{"doi":"10.1210/clinem/dgaf324","title":"Beneficial Effects of Carbohydrate Restriction in Type 2 Diabetes Can Be Traced to Changes in Hepatic Metabolism","abstract":"CONTEXT: Carbohydrate restriction benefits metabolic health in patients with type 2 diabetes (T2D), possibly through changes in hepatic metabolism. OBJECTIVE: To test the hypothesis that the ketogenic diet (KD) would decrease de novo lipogenesis (DNL) and liver fat, which would be associated with restored beta-cell function. METHODS: Participants were 57 adults with mild T2D. A hyperglycemic clamp was used to assess acute C-peptide response (ACP), and magnetic resonance imaging to assess hepatic fat fraction, at baseline and after 12 weeks of either a eucaloric KD (∼9% energy from carbohydrate, 65% energy from fat) or a eucaloric low-fat diet (LFD) (∼55% energy from carbohydrate, 20% energy from fat). RESULTS: The KD led to decreases in pyruvate (-23%, P < .001) and palmitoleic acid, a marker of DNL (-32%, P < .01). Participants on the KD had higher fasting glucagon (25%, P < .05) and lower liver fat (28%, P < .05) at week 12 than those on the LFD. In all combined, the change in liver fat was positively associated with the change in pyruvate (r = 0.45, P = .05), and inversely associated with changes in glucagon (r = -0.34, P < .05), the glucagon to C-peptide ratio (r = -0.44, P < .01), and ACP (r = -0.34, P < .05). The change in ACP was inversely associated with the change in pyruvate in the KD group (r = -0.5, P < .05), but not in the LFD group. CONCLUSION: A shift in hepatic metabolism to favor fat oxidation over DNL may underlie the beneficial effects of carbohydrate restriction on hepatic steatosis and glucose-induced insulin secretion.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2025,"id":519651,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.965,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1388058,"name":"MARIAN L. YURCHISHIN","orcid":"0000-0003-1544-6841","position":1,"is_corresponding":false},{"id":684837,"name":"Amy M. Goss","orcid":"0000-0001-8772-2935","position":2,"is_corresponding":false},{"id":297969,"name":"John Knight","orcid":"0000-0002-9683-8064","position":3,"is_corresponding":false},{"id":557032,"name":"W. Timothy Garvey","orcid":"0000-0003-0822-0860","position":4,"is_corresponding":false},{"id":321518,"name":"Barbara A. Gower","orcid":"0000-0001-8461-4613","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:49:18.751199Z","pmid":"40448689","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}