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Epiphaniae medicorum, uroscopy and ring of flasks (Diagnosing diabetes: a wee taste of honey)… “no essential part of the drink is absorbed by the body while great masses of the flesh are liquefied into urine.”- Aretaeus of Cappadocia[1]Although it seems to have gained notoriety only recently as increasing numbers of people across the globe have fallen prey to the disease, countless brilliant minds have played a part in the fascinating history of diabetes mellitus. Scientists and physicians have been chronicling this devastating medical condition for more than 3,000 years, from the origins of its discovery to the dramatic breakthroughs in its treatment. In antiquity, a diagnosis of diabetes was likely a death sentence.Cedar wood panel depicting Hesy-Ra (Hesy-Ra - Wikipedia)The first known mention of diabetes symptoms was in the Ebers Papyrus 1552 B.C., where Hesy-Ra a third dynasty physician (whose title was Wer-ibeh-senjw, meaning either "Great one of the ivory cutters" or "Great one of the dentists"), documented frequent urination as a symptom of a mysterious disease that also caused emaciation. Hesy-Ra mentions the “too great emptying of the urine'.The following mixture was prescribed for the treatment of polyuria (excessive urination): ‘A measuring glass filled with Water from the Bird pond, Elderberry, Fibres of the asit plant, Fresh Milk, Beer-Swill, Flower of the Cucumber, and Green Dates”.[2]It's unclear whether the condition described was excessive urine (polyuria), which may have been symptomatic of diabetes, or increased frequency of urine, resulting from a urinary tract infection[3] . Urinary troubles were corrected with rectal injections of olive oil, honey, sweet beer, sea salt, and seeds of the wonderfruit.[4]Egyptian medicine influenced the medical practices of neighboring cultures, including the culture of ancient Greece. Although the Greek physician Hippocrates, the father of medicine, did not specifically mention diabetes in his writings, there are accounts in the Hippocratic writings that are consistent with the signs and symptoms of diabetes.[5] There are references to excessive urinary flow with wasting of the body. Hippocrates promoted the concept of preventive medicine, stressimg the influence of diet, exercise, and lifestyle on health.[6](Origin of surgery Sushruta (Origin of surgery Sushruta - Fancy Frindle)The ancient Indian physician, Sushruta (6th century BC), and the surgeon Charaka (400–500 A.D.) were able to identify the two types, later to be named Type I and Type II diabetes.[7] Sushruta called diabetes the disease of madhu-meha, i.e., sweet urine.[8] The first clinical test of diabetes was devised in Ancient India, where patients exhibiting the common diabetes symptoms described above, had their urine analyzed with the help of ants.[9] If the sugar-loving ants came rushing to the urine, a diagnosis of “madhumeha” was given, indicating the patient had “honey urine”, with elevated levels of glucose in the urine.[10]Another ancient Ayurveda physician, Charaka, who lived in the 3rd century BCE called diabetes the disease of prameha, referring to abnormally high outputs of urine.[11] Both physicians advocated abstaining from sweet foods and reducing the intake of rice and other grains as part of the treatment of diabetes.[12]Apollonius of Memphis (A history of Diabetes timeline)There are two contenders for coining the term diabetes meaning to pass through. The first is Apollonius of Memphis, around 250 BC, while the second is Demetrius of Apamea (1st century BCE).[13] Apollonius of Memphis. is credited with naming the disorder for its top symptom: the excessive passing of urine through the body’s system.[14] Demetrius, likened polyuria to the siphoning of wine between pots—a practice now called "racking," which has long been used during fermentation to remove the sediment of dead yeast and promote proper aging.[15]Caelius Aurelianus prepared a Latin version of the works of Soranus, including in the index a subject heading for "Diabetes”. Caelius quotes Apollonius of Memphis as separating two forms of dropsy, one marked by retention of fluid and the other by the inability to retain fluid; the patient discharges whatever he drinks as if it were passed through a pipe. Caelius Aurelianus continues by stating that Demetrius distinguishes this disease from dropsy in which any fluid that is drunk is discharged as urine. Demetrius calls this condition diabetes.[16]Aulus (Aurelius) Cornelius Celsus, a Roman physician, was credited with the first recording of the cardinal signs of inflammation, which included calor (warmth), dolor (pain), tumor (swelling), and rubor (redness and hyperemia).