Rolf Luft (1914-2007), a Professor at the Karolinska Institute, is remembered for a range of contributions to medical science, including the first description of a mitochondrial disease in humans. He was a noted endocrinologist who did pioneering studies on the pituitary-adrenal axis, growth hormone and somatostatin, including the recognition that somatostatin is produced in the delta cells of the pancreatic islets. His contributions to diabetes include the introduction of hypophysectomy as a treatment for advanced diabetic retinopathy, the recognition that deficient insulin secretion plays a key role in the pathogenesis of type 2 diabetes, and identification of loss of first phase insulin secretion in response to the intravenous glucose tolerance test as an early hallmark of type 2 diabetes.
Rolf LuftRolf Luft was born to working class Jewish parents in Stockholm, and supported his own studies by winning scholarships. He qualified in Medicine in 1940, and submitted his doctoral thesis on Cushing's syndrome four years later. In 1946 he spent a period in the USA in order to pursue his interest in the pituitary-adrenal axis, on which he published many papers.
Hypophysectomy for Diabetic Retinopathy
From there his interest moved to growth hormone; stimulated by the observation that diabetic retinopathy regressed in a women with Sheehan's syndrome (post-partum pituitary infarction and diabetes), which appeared to confirm the contemporary belief that growth hormone was responsible for diabetic microvascular disease, he pioneered the use of hypophysectomy together with a surgical colleague H. Olivecrona.
The results would not currently be considered that promising: of the first 20 patients (aged 20-33) to undergo the procedure 7 died within 19 months. Of 10 in whom adequate retinal follow-up was possible, one showed marked progression, three suffered acute retinal haemorrhages, but longer term signs of improvement were considered to be present in all 9 .
These results appear horrific to modern eyes, but the fact that people persevered with this treatment testifies to the dreadful prognosis of juvenile diabetes at that period. Luft and Olivecrona also tested hypophysectomy for diabetic nephropathy and breast cancer, and it remained the staple treatment for severe retinopathy until the introduction of laser photocoagulation in the 1970s.
Growth Hormone and Somatostatin
Before biosynthetic endocrine therapies became available, the only therapeutic source of human growth hormone (GH) was post-mortem pituitaries. Luft pioneered GH treatment of hypopituitarism, and production was transferred to the pharmaceutical company Kabi, which went on to manufacture recombinant human GH when the technology became available.
Somatostatin was first identified (and initially named growth hormone-inhibiting hormone) in the hypothalamus in 1973. Luft and Efendic are credited with the demonstration of somatostatin-containing delta cells in the pancreatic islets, and went on to perform a number of ground-breaking studies with somatostatin analogues.
By an extraordinary feat of clinical induction, Luft was able to account for the bizarre and apparently inexplicable symptoms of a 30 year old patient with profuse perspiration, very high energy intake and myopathy. He was able to demonstrate that these symptoms were due to inefficient mitochondrial respiration with reduced ability to generate ATP, thus forcing the body to consume fuel more rapidly to supply its energy needs. This accounted for the patient's increased heat production and high energy requirements; it was the first demonstration of mitochondrial disease in humans.
Insulin deficiency and type 2 diabetes
In the 1960s and 1970s it was widely assumed that type 2 diabetes was produced by insulin resistance. Cerasi and Luft were among the first to challenge this dogma, arguing that diminished insulin response to glucose was the hallmark of diabetes and "prediabetes". The concept of insulin deficiency in type 2 diabetes, now well established, has been elaborated far beyond their original concept, but they made a further lasting contribution in identifying deficient first phase insulin response to the intravenous glucose tolerance test as the hallmark of early diabetes.
Rolf LuftRolf Luft started the first national programme for diabetes in Sweden in 1967 and founded a WHO centre for education in diabetes. He was IDF President from 1973-9, and was also President of the Nobel Committee for Physiology and Medicine (1976-9).
He was a man of wide interests and extraordinary humanity, active in many causes outside medicine, a keen sportsman and gardener, and - right up to the end - characterised by an insatiable thirst for knowledge and understanding.
Berggren P-O, Brismar K. Professor Rolf Luft, 1914-2007. Diabetologia 2008;51(5):697-99 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292419/
DiMauro S et al. Rolf Luft, MD, PhD (1914-2007). JAMA Neurology 2007;64(9):1353. http://archneur.jamanetwork.com/article.aspx?articleid=794497
^ Luft R et al. Hypophysectomy in man. Further experiences in severe diabetes mellitus. BMJ 1955;ii:752-6 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1980914/pdf/brmedj03226-0016.pdf
^ Cerasi E, Luft R. The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocr (kbh) 1967;278-304
^ Efendic S et al. Insulin release, insulin sensitivity, and glucose intolerance. Proc Natl Acad Sci USA 1980;77(12):7425-9 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC350516/