Lund 3 rd November 2006 The early history of research on the Metabolic Syndrome Peter Nilsson, MD, PhD Department of Clinical Sciences Medicine University Hospital MAS, Malmö Department for History of Medicine University of Lund
Metabolic syndrome Genes Lifestyle Increased risk: cardiovascular disease, PCO type-2 diabetes, cognitive decline
Gerald Reaven, Banting Lecture 1988
Cornerstones in the Insulin Resistance Syndrome (IRS) Glucose visceral obesity hypertension liver steatosis dyslipidemia Insulin resistance endothelial dysfunction chronic inflammation Free Fatty Acids heredity (genes) lifestyle Insulin
Giovanni Battista Morgagni: De Sedibus et Causis Morborum per Anatomen Indagata (Padova,1765) 250 years ago, Morgagni with the help of a knife for anatomical dissection an observational skillfulness decribed the association between visceral obesity, hypertension, hyperuricemia, atherosclerosis and obstructive sleep apnea (Enzi et al. International Journal of Obesity, 2002)
Kaiserin-Elisabeth-Spital, Wien
Karl Hitzenberger, Vienna, Austria: Described the Metabolic syndrome in 1921 on the basis of studies carried out in 1915/16
The early research in Wien on the Metabolic Syndrome (1) During the First World War two Austrian researchers worked on the Metabolic Syndrome in Wien; Karl Hitzenberger and Martin Richter-Quittner They described the Metabolic syndrome, based on clinical studies, but could not publish until after the war (1921) Contemporary researchers in other countries picked up the description; Eskil Kylin (Sweden) and Gregorio Maranon (Spain), but also in other countries Sarafidis P, Nilsson PM, J Hypertens 2006
The early research in Wien on the Metabolic Syndrome (2) Karl Hitzenberger, privatdozent Martin Richter-Quittner Clinical examinations made in 1915/1916 Publication in Wiener Arch Innere Med Band II, 1921 Proposal of a Metabolic syndrome based on hypertension, hyperglycaemia, and hyperuricaemia, provoked by adrenaline action
Kylin E. Studien über das Hypertonie- Hyperglykemie- Hyperurikemiesyndrom. Zentralblatt für Innere Medizin 1923;7:105 Eskil Kylin (1889 1975)
Personal biography of Eskil Kylin (1889-1975) Born in 1886, son of a farmer in western Sweden Medical studies in Uppsala and Göteborg Thesis in 1921 on hypertension Interested in cardiovascular medicine and regulation of metabolism A long list of published scientific papers, most of them in German
The city hospital in Jönköping, Sweden
Kylin s thinking about the Metabolic Syndrome Based on observations of glucosuria and impaired carbohydrate tolerance following glucose/fructose intake in patients with essential hypertension Effects of adrenaline injection s.c. included blood glucose elevation, increased blood pressure and pulse rate in patients. Kylin proposed the hypothesis that there was an imbalance in the autonomic nervous system - with focus on vagal neurogenic function Hyperuricaemia and lymfocytosis were often found in hypertensive patients and part of the syndrome Kylin E, Zentralblatt f. Innere Med 1921, 1923
Prevalence (%) of hypertension in patients with diabetes case series Age (year) 41-50 51-60 60+ n 7 22 27 SBP (mmhg) 110-140 43 18 -- 141-180 43 59 29 180 + 14 23 72 Kylin E., 1923
Mean BP in patients with diabetes Age n Mean SBP (mmhg) 40-50 7 142 51-60 22 163 61-70 22 190 71-80 5 183 Total 56 Kylin E., 1923
Kylin s early contacts with contemporary research - references made to work by others Germany; München, Halle: Bergmann 1918, Franz Volhard 1918 Spain: G. Marańon. Zentralblatt Innere Med 1921 Austria: K. Hitzenberger, M. Richter-Quittner. Wiener Archiev f. Innere Med (Band II), 1921 Finland: Kerppola. Acta Med Scand (Band 57), 1923
Gregorio Marañon Spanish Endocrinologist Hospital in Madrid
Two main forms of hypertension HT - glomerulonephritis Visible capillary changes Oedema common increased capillary pressure Normal BP day-time variation Normal blood glucose Following acute infection Essential hypertension No capillary changes No oedema Normal capillary pressure Increased day-timebp variability Often increased blood glucose Often risk of diabetes Slowly progressing with relation to menopause, endocrine disturbances, pituitary dysfunction Kylin E., 1923