William Knowler, M.D., Dr.P.H., Scientist Emeritus

Scientist Emeritus: Phoenix Epidemiology & Clinical Research Branch

Scientific Focus Areas: Clinical Research, Epidemiology, Genetics and Genomics, Social and Behavioral Sciences

knowler@nih.gov 602-317-1751 Add to Contacts

Publications

A selection of recent and significant publications can be viewed below.

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Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM, Diabetes Prevention Program Research Group.

N Engl J Med (2002 Feb 7) 346:393-403. Abstract/Full Text

Childhood obesity, other cardiovascular risk factors, and premature death.

Franks PW, Hanson RL, Knowler WC, Sievers ML, Bennett PH, Looker HC.

N Engl J Med (2010 Feb 11) 362:485-93. Abstract/Full Text

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

Vijayakumar P, Nelson RG, Hanson RL, Knowler WC, Sinha M.

Diabetes Care (2017 Jan) 40:16-21. Abstract/Full Text

Vitamin D Supplementation and Prevention of Type 2 Diabetes.

Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O'Neil P, Park J, Peters A, Phillips LS, Pratley R, Raskin P, Rasouli N, Robbins D, Rosen C, Vickery EM, Staten M, D2d Research Group.

N Engl J Med (2019 Aug 8) 381:520-530. Abstract/Full Text

10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.

Diabetes Prevention Program Research Group, Knowler WC, Fowler SE, Hamman RF, Christophi CA, Hoffman HJ, Brenneman AT, Brown-Friday JO, Goldberg R, Venditti E, Nathan DM.

Lancet (2009 Nov 14) 374:1677-86. Abstract/Full Text

Additional Publications

Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged and Older Adults With Type 2 Diabetes: The Look AHEAD Study.

Houston DK, Neiberg RH, Miller ME, Hill JO, Jakicic JM, Johnson KC, Gregg EW, Hubbard VS, Pi-Sunyer X, Rejeski WJ, Wing RR, Bantle JP, Beale E, Berkowitz RI, Cassidy-Begay M, Clark JM, Coday M, Delahanty LM, Dutton G, Egan C, Foreyt JP, Greenway FL, Hazuda HP, Hergenroeder A, Horton ES, Jeffery RW, Kahn SE, Kure A, Knowler WC, Lewis CE, Martin CK, Michaels S, Montez MG, Nathan DM, Patricio J, Peters A, Pownall H, Regensteiner J, Steinburg H, Wadden TA, White K, Yanovski SZ, Zhang P, Kritchevsky SB.

J Gerontol A Biol Sci Med Sci (2018 Oct 8) 73:1552-1559. Abstract/Full Text

Analysis of type 2 diabetes and obesity genetic variants in Mexican Pima Indians: Marked allelic differentiation among Amerindians at HLA.

Hsueh WC, Bennett PH, Esparza-Romero J, Urquidez-Romero R, Valencia ME, Ravussin E, Williams RC, Knowler WC, Baier LJ, Schulz LO, Hanson RL.

Ann Hum Genet (2018 Sep) 82:287-299. Abstract/Full Text

White blood cell fractions correlate with lesions of diabetic kidney disease and predict loss of kidney function in Type 2 diabetes.

Wheelock KM, Saulnier PJ, Tanamas SK, Vijayakumar P, Weil EJ, Looker HC, Hanson RL, Lemley KV, Yee B, Knowler WC, Hadjadj S, Najafian B, Mauer M, Nelson RG.

Nephrol Dial Transplant (2018 Jun 1) 33:1001-1009. Abstract/Full Text

Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population.

Tanamas SK, Reddy SP, Chambers MA, Clark EJ, Dunnigan DL, Hanson RL, Nelson RG, Knowler WC, Sinha M.

Pediatr Diabetes (2018 Jun) 19:622-629. Abstract/Full Text

One-Hour Plasma Glucose Compared With Two-Hour Plasma Glucose in Relation to Diabetic Retinopathy in American Indians.

Paddock E, Looker HC, Piaggi P, Knowler WC, Krakoff J, Chang DC.

Diabetes Care (2018 Jun) 41:1212-1217. Abstract/Full Text

Cytosine methylation predicts renal function decline in American Indians.

Qiu C, Hanson RL, Fufaa G, Kobes S, Gluck C, Huang J, Chen Y, Raj D, Nelson RG, Knowler WC, Susztak K.

Kidney Int (2018 Jun) 93:1417-1431. Abstract/Full Text

Identification and functional analysis of a novel G310D variant in the insulin-like growth factor 1 receptor (IGF1R) gene associated with type 2 diabetes in American Indians.

