11.09.201 A case of repeated hypoglycaemic episodes in a case of liver damage. Hypoglycaemia is the cause or effect of liver damage? This case is about T2DM of about one year duration in 82 years old man. He is normotensive. His sugar was moderately high. Initially he was on 1000 mg of Metformin. Considering his high sugar it was increased to 1500 mg and 2 mg of Glimiperide was added. About a week ago he developed jaundice. Liver enzymes and other biochemical values were very high. Serological test for HBsAG was positive. Lab report is enclosed herewith. He was brought to me for second opinion about 5 days back. In view of his age and liver damage Metformin was withdrawn and Glimeperide was reduced to 0.5 mg a day (1/4th of the previous dose). In addition he was put on B-complex, dietary advice was also given. He was advised to come for follow up after a week. Today morning his son calls me on phone at about 7.30 to inform me that his father has become suddenly semi-conscious and they don't know what to do. Patient was sweating a lot too. Hypoglycaemia was suspected, therefore the son was asked to forcefully give his father about 3-4 spoonful of sugar and report the developments after about 15 minutes. Accordingly he called me to say that his father has started blinking and recovering. I too was happy. But this didn't last long, he had one more such episode after about an hour, one more round of sugar, made him recover. He was advised to visit me for a thorough checkup. He looked like any other normal person waiting for his turn in the clinic. He had his breakfast about an hour ago, his capillary blood sugar was astonishingly as low as 32 mg/dl. Doubting about a possible defect in my Glucometer itself I checked my own blood sugar for verification. It was as it should be, meaning thereby that the device was normal. He was given sumptuous sugar and a repeat test was done after 20 minutes. He was advised to stop Glimmiperide till further instructions. The value was a mere 80 mg/dl. At night after his dinner his sugar was again checked, it was again a mere 74 mg/dl. In view of repeated episodes he was hospitalised. Points to ponder: Evidently it was a case of hypoglycaemia on all the four occasions. But why should he go into hypoglycaemia inspite of Metformin withdrawal and reducing Glimiperide to 0.5 from 2.0 mg OD. The case will be further discussed after 2-3 days. If you have anything to add or ask, kindly do so, I will try to answer. There will be someone who can highlight on this case, if I fail to comply.
First my congrats for very scientific management of the case. This is an open and shut case. A little consideration of physiology will explain the riddle. Body' defence against secondery hypoglycemias is by dumpihg glucose by gluconeogenisis. This calls for interplay of glucogon and liverglycogen. When both are normal the physiological compe nsatory mechanism is effective. Change ib eitherside of equation ie more of "glucogon" or less of " liver glycogen" Make inaffective this compensation. Glucogan excess ( say due to glucogon secreting tumor) is a rare ossibility but worth considering if the conter part, the liver glycogen is alright. Here there is jaundice when the sick liver cells are naturally unable to do their normal function of storing the 'glycogen the buffer glucose' in fact in viral hepatititis , the pathology text books describe the histologic picture as if " the liver cells are blown off ". So it is with the glycogen stored in it !. This duel defect ie failure of 'sick' hepatocytes to synthesise ' new hlycogen ' and the ' blown up ' cells squandering the stored glycogen make the compensatory mechanism in effective. ! The severity of defect is proportionate to extent of liver cell damage which can be assessed by high vales of liver enzmes especially SGOT AND SGPT.- WHICH T SAID TO BE HIGH IN THIS CASE. IF ANY DOUBT EXISTS ABOUT THE EXPLANATION , LIVER GLYCOGEN MAY BE ESTIMATED WHICH WILL BE LESS THAN 30 GMS UNDOUBTEDLY. THIS OVER CONFIDENCE IS BECAUSE OFTEN ' INTER CORRELATION OF KNOWN FACTS' ARE NOT EXCERCISED UNLESS IT IS EXPLAINED. To put it in terms of great ' BOYD'- " WHAT THE MIND DOES NOT KNOW THE EYE DOESNOT SEE" I DARE TO SAY THAT THE REVERSE IS ALSO TRUE- "WHAT THE EYE DOESN'T SEE, THE MIND DOESN'T KNOW ! The reference is to the fact that everybody knows that in jaundice glucose is advised in good anounts why ? It is taught in our books ' as it protects the liver cells' - in fact it ' protects against the possible hypoglycemia ' if such is the case with normal person what about with a pt who is on more than required OHA? It must also be remembered that " untill the whole lot of glimeperide dumped in is cleared , the pt is not free from risk of hypogycemia. So giving suger once doesnot carry forward its benifits. So once it did the job where is the protection for further period till full clearance of the drug? So naturally the pt goes into hypo again and again. ! Which is what happened here. So the hospital can " stop being busy " with unnecessary investigations by giving continuous slow drip of 10% dextrose for a day or two followed by oral glucose for a fortnight or so, or a week after liver pathology is corrected. So his diabetic control in hospital while on glucose can be met with by titrated dose of tegular insulin after stoopping OHA the goal being to achieve euglycemia and titrate upward the OHA dose starting with mono therapy. Badly managed DM2 b 4 and avoidable cofusion later.