The effects of trans-resveratrol on insulin resistance, inflammation, and microbiota in men with the metabolic syndrome: A pilot randomized, placebo-controlled clinical trial
Bibliographic record
Abstract
Background and Aim: The metabolic syndrome (MetS) is a pathological condition comprised of abdominal obesity, insulin resistance, hypertension and hyperlipidemia. It has become a major threat globally, resulting in rapidly increasing rates of diabetes, coronary heart disease and stroke. The polyphenol resveratrol (RES) is believed to improve glucose homeostasis and insulin resistance by activating sirtuin, which acetylates and co-activates downstream targets and affects glucose and lipid homeostasis in the liver, insulin secretion in the pancreas, and glucose uptake in skeletal muscle. We studied the effects of RES on insulin resistance, glucose homeostasis and concomitant effects on adipose tissue metabolism and fecal microbiota in insulin resistant subjects with the metabolic syndrome. Methods: Twenty-eight obese men with the metabolic syndrome were studied during a 35-day stay in the Rockefeller University Hospital metabolic unit. Subjects were randomized to receive resveratrol 1 gram orally twice daily or placebo, while kept weight stable and consuming a Western style diet. At baseline, and after 30 days of resveratrol or placebo administration, subjects underwent testing that included a euglycemic, hyperinsulinemic clamp, 2- hour oral glucose tolerance test, resting energy expenditure (REE), daily blood pressure monitoring, abdominal adipose tissue biopsy, and fecal and blood collections. Results: RES induced no changes in insulin resistance, but reduced the 120-minute time point and the area under the curve for glucose concentration in the two-hour glucose tolerance test (GTT). In post hoc analysis, Caucasian subjects showed a significant improvement in insulin sensitivity and glucose homeostasis after GTT, whereas non-Caucasians showed no similar effects. Levels of fasting plasma RES and its primary metabolite dihydroresveratrol (DHR) were variable, and did not explain the racial differences in glucose homeostasis. RES administration to Caucasian subjects lead to an increase in several taxa including Akkermansia mucinophila. Conclusions: Resveratrol 2 grams administered orally to obese men with metabolic syndrome and insulin resistance marginally altered glucose homeostasis. However, in a small group of Caucasians, insulin resistance and glucose homeostasis improved. No concomitant changes in adipose tissue metabolism occurred, but fecal microbiota showed RES-induced changes. Relevance for patients: The metabolic syndrome increases the risk of diabetes, heart disease and stroke. A major component of the syndrome is insulin resistance, resulting in systemic inflammation and hyperinsulinemia. The primary treatment consists of lifestyle changes, improved diet and increased physical activity. This is often unsuccessful. In this study, RES was well tolerated. In Caucasian men it significantly improved insulin sensitivity and glucose homeostasis. Similar results were found in studies that consisted exclusively of Caucasian men. However, RES presents a novel addition to the current treatment of the MetS and its sequelae.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.002 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".