Muller YL, Skelton G, Piaggi P, Chen P, Nair A, Kobes S, Hsueh WC, Knowler WC, Hanson RL, Baier LJ, Bogardus C.

Diabetes Metab Res Rev (2018 May) 34:e2994. Abstract/Full Text

Long-Term Effects of an Intensive Lifestyle Intervention on Electrocardiographic Criteria for Left Ventricular Hypertrophy: The Look AHEAD Trial.

Brinkley TE, Anderson A, Soliman EZ, Bertoni AG, Greenway F, Knowler WC, Glasser SP, Horton ES, Espeland MA, Look AHEAD Research Group.

Am J Hypertens (2018 Apr 13) 31:541-548. Abstract/Full Text

Erratum. Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation. Diabetes Care 2017;40:1668-1677.

Herman WH, Pan Q, Edelstein SL, Mather KJ, Perreault L, Barrett-Connor E, Dabelea DM, Horton E, Kahn SE, Knowler WC, Lorenzo C, Pi-Sunyer X, Venditti E, Ye W, Diabetes Prevention Program Research Group.

Diabetes Care (2018 Apr) 41:913. Abstract/Full Text

Erratum. Effect of Losartan on Prevention and Progression of Early Diabetic Nephropathy in American Indians With Type 2 Diabetes. Diabetes 2013;62:3224-3231.

Weil EJ, Fufaa G, Jones LI, Lovato T, Lemley KV, Hanson RL, Knowler WC, Bennett PH, Yee B, Myers BD, Nelson RG.

Diabetes (2018 Mar) 67:532. Abstract/Full Text

Secular changes in physical growth and obesity among southwestern American Indian children over four decades.

Vijayakumar P, Wheelock KM, Kobes S, Nelson RG, Hanson RL, Knowler WC, Sinha M.

Pediatr Obes (2018 Feb) 13:94-102. Abstract/Full Text

Depressive Symptoms, Antidepressant Medication Use, and Inflammatory Markers in the Diabetes Prevention Program.

de Groot M, Marrero D, Mele L, Doyle T, Schwartz F, Mather KJ, Goldberg R, Price DW, Ma Y, Knowler WC, Diabetes Prevention Program Research Group.

Psychosom Med (2018 Feb/Mar) 80:167-173. Abstract/Full Text

Serum lipids and mortality in an American Indian population: A longitudinal study.

Tanamas SK, Saulnier PJ, Hanson RL, Nelson RG, Hsueh WC, Sievers ML, Bennett PH, Knowler WC.

J Diabetes Complications (2018 Jan) 32:18-26. Abstract/Full Text

Exploring residual risk for diabetes and microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS).

Perreault L, Pan Q, Aroda VR, Barrett-Connor E, Dabelea D, Dagogo-Jack S, Hamman RF, Kahn SE, Mather KJ, Knowler WC, Diabetes Prevention Program Research Group.

Diabet Med (2017 Dec) 34:1747-1755. Abstract/Full Text

Impact of Lifestyle and Metformin Interventions on the Risk of Progression to Diabetes and Regression to Normal Glucose Regulation in Overweight or Obese People With Impaired Glucose Regulation.

Herman WH, Pan Q, Edelstein SL, Mather KJ, Perreault L, Barrett-Connor E, Dabelea DM, Horton E, Kahn SE, Knowler WC, Lorenzo C, Pi-Sunyer X, Venditti E, Ye W, Diabetes Prevention Program Research Group.

Diabetes Care (2017 Dec) 40:1668-1677. Abstract/Full Text

Growth Tracking in Severely Obese or Underweight Children.

Chambers M, Tanamas SK, Clark EJ, Dunnigan DL, Kapadia CR, Hanson RL, Nelson RG, Knowler WC, Sinha M.

Pediatrics (2017 Dec) 140. Abstract/Full Text

Identity-by-Descent Mapping Identifies Major Locus for Serum Triglycerides in Amerindians Largely Explained by an APOC3 Founder Mutation.

Hsueh WC, Nair AK, Kobes S, Chen P, Göring HHH, Pollin TI, Malhotra A, Knowler WC, Baier LJ, Hanson RL.

Circ Cardiovasc Genet (2017 Dec) 10. Abstract/Full Text

The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial.

Johnson KC, Bray GA, Cheskin LJ, Clark JM, Egan CM, Foreyt JP, Garcia KR, Glasser S, Greenway FL, Gregg EW, Hazuda HP, Hergenroeder A, Hill JO, Horton ES, Jakicic JM, Jeffery RW, Kahn SE, Knowler WC, Lewis CE, Miller M, Montez MG, Nathan DM, Patricio JL, Peters AL, Pi-Sunyer X, Pownall HJ, Reboussin D, Redmon JB, Steinberg H, Wadden TA, Wagenknecht LE, Wing RR, Womack CR, Yanovski SZ, Zhang P, Schwartz AV, Look AHEAD Study Group.

