Trial reportThe Journal of clinical investigation2020
Free fatty acid processing diverges in human pathologic insulin resistance conditions.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Natural History of Disorders of Insulin Resistance
Phase II Trial of Effect of Metreleptin Therapy in Severe Insulin Resistance
Short Term Effects of Leptin Withdrawal or Initiation in Lipodystrophy Independent of Energy Intake
Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in Patients With Insulin Receptor Mutations
Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2024Trial
- Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2021Trial
- Article
- Review
- Metabolic liver disease: A summary of major guidelines and identifying opportunities to improve future guidelines.Diabetes, obesity & metabolism · 2026Review
- Serum Proteomics of Insulin Resistance Disorders Distinguish MASLD From Lipodystrophy and Insulin Receptor Defects.The Journal of clinical endocrinology and metabolism · 2026Article
- Combined association of triglyceride-glucose index and the atherogenic index of plasma with the incidence of cardiovascular diseases among middle-aged and older population.Cardiovascular diabetology · 2025Article
- The neglected PCK1/glucagon (inter)action in nutrient homeostasis beyond gluconeogenesis: Disease pathogenesis and treatment.Molecular metabolism · 2025Review
- Fatty Liver Index vs. Biochemical-Anthropometric Indices: Diagnosing Metabolic Dysfunction-Associated Steatotic Liver Disease with Non-Invasive Tools.Diagnostics (Basel, Switzerland) · 2025Article
- Targeting fibroblast growth factor (FGF)-21: a promising strategy for metabolic dysfunction-associated steatotic liver disease treatment.Frontiers in pharmacology · 2025Review
- Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats.Diabetology & metabolic syndrome · 2024Article
- Replacement of Dietary Carbohydrate with Protein versus Fat Differentially Alters Postprandial Circulating Hormones and Macronutrient Metabolism in Dogs.Metabolites · 2024Article
- A mediation analysis of the role of total free fatty acids on pertinence of gut microbiota composition and cognitive function in late life depression.Lipids in health and disease · 2024Article
- Protective Effects of Curcumin and its AnaloguesCurrent medicinal chemistry · 2024Review
- Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.Frontiers in pharmacology · 2024Article
- Leptin Decreases Gluconeogenesis and Gluconeogenic Substrate Availability in Patients With Lipodystrophy.The Journal of clinical endocrinology and metabolism · 2023Article
- The Impact and Burden of Dietary Sugars on the Liver.Hepatology communications · 2023Review
- A Review of micro RNAs changes in T2DM in animals and humans.Journal of diabetes · 2023Review
- Liver insulinization as a driver of triglyceride dysmetabolism.Nature metabolism · 2023Review
- Serum metabolomics profiling by proton nuclear magnetic resonance spectroscopy reveals sexual dimorphism and masculinization of intermediate metabolism in women with polycystic ovary syndrome (PCOS).Biology of sex differences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUNDPostreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g., insulin receptor pathogenic variants, INSR) causes hyperglycemia without steatosis. We examined 4 pathologic conditions of IR in humans to examine pathways controlling lipid metabolism and gluconeogenesis.METHODSCross-sectional study of severe receptor IR (INSR, n = 7) versus postreceptor IR that was severe (lipodystrophy, n = 14), moderate (type 2 diabetes, n = 9), or mild (obesity, n = 8). Lipolysis (glycerol turnover), hepatic glucose production (HGP), gluconeogenesis (deuterium incorporation from body water into glucose), hepatic triglyceride (magnetic resonance spectroscopy), and hepatic fat oxidation (plasma β-hydroxybutyrate) were measured.RESULTSLipolysis was 2- to 3-fold higher in INSR versus all other groups, and HGP was 2-fold higher in INSR and lipodystrophy versus type 2 diabetes and obesity (P < 0.001), suggesting severe adipose and hepatic IR. INSR subjects had a higher contribution of gluconeogenesis to HGP, approximately 77%, versus 52% to 59% in other groups (P = 0.0001). Despite high lipolysis, INSR subjects had low hepatic triglycerides (0.5% [interquartile range 0.1%-0.5%]), in contrast to lipodystrophy (10.6% [interquartile range 2.8%-17.1%], P < 0.0001). β-hydroxybutyrate was 2- to 7-fold higher in INSR versus all other groups (P < 0.0001), consistent with higher hepatic fat oxidation.CONCLUSIONThese data support a key pathogenic role of adipose tissue IR to increase glycerol and FFA availability to the liver in both receptor and postreceptor IR. However, the fate of FFA diverges in these populations. In receptor-level IR, FFA oxidation drives gluconeogenesis rather than being reesterified to triglyceride. In contrast, in postreceptor IR, FFA contributes to both gluconeogenesis and hepatic steatosis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778556, NCT00001987, and NCT02457897.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases, US Department of Agriculture/Agricultural Research Service 58-3092-5-001.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.