[17] He describes a condition likely to be diabetes, calling it "excessive pouring out of urine" causing "emaciation and danger”.[18]In the first century A.D., ancient Greek physician Aretaeus vividly described the destructive nature of an illness which he named diabetes derived from the Greek word “siphon” (meaning flowing through).[19]Diabetes is … not very frequent ... being a melting down of the flesh and limbs into urine … for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. It consists in the flesh and bones running together into the urine … the illness develops very slowly. The nature of the disease is chronic, and it takes a long period to form; but the patient does not live long once the disease is fully established; for the melting is rapid, the death speedy. Moreover life is disgusting and painful; thirst, unquenchable … and one cannot stop them either from drinking or making water".[20]Diabetes indeed appears to have been a death sentence in the ancient era: Aretaeus did attempt to treat it, but could not provide a good prognosis. He commented that "life (with diabetes) is short, disgusting and painful”.[21] In 164 AD, building upon Aretaeus’ assessment, Greek physician, Galen of Pergamum, categorized diabetes as an ailment of the kidneys.[22]The Origins of Diabetes | St. Hope FoundationFor several hundred years, the treatises of Aretaeus and Galen remained the definitive reference for the diagnosis of diabetes, but offered no cures. To the east, Chinese physicians described the disease similarly, labeling it xiao ke (wasting and thirsting), a term still used today.[23] Xiaoke tea, a traditional Chinese treatment for diabetes mellitus was thought to lower blood glucose concentrations.[24]As the Middle Ages began, diabetes was known as the “pissing evil”[25] , commonly diagnosed by “water tasters”, who tasted the urine of people thought to have diabetes to see if the excretion was sweet like honey.[26] Avicenna (980–1037 A.D.), the great Persian physician, in The Canon of Medicine not only referred to abnormal appetite and the decline of sexual functions, but observed diabetic gangrene but also concocted a mixture of seeds (lupin, fenugreek, zedoary) as a panacea.[27]Thomas Willis in the late 1600s added the term mellitus or "from honey" to separate the condition from diabetes insipidus, which is also associated with frequent urination.[28] Willis was infamous for his diagnosis of diabetes, which involved tasting the urine of his patients.[29] He associated diabetes with depression (“diabetes is caused by melancholy”), an observation that was only rediscovered three centuries later.[30]With little understanding of pathophysiology, early remedies for diabetes included diverse and interesting prescriptions like “oil of roses, dates, raw quinces and gruel, jelly of viper’s flesh, broken red coral, sweet almonds and fresh flowers of blind nettles” representing a variety of beliefs and practices of the times.[31] The prescribed treatment was exercise, which is consistent with medical advice for today, but with one difference: the preferred method of exercise was horseback riding.[32] It was thought that this would decrease urination frequency.Later, in the pre-insulin era, calorie restriction reigned supreme, and graphic accounts of the terminal gasping and sighing and sweet smell (ketosis) surrounding the patient in a diabetic coma abound in the volumes written on the disease.[33]Research published in the journal ‘Nature’ reveals that the likelihood of non-African Homo sapiens developing conditions, particularly auto-immune disorders, which can be determined by Neanderthal alleles. DNA sequencing was conducted on a recent skeletal discovery from Denisova Cave, indicating that what were considered modern diseases originated in our Neanderthal ancestors.[34] The diseases included type two diabetes, Crohn's disease, lupus and biliary cirrhosis.[35]The deep roots of diabetesThe diagnosis of diabetes mellitus from skeletal remains is very difficult given the complexity of the disease and the fact that there are no pathological skeletal characteristics exclusively associated with the condition.[36] Skeletal identification of diabetes mellitus may only be possible through differential diagnosis, when several pathological changes are present. Skeletal and dental changes associated with diabetes mellitus include Charcot's joint (neuropathic arthropathy), osteoporosis, osteoarthritis, diffuse idiopathic skeletal hyperostosis (DISH, or Forestier's disease), adhesive capsulitis (frozen shoulder), dental caries, periodontal disease, and antemortem tooth loss.