J Bone Miner Res (2017 Nov) 32:2278-2287. Abstract/Full Text

Autoantibodies against PFDN2 are associated with an increased risk of type 2 diabetes: A case-control study.

Chang DC, Piaggi P, Hanson RL, Knowler WC, Bogardus C, Krakoff J.

Diabetes Metab Res Rev (2017 Nov) 33. Abstract/Full Text

A Loss-of-Function Splice Acceptor Variant in IGF2 Is Protective for Type 2 Diabetes.

Mercader JM, Liao RG, Bell AD, Dymek Z, Estrada K, Tukiainen T, Huerta-Chagoya A, Moreno-Macías H, Jablonski KA, Hanson RL, Walford GA, Moran I, Chen L, Agarwala V, Ordoñez-Sánchez ML, Rodríguez-Guillen R, Rodríguez-Torres M, Segura-Kato Y, García-Ortiz H, Centeno-Cruz F, Barajas-Olmos F, Caulkins L, Puppala S, Fontanillas P, Williams AL, Bonàs-Guarch S, Hartl C, Ripke S, Diabetes Prevention Program Research Group, Tooley K, Lane J, Zerrweck C, Martínez-Hernández A, Córdova EJ, Mendoza-Caamal E, Contreras-Cubas C, González-Villalpando ME, Cruz-Bautista I, Muñoz-Hernández L, Gómez-Velasco D, Alvirde U, Henderson BE, Wilkens LR, Le Marchand L, Arellano-Campos O, Riba L, Harden M, Broad Genomics Platform, Gabriel S, T2D-GENES Consortium, Abboud HE, Cortes ML, Revilla-Monsalve C, Islas-Andrade S, Soberon X, Curran JE, Jenkinson CP, DeFronzo RA, Lehman DM, Hanis CL, Bell GI, Boehnke M, Blangero J, Duggirala R, Saxena R, MacArthur D, Ferrer J, McCarroll SA, Torrents D, Knowler WC, Baier LJ, Burtt N, González-Villalpando C, Haiman CA, Aguilar-Salinas CA, Tusié-Luna T, Flannick J, Jacobs SBR, Orozco L, Altshuler D, Florez JC, SIGMA T2D Genetics Consortium.

Diabetes (2017 Nov) 66:2903-2914. Abstract/Full Text

A High-Carbohydrate, High-Fiber, Low-Fat Diet Results in Weight Loss among Adults at High Risk of Type 2 Diabetes.

Sylvetsky AC, Edelstein SL, Walford G, Boyko EJ, Horton ES, Ibebuogu UN, Knowler WC, Montez MG, Temprosa M, Hoskin M, Rother KI, Delahanty LM, Diabetes Prevention Program Research Group.

J Nutr (2017 Nov) 147:2060-2066. Abstract/Full Text

H. pylori seroprevalence and risk of diabetes: An ancillary case-control study nested in the diabetes prevention program.

Alzahrani S, Nelson J, Moss SF, Paulus JK, Knowler WC, Pittas AG, Diabetes Prevention Program Research Group.

J Diabetes Complications (2017 Oct) 31:1515-1520. Abstract/Full Text

One-hour and two-hour postload plasma glucose concentrations are comparable predictors of type 2 diabetes mellitus in Southwestern Native Americans.

Paddock E, Hohenadel MG, Piaggi P, Vijayakumar P, Hanson RL, Knowler WC, Krakoff J, Chang DC.

Diabetologia (2017 Sep) 60:1704-1711. Abstract/Full Text

Cardiometabolic risk profile based on body mass index in American Indian children and adolescents.

Wheelock KM, Fufaa GD, Nelson RG, Hanson RL, Knowler WC, Sinha M.

Pediatr Obes (2017 Aug) 12:295-303. Abstract/Full Text

Variation in Maturity-Onset Diabetes of the Young Genes Influence Response to Interventions for Diabetes Prevention.

Billings LK, Jablonski KA, Warner AS, Cheng YC, McAteer JB, Tipton L, Shuldiner AR, Ehrmann DA, Manning AK, Dabelea D, Franks PW, Kahn SE, Pollin TI, Knowler WC, Altshuler D, Florez JC, Diabetes Prevention Program Research Group.