- This is my personal opinion only. Pt should not drink alchohol for a month or so ( afterwards it his pleasure!).
Glimipride is known to cause such episodes of hypoglycaemia .This is not a surprise as patient is a case of hepatitis B with CLD . Since oral uptake of.such patients is low he may not need HOG. If at blood sugar levels raise again an ayurvedic preparation like BGR or IME 9 should be added as there is no danger of hypoglycaemia
Case of CLD with type 2 diabetes I presume he has no CKD , he had multiple symptomatic episodes of hypoglycaemic though it was only documented once 32mg/ dl on other two occasions he had 80 and 74 mg/l which is not hypoglycaemia as per definition . Now coming to the main point , why is he getting recurrent symptomatic episodes of hypoglycaemia?? You have stopped the Metformin but, metformin is not known to cause hypoglycaemia. Reducing the dose of Glimipride form 2 to 0.5 mg can still be a culprit here , he has CLD and metabolism of Glimipride is decreased in CLD that is one possible cause . Another possible cause apart from reduced gluconeogenesis is low glycogen storage in the liver due to CLD , which means less Glycogenolysis which is the one of main pathway involved when a person gets hypoglycaemia. 3rd possible cause in this patient with CLD is poor nutrition, after any severe hypoglycaemia one golden rule is make sure patient has a proper meal , what this does is it replenishes the glycogen storage in the liver which prevent further hypoglycaemia but in this particular case as he has CLD so glycogen synthesis will be still hampered . Keeping his age into consideration, we should not bother about his hyperglycaemia rather hypoglycaemia which could prove fatal. So stop all oral drugs including 0.5mg Glimipride. Manage his diabetes by medical nutritional therapy (MNT) only , give multiple small meals every 2-3 hourly . Maintain his good SMBG record and manage his PP sugars with rapid acting insulin analogue and fasting sugars with long acting analogue , if needed . Thanks
Here the culprit is SU like gilmepride that should be cleared completely ,this drug is most probably cause of recurrent hypoglycaemic episodes, liver glycogen burnt out in hepatitis is one more answer to hypoglycemia
I should have kept my promise to update you on this case after two days of posting this case, thinking the patient would be discharged by then. He is still in the hospital, as hypoglycaemic episodes are continuing to occur even on 4th day, he is under observation and more investigations are called for. His relatives have been informed that he has CKD and both the kidneys have shrunken. Details are not available. Metformin was withdrawn in view of his high liver enzymes and also looking at his age (82). Glimiperide was reduced to 0.5 from 2 mg, keeping his high sugar values. He was alright for 5 days on this new regime but the hypos started from 6th day. The logical conclusion is Glimiperide is metabolized extensively by hepatic P450 enzyme CYP2C9 to less-active metabolites, cyclohexyl hydroxy methyl derivative (M1; mildly active) and the carboxyl derivative (M2; inactive). In this case because of hepatic injury this was probably hindered and there was cumulative effect of un-metabolised Glimiperide causing hypos. Secondly because of his newly detected kidney problems even the elimination of Glimiperide from the body is delayed which may further precipitate hypos. All in all 100% bioavailability, incomplete degradation in the liver and poor elimination from the kidneys must have led to this episode. Insulinomas are a remote possibility. Finally the question “Hypoglycaemia, is it the cause or effect of Liver damage?”. The emphatic answer is “It can be both, Glimiperide can cause both”. An honourable member has opined that 74 and 80 mg of sugar are not indicative of hypoglycaemic episodes, I agree with the views, my contention was they are the indices of further management, if value dips it means he is heading for hypo, and it mounts he is improving. I have come across good number of cases of hypos and everyone was managed successfully and no one was hospitalised. But this case, OMG.
