Retrospective study on Professor Zhongying Zhou's experience in Traditional Chinese Medicine treatment on diabetic nephropathy.

OBJECTIVE: To study and analyze the etiology and pathogenesis, diagnosis and prescription for cases of diabetic nephropathy (DN) treated by Professor Zhongying Zhou (Prof. Zhou) with the help of dada mining technique, so as to inherit his clinical experience and academic thoughts. METHODS: After pretreatment of the medical record information, statistical software SPSS 13.0 was used to analyze and process the standardized data using the descriptive analysis, cluster analysis and association rules. RESULTS: Ninety-four entries derived from Traditional Chinese Medicine (TCM) four-diagnostic information were selected. Through data mining, the highest frequency was yellow-thin-greasy tongue coating, followed by dark tongue, and then by thready-slippery pulse. The main self-conscious symptoms were limb numbness, dry mouth, frequent micturition, etc. With respect to pathogenesis, the etiology related to kidney reached 73.46%. The frequency of pathological factors for deficiency, blood stasis, heat, dampness, phlegm and dryness were 137.65%, 80.25%, 78.40% , 48.77%, 21.60%, and 14.20% respectively. A total of 236 kinds of herbs were used 2913 person times, averaging 17.98 herbs per prescription. CONCLUSION: The pathological location of DN is in the kidney. The pathogenesis of the disease is deficiency in origin and excess in superficiality, the former of which include deficiency of the liver and kidney, and deficiency of both Qi and Yin. The main pathological factors are blood stasis, heat, dampness, phlegm, and dryness; and they act upon each other to form the complex pathogenesis in terms of blood stasis-heat, dampness-heat, phlegm-heat, and dryness-heat. All the above factors are always crucial in the aggravation of DN throughout the whole course of its pathological evolution.

Disease of the Sultans: metabolic syndrome in Ottoman dynasty.

Metabolic syndrome is generally considered as a complication of modernity. Here we searched for the presence of metabolic syndrome components among the Ottoman emperors who lived between 1258 and 1926. Collections of historical archives, which were published as books specifically about morbidity and mortality of Ottoman emperors were reviewed to diagnose metabolic syndrome according to modified criteria by American College of Endocrinology and American Association of Clinical Endocrinologists. Nineteen of 36 dynasty members (53%) had fatal or non-fatal cardiovascular events. Twenty-nine of the dynasty (81%) members were either depicted as truncal obese or reported to have obesity. Thirteen emperors (36%) satisfied diagnostic criteria for metabolic syndrome, retrospectively. Overall, 42% of non-commanding emperors, but 26% of commanding-emperors (who were assumed to be athletically grown and physically more active) were found to have metabolic syndrome (p=0.553). We suggest firstly here that sedentary palace lifestyle exacerbated metabolic syndrome in Ottoman dynasty especially in elderly members, thereafter complicated by cardiovascular events, even in pre-modern era.

Aspectos diferenciales del manejo del paciente diabético con insuficiencia renal en diálisis peritoneal o hemodiálisis / Differential aspects in management of diabetic patient with renal insufficiency under peritoneal dialysis or hemodialysis

Aunque la aparición y la progresión de la nefropatía diabética pueden retrasarse mediante el control de la hipertensión, el control estricto de la glucemia y el control de todos los factores de riesgo modifi cables, de todas formas muchos pacientes progresan hacia la insufi ciencia renal terminal. En los últimos 15-20 años se ha apreciado un incremento progresivo de pacientes con diabetes tipo 2 que alcanzan enfermedad renal en estadios avanzados. Las razones de este incremento son múltiples. Entre las más importantes fi guran la aparición de la diabetes en edades más precoces y la mejor supervivencia de estos pacientes, sobre todo en los que tienen un riesgo vascular elevado. La supervivencia de los pacientes con diabetes en diálisis es inferior a la de los pacientes no diabéticos. Las complicaciones cardiovasculares son la causa más importante de mortalidad (~50%), y condicionan gravemente el pronóstico si están presentes antes de iniciar el tratamiento con diálisis. Sin embargo, en los últimos años la morbilmortalidad de los pacientes en diálisis ha mejorado de modo signi- fi cativo. Además, los pacientes diabéticos sometidos a trasplante renal tienen aún mayor supervivencia, calidad de vida y mejor rehabilitación que los pacientes sometidos a tratamiento con diálisis, lo que en parte tiene que ver con los criterios de selección de los candidatos para trasplante. No parecen existir diferencias claras en la supervivencia y en la morbilidad entre los pacientes en hemodiálisis y los pacientes con diálisis peritoneal. Si hasta ahora se admitía que los pacientes tratados con diálisis peritoneal presentaban una mayor supervivencia, los recientes resultados del estudio USRDS sugieren que la mortalidad podría ser mayor en pacientes diabéticos en diálisis peritoneal que en los tratados con hemodiálisis. En consecuencia, por el momento no puede establecerse una diferencia signifi cativa en cuanto a supervivencia entre los pacientes con diabetes tratados con uno u otro tipo de diálisis (AU)