[37]It should not be understood that Neanderthals had diabetes. Type 2 diabetes is a disease of the modern world, borne of a mismatch between modern, unhealthy lifestyles and a metabolism that, for the vast majority of our evolutionary history, existed in an environment where food was relatively scarce and lots of physical activity was necessary to survive.[38] In the harsh environment of the Ice Age, even individuals carrying genes that contribute to diabetes when food is plentiful and sedentary lifestyles are common are unlikely to develop diabetes.Skeletal remains of an adult male from the Egyptian archaeological site of Dayr al Barsha dated to the Middle Kingdom (ca. 2055–1650 BC), display a myriad of pathological conditions that, when considered together, indicate the presence of diabetes mellitus.[39] This diagnosis represents the earliest, and possibly the only recorded, archaeological Raf inhibitor skeletal evidence for this disease.(Ancient Mummy Suffered Rare And Painful Disease)Around 2,900 years ago, an ancient Egyptian man, likely in his 20s, passed away after suffering from a rare, cancer-like disease that may also have left him with a type of diabetes. His mummy showed telltale signs that he suffered from Hand-Schuller-Christian disease an enigmatic condition in which Langerhans cells, a type of immune cell found in the skin, multiply rapidly.[40] They tend to replace normal structure of the bone and all other soft tissues.The disease seems to have taken a terrible toll on the ancient man’s body, as it destroyed parts of his skeleton, leaving lytic lesions throughout his spine and skull.[41] Scans also indicated what looks like a giant hole in his skull’s frontal-parietal bone, and destruction of a section of one of his eye sockets, known as the orbital wall. The effects of the disease would have been excruciating and would have affected the man’s appearance. In addition, it may have led him to suffer from a form of diabetes. The scans show that his sella turcica, part of the skull that holds the pituitary gland, is shallow, which suggests that this gland was also affected by the disease.[42]Researchers believe the condition could have lead to diabetes insipius. The condition would have made it difficult for his kidneys to conserve water, something that would have worsened the man’s predicament.[43] In all likelihood, he suffered from continuous thirst and hunger, urinating frequently.Hatsheput (Metropolitan Museum of Art - Wikipedia)Recent examination of a mummy considered to be Hatshesput (Pharoah of the XVIIIth dynasty 1503 and 1482BC) suggests she probably died of an infection caused by an abscessed tooth, with complications from advanced bone cancer and possibly diabetes.[44] Amenhotep III, the ninth pharaoh of the Eighteenth Dynasty of Egypt, may have suffered from diabetes as well.[45]Archaeological evidence indicates that certain groups of Paleo-Indians maintained an arctic-like hunter-gatherer life-style in temperate areas of North America ranging from Wyoming to Arizona. This life-style featured a reliance on unpredictable big game species as a major food source. However, at this time, big game species were becoming extinct. It is hypothesized that those Paleo-Indians who relied on big game as a food source developed a “thrifty” genotype,[46] that allowed a selective advantage during the periods of fasting that occurred between big game kills.Insulin resistance has previously been proposed as a mechanism for coping with variable food intake during evolution. Neel's thrifty gene hypothesis postulates that cycles of feast and famine selected for a “quick insulin trigger” (postprandial hyperinsulinemia) as a mechanism to increase fat stores during food abundance and available during food scarcity.[47]There is a high prevalence of (Non-Insulin Dependent Diabetes (NIDDM) susceptible genotypes in several distinct populations: American Indians, Australian Aborigines, and Pacific Islanders.[48] The susceptible genotype may have been selected into these populations because of unusually frequent food shortages that occurred during the initial colonization of 'new worlds'. NIDDM has been shown to have a strong genetic component that may include a 'thrifty' genotypes.[49] The 'thrifty' genotypes may have once allowed founding populations to survive feast' and 'famine' conditions for several generations. With an assured food supply and a sedentary lifestyle, however, the 'thrifty' genotype(s) becomes disadvantageous, leading to obesity, increased insulin resistance, beta cell decompensation, and NIDDM.