Glycemic Control and Metabolic Adaptation in Response to High-Fat versus High-Carbohydrate Diets—Data from a Randomized Cross-Over Study in Healthy Subjects

Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.

Effects of two consecutive mixed meals high in palmitic acid or stearic acid on 8-h postprandial lipemia and glycemia in healthy-weight and overweight men and postmenopausal women: a randomized controlled trial

Purpose Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia. Methods In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend. Results Postprandial concentrations of triacylglycerol (diet-effect: − 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: − 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC0–8 h) and first meal (iAUC0–4 h) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC4–8 h) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p < 0.001 and p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC0–8 h, dAUC0–4 h, and dAUC4–8 h for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC4–8 h) tended to be lower after stearic-acid intake (p < 0.10). Conclusion Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.

‘Low-Salt’ Bread as an Important Component of a Pragmatic Reduced-Salt Diet for Lowering Blood Pressure in Adults with Elevated Blood Pressure

Reformulation of bread in terms of salt content remains an important measure to help achieve a reduction in salt intake in the population and for the prevention of hypertension and elevated blood pressure (BP). Our fundamental studies on the reduction of salt on dough and bread characteristics showed that wheat breads produced with 0.3 g salt/100 g (“low-salt”) were found to be comparable quality to that produced with the typical level of salt (1.2%). This food-based intervention trial examined, using a 5 week cross-over design, the potential for inclusion of “low-salt” bread as part of a pragmatic reduced-salt diet on BP, markers of bone metabolism, and plasma lipids in 97 adults with slightly to moderately elevated BP. Assuming all sodium from dietary intake was excreted through the urine, the intake of salt decreased by 1.7 g/day, on average, during the reduced-salt dietary period. Systolic BP was significantly lower (by 3.3 mmHg on average; p < 0.0001) during the reduced-salt dietary period compared to the usual-salt dietary period, but there was no significant difference (p = 0.81) in diastolic BP. There were no significant differences (p > 0.12, in all cases) in any of the urinary- or serum-based biochemical indices of calcium or bone metabolism or in plasma lipids between the two periods. In conclusion, a modest reduction in dietary salt intake, in which the use of “low-salt” (i.e., 0.3 g/100g) bread played a key role along with dietary advice, and led to a significant, and clinically meaningful, decrease in systolic, but not diastolic, BP in adults with mildly to moderately elevated BP.

Liraglutide improves hepatic steatosis and metabolic dysfunctions in a 3-week dietary mouse model of non-alcoholic steatohepatitis

ABSTRACTAimNon-alcoholic steatohepatitis (NASH) is an emerging health problem worldwide. However, efficacious pharmacological treatment for NASH is lacking. A major issue for preclinical evaluation of potential therapeutics for NASH is the limited number of appropriate animal models, i.e., models that do not require long-term dietary intervention and adequately mimic disease progression in humans. The present study aimed to evaluate a 3-week dietary mouse model of NASH and to validate it by studying the effects of liraglutide, a compound in advanced clinical development for NASH.MethodsC57BL6/J mice were fed a diet high in fat (60%), cholesterol (1.25%) and cholic acid (0.5%) along with 2% hydroxypropyl-β-cyclodextrin in drinking water (HFCC-CDX diet). Histological and biological parameters were measured at 1 and 3 weeks. Following 1-week diet induction, liraglutide was administrated daily for 2 weeks, and then NASH-associated phenotypic aspects were evaluated in comparison with control mice.ResultsPrior to treatment with liraglutide, mice fed the HFCC-CDX diet for 1 week developed liver steatosis and had increased levels of oxidative-stress markers and hepatic and systemic inflammation. For mice not treated with liraglutide, these aspects were even more pronounced after 3 weeks of the dietary period, with additional liver insulin resistance and fibrosis. Liraglutide treatment corrected the diet-induced alterations in glucose metabolism and significantly reduced hepatic steatosis and inflammation.ConclusionThis study provides a novel 3-week dietary model of mice that rapidly develop NASH features, and this model will be suitable for evaluating the therapeutic efficacy of compounds in preclinical drug development for NASH.

Case Study: Utilizing a Low FODMAP Diet to Combat Exercise-Induced Gastrointestinal Symptoms

Athletes employ various dietary strategies in attempts to attenuate exercise-induced gastrointestinal (GI) symptoms to ensure optimal performance. This case-study outlines one of these GI-targeted approaches via the implementation of a short-term low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols) diet, with the aim to attenuate persistent running specific GI symptoms in a recreationally competitive multisport athlete (male, 86 kg, 57.9 ml·kg·min-1 V02max, 10–15 hr/week training, with no diagnosed GI disorder). Using a single-blinded approach a habitual diet was compared with a 6-day low FODMAP intervention diet (81 ± 5g vs 7.2 ± 5.7g FODMAP s/day) for their effect on GI symptoms and perceptual wellbeing. Training was similar during the habitual and dietary intervention periods. Postexercise (During) GI symptom ratings were recorded immediately following training. Daily GI symptoms and the Daily Analysis of Life Demands for Athletes (DALDA) were recorded at the end of each day. Daily and During GI symptom scores (scale 0–9) ranged from 0–4 during the habitual dietary period while during the low FODMAP dietary period all scores were 0 (no symptoms at all). DALDA scores for worse than normal ranged from 3–10 vs 0–8 in the habitual and low FODMAP dietary periods, respectively, indicating improvement. This intervention was effective for this GI symptom prone athlete; however, randomized-controlled trials are required to assess the suitability of low FODMAP diets for reducing GI distress in other symptomatic athletes.

