2023
Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity
Galderisi A, Tricò D, Lat J, Samuels S, Weiss R, Van Name M, Pierpont B, Santoro N, Caprio S. Incretin effect determines glucose trajectory and insulin sensitivity in youths with obesity. JCI Insight 2023, 8: e165709. PMID: 37847560, PMCID: PMC10721315, DOI: 10.1172/jci.insight.165709.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBlood GlucoseDiabetes Mellitus, Type 2GlucoseHumansIncretinsInsulinInsulin ResistanceObesityConceptsOral glucose tolerance testΒ-cell functionIncretin effectBeta-cell functionInsulin sensitivityInsulin secretionGlucose levelsCell functionIsoglycemic intravenous glucose infusionGreater insulin sensitivityIntravenous glucose infusionPubertal transitionGlucose tolerance testGLP-17Glucagon suppressionGlucose infusionObesityLongitudinal increaseBaselineOGTTEffect groupGreater increaseLongitudinal trajectoriesSecretionGroupHigh-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities
Bloyd M, Sinaii N, Faucz F, Iben J, Coon S, Caprio S, Santoro N, Stratakis C, London E. High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities. Frontiers In Endocrinology 2023, 14: 1272939. PMID: 38027204, PMCID: PMC10679389, DOI: 10.3389/fendo.2023.1272939.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultChildDiabetes Mellitus, Type 2Genome-Wide Association StudyHumansMutationPediatric ObesityConceptsGenome-wide association studiesSignaling-related genesProtein kinaseHigh-frequency variantsCAMP-dependent protein kinaseLarge-scale genome-wide association studiesNew genetic associationsPDE11A geneGenomic DNAAssociation studiesMonogenic obesityTargeted exome sequencingGenesGenetic variantsEnergy metabolismGenetic associationExome sequencingNovel variantsVariant searchMetabolic characteristicsVariantsKinaseType II diabetesLociSequencing
2019
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls
Flannick J, Mercader JM, Fuchsberger C, Udler MS, Mahajan A, Wessel J, Teslovich TM, Caulkins L, Koesterer R, Barajas-Olmos F, Blackwell TW, Boerwinkle E, Brody JA, Centeno-Cruz F, Chen L, Chen S, Contreras-Cubas C, Córdova E, Correa A, Cortes M, DeFronzo RA, Dolan L, Drews KL, Elliott A, Floyd JS, Gabriel S, Garay-Sevilla ME, García-Ortiz H, Gross M, Han S, Heard-Costa NL, Jackson AU, Jørgensen ME, Kang HM, Kelsey M, Kim BJ, Koistinen HA, Kuusisto J, Leader JB, Linneberg A, Liu CT, Liu J, Lyssenko V, Manning AK, Marcketta A, Malacara-Hernandez JM, Martínez-Hernández A, Matsuo K, Mayer-Davis E, Mendoza-Caamal E, Mohlke KL, Morrison AC, Ndungu A, Ng MCY, O’Dushlaine C, Payne AJ, Pihoker C, Post W, Preuss M, Psaty B, Vasan R, Rayner N, Reiner A, Revilla-Monsalve C, Robertson N, Santoro N, Schurmann C, So W, Soberón X, Stringham H, Strom T, Tam C, Thameem F, Tomlinson B, Torres J, Tracy R, van Dam R, Vujkovic M, Wang S, Welch R, Witte D, Wong T, Atzmon G, Barzilai N, Blangero J, Bonnycastle L, Bowden D, Chambers J, Chan E, Cheng C, Cho Y, Collins F, de Vries P, Duggirala R, Glaser B, Gonzalez C, Gonzalez M, Groop L, Kooner J, Kwak S, Laakso M, Lehman D, Nilsson P, Spector T, Tai E, Tuomi T, Tuomilehto J, Wilson J, Aguilar-Salinas C, Bottinger E, Burke B, Carey D, Chan J, Dupuis J, Frossard P, Heckbert S, Hwang M, Kim Y, Kirchner H, Lee J, Lee J, Loos R, Ma R, Morris A, O’Donnell C, Palmer C, Pankow J, Park K, Rasheed A, Saleheen D, Sim X, Small K, Teo Y, Haiman C, Hanis C, Henderson B, Orozco L, Tusié-Luna T, Dewey F, Baras A, Gieger C, Meitinger T, Strauch K, Lange L, Grarup N, Hansen T, Pedersen O, Zeitler P, Dabelea D, Abecasis G, Bell G, Cox N, Seielstad M, Sladek R, Meigs J, Rich S, Rotter J, Altshuler D, Burtt N, Scott L, Morris A, Florez J, McCarthy M, Boehnke M. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls. Nature 2019, 570: 71-76. PMID: 31118516, PMCID: PMC6699738, DOI: 10.1038/s41586-019-1231-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCase-Control StudiesDecision Support TechniquesDiabetes Mellitus, Type 2ExomeExome SequencingFemaleGene FrequencyGenome-Wide Association StudyHumansMaleMiceMice, KnockoutConceptsExome-wide significanceProtein-coding genetic variantsDrug targetsRare variantsGene-level associationsType 2 diabetesRare variant associationsGene setsCandidate genesExome sequencing analysisGenetic variantsNon-diabetic control participantsExome sequencingGenesKnockout micePrioritization effortsDisease riskVariantsFuture targetsControl participantsTargetDiabetesEffect sizeSequencingHeritability