Although the appearance and progression of diabetic nephropathy may be retarded by normalization of the blood pressure, tight glycemic control and management of other risk factors, many patients still progress to end-stage renal disease. Over the last 15 to 20 years, it has been observed a progressive increment of type 2 diabetic patients developing end-stage renal disease. The underlying reasons for this increase are multiple. Among the most important are the development of diabetes at earlier age and better survival of patients, especially those at higher vascular risk. Diabetic patients have lower survival on dialysis than non-diabetic patients. Cardiovascular complications are the most important cause death (~50%), also conditioning prognosis if they are present before dialysis is initiated. However, in the last years, morbidity and mortality of patients in dialysis has signifi cantly improved. Furthermore, diabetic patients undergoing renal transplantation have even better survival, quality of life and an improved degree of rehabilitation than those in dialysis therapy, due in part to selection bias of transplant candidates. Among hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), there are no clear differences on survival or morbidity. Although it was accepted that CAPD was associated with better survival rates, recent data from the USRDS suggest that mortality may be increased in diabetic patients treated with CAPD rather than with hemodialysis. Therefore, currently no signifi cant differences in survival can be established in diabetic patients treated either with hemodialysis or CAPD (AU)

The discovery of diabetic nephropathy: from small print to centre stage.

Until the early nineteenth century, diabetes mellitus was regarded as a disease of the kidney, in which there was an increase in the volume of urine and a wasting of the flesh. With the identification of glucose in blood and urine in the late eighteenth century, first it was re-framed as a disease of assimilation and only then became a metabolic disorder. Whilst these changing concepts were debated, it was noted in parallel that diabetics might show coagulable urine containing albumin, even before Bright and others had established this as a sign of kidney disease. Wilhelm Griesinger (1817-1868) was perhaps the first to suggest in 1859 that the diabetes might be causing the Bright's disease, with the latter as a 'complication'. During the next half-century the observation that as albuminuria appeared and increased, so glycosuria improved or might remit, with a parallel or subsequent evolution into uraemia. Glomerulosclerosis and arteriolosclerosis were described in occasional patients during the same period, but text-books of pathology ignored these observations. Thus it was only when diabetics began to survive longer using insulin treatment in the early 1920s that a diabetic nephropathy became widely recognized. After a few isolated descriptions which were ignored, the now famous paper of Paul Kimmelstiel and Clifford Wilson appeared in 1935 detailing nodular renal lesions in just 8 maturity-onset (48-68 year old) diabetics. They barely noted the association with diabetes however, and it was Arthur Allen in 1941 who clarified the association in 105 patients with diabetes, again all aged over 40. Despite the age of the patients in these early studies, diabetic nephropathy became thought of as a disease of young diabetics as a cohort of survivors of juvenile diabetes passed 15 years or more of disease and more than half developed nephropathy. In the 1950s the technique of renal biopsy was rapidly applied to the study of diabetics, and the early lesions defined using electron microscopy as well as optical methods. Then the role of diabetic nephropathy as a cause of renal failure changed: to begin with numbers of young insulin-requiring diabetics were small and infrequently referred for dialysis treatment or transplantation. Then in the 1970s and 1980s the proportion of such juvenile-onset diabetics developing renal failure gradually fell, but at the same time much larger numbers of older diabetics survived their vascular disease and required treatment for renal failure. World-wide, today diabetes accounts for 20-50% of patients entering established renal failure programs, and absolute numbers increase as greater longevity and western-style living has promoted an 'epidemic' of diabetes at all ages.

A history of diabetes mellitus -- a disease of the kidneys that became a kidney disease.