DASH-Like Diets High in Protein or Monounsaturated Fats Improve Metabolic Syndrome and Calculated Vascular Risk

Weight-loss diets with varying proportions of macronutrients have had varying effects on weight loss, and components of metabolic syndrome and risk factors for vascular diseases. However, little work has examined the effect of weight-neutral dietary changes in macronutrients on these factors. This is an investigation using the OMNI Heart datasets available from the NHLBI BioLINCC program. This study compared a DASH-like diet high in carbohydrates with similar diets high in protein and high in unsaturated fats. Measures of metabolic syndrome, except waist, and measures of risk factors for vascular diseases were taken at the end of each dietary period. All 3 diets significantly lowered the number of metabolic syndrome components (p ≤ 0.002) with a standardized measure of changes in metabolic syndrome components, suggesting that the high-protein, high-fat diet was most efficacious overall (p = 0.035). All 3 diets lowered a calculated 10-year risk of cardiovascular disease, with the high-protein and unsaturated fat diet being the most efficacious (p < 0.001). Only the unsaturated fat diet showed a slightly decreased calculated 9-year risk of diabetes (p = 0.11). Of the 3 weight-neutral diets, those high in protein and unsaturated fats appeared partially or wholly most beneficial.

Carbohydrate-Induced Hypertriglyceridemia: An Insight into the Link between Plasma Insulin and Triglyceride Concentrations*

This study was initiated to test the hypothesis that endogenous hypertriglyceridemia results from a defect in the ability of insulin to inhibit the release of very low-density lipoprotein-triglyceride (TG) from the liver. To accomplish this goal, plasma glucose, insulin, free fatty acid (FFA), and TG concentrations were compared in 12 healthy volunteers, in response to diets containing either 40% or 60% of total calories as carbohydrate (CHO). The protein content of the two diets was similar (15% of calories), and the fat content varied inversely with the amount of CHO (45% or 25%). The diets were consumed in random order, and measurements were made of plasma glucose, insulin, FFA, and TG concentrations at the end of each dietary period, fasting, and at hourly intervals following breakfast and lunch. The results indicated that the 60% CHO diet resulted in higher fasting plasma TG concentrations associated with higher day-long plasma insulin and TG concentrations, and lower FFA concentrations. These results do not support the view that hypertriglyceridemia is secondary to a failure of insulin to inhibit hepatic TG secretion.

Effects of hypocholesterolemic dietary and drug therapy on measures of dysphoric emotions

SummaryThe question of whether hypocholesterolemic treatment is associated with increased mortality due to suicide, violence and car accidents is controversial and of great importance. We investigated the effect of hypocholesterolemic dietary and drug therapy on dysphoric emotions. Twenty-five hypocholesterolemic men were started on a 3-month dietary modification plan; those who showed unsatisfactory cholesterol reduction were given, in addition, a hypocholesterolemic drug for up to 1 year. Lipid profile and change in dysphoric emotions were measured. During the whole period, a negative correlation was found between cholesterol level and depression. During the dietary period, a significant improvement in depression and guilt with no change in lipid profile was noted. Drug therapy significantly reduced cholesterol levels, with a trend toward increased depression (after 3 months) and a significant increase in aggression and guilt (after 1 year). We conclude that changes in dysphoric emotions occurring during hypocholesterolemic therapy cannot be completely explained by the changes in cholesterol levels.

The effect of dietary sodium intake on biochemical markers of bone metabolism in young women

To investigate the effect of a low (80 mmol/d) or high (180 mmol/d) Na intake for 14 d on biochemical markers of bone turnover in Na-sensitive and Na-non-sensitive healthy young women, twenty-nine subjects were screened for responsiveness of urinary Ca excretion to increasing dietary Na intake (40, 80, 120 and 200mmol/d for 7d). In a crossover study, the eight Na-sensitive and eight of the twenty-one Na-non-sensitive subjects were randomly assigned to diets containing either 80 or 180 mmol Na/d for 14 d followed by crossover to the alternative diet for a further 14 d. Dietary Ca was restricted to 12.5mmol/d throughout. During each dietary period, fasting morning first void urine samples (last 3 d) and fasting blood serum samples (morning of twelfth day) were collected. Increasing Na intake from 80 to 180 mmol/d increased urinary Na about twofold in both the Na-sensitive and Na-non-sensitive groups and increased urinary Ca excretion (by 73%) in the Na-sensitive group only. Biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline) and bone formation (serum osteocalcin and bone-specific alkaline phosphatase;EC3.1.3.1) were unaffected by increasing dietary Na in either group. It is concluded that the Na-induced calciuria observed in the Na-sensitive healthy young women did not result in increased bone resorption or turnover and, despite restricted Ca intake, adaptation of dietary Ca absorption may have compensated for the increased urinary Ca loss.