This patient now in hupoglycemic state with abnormal LFT which looks like Acute on Chronic Liver Disease due to HVB.HERE may I suggest Tumor Markers and K+ &Na+ for ruling out Addison 's disease.Repeated hupoglycemic episodes may be present in Hepatoma. I have seen this in one case that patient was around 45 yrs.I don't know malignancy may be present in this age!
Hepatic Gluconeogenesis is impaired due to Liver Damage Glimeperide will have longer duration of action due to hepatic damage as well
Sir due to jaundice n viral infection, Liver not able to maintain digestive activity well n along with hepatocellular destruction gluconeogenesis is very poor, as well as Glimperide is going on which resulted into this.... So Glimperide be omitted n to normalize the liver 1st must be priority as far as I think. And further USg n appropriate investigation must be done
I should have kept my promise to update you on this case after two days of posting this case, thinking the patient would be discharged by then. He is still in the hospital, as hypoglycaemic episodes are continuing to occur even on 4th day, he is under observation and more investigations are called for. His relatives have been informed that he has CKD and both the kidneys have shrunken. Details are not available. Metformin was withdrawn in view of his high liver enzymes and also looking at his age (82). Glimiperide was reduced to 0.5 from 2 mg, keeping his high sugar values. He was alright for 5 days on this new regime but the hypos started from 6th day. The logical conclusion is Glimiperide is metabolized extensively by hepatic P450 enzyme CYP2C9 to less-active metabolites, cyclohexyl hydroxy methyl derivative (M1; mildly active) and the carboxyl derivative (M2; inactive). In this case because of hepatic injury this was probably hindered and there was cumulative effect of un-metabolised Glimiperide causing hypos. Secondly because of his newly detected kidney problems even the elimination of Glimiperide from the body is delayed which may further precipitate hypos. All in all 100% bioavailability, incomplete degradation in the liver and poor elimination from the kidneys must have led to this episode. Insulinomas are a remote possibility. Finally the question “Hypoglycaemia, is it the cause or effect of Liver damage?”. The emphatic answer is “It can be both, Glimiperide can cause both”. An honourable member has opined that 74 and 80 mg of sugar are not indicative of hypoglycaemic episodes, I agree with the views, my contention was they are the indices of further management, if value dips it means he is heading for hypo, and it mounts he is improving. I have come across good number of cases of hypos and everyone was managed successfully and no one was hospitalised. But this case, OMG.
