: 41.1 +/- 0.4) or a high-GI (HiGI + EX: 80.9 +/- 0.6) diet. All meals were provided and were isocaloric to individual energy requirements. Insulin sensitivity and hepatic glucose production were assessed with a 40-mU x m(-2) x min(-1) hyperinsulinemic euglycemic clamp combined with a [6,6-(2)H(2)]-glucose infusion. RESULTS: After the intervention, small decreases were observed in body weight (-1.6 +/- 0.2 kg; P < 0.0001) and fat mass (-1.7 +/- 0.9%; P = 0.004) in both groups. Maximal aerobic capacity ( O(2)max) also improved slightly (0.06 +/- 0.02 L/min; P = 0.004). Resting systolic blood pressure, fasting glucose, insulin, triglycerides, and cholesterol all decreased after the study (all P < 0.05). Larger changes in systolic blood pressure and O(2max) were seen in the LoGI + EX group. Insulin-stimulated glucose disposal (P < 0.001), insulin suppression of hepatic glucose production (P = 0.004), and postabsorptive fat oxidation (P = 0.03) improved equally in both groups after the intervention. CONCLUSIONS: These findings suggest that the metabolic improvements after short-term exercise training in older obese individuals are dependent on increased physical activity and are not influenced by a low-GI diet. However, a low-GI diet has added benefit in alleviating hypertension, thus reducing the risk of diabetic and vascular complications.

Exercise training and dietary glycemic load may have synergistic effects on insulin resistance in older obese adults.

BACKGROUND/AIMS: The aim of this study was to assess the combined effects of exercise and dietary glycemic load on insulin resistance in older obese adults. METHODS: Eleven men and women (62 +/- 2 years; 97.6 +/- 4.8 kg; body mass index 33.2 +/- 2.0) participated in a 12-week supervised exercise program, 5 days/week, for about 1 h/day, at 80-85% of maximum heart rate. Dietary glycemic load was calculated from dietary intake records. Insulin resistance was determined using the euglycemic (5.0 mM) hyperinsulinemic (40 mU/m(2)/min) clamp. RESULTS: The intervention improved insulin sensitivity (2.37 +/- 0.37 to 3.28 +/- 0.52 mg/kg/min, p < 0.004), increased VO(2max) (p < 0.009), and decreased body weight (p < 0.009). Despite similar caloric intakes (1,816 +/- 128 vs. 1,610 +/- 100 kcal/day), dietary glycemic load trended towards a decrease during the study (140 +/- 10 g before, vs. 115 +/- 8 g during, p < 0.04). The change in insulin sensitivity correlated with the change in glycemic load (r = 0.84, p < 0.009). Four subjects reduced their glycemic load by 61 +/- 8%, and had significantly greater increases in insulin sensitivity (78 +/- 11 vs. 23 +/- 8%, p < 0.003), and decreases in body weight (p < 0.004) and plasma triglycerides (p < 0.04) compared to the rest of the group. CONCLUSION: The data suggest that combining a low-glycemic diet with exercise may provide an alternative and more effective treatment for insulin resistance in older obese adults.

A high glycemic meal suppresses the postprandial leptin response in normal healthy adults.

BACKGROUND/AIMS: To evaluate the metabolic effects of meals with varying glycemic index (GI). METHODS: We measured the glucose, insulin and leptin responses to two contrasting breakfast cereals in a group of 10 young healthy volunteers. Meals were provided on two separate occasions in random order after a 12-hour overnight fast, and consisted of 50 g of available carbohydrate from either Corn Flakes (Kellogg's), or Fiber One (General Mills). Blood samples were obtained at rest, and 30, 60, 90 and 120 min after eating. The GI was calculated from the glucose response to the test meal normalized against a 50 g oral glucose load. RESULTS: The GI for Corn Flakes was 125 +/- 17 units and 49 +/- 8 units for Fiber One(R). These meals were classified as high GI and low GI, respectively, and were significantly different from each other (p < 0.0003). The area under the insulin response curve (AUC) following the low glycemic meal was significantly attenuated compared to the high glycemic meal (14,064 +/- 2,694 vs. 6,828 +/- 1,182 pmol/l.min, p < 0.02). The leptin AUC revealed that circulating leptin was suppressed by the high glycemic meal compared to the low (3.1 +/- 1.5 vs. 9.6 +/- 3.6 ng/ml.min, p < 0.04). CONCLUSIONS: Lower insulin and higher leptin suggests that low glycemic meals promote a postprandial metabolic milieu that is favorable for reduced food consumption; this may be advantageous in the control of obesity and related disorders including insulin resistance and type 2 diabetes.