Throughout most of its history, diabetes mellitus was considered, classified and promulgated as a disease of the kidneys. Recognized early in Antiquity by its excessive urine output, its clinical features and fatal outcome were recorded by the end of the first century A.D. by Areteus of Cappadocia and attributed to a weakness of the retentive ability of the kidneys by Galen. The saccharine character of the urine recognized from the sweetness of its taste in 1674 and that of the blood in 1774, was identified as due to glucose in 1815. Refinements in the measurement of glucose ascribed diabetes to increased blood sugar and early attempts at its dietary therapy, but the appearance of sugar in the urine continued to be attributed to the decreased retentive properties of the kidneys well into the middle of the 19th century. The experimental production of diabetes in pancreatectomized dogs in 1889, and ultimately the isolation of insulin in 1922, clearly established diabetes as an endocrine disease due to insulin deficiency that could be controlled by replacement therapy. The history of diabetes as a disease of the kidneys was now over. That of diabetes as a cause of kidney disease was launched shortly thereafter, in 1936.

A history of diabetes mellitus or how a disease of the kidneys evolved into a kidney disease.

Diabetes mellitus has a long history during which it was considered to be a disease of the kidneys well into the middle of the 19th century. Recognized in antiquity from its excessive urine output and described as a disease of the urinary tract, its clinical features and fatal outcome were quite accurately recorded by the 1st century ad . Galen (129-200) described it as a disease specific to the kidneys because of a weakness in their retentive faculties. The sweet taste of diabetic urine, which is described in ancient Indian texts and noted by Avicenna (980-1037) and Morgagni (1635-1683), was attributed to the passage of absorbed water and nutrients unchanged into the urine. In 1674, Thomas Willis (1621-1675) first differentiated diabetes from other causes of polyuria by the sweet taste (quasi melle) of diabetic urine and suggested that the sweetness first appears in the blood. A century later, Matthew Dobson (1732-1784) showed that the urine sweetness was because of sugar and was preceded and accompanied by sugar in the blood. Although diabetes then came to be ascribed to increased sugar in the blood, the presence of sugar in the urine continued to be attributed to the decreased retentive properties of the kidneys. The experimental production of diabetes in pancreatectomized dogs that could be reversed by subcutaneous pancreatic transplantation in 1889, and ultimate isolation of insulin in 1922 clearly established diabetes as an endocrine disease. The stage of diabetes as a disease of the kidneys was now over but that of diabetes as a cause of kidney disease was yet to come. Diabetes as a cause of end stage kidney disease was first described in 1936 and extensively documented shortly thereafter, whereas the evidence of its increasing prevalence as a cause of chronic kidney disease continues to accrue.

[Historical Archives of Italian Nephrology. Diabetic nephropathy and insulin discovery: two parallel histories]. / Archivi storici della Nefrologia Italiana. Nefropatia diabetica e scoperta dell'insulina: due storie parallele.

In 1936, Kimmelstiel and Wilson described the nodular glomerulosclerosis in patients with diabetes mellitus on insulin treatment. The nodular glomerulosclerosis is referred to as diabetic nephropathy. Fifteen years earlier insulin was discovered. This discovery at the University of Toronto (Canada) in 1921-22 by Banting, Macleod, Best and Collip was one of the most dramatic events in the history of the treatment of the disease. The impact of insulin was so sensational because of the incredible effect it had on diabetic patients. Those who first watched starved, sometimes comatose, diabetics receive insulin and return to life witnessed one of the genuine miracles of modern medicine. The discovery has became the "elixir of life" for millions of human beings around the world. Insulin had not emerged out of a vacuum but was the culmination of years of work by dozens of scientists in many countries. The Canadian scientists were the first to succeed in isolating insulin. Their work, however, was accurately constructed to confirm the ideas of earlier researchers, such as Murray, Paulesco, Allen, Minkowski, Derwitt, Zuelzer. These men, in addition to Banting, Macleod, Best and Collip, knew they were making medical history but paradoxically, with their "elixir of life" they allowed some complications of diabetes to emerge. Diabetic nephropathy was one of them. The struggle of the "Toronto quartet" for credit was inspired by man's desire to have a place in history, to have a sort of immortality open to him, an aspiration that is certainly legitimate. But perhaps the Canadian group misjudged both their situation and posterity's point of view. They probably failed to consider the unintentional effect of insulin treatment: diabetic nephropathy as a consequence of adding years to a diabetic's life.

In memory of a legendary athlete: measured success in diabetic nephropathy.

Historically diabetic nephropathy has been a devastating complication of both type I and type II diabetes. The past 2 decades have seen enormous conceptual advances in understanding the pathogenesis of diabetic nephropathy. The genetic determinants of diabetic renal disease have also been elucidated as well as biochemical events and cytokine interactions. Most importantly, key clinical trials have identified therapeutic interventions which can slow or halt the progression of diabetic nephropathy, specifically the therapeutic use of angiotensin-converting enzyme inhibition and intensive blood sugar control. Multiple treatment modalities for patients once they reach end-stage renal disease are also available and great strides have been improving outcomes in these areas as well.

