Paul Zimmet Discusses the Evolution of Metabolic Syndrome

Special Topic of Metabolic Syndrome Interview, September 2011

Paul Zimmet

According to our Special Topics analysis on metabolic syndrome over the past decade, the work of Professor Paul Zimmet ranks at #2 by total cites, #5 by number of papers, and #18 by cites per paper, based on 64 papers cited a total of 6,093 times. Three of these papers appear among the top 20 papers over the past decade and over the past two years.

In Essential Science IndicatorsSM from Thomson Reuters, his record includes 164 papers, the majority of which are classified in the field of Clinical Medicine, cited a total of 11,587 times between January 1, 2001 and April 30, 2011.

Zimmet is Director Emeritus and Director of International Research of the Baker IDI Heart and Diabetes Institute, Foundation Director of the International Diabetes Institute, and Hon. Professor at Monash and Deakin Universities in Melbourne, Australia, as well as Adjunct Professor at the Graduate School of Public Health of the University of Pittsburgh, Pennsylvania. He is Head of WHO Collaborating Centre for the Epidemiology of Diabetes Mellitus.

Below, correspondent Gary Taubes talks with Zimmet about his highly cited work as it relates to metabolic syndrome.

SW: Please tell us about your educational background and research experiences.

I initially set out to go into general practice to follow in the footsteps of my father, a dedicated and much-loved general practitioner in Adelaide. After my first year residency, I went to Melbourne for one year and was offered the position as Registrar, Diabetes and Metabolic Unit at The Alfred Hospital. I focused on diabetes from there and I was talked into undertaking a Ph.D. on the role of growth hormone in diabetes.

Having completed that at Monash University, I spent a year in London for post-doctoral work at Guy's Hospital under Professor Harry Keen. He convinced me that combining a clinical job with research, particularly in epidemiology and public health, was the direction I should take and that very much shaped my subsequent career. As Harry Keen had fuelled my interest in epidemiology, upon my return to Melbourne, I decided to undertake studies of diabetes epidemiology in the Pacific Islands.

My first survey was in Nauru in 1975 and that's when I discovered a population with the highest rate of diabetes in the world—one-third of the adult population had type 2 diabetes*. Subsequently my team undertook studies in eight other island communities, including Western Samoa, Papua New Guinea, the Cook Islands, and Fiji. In all of these countries, the prevalence of diabetes was substantially higher than those that had been previously reported in European communities.

I was also continuing to do laboratory research, including the development of the first immunoassay for GAD antibodies, a predictive test for type 1 diabetes, and following-up a discovery from my PhD towards developing a drug for type 2 diabetes.

SW: What first drew you to work with metabolic syndrome?

My diabetes research was a natural entry into the world of the metabolic syndrome. It became quite clear to me (and to others) that type 2 diabetes was a heterogeneous disorder and, in most instances, it was associated with other cardiovascular disease risk factors such as central obesity, dyslipidemia, and hypertension. This seemed to fit well with the known fact that persons with diabetes (and indeed pre-diabetes) were at higher risk of cardiovascular disease.

Paul Zimmet
Field work in Mauritius; on-site at National Survey for Diabetes, Metabolic Syndrome and Cardiovascular disease.

My thoughts on this all came together in 1989 with a paper I wrote for Diabetic Medicine—"Non-Insulin Dependent (Type 2) Diabetes Mellitus: Does It Really Exist?"The basis of this paper was that these cardiovascular risk factors had a common etiology, possibly through insulin resistance or hyperinsulinemia. I concluded "any attempt to delete NIDDM as a major component of the diabetes mellitus syndrome is certain to meet major resistance." However, the purpose of this paper was to review the evidence that suggests the term may be inappropriate. In future reviews of the classification of diabetes, this evidence will need to be seriously considered.

SW: Your most highly cited papers are consensus statements either defining metabolic syndrome. Can you talk a little bit about the evolution of these definitions?

The first report of the metabolic syndrome was in 1923 by Kylin, a Swedish physician. Not long after, in 1926, Maranon, a Spanish physician, described a similar condition, and Vague in 1947, Avagaro and Crepaldi in 1967, and then Gerald Reaven in 1988 described his version of the syndrome.

In 1998, Professor Sir George Alberti and I co-chaired a World Health Organization (WHO) consultation on "Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications." That consultation resulted in the first "official" definition of the Metabolic Syndrome by WHO and the suggested components were impaired glucose regulation diabetes, insulin resistance, raised arterial blood pressure (greater than 149/90mmhg), raised plasma triglycerides, central obesity, and microalbuminuria.

We recognized that several other components had also been described—for example, hyperuricemia, coagulation disorders, and raised PAI-1, etc.—but we didn't consider them necessary for the recognition of the condition. We also called for internationally agreed criteria for central obesity, insulin resistance, and hyperinsulinemia, saying this would be of major assistance.

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