[50]New DNA techniques will spark archeology revolution, expert saysDuring the same time period, across the Atlantic Ocean, it is believed that inhabitants began to exhibit symptoms of what would eventually be classified as Juvenile diabetes. During a 1000 year climatic reversal known as the Younger Dryas, temperatures dropped by 10 degrees Fahrenheit, causing those who did not die from the artic conditions to move South.[51] Researchers from Mount Sinai School of Medicine of New York suggest that some individuals adapted to the extreme conditions. High levels of blood glucose prevent cells and tissue form forming ice crystals. Basically, Type 1 diabetes prevented some from freezing to death.[52]Food during the last Ice Age was almost certainly limited, meaning that dietary blood sugar likely followed suit. Therefore, the insulin of a diabetic from this epoch may have never come close to reaching dangerous levels.The following quote is from Sharon Moalem:Imagine that some small group of people had a different response to the cold. Faced with year-round frigid temperatures, their insulin supply slowed, allowing their blood sugar to rise somewhat. As in the wood frog, this would have lowered the freezing point of their blood. They urinated frequently, to keep internal water levels low… Suppose these people used their brown fat to burn that oversupply of sugar in their blood to create heat. Perhaps they even produced additional clotting factor to repair tissue damage caused by particularly deep cold snaps. It’s not hard to imagine that these people might have had enough of an advantage over other humans… to make it more likely that they would survive long enough to reach reproductive age.”[53]Many in the medical community are skeptical, asserting that the study fails to account for dangerous complications such as ketoacidosis and early death.[54] However, since the average age of death was 25, those with high glucose would not have lived long enough to succomb to complications. They would however, despite the extreme conditions, live long enough to reproduce, resulting in genetic adaptations over a few generations.[55]While this may sound highly speculative, there’s actually a decent amount of evidence to support the notion. Lab rats essentially become diabetic (that is, they grow resistant to their own insulin) when exposed to cold temperatures.[56]More Northern Hemisphere inhabitants are diagnosed with diabetes between November and February than between June and September, theoretically due to the noticable drop in temperature during the former period.[57] Almost invariably, children are diagnosed with Type 1 diabetes during the late fall as temperatures drop. An extensive study of U.S. veterans, revealed that not only do the subjects’ blood sugar levels spike while winter is at hand, but that those who hail from environments with a great deal of variation in seasonal temperature (ie: colder districts) had a particularly extreme physiological contrast in this regard.[58]Footnotes[1] Aretaeus of Cappadocia[2] Polyuria - Genitourinary Disorders - Merck Manuals Professional Edition[3] MECHANISMS OF PAIN FROM URINARY TRACT INFECTION[4] The Ebers Papyrus: Medico-Magical Beliefs and Treatments Revealed in Ancient Egyptian Medical Text[5] Historical Diabetes Remedies[6] Diagnosing Diabetes: A Practitioner's Plea: Keep It Simple[7] The History of Diabetes Mellitus[8] History of Diabetes Mellitus[9] https://mysugr.com/en/blog/ants-with-diabetes[10] https://www.nhp.gov.in/Madhumeha-(Diabetes-mellitus)_mtl[11] https://www.google.com/url?sa=t&source=web&rct=j&url=http://www.jsirjournal.com/Vol4_Issue4_08.pdf&ved=2ahUKEwiqseuKlpzlAhUQpJ4KHWgLBZ8QFjAFegQICxAB&usg=AOvVaw275X45OeYFJcauml-J1PW7[12] Diabetes in Ancient Literature[13] Diabetes Detectives[14] The Origins of Diabetes | St. Hope Foundation[15] The Discovery of Insulin: An Important Milestone in the History of Medicine[16] Diabetes Its Medical and Cultural History[17] Inflammation, Insulin Resistance, and Type 2 Diabetes: Back to the Future?[18] https://www.google.com/url?sa=t&source=web&rct=j&url=https://friedmanfellows.com/assets/pdfs/elibrary/Principles%2520of%2520Diabetes%2520Mellitus%2520-%2520Ch1Final.pdf&ved=2ahUKEwiM6b2smJzlAhXYvJ4KHSVgCQEQFjAKegQICRAB&usg=AOvVaw0kllZ_wHWefc_uHQif9Eqd&cshid=1571071278134[19] Aretaeus of Cappadocia and the first description of diabetes.[20] Aretaeus of Cappadocia[21] History of diabetes: early science, early treatment, insulin[22] On the term diabetes in the works of Aretaeus and Galen | Medical History | Cambridge Core[23] Xiaoke, a traditional Chinese treatment for diabetes. Studies in streptozotocin diabetic mice and spontaneously diabetic BB/E rats.