What is renal function test . Being 85 yr old n underlying occult diab nephropathy plus poor hepatic metabolism of OAD having repeated episode of hypoglycaemia. Stop all OAD and after through examination and investigation can star rapid insulin if reqd
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Hepatitis *Hepatitis* refers to an inflammatory condition of the liver. It’s commonly caused by a viral infection, but there are other possible causes of hepatitis. These include autoimmune hepatitis and hepatitis that occurs as a secondary result of medications, drugs, toxins, and alcohol. Autoimmune hepatitis is a disease that occurs when your body makes antibodies against your liver tissue.  Timeline 8th Century: Infectious Nature of HBV suggested 17th-19th Centuries: Outbreaks of epidemics of jaundice in military and civilian populations during wars 1883: Lurman reports outbreaks of serum hepatitis follwing vaccination of dockers 1908: McDonald postulates that the infectious jaundice is caused by a virus 1939-1945: WWII-A series of outbreaks after vaccination for measles and yellow fever 1947: MacCallum classifies viral hepatitis into two types- Viral hepatitis A—> Infectious hepatitisViral hepatitis B—> Serum hepatitis 1965: Blumberg discovers Australia antigen (HBsAg) in aborigines and shows presence of antigen at high frequency in patients with leukemia and children with Down’s syndrome 1970: Dane discovers the Dane particle (complete HBV particle) 1972: Discovers HBeAg 1973: Feinstone and Purcell identifies HAV 1977: Rizzetto describes delta antigen HDV 1983: Recovery of HEV 1988: Chiron group (Choo, Kuo, Houghton) closes and identifies HCV. 1995: Abbot group reports GB Virus-C (GBV-C) and Genelabs group reports in 1996 hepatitis G virus (HGV)—GBV-C=HGV 1996: Chang’s group at NTUH reports in JAMA the successful prevention of HBV infection by nation-wide vaccination on newborn babies launched in 1984 in Taiwan. 1997: Chang’s group at NTUH reports in NEJM a decrease in annual incidence rate of hepatocellular carcinoma in children ascribed to nation-wide vaccination against HBV on newborn babies launched in 1984 in Taiwan. Epidemiology Globally, viral It was the seventh leading cause of death in 2013, up from the 10th leading cause in 1990. Worldwide, HAV is responsible for an estimated 1.4 million infections annually. About 2 billion people in the world have evidence of past or current HBV infection, with 240 million chronic carriers of HBsAg. HBV, along with the associated infection by the hepatitis D virus, is one of the most common pathogens afflicting humans. HBV leads to 650,000 deaths annually as a result of viral hepatitis–induced liver disease. The worldwide annual incidence of acute HCV infection is not easily estimated, because patients are often asymptomatic. An estimated 71 million people are chronically infected with HCV worldwide. About 55-85% of these people infected progress to chronic HCV infection, with a 15-30% risk of developing liver cirrhosis within two decades. China, the United States, and Russia have the largest populations of anti-HCV positive injection drug users (IDUs). It is estimated that 6.4 million IDUs worldwide are positive for antibody to hepatitis B core antigen (HBcAg) (anti-HBc), and 1.2 million are HBsAg-positive. Types and causes Viral infections of the liver that are classified as hepatitis include hepatitis A, B, C, D, and E. A different virus is responsible for each type of virally transmitted hepatitis. Hepatitis A is always an acute, short-term disease, while hepatitis B, C, and D are most likely to become ongoing and chronic. Hepatitis E is usually acute but can be particularly dangerous in pregnant women. Hepatitis A Hepatitis A is caused by an infection with the hepatitis A virus (HAV). This type of hepatitis is most commonly transmitted by consuming food or water contaminated by feces from a person infected with hepatitis A. Hepatitis B Hepatitis B is transmitted through contact with infectious body fluids, such as blood, vaginal secretions, or semen, containing the hepatitis B virus (HBV). Injection drug use, having sex with an infected partner, or sharing razors with an infected person increase your risk of getting hepatitis B. It’s estimated by the CDC that 1.2 million people in the United States and 350 million people worldwide live with this chronic disease. Hepatitis C Hepatitis C comes from the hepatitis C virus (HCV). Hepatitis C is transmitted through direct contact with infected body fluids, typically through injection drug use and sexual contact. HCV is among the most common bloodborne viral infections in the United States. Approximately 2.7 to 3.9 million Americans are currently living with a chronic form of this infection. Hepatitis D Also called delta hepatitis, hepatitis D is a serious liver disease caused by the hepatitis D