J Clin Endocrinol Metab (2017 Aug 1) 102:2678-2689. Abstract/Full Text

A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in GPR158 Associated With Reduced Energy Expenditure in American Indians.

Piaggi P, Masindova I, Muller YL, Mercader J, Wiessner GB, Chen P, SIGMA Type 2 Diabetes Consortium, Kobes S, Hsueh WC, Mongalo M, Knowler WC, Krakoff J, Hanson RL, Bogardus C, Baier LJ.

Diabetes (2017 Aug) 66:2284-2295. Abstract/Full Text

Associations between persistent organic pollutants, type 2 diabetes, diabetic nephropathy and mortality.

Grice BA, Nelson RG, Williams DE, Knowler WC, Mason C, Hanson RL, Bullard KM, Pavkov ME.

Occup Environ Med (2017 Jul) 74:521-527. Abstract/Full Text

Effects of a long-term lifestyle modification programme on peripheral neuropathy in overweight or obese adults with type 2 diabetes: the Look AHEAD study.

Look AHEAD Research Group.

Diabetologia (2017 Jun) 60:980-988. Abstract/Full Text

Effect of a long-term intensive lifestyle intervention on prevalence of cognitive impairment.

Espeland MA, Luchsinger JA, Baker LD, Neiberg R, Kahn SE, Arnold SE, Wing RR, Blackburn GL, Bray G, Evans M, Hazuda HP, Jeffery RW, Wilson VM, Clark JM, Coday M, Demos-McDermott K, Foreyt JP, Greenway F, Hill JO, Horton ES, Jakicic JM, Johnson KC, Knowler WC, Lewis CE, Nathan DM, Peters A, Pi-Sunyer X, Pownall H, Wadden TA, Rapp SR, Look AHEAD Study Group.

Neurology (2017 May 23) 88:2026-2035. Abstract/Full Text

Assessing variation across 8 established East Asian loci for type 2 diabetes mellitus in American Indians: Suggestive evidence for new sex-specific diabetes signals in GLIS3 and ZFAND3.

Muller YL, Piaggi P, Chen P, Wiessner G, Okani C, Kobes S, Knowler WC, Bogardus C, Hanson RL, Baier LJ.

Diabetes Metab Res Rev (2017 May) 33. Abstract/Full Text

Effect of a Long-Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study.

Rapp SR, Luchsinger JA, Baker LD, Blackburn GL, Hazuda HP, Demos-McDermott KE, Jeffery RW, Keller JN, McCaffery JM, Pajewski NM, Evans M, Wadden TA, Arnold SE, Espeland MA, Look AHEAD Research Group.

J Am Geriatr Soc (2017 May) 65:966-972. Abstract/Full Text

Differential methylation of genes in individuals exposed to maternal diabetes in utero.

Chen P, Piaggi P, Traurig M, Bogardus C, Knowler WC, Baier LJ, Hanson RL.

Diabetologia (2017 Apr) 60:645-655. Abstract/Full Text

Effect of different methods of accounting for antihypertensive treatment when assessing the relationship between diabetes or obesity and systolic blood pressure.

Tanamas SK, Hanson RL, Nelson RG, Knowler WC.

J Diabetes Complications (2017 Apr) 31:693-699. Abstract/Full Text

Preventing diabetes in obese Latino youth with prediabetes: a study protocol for a randomized controlled trial.

Soltero EG, Konopken YP, Olson ML, Keller CS, Castro FG, Williams AN, Patrick DL, Ayers S, Hu HH, Sandoval M, Pimentel J, Knowler WC, Frick KD, Shaibi GQ.

BMC Public Health (2017 Mar 16) 17:261. Abstract/Full Text

Cost of intervention delivery in a lifestyle weight loss trial in type 2 diabetes: results from the Look AHEAD clinical trial.

Rushing J, Wing R, Wadden TA, Knowler WC, Lawlor M, Evans M, Killean T, Montez M, Espeland MA, Zhang P, Look AHEAD Research Group.

Obes Sci Pract (2017 Mar) 3:15-24. Abstract/Full Text

Replication of the Association of BDNF and MC4R Variants With Dietary Intake in the Diabetes Prevention Program.

McCaffery JM, Jablonski KA, Franks PW, Delahanty LM, Aroda V, Marrero D, Hamman RF, Horton ES, Dagogo-Jack S, Wylie-Rosett J, Barrett-Connor E, Kitabchi A, Knowler WC, Wing RR, Florez JC, Diabetes Prevention Program Research Group.

Psychosom Med (2017 Feb/Mar) 79:224-233. Abstract/Full Text

The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study.