[24] Xiaoke Tea, a Chinese Herbal Treatment for Diabetes Mellitus[25] Dark Ages of Diabetes[26] https://www.google.com/url?sa=t&source=web&rct=j&url=https://vanderbilt.edu/olli/class-materials/2017Winter.ISWk1.pdf&ved=2ahUKEwji5NfznJzlAhXuFzQIHRCVBqUQFjACegQIDxAI&usg=AOvVaw1p-b95HZqhfFGFvH7c8NKE[27] The History of Diabetes Mellitus[28] Sickening Sweet[29] Diapedia, The Living Textbook of Diabetes[30] Diabetes and Depression[31] http://diabeteshealth.com/read/2008/12/17/715/the-history-of-diabetes/[32] History of Diabetes[33] Diabetic Coma - an overview[34] https://www.google.com/url?sa=t&source=web&rct=j&url=http://blogs.discovermagazine.com/deadthings/2019/01/30/denisova-cave-dates/&ved=2ahUKEwiE652zoZzlAhWnmuAKHYgmA54QFjAAegQIARAB&usg=AOvVaw3DibYrT_iwjzC4z6WNvVpW[35] Neanderthal genes linked to diseases in modern day humans including[36] Determinants of Bone Strength and Quality in Diabetes Mellitus in Humans[37] Pathological skeletal remains from ancient Egypt: the earliest case of diabetes mellitus?[38] The deep roots of diabetes[39] Skeletal and dental changes associated with diabetes mellitus inc[40] Hand–Schüller–Christian disease - Wikipedia[41] Ancient Mummy Suffered Rare And Painful Disease[42] Ancient Egyptian Mummies Show Signs of Crippling Spinal Disease[43] McDougall Newsletter: May 2011[44] The King Herself[45] Ancestry and Pathology in King Tutankhamun's Family[46] Archaeology of NIDDM: Excavation of the “Thrifty” Genotype[47] Evolutionary origins of insulin resistance: a behavioral switch hypothesis[48] https://www.ncbi.nlm.nih.gov/m/pubmed/1991567/[49] Google Scholar[50] Archaeology of NIDDM: Excavation of the “Thrifty” Genotype[51] Ice Age Diabetics?[52] Is diabetes a result of ice age?[53] Survival of the Sickest: A Medical Maverick Discovers Why We Need Disease[54] Ice Age Diabetics?[55] The sweet thing about Type 1 diabetes: a cryoprotective evolutionary adaptation.[56] Ice Age Diabetics?[57] Diabetic-level glucose spikes seen in healthy people[58] Diabetes in the Military - Learning About Diabetes | Diabetes Self-Management

While I was in training in the midwest, I had an autopsy with a somewhat unusual clinical history, which I received on only three sheets of paper, one from the EMTs who had been called to his home, one from the intake triage nurse at the emergency department of the hospital, and the third from the emergency department physician who talked with the patient’s wife briefly.The patient was a male in his late 20s with a history of chronic alcoholism. He was found by the EMTs to be unresponsive, and his blood glucose level when they initially evaluated him with a POC (point of care) test was zero. They hung some D5/NS (5% glucose in normal saline) and brought him to the hospital. He was an insulin-dependent diabetic who had been drinking very heavily for several days, and the three histories were discordant on one point: the first said he had been taking his insulin, the second said he hadn’t, and the third said he hadn’t, but his wife knew that he needed it, so she gave it to him, but didn’t know how to measure it up. That explained the glucose reading. The patient was mildly febrile, decidedly tachycardic, and quite obtunded. I can’t remember what the other laboratory results were. He was transferred to the ICU and died as he arrived there.At autopsy, performed at 10 hours post-mortem, the patient was seen to be a well-nourished, normally-developed male who appeared his stated age. The first thing one does after checking the paperwork (is there a properly executed autopsy permit?), identifying the body (toe tag, wristband, or whatever), and performing an external examination is to draw some blood samples, which I did. I then began the dissection. Behind me, I heard a small “pop!” I turned around. The blood sample tube had blown its top! At this point, I already had a diagnosis. The patient had a massive infection with gas-forming bacteria, and because of the speed of this development, probably an anaerobic species. The gross appearance of the organs of the body showed two particular abnormalities:The lining of the arterial vessels and the left side of the heart showed normal pink-tan coloration. The right side of the heart and the lining of large veins showed a purple-gray color. (One will encounter “pink-tan” twenty times in the course of the usual gross autopsy description, and “purple-gray” almost never, except for the description of the capsule of the spleen.)The distal stomach and the duodenum were soft and grayish-brown, indicating early decay, a highly unusual finding in a patient who undergoes a prompt post-mortem examination.On the basis of the behavior of the blood