virus (HDV). HDV is contracted through direct contact with infected blood. Hepatitis D is a rare form of hepatitis that only occurs in conjunction with hepatitis B infection. The hepatitis D virus can’t multiply without the presence of hepatitis B. It’s very uncommon in the United States. Hepatitis E Hepatitis E is a waterborne disease caused by the hepatitis E virus (HEV). Hepatitis E is mainly found in areas with poor sanitation and typically results from ingesting fecal matter that contaminates the water supply. This disease is uncommon in the United States. However, cases of hepatitis E have been reported in the Middle East, Asia, Central America, and Africa, according to the CDC. Autoimmune Hepatitis Autoimmune hepatitis is a rare form of chronic hepatitis. Like other autoimmune disorders, its exact cause is unknown. Autoimmune hepatitis may develop on its own or it may be associated with other autoimmune disorders, such as systemic lupus erythematosus. In autoimmune disorders, a misdirected immune system attacks the body’s own cells and organs (in this case the liver). Symptoms When symptoms occur, they can include: Jaundice (a yellowing of the skin and eyes)Abdominal painLoss of appetiteNausea and vomitingDiarrheaFeverClay-colored bowel movementsPainful joints  Yellowing of skin and eye  Complications of hepatitis Chronic hepatitis B or C can often lead to more serious health problems. Because the virus affects the liver, people with chronic hepatitis B or C are at risk for: Chronic liver diseaseCirrhosisLiver cancer When your liver stops functioning normally, liver failure can occur. Complications of liver failure include: Bleeding disordersA buildup of fluid in your abdomen, known as ascitesIncreased blood pressure in portal veins that enter your liver, known as portal hypertensionKidney failureHepatic encephalopathy , which can involve fatigue, memory loss, and diminished mental abilities due to the buildup of toxins, like ammonia, that affect brain functionHepatocellular carcinoma, which is a form of liver cancerDeath People with chronic hepatitis B and C are encouraged to avoid alcohol because it can accelerate liver disease and failure. Certain supplements and medications can also affect liver function. If you have chronic hepatitis B or C, check with your doctor before taking any new medications. Diagnosis and test History and physical exam To diagnose hepatitis, first your doctor will take your history to determine any risk factors you may have for infectious or noninfectious hepatitis. During a physical examination, your doctor may press down gently on your abdomen to see if there’s pain or tenderness. Your doctor may also feel to see if your liver is enlarged. If your skin or eyes are yellow, your doctor will note this during the exam. Liver function tests Liver function tests use blood samples to determine how efficiently your liver works. Abnormal results of these tests may be the first indication that there is a problem, especially if you don’t show any signs on a physical exam of liver disease. High liver enzyme levels may indicate that your liver is stressed, damaged, or not functioning properly. Other blood tests If your liver function tests are abnormal, your doctor will likely order other blood tests to detect the source of the problem. These tests can check for the viruses that cause hepatitis. They can also be used to check for antibodies that are common in conditions like autoimmune hepatitis. Ultrasound An abdominal ultrasound uses ultrasound waves to create an image of the organs within your abdomen. This test allows your doctor to take a close at your liver and nearby organs. It can reveal: Fluid in your abdomenLiver damage or enlargementLiver tumoursAbnormalities of your gallbladder Sometimes the pancreas shows up on ultrasound images as well. This can be a useful test in determining the cause of your abnormal liver function. Liver biopsy A liver biopsy is an invasive procedure that involves your doctor taking a sample of tissue from your liver. It can be done through your skin with a needle and doesn’t require surgery. Typically, an ultrasound is used to guide your doctor when taking the biopsy sample. This test allows your doctor to determine how infection or inflammation has affected your liver. It can also be used to sample any areas in your liver that appear abnormal. Treatment and medications Treatment options are determined by which type of hepatitis you have and whether the infection is acute or chronic. Hepatitis A Hepatitis A usually doesn’t require treatment because it’s a short-term illness. Bed rest may be recommended if symptoms cause a great deal of discomfort. If you experience vomiting or diarrhea , follow your doctor’s orders for hydration and nutrition. The hepatitis A vaccine is available to prevent this infection. Most children begin vaccination