William Knowler, M.D., Dr.P.H., Scientist Emeritus
- Scientist Emeritus, 2021-present
- Previously Chief, Diabetes Epidemiology and Clinical Research Section, NIDDK, 1979-2021
- Staff Associate/Staff Physician, NIDDK, 1975-1979
- Resident in Preventive Medicine, Harvard School of Public Health, 1974-1975
- Intern in internal medicine, Faulkner and Lemuel Shattuck Hospitals, Boston, 1973-1974
- Statistician, Sheller-Globe Corporation (chemical manufacturing), 1966-1969
- DrPH, Harvard School of Public Health, 1980
- MD, Harvard Medical School, 1973
- MPH, Harvard School of Public Health, 1973
- BA, University of Iowa, 1968
Our goal is to advance knowledge of causes of type 2 diabetes, obesity, and their complications, especially among Southwestern U.S. minority populations, with the aim of improving prevention and treatment of these conditions.
My work advances knowledge about prevention and treatment of diabetes, obesity, and their complications through research using methods of epidemiology, genetics, and randomized clinical trials. My major research programs have been a 43-year longitudinal population study of type 2 diabetes and related conditions and two multi-center randomized clinical trials – the Diabetes Prevention Program (DPP) with its follow-up study, the Diabetes Prevention Program Outcomes Study (DPPOS), and Action for Health in Diabetes (Look AHEAD).
The longitudinal population study has had world-wide impact in elucidating risk factors for type 2 diabetes and its complications and in establishing diagnostic criteria. Other findings concern the long-term effects of maternal diabetes in pregnancy on the offspring and problems related to obesity and type 2 diabetes in children. Our research has expanded knowledge of the genetic bases for type 2 diabetes and obesity. The genetic studies have been extended through participation in a multi-center study of genetic susceptibility to diabetic nephropathy – the Family Investigation of Nephropathy and Diabetes (FIND).
DPP and DPPOS showed that the development of type 2 diabetes could be greatly reduced or delayed in high-risk adults either by a behavioral weight-loss intervention or the drug metformin. The DPPOS is examining long-term durability of diabetes prevention/delay and its effects on other health outcomes including microvascular complications, cancer, and cardiovascular disease. In Look AHEAD, a behavioral weight-loss intervention in adults with type 2 diabetes reduced cardiovascular disease risk factors (but not events), health care costs, and the development of advanced kidney disease.
Our main current projects include continuing and analyzing the clinical trials, expanding our studies of mothers and children, and analyzing epidemiologic and genetic data (including genome-wide association and whole exome sequencing data).
Applying our Research
Results of the longitudinal population study have had widespread influence on research and practice related to type 2 diabetes, and have been instrumental in development of national and international criteria for diagnosing diabetes and classifying risk conditions. The DPP results are widely implemented in clinical practice with the support of several health care organizations and payers, including the U.S. government’s Indian Health Service and Centers for Medicare and Medicaid Services.
Need for Further Study
Despite substantial progress, the environmental, behavioral, and genetic causes of type 2 diabetes, obesity, and their complications are only partially understood. Similarly, while we have shown that lifestyle interventions and drug treatments have substantial health benefits, they can be difficult for health practitioners to administer and for individuals to follow. Their effects on health risks are sometimes modest, and their long-term durability is uncertain. Therefore, we need better knowledge of the risk factors for these diseases and how that knowledge can be translated into better prevention and treatment strategies.
- 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
Research in Plain Language
My research is devoted to advancing knowledge about prevention and treatment of type 2 diabetes, obesity, and their complications. My major research programs have been a 43-year longitudinal population study of type 2 diabetes and related conditions and two multi-center randomized clinical trials – the Diabetes Prevention Program (DPP) and Action for Health in Diabetes (Look AHEAD). This research has influenced how doctors and scientists define diabetes, classify its type, and identify factors that make some people more likely to develop type 2 diabetes. It has shown that diabetes in pregnant women affects not only their own health, but the health of their children for years to come. The DPP and Look AHEAD clinical trials study the health benefits of lifestyle changes (primarily weight loss) in persons who are at risk of getting type 2 diabetes or already have the disease. They showed that weight loss or the medicine metformin can help people prevent or delay getting diabetes, and that weight loss can improve several aspects of health in adults with type 2 diabetes.