Effect of Dietary Glycemic Index on ß-Cell Function in Prediabetes: A Randomized Controlled Feeding Study.

The glycemic index (GI) reflects the relative ability of carbohydrates to raise blood glucose. We utilized a controlled feeding study to assess the impact of the dietary GI on ß-cell function in adults with prediabetes (17F/18M, mean ± SEM: BMI 32.44 ± 0.94 kg/m2, age 54.2 ± 1.57 years). Following a 2 week Control diet (GI = 55-58), participants were randomized to either a 4 week low GI (LGI: GI < 35, n = 17) or high GI (HGI: GI > 70, n = 18) diet (55% of energy from carbohydrate/30% fat/15% protein). The data from 4 h meal tolerance tests (MTTs) underwent mathematical modeling to assess insulin sensitivity, insulin secretion and ß-cell function. Glucose concentrations during the MTT decreased on the LGI diet (p < 0.001) and trended to increase on the HGI diet (p = 0.14; LGI vs. HGI p < 0.001), with parallel changes in insulin and C-peptide concentrations. Total insulin secretion, adjusted for glucose and insulin sensitivity, increased on the LGI diet (p = 0.002), and trended lower on the HGI diet (p = 0.10; LGI vs. HGI p = 0.001). There was no significant diet effect on insulin sensitivity or other measures of ß-cell function. Total insulin clearance increased on the LGI diet (p = 0.01; LGI vs. HGI p < 0.001). We conclude that short-term consumption of an LGI diet reduced glucose exposure and insulin secretion but had no impact on measures of ß-cell function.

Small changes in glucose variability induced by low and high glycemic index diets are not associated with changes in ß-cell function in adults with pre-diabetes.

Oscillating glucose levels can increase oxidative stress and may contribute to ß-cell dysfunction. We tested the hypothesis that increased glycemic variability contributes to ß-cell dysfunction by experimentally altering glucose variability with controlled diets varying in glycemic index (GI). Fifty-two adults with prediabetes received a 2-week moderate GI (GI = 55-58) control diet followed by randomization to a four-week low GI (LGI: GI < 35) or high GI (HGI HI > 70) diet. Those on the HGI diet were randomized to placebo or the antioxidant N-acetylcysteine (NAC). Participants underwent blinded CGMS, fasting oxidative stress markers and an intravenous glucose tolerance test to estimate ß-cell function (disposition index: DI). On the control diet, DI was inversely correlated with SD glucose (r = -0.314, p = 0.03), but neither DI nor glucose variability were associated with oxidative stress markers. The LGI diet decreased SD glucose (Control 0.96 ±â€¯0.08 vs. LGI 0.79 ±â€¯0.06, p = 0.02) while the HGI diet increased it (Control 0.88 ±â€¯0.06 vs. HGI 1.06 ±â€¯0.07, p = 0.03). Neither DI nor oxidative stress markers changed after the LGI or HGI diets. NAC had no effect on DI, glucose variability or oxidative stress markers. We conclude small changes in glucose variability induced by dietary GI in adults with pre-diabetes are unlikely to contribute to ß-cell dysfunction.

Consuming glucose-sweetened, not fructose-sweetened, beverages increases fasting insulin in healthy humans.

Fructose-, compared to glucose-, sweetened beverages increase liver triglyceride content in the short-term, prior to weight gain. In secondary analyses of a randomized cross-over design study during which 24 healthy adults consumed 25% of their estimated energy requirement in the form of glucose-, fructose-, and high-fructose corn syrup-sweetened beverages in addition to an identical ad libitum diet for three periods of 8 days each, we investigated the hypothesis that fructose in sweetened beverages also triggers insulin resistance in the short term. Total energy intake, body weight, and fasting glucose did not differ among diet phases. However, there was a significant trend for higher fasting insulin (p = 0.042 for trend) and, among normal-weight participants, homeostasis model assessment index of insulin resistance (p = 0.034 for diet × adiposity interaction) according to the glucose content of the beverages. In conclusion, in contrast to our hypothesis, insulin resistance was increased with higher glucose vs. fructose content of the beverages in this short-term trial.