sample (pop!), the gross findings described above, and the blood bacterial culture (positive for Clostridium perfringens) and Gram stain results on the gastric and duodenal microscopic sections (Gram-positive spore-forming rods), we had a case of small bowel clostridial enteritis. The difference in the arterial and venous circulation was due to the higher oxygen content of the arterial blood, which kept the anaerobic bacteria from proliferating in that part of the circulation, whereas in the lower-oxygen environment of the venous side, the bacteria grew, and, releasing proteolytic enzymes, caused breakdown of the red cells with staining of the endothelial linings.This disease is virtually never seen in the U.S. (I think one case in a diabetic woman who did survive made it onto a medical mystery TV program). It was noted in post-war (WWII) Scandinavia and Germany, where it was called “Darmbrand” (“burning guts” in German) and is presently confined to Papua-New Guinea, where it is called “Pig-bel,” pidgin English for “pig belly,” because of its onset in natives who eat pig rarely, in a ceremony where the whole, un-eviscerated pig is thrown into a pit filled with hot coals and then eaten by everyone in the village after the cooking is finished. Predisposing factors are protein-poor nutrition (which results in a lower level of proteolytic digestive enzymes in the stomach) and exposure to clostridial spores.In the case of the Papuans, this cooking of the pig with included intestines will spread the clostridial spores from the pig’s gut (where they form only a small minority of the intestinal flora) onto the rest of the meat, and as the Papuans are usually on a rather protein-poor diet, they’ll also have a lower lever of protein-digesting enzymes, which is thought to render them more susceptible to infection by the Clostridia.In post-war Europe, protein deficiency was widespread. If there was any increase in environmental Clostridia, I’m unaware of it.In the case of our patient, his stomach contained some partially digested lima beans. Although he had good body habitus, he was somewhat malnourished from his binge drinking of a few days, and the beans may have contributed legume trypsin inhibitor (which interferes with protein digestion) to the mix, as well as the immunosuppression that occurs in diabetes mellitus. How much the severe hypoglycemia contributed to the patient’s course I cannot say.Finally, it is said that resting pulse rate in the presence of fever increases at about 10 bpm (beats per minute) with each degree of temperature rise. In clostridial infection, the increase is much higher, explaining the tachycardia. (This finding is non-specific, as many things can cause tachycardia.)

Be strong I am going to tell you some normally abnormal things what a medical student has to do :You must get used to human odour of any form be it fresh fragrance from medico sitting next to you or postmortem decaying flesh. Nowhere you will get that smell apart from postmortem room. One minute, have you smelled burgers foot or a Diabetic ulcer?You have to learn how to insert your finger in anal canal;yes, and it should not pain.You have to note the colour and consistency of that fresh sputum.Snacks during dissection, yes many of us has enjoyed in dissection room. Believe me i can still smell that formalin.My BD Chaurasia may still have some muscle fibres in between pages.Before dissecting the body I was alloted, I clicked a photo with my cadever, still remember those white shinning teeth.You have to wait for patient to fart in post op setting. It brings smile.You have to learn to control emotions. Yes, declaring Death of a neonate or a young beautiful or handsome patient of your age, demands courage.Be ready to donate blood while in obs or surgery posting. I did because patient’s incision was blood less pale white,and her husband has already donated.Be ready to see extreme poverty. Once a victim of snake bite was brought by his wife in 60s and God, she didn't have money to buy neostigmime. The distance between death and life was only rs 100.Be strong to endure humiliations from the consultant.Be ready to skip meals, skip sleep and endure breakups, yes if he or she is non medico, they won't understand us.Hide the disastrous OT details.Have you sucked blood via wintrobes? It tastes metallic.Yes we prick our fingers to get blood and count our own cells.Nude patients are just bodies for us.. No male no female.. Its just a body.In our teenage, a high end littman stetho excite us more than the new market rocking iPhone.Always doubt your patient and his version of history. Yes doubt. You will learn soon.Will add more