Diabetic renal disease: the quest for normotension--and beyond.

Over the past two decades there has been an increasing interest in hypertension as a risk factor for diabetic renal disease and in particular for the possibility of early antihypertensive intervention. Therefore, it would seem timely to review the history of hypertension in diabetes, with special reference to renal disease and the need for normotension, in a manner resembling glycaemic control. Elevated blood pressure (BP) associated with diabetes mellitus has been recognized since the beginning of the century and was initially particularly documented in association with the demonstration of the striking histological lesion in glomeruli, starting with the observation of Kimmelstiel and Wilson in 1936. These patients in many cases also showed hypertension, as confirmed in several subsequent reports, very similar to the studies of Kimmelstiel and Wilson. However, the development was hampered by the lack of effective antihypertensive agents and also by some who believed that elevated BP could be of importance to preserve renal function in these individuals. Indeed, it was suggested that reduction of BP could mean permanent deterioration in renal function. BP remained very high in the standard care of diabetic patients up to the middle 1970s. At this time it was documented that elevated BP was very closely related to development of diabetic renal disease in Type 1 (insulin-dependent) diabetic (IDDM) patients, and studies also showed a correlation between blood pressure and rate of progression. This correlation stimulated research in intervention, and indeed in the 1980s and 1990s several long-term studies reported that antihypertensive treatment can reduce the rate of decline in glomerular filtration rate (GFR) from about 12 ml min-1 yr-1 down to about 2 ml min-1 yr-1 in the most optimistic reports; usually a mean level of 2-5 ml min-1 yr-1 is achievable by antihypertensive treatment, in clinical situations where glycaemic control often is far from perfect. Many studies have also documented that BP starts to rise in the early phase of incipient diabetic nephropathy characterized by microalbuminuria. This is a stage with well-preserved GFR and therefore probably an ideal stage for intervention in these at risk patients. Many studies, in particular those employing angiotensin converting enzyme (ACE) inhibitors based on important pathophysiological concepts proposed by Brenner, have shown that microalbuminuria can be reduced or stabilized by early antihypertensive treatment, just as we see with optimized glycaemic control. ACE inhibitors have also been widely used in patients with overt nephropathy and the rate of decline in GFR has been reduced considerably.(ABSTRACT TRUNCATED AT 400 WORDS)

Luciano Armanni.

Luciano Armanni (1839-1903) worked as an assistant to Schrön in Naples after graduating in medicine. He was later appointed as Professor of Histopathology, and in 1887 became a full professor. During his life he was Dissector of the Anatomic Institute of the Ospedale degli Incurabili and later director of this hospital. He founded many institutions, including the Cotugno Hospital, but died poor and suffering from diabetes mellitus and tuberculosis, contracted during a post-mortem examination. Armanni is given credit for discovering the contagious nature and specificity of the lesions due to caseous material in tuberculosis, and also the renal lesion in diabetes mellitus that now bears his name (Armanni-Ebstein lesion).

Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota.

Transplantation began at the University of Minnesota in 1963. Treatment of diabetes and its complications has been emphasized since 1966, when the first pancreas-kidney transplant was done. Of 3,640 kidneys transplanted by 1992, 1,373 were for diabetic recipients, including 658 from living donors and 715 from cadaver donors. The results progressively improved; since 1984, survival rates of kidney grafts have been similar for diabetic and nondiabetic recipients, with three fourths of the grafts functioning at 4 years. As of 1992, 501 pancreas transplants had been done, including 170 simultaneous with a kidney, 142 after a kidney, and 188 alone for nonuremic diabetic patients; again, the results have improved: by the 1990s, graft survival rates were similar in the 3 recipient categories. Successful pancreas transplants have been shown by our coworkers to stabilize or improve neuropathy and prevent recurrence of diabetic nephropathy in kidney grafts. In an attempt to simplify endocrine replacement therapy, we have done 63 human islet transplants, 34 as allografts for patients with type I diabetes and 29 as autografts after total pancreatectomy to treat chronic pancreatitis. Insulin independence occurs for about 50% of islet autograft recipients. Two recent islet allograft recipients treated with 15-deoxyspergualin have had sustained insulin independence. We anticipate that endocrine replacement therapy by transplantation will become routine for diabetic patients as methods to prevent rejection are refined.