Intraindividual Variation in Markers of Intestinal Permeability and Adipose Tissue Inflammation in Healthy Normal-Weight to Obese Adults.

BACKGROUND: Intestinal permeability and adipose tissue inflammation are considered mechanistic links in the relationship between diet, obesity, and chronic disease. However, methods to measure both are not well standardized, and the reliability of commonly used measures is not known. METHODS: We calculated the intraclass correlation coefficient (ICC) for several common measures of intestinal permeability and adipose tissue inflammation from a randomized clinical trial of cross-over design in which normal-weight (n = 12) or overweight/obese (n = 12) individuals each completed three 8-day dietary intervention periods. RESULTS: For biomarkers of intestinal permeability, plasma zonulin, and lipopolysaccharide-binding protein, ICCs were "excellent" (i.e., >0.9). The direct measure of intestinal permeability, the lactulose/mannitol test, exhibited "fair" reliability (ICC = 0.53). A wider range of ICCs (0.6-0.9), suggesting "good" to "excellent" reliability, were obtained for measures of adipose tissue expression of genes encoding major mediators of inflammation. Similarly, individual immune cell populations isolated from adipose tissue, expressed as a percentage of all CD45+ cells, also had "good" to "excellent" ICCs. However, when these populations were expressed as number of cells per gram of tissue, ICC values were "fair," falling below 0.6. CONCLUSIONS: Due to the repeated measures design, our study offered a unique opportunity to assess reliability of commonly used biomarkers of intestinal permeability and adipose tissue inflammation. Our findings suggest that these measures were generally highly reliable in the short-term. IMPACT: Along with other factors, particularly validity, the demonstrated reliabilities can help inform the choice of endpoints in studies of intestinal permeability and adipose tissue inflammation.

Subjective mood and energy levels of healthy weight and overweight/obese healthy adults on high-and low-glycemic load experimental diets.

Emerging evidence suggests a positive association of diet and obesity with depression. Researchers have examined several diet-mood hypotheses, including investigating the extent to which carbohydrates may impact mood. There is limited research on how glycemic load, a characteristic of carbohydrates, impacts mood in healthy adults. Eighty-two healthy weight and overweight/obese, but otherwise healthy, adults enrolled in a randomized, crossover controlled feeding study testing low-compared to high-glycemic load diets. All participants completed self-report mood and energy level questionnaires during each arm of the intervention. Diets were isocaloric and were matched by macronutrient content as a percent of total energy. Mood was assessed with the Profile of Mood States (POMS) subscales; tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment, total mood disturbance (TMD), and negative affect (NA) in addition to the Center for Epidemiological Studies - Depression (CES-D) scale at baseline and end of both 28-day feeding periods. Linear mixed models tested the intervention effect on mood, controlling for baseline POMS and CES-D scores, diet type, diet sequence, feeding period, sex, and percent body fat classification. The consumption of the high-glycemic load diet resulted in a 38% higher score for depressive symptoms on the CES-D (P = 0.002) compared to the low-glycemic load diet as well as 55% higher score for TMD (P = 0.05), and 26% higher score for fatigue/inertia (P = 0.04). In subgroup analyses, the overweight/obese participants had 40% higher scores on the CES-D scale compared to healthy weight participants (P = 0.05). In conclusion, a high-glycemic load diet was associated with higher depression symptoms, total mood disturbance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but otherwise healthy, adults. This trial was registered at clinicaltrials.gov: NCT00622661.

No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial.

BACKGROUND: Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. OBJECTIVE: We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. DESIGN: We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. RESULTS: Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). CONCLUSION: Excessive amounts of fructose, HFCS, and glucose from SSBs consumed over 8 d did not differentially affect low-grade chronic systemic inflammation in normal-weight to obese adults. This trial was registered at clinicaltrials.gov as NCT01424306.

Metabolic responses to a traditional Mexican diet compared with a commonly consumed US diet in women of Mexican descent: a randomized crossover feeding trial.

BACKGROUND: Mexican immigrants are disproportionally affected by diet-related risk of metabolic dysfunction. Whether adhering to a traditional Mexican diet or adopting a US diet contributes to metabolic changes associated with future risk of type 2 diabetes and other chronic diseases has not been investigated. OBJECTIVE: The purpose of this study was to test in a randomized crossover feeding trial the metabolic responses to a Mexican diet compared with a commonly consumed US diet. DESIGN: First- and second-generation healthy women of Mexican descent (n = 53) were randomly assigned in a crossover design to consume a Mexican or US diet for 24 d each, separated by a 28-d washout period. Diets were eucaloric and similar in macronutrient composition. The metabolic responses to diets were assessed by measuring fasting serum concentrations of glucose, insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), adiponectin, C-reactive protein (CRP), and interleukin 6 (IL-6), as well as the homeostasis model assessment of insulin resistance (HOMA-IR) at the beginning and end of each period. Linear mixed models tested the intervention effect on the biomarkers, while adjusting for diet sequence, feeding period, baseline and washout biomarker concentrations, age, acculturation, and BMI. RESULTS: Compared with the US diet, the Mexican diet reduced insulin by 14% [geometric means (95% CIs): 9.3 (8.3, 10.3) compared with 8.0 (7.2, 8.9) µU/mL; P = 0.02], HOMA-IR by 15% [2.0 (1.8, 2.3) compared with 1.7 (1.6, 2.0); P = 0.02], and IGFBP-3 by 6% (mean ± SEM: 2420 ± 29 compared with 2299 ± 29 ng/mL; P < 0.01) and tended to reduce circulating concentrations of IGF-1 by 4% (149 ± 2.6 compared with 144 ± 2.5 ng/mL; P = 0.06). There was no significant intervention effect on serum concentrations of glucose, adiponectin, CRP, or IL-6 in the US compared with the Mexican diet. CONCLUSION: Compared with the commonly consumed US diet, the traditional Mexican diet modestly improved insulin sensitivity under conditions of weight stability in healthy women of Mexican descent, while having no impact on biomarkers of inflammation. This trial was registered at clinicaltrials.gov as NCT01369173.

No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial.

BACKGROUND: Increased energy intake is consistently observed in individuals consuming sugar-sweetened beverages (SSBs), likely mainly because of an inadequate satiety response to liquid calories. However, SSBs have a high content of fructose, the consumption of which acutely fails to trigger responses in key signals involved in energy homeostasis. It is unclear whether the fructose content of SSBs contributes to the increased energy intake in individuals drinking SSBs. OBJECTIVE: We investigated whether the relative amounts of fructose and glucose in SSBs modifies ad libitum energy intake over 8 d in healthy adults without fructose malabsorption. DESIGN: We conducted 2 randomized, controlled, double-blind crossover studies to compare the effects of consuming 4 servings/d of a fructose-, glucose-, or aspartame-sweetened beverage (study A; n = 9) or a fructose-, glucose-, or high-fructose corn syrup (HFCS)-sweetened beverage (study B; n = 24) for 8 d on overall energy intake. SSBs were provided at 25% of estimated energy requirement, or an equivalent volume of the aspartame-sweetened beverage, and consumption was mandatory. All solid foods were provided at 125% of estimated energy requirements and were consumed ad libitum. RESULTS: In study A, ad libitum energy intake was 120% ± 10%, 117% ± 12%, and 102% ± 15% of estimated energy requirements when subjects consumed the fructose-, glucose-, and aspartame-sweetened beverages. Energy intake was significantly higher in the fructose and glucose phases than in the aspartame phase (P < 0.003 for each), with no difference between the fructose and glucose phases (P = 0.462). In study B, total energy intake during the fructose, HFCS, and glucose phases was 116% ± 14%, 116% ± 16%, and 116% ± 16% of the subject's estimated total energy requirements (P = 0.880). CONCLUSIONS: In healthy adults, total 8-d ad libitum energy intake was increased in individuals consuming SSBs compared with aspartame-sweetened beverages. The energy overconsumption observed in individuals consuming SSBs occurred independently of the relative amounts of fructose and glucose in the beverages. These trials were registered at clinicaltrials.gov as NCT00475475 and NCT01424306.

Development and Use of a Traditional Mexican Diet Score in Relation to Systemic Inflammation and Insulin Resistance among Women of Mexican Descent.

BACKGROUND: Women of Mexican descent are disproportionally affected by obesity, systemic inflammation, and insulin resistance (IR). Available approaches used to give scores to dietary patterns relative to dietary guidelines may not effectively capture traditional diets of Mexicans, who comprise the largest immigrant group in the United States. OBJECTIVES: We characterized an a priori traditional Mexican diet (MexD) score high in corn tortillas, beans, soups, Mexican mixed dishes (e.g., tamales), fruits, vegetables, full-fat milk, and Mexican cheeses and low in refined grains and added sugars and evaluated the association of the MexD score with systemic inflammation and IR in 493 postmenopausal participants in the Women's Health Initiative (WHI) who are of Mexican ethnic descent. METHODS: The MexD score was developed from the baseline (1993-1998) WHI food frequency questionnaire, which included Hispanic foods and was available in Spanish. Body mass index (BMI) was computed from baseline measured weight and height, and ethnicity was self-reported. Outcome variables were high sensitivity C-reactive protein (hsCRP), glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride concentrations measured at follow-up (2012-2013). Multivariable linear and logistic regression models were used to test the associations of the MexD score with systemic inflammation and IR. RESULTS: The mean ± SD MexD score was 5.8 ± 2.1 (12 maximum points) and was positively associated with intakes of carbohydrates, vegetable protein, and dietary fiber and inversely associated with intakes of added sugars and total fat (P < 0.01). Women with high compared with low MexD scores, consistent with a more-traditional Mexican diet, had 23% and 15% lower serum hsCRP (P < 0.05) and insulin concentrations, respectively (P < 0.05). Baseline BMI modified these associations such that lower MexD scores were associated with higher insulin and HOMA-IR in overweight/obese women (P-interaction <0.05). CONCLUSION: These findings suggest that greater adherence to a traditional Mexican diet could help reduce the future risk of systemic inflammation and IR in women of Mexican descent.

Low glycemic load experimental diet more satiating than high glycemic load diet.

Effective strategies for reducing food intake are needed to reduce risk of obesity-related cancers. We investigated the effect of low and high glycemic load (GL) diets on satiety and whether satiety varied by body mass index (BMI), gender, and serum leptin. Eighty normal weight (BMI = 18.5-24.9 kg/m²) and overweight/ obese (BMI = 28.0-40.0 kg/m²) adults participated in a randomized, crossover controlled feeding study testing low GL vs. high GL diets. The 28-day diets were isocaloric with identical macronutrient distributions, differing only in GL and fiber. Participants completed visual analog satiety surveys and fasting serum leptin after each 28-day period. T-tests compared mean within- and between-person satiety scores and leptin values. Participants reported 7% greater satiation on the low GL vs. the high GL diet (P = 0.03) and fewer food cravings on the low GL vs. the high GL diet (P < 0.001). Compared to males, females reported less hunger (P = 0.05) and more satiety on the low GL vs. the high GL diet (P < 0.01). Participants with low body fat (<25.0% for men; <32.0% for women) and BMI <25.0 kg/m² reported study food was tastier on the low GL vs. the high GL diet (P = 0.04 and P = 0.05, respectively). In summary, reducing GL, and/or increasing fiber, may be an effective way to lower calories consumed, improve energy balance, and ultimately reduce cancer risk.