Petersen 2018: Mechanisms of Insulin Action and Insulin Resistance
Petersen & Shulman • Physiological Reviews • 2018
Ectopic lipid in liver and muscle is the primary driver of insulin resistance
The research behind Metabolicum's evidence-based approach
Not all research is equal. We assign confidence grades to each source based on study design, sample size, replication status, and methodology. This helps you understand how confident you can be in each finding.
High Confidence
Replicated findings across multiple well-designed studies
Good Confidence
Well-designed single studies with strong methodology
Moderate Confidence
Observational data with consistent patterns
Emerging Evidence
Mechanistic or theoretical - interpret cautiously
Clinical Consensus
Practitioner experience without formal trials
Why are we so careful about evidence grading? Because a significant portion of published research fails to replicate.
| Study | Finding | Grade |
|---|---|---|
| Begley & Ellis, 2012 | Only 21% of landmark cancer studies could be replicated | A |
| Open Science Collaboration, 2015 | Only 36% of psychology studies replicated | A |
| Ioannidis, 2005 | Theoretical framework explaining why most findings are false | A |
This doesn't mean you should distrust all research. It means:
We grade evidence honestly so you can calibrate your confidence appropriately.
In-depth analysis of foundational studies with translated summaries
Showing 4 studies
Petersen & Shulman • Physiological Reviews • 2018
Ectopic lipid in liver and muscle is the primary driver of insulin resistance
Freeman et al. • StatPearls Publishing • 2023
HOMA-IR is the most practical clinical tool for assessing insulin resistance
Hallberg et al. • Diabetes Therapy • 2018
60% achieved diabetes reversal while 94% reduced or eliminated insulin
Sutton et al. • Cell Metabolism • 2018
Early 6-hour eating window improved insulin sensitivity by 36% without weight loss
Primary thresholds come from Grade A sources. When Grade A evidence suggests a range rather than a single value, we present the range with context.
We draw on Grades A-C for educational claims, clearly labeling evidence quality. Grade D and E content is marked as theoretical or practitioner-derived.
This bibliography contains the research supporting Metabolicum's evidence-based approach.
Last comprehensive review: December 2025