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 In