Grau-Pérez M, Kuo CC, Spratlen M, Thayer KA, Mendez MA, Hamman RF, Dabelea D, Adgate JL, Knowler WC, Bell RA, Miller FW, Liese AD, Zhang C, Douillet C, Drobná Z, Mayer-Davis EJ, Styblo M, Navas-Acien A.

Diabetes Care (2017 Jan) 40:46-53. Abstract/Full Text

Association of Serum Amyloid A with Kidney Outcomes and All-Cause Mortality in American Indians with Type 2 Diabetes.

Saulnier PJ, Dieter BP, Tanamas SK, McPherson SM, Wheelock KM, Knowler WC, Looker HC, Meek RL, Nelson RG, Tuttle KR.

Am J Nephrol (2017) 46:276-284. Abstract/Full Text

Advanced Glycation End Products Predict Loss of Renal Function and Correlate With Lesions of Diabetic Kidney Disease in American Indians With Type 2 Diabetes.

Saulnier PJ, Wheelock KM, Howell S, Weil EJ, Tanamas SK, Knowler WC, Lemley KV, Mauer M, Yee B, Nelson RG, Beisswenger PJ.

Diabetes (2016 Dec) 65:3744-3753. Abstract/Full Text

Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program.

Varga TV, Winters AH, Jablonski KA, Horton ES, Khare-Ranade P, Knowler WC, Marcovina SM, Renström F, Watson KE, Goldberg R, Florez JC, Pollin TI, Franks PW.

Circ Cardiovasc Genet (2016 Dec) 9:495-503. Abstract/Full Text

Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial.

Look AHEAD Research Group, Gregg EW, Jakicic JM, Blackburn G, Bloomquist P, Bray GA, Clark JM, Coday M, Curtis JM, Egan C, Evans M, Foreyt J, Foster G, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jeffery RW, Johnson KC, Kitabchi AE, Knowler WC, Kriska A, Lang W, Lewis CE, Montez MG, Nathan DM, Neiberg RH, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Redmon B, Regensteiner J, Rejeski J, Ribisl PM, Safford M, Stewart K, Trence D, Wadden TA, Wing RR, Yanovski SZ.

Lancet Diabetes Endocrinol (2016 Nov) 4:913-921. Abstract/Full Text

Long-term Effect of Losartan on Kidney Disease in American Indians With Type 2 Diabetes: A Follow-up Analysis of a Randomized Clinical Trial.

Tanamas SK, Saulnier PJ, Fufaa GD, Wheelock KM, Weil EJ, Hanson RL, Knowler WC, Bennett PH, Nelson RG.

Diabetes Care (2016 Nov) 39:2004-2010. Abstract/Full Text

Selecting SNPs informative for African, American Indian and European Ancestry: application to the Family Investigation of Nephropathy and Diabetes (FIND).

Williams RC, Elston RC, Kumar P, Knowler WC, Abboud HE, Adler S, Bowden DW, Divers J, Freedman BI, Igo RP Jr, Ipp E, Iyengar SK, Kimmel PL, Klag MJ, Kohn O, Langefeld CD, Leehey DJ, Nelson RG, Nicholas SB, Pahl MV, Parekh RS, Rotter JI, Schelling JR, Sedor JR, Shah VO, Smith MW, Taylor KD, Thameem F, Thornley-Brown D, Winkler CA, Guo X, Zager P, Hanson RL, FIND Research Group.

BMC Genomics (2016 May 4) 17:325. Abstract/Full Text

Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study.

Aroda VR, Edelstein SL, Goldberg RB, Knowler WC, Marcovina SM, Orchard TJ, Bray GA, Schade DS, Temprosa MG, White NH, Crandall JP, Diabetes Prevention Program Research Group.

J Clin Endocrinol Metab (2016 Apr) 101:1754-61. Abstract/Full Text

Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children.

Wheelock KM, Sinha M, Knowler WC, Nelson RG, Fufaa GD, Hanson RL.

J Clin Endocrinol Metab (2016 Apr) 101:1437-44. Abstract/Full Text

Books & Book Chapters

"Prevention of type 2 diabetes."

Crandall JP, Chiasson JL, Knowler WC, Nathan DM.

Diabetes in America. 3rd Edition.

Barrett-Connor E, Becker DJ, Brancati FL, Boyko EJ, Casagrande SS, Cissell MA, Cowie CC, Eberhardt MS, Fradkin JE, Gregg EW, Herman WH, Howard BV, Knowler WC, Meigs JB, Menke A, Narayan KMV, Rewers M, eds.

National Institutes of Health (Bethesda, MD). (2017) NIH Pub No. 17-1468. Abstract/Full Text (PDF, 509 KB)