between ages 12 and 18 months. It’s a series of two vaccines. Vaccination for hepatitis A is also available for adults and can be combined with the hepatitis B vaccine. Hepatitis B Acute hepatitis B doesn’t require specific treatment. Chronic hepatitis B is treated with antiviral medications. This form of treatment can be costly because it must be continued for several months or years. Treatment for chronic hepatitis B also requires regular medical evaluations and monitoring to determine if the virus is responding to treatment. Hepatitis B can be prevented with vaccination. The CDC recommends hepatitis B vaccinations for all newborns. The series of three vaccines is typically completed over the first six months of childhood. The vaccine is also recommended for all healthcare and medical personnel. Hepatitis C Antiviral medications are used to treat both acute and chronic forms of hepatitis C. People who develop chronic hepatitis C are typically treated with a combination of antiviral drug therapies. They may also need further testing to determine the best form of treatment. People who develop cirrhosis (scarring of the liver) or liver disease as a result of chronic hepatitis C may be candidates for a liver transplant . Currently, there is no vaccination for hepatitis C. Hepatitis D No antiviral medications exist for the treatment of hepatitis D at this time. According to a 2013 study , a drug called alpha interferon can be used to treat hepatitis D, but it only shows improvement in about 25 to 30 percent of people. Hepatitis D can be prevented by getting the vaccination for hepatitis B, as infection with hepatitis B is necessary for hepatitis D to develop. Hepatitis E Currently, no specific medical therapies are available to treat hepatitis E. Because the infection is often acute, it typically resolves on its own. People with this type of infection are often advised to get adequate rest, drink plenty of fluids, get enough nutrients, and avoid alcohol. However, pregnant women who develop this infection require close monitoring and care. Autoimmune hepatitis Corticosteroids, like prednisone or budesonide, are extremely important in the early treatment of autoimmune hepatitis. They’re effective in about 80 percent of people with this condition.Azothioprine ( Imuran ), a drug that suppresses the immune system, is often included in treatment. It can be used with or without steroids.Other immune suppressing drugs like mycophenolate (CellCept), tacrolimus (Prograf) and cyclosporine (Neoral) can also be used as alternatives to azathioprine for treatment. Prevention There are many steps you can take to reduce the risk of viral hepatitis: Consider getting vaccinated against hepatitis A and B if you weren’t vaccinated as a child. This is the number one way to prevent these illnesses.Wash your hands with soap and water after using the bathroom or changing a baby’s diaper and before handling food.When traveling in developing countries, avoid unpeeled or raw foods. Drink only bottled, boiled or chemically treated water.Practice safe sex. Hepatitis B is about 50–100 times more transmissible during sex than HIV. Condoms and other barrier methods greatly reduce the risk.Never share syringes, shaving razors, toothbrushes or tattooing or piercing supplies.Wear gloves when performing first aid.Disinfect blood spills (including dried ones) with diluted bleach and wear gloves during clean-up.Follow all occupational safety precautions in your workplace.If you are pregnant, seek early and regular prenatal care. To reduce the risk of non-viral hepatitis, avoid excessive alcohol consumption and consult with a healthcare professional about medications and supplements.
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A 40 yr old lady presented with the history of jaundice for 2 weeks. There were associated prodromal symptoms. Jaundice was progressively increasing at the time of presentation. No associated fever or abdominal pain. Patient was not on any treatment prior to these symptoms and there was no history of indigenous medicine intake. Examination revealed Icterus, firm hepatomegaly. No splenomegaly or ascites. Investigations are attached in the table. USG ABDOMEN was done: coarse liver echotexture, Portal vein 11mm, mild splenomegaly. No ascites. HBsAg and anti HCV were negative. Patient was treated with symptomatic treatment. UDCA was added. The patient improved over next few days, symptoms improved (appetite improved, vomiting decreased and jaundice started decreasing). Repeat investigations are shown in the same table. IgM anti HAV and IgM anti HEV were negative. The patient improved over next month. What is the likely diagnosis? Are any further investigations warranted? Or is it enough to keep the patient under follow up?
Dr. Nitin Gupta16 Likes30 Answers
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