Kristin M. Nieman

Insulin administration abrogates perturbation of methyl group and homocysteine metabolism in streptozotocin-treated type 1 diabetic rats

Modifications in methyl group and homocysteine metabolism are associated with a number of pathologies, including vascular disease, cancer, and neural tube defects. A diabetic state is known to alter both methyl group and homocysteine metabolism, and glycine N-methyltransferase (GNMT) is a major regulatory protein that controls the supply and utilization of methyl groups. We have shown previously that diabetes induces GNMT expression and reduces plasma homocysteine pools by stimulating both its catabolism and folate-independent remethylation. This study was conducted to determine whether insulin plays a role in the control of homocysteine concentrations and GNMT as well as other key regulatory proteins. Male Sprague-Dawley rats were randomly assigned to one of three groups: control, streptozotocin (STZ)-induced diabetic (60 mg/kg body wt), and insulin-treated diabetic (1.0 U bid). After 5 days, rats were anesthetized (ketamine-xylazine) for procurement of blood and tissues. A 1.5-fold elevation in hepatic GNMT activity and hypohomocysteinemia in diabetic rats was completely prevented by insulin treatment. Additionally, diabetes-mediated alterations in methionine synthase, phosphatidylethanolamine N-methyltransferase, and DNA methylation were also prevented by insulin. We hypothesize that the concentration of blood glucose may represent a regulatory signal to modify GNMT and homocysteine. In support of this, blood glucose concentrations were negatively correlated with total plasma homocysteine (r = -0.75, P < 0.001) and positively correlated with GNMT activity (r = 0.77, P < 0.001). Future research will focus on further elucidating the role of glucose or insulin as a signal for regulating homocysteine and methyl group metabolism.

Sugar-Sweetened Product Consumption Alters Glucose Homeostasis Compared with Dairy Product Consumption in Men and Women at Risk of Type 2 Diabetes Mellitus

BACKGROUND Dietary patterns characterized by high intakes of fruits and vegetables, whole grains, low-fat dairy products, and low glycemic load have been associated with lower type 2 diabetes mellitus (T2DM) risk. In contrast, dietary patterns that include high intakes of refined grains, processed meats, and high amounts of added sugars have been associated with increased T2DM risk. OBJECTIVE This randomized, 2-period crossover trial compared the effects of dairy and sugar-sweetened product (SSP) consumption on insulin sensitivity and pancreatic β-cell function in men and women at risk of the development of T2DM who habitually consume sugar-sweetened beverages. METHODS In a randomized, controlled crossover trial, participants consumed dairy products (474 mL/d 2% milk and 170 g/d low-fat yogurt) and SSPs (710 mL/d nondiet soda and 108 g/d nondairy pudding), each for 6 wk, with a 2-wk washout between treatments. A liquid meal tolerance test (LMTT) was administered at baseline and the end of each period. RESULTS Participants were 50% female with a mean age and body mass index of 53.8 y and 32.2 kg/m(2), respectively. Changes from baseline were significantly different between dairy product and SSP conditions for median homeostasis model assessment 2-insulin sensitivity (HOMA2-%S) (1.3 vs. -21.3%, respectively, P = 0.009; baseline = 118%), mean LMTT disposition index (-0.03 vs. -0.36, respectively, P = 0.011; baseline = 2.59), mean HDL cholesterol (0.8 vs. -4.2%, respectively, P = 0.015; baseline = 44.3 mg/dL), and mean serum 25-hydroxyvitamin D [25(OH)D] (11.7 vs. -3.3, respectively, P = 0.022; baseline = 24.5 μg/L). Changes from baseline in LMTT Matsuda insulin sensitivity index (-0.10 vs. -0.49, respectively; baseline = 4.16) and mean HOMA2-β-cell function (-2.0 vs. 5.3%, respectively; baseline = 72.6%) did not differ significantly between treatments. CONCLUSION These results suggest that SSP consumption is associated with less favorable values for HOMA2-%S, LMTT disposition index, HDL cholesterol, and serum 25(OH)D in men and women at risk of T2DM vs. baseline values and values during dairy product consumption. This trial was registered at clinicaltrials.gov as NCT01936935.

Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides

Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles.Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m2), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (-34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (-13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.

Safety and tolerability of a dried aqueous spearmint extract

&NA; Spearmint (Mentha spicata L.) and spearmint extracts are Generally Recognized as Safe (GRAS) for use as flavoring in beverages, pharmaceuticals, and confectionaries. Studies of spearmint extracts in humans and animals have reported conflicting results with respect to toxicity. Since the chemical composition of these extracts was not reported and the spearmint source material was different, the relevance of these existing data to evaluating the risks associated with ingestion of a dried aqueous spearmint extract standardized to rosmarinic acid is not clear. Hence, the safety and tolerability of the dried aqueous spearmint extract was evaluated as part of a double‐blind, randomized, placebo‐controlled trial in healthy adults with age‐associated memory impairment. Ingestion of both 600 and 900 mg/day for 90 days had no effect on plasma levels of follicular stimulating hormone, luteinizing hormone, or thyroid stimulating hormone, or other safety parameters including vital signs, plasma chemistry or whole blood hematology values. Additionally, there were no reported severe adverse events, no significant between‐group differences in the number of subjects reporting adverse effects and the adverse events reported could not be attributed to ingestion of the extract. These results therefore show that ingestion of the aqueous dried spearmint extract is safe and well‐tolerated. Graphical abstract Figure. No caption available. HighlightsIn a 90‐day randomized clinical trial, safety of a spearmint extract was assessed.Placebo, 600 and 900 mg spearmint extract containing rosmarinic acid were tested.The extract had no effect on FSH, LH, TSH, vital signs and blood chemistries.There were no treatment‐related or between‐group differences for adverse events.The extract is safe and well‐tolerated under the conditions of use described.

The Effect of Cranberry Juice Consumption on the Recurrence of Urinary Tract Infection: Relationship to Baseline Risk Factors

ABSTRACT Objective: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. Methods: Participants consumed a cranberry (n = 185) or placebo (n = 188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. Results: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having ≥ 1 UTI: intercourse frequency ≥ 1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p = 0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p = 0.016), most recent UTI < 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p = 0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p = 0.024). Three propensity categories were investigated (24-week probability < 10%, 10%–21%, and > 21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p = 0.663) for those with < 10% probability, 0.73 (95% CI: 0.35, 1.53; p = 0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p = 0.039) for those with > 21% probability. Conclusions: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.

Wheat Fiber in Postprandial Metabolic Profile and Health

Abstract Observational evidence suggests that increased intake of dietary fiber is associated with a reduction in chronic disease risk, particularly cardiovascular disease and type 2 diabetes mellitus. One potential mechanism whereby fiber may reduce risk for these diseases is by creating a viscous solution when mixed with gastrointestinal contents. When such viscous fibers are consumed as part of a carbohydrate-containing meal, glucose absorption is delayed, resulting in lower peak postprandial glucose concentrations, and often attenuated insulin concentrations. However, prospective cohort studies have shown that cereal fiber, and not soluble fiber from fruit and vegetables, is more strongly correlated with disease risk. Wheat is the most frequently consumed cereal grain in the US. Acute intervention studies have shown that whole wheat kernels and wheat fiber reduce postprandial glucose and insulin responses, but findings from chronic studies are inconsistent. Although mechanisms remain incompletely understood, wheat-induced changes in short-chain fatty acids, incretin hormones, and transit time may contribute to metabolic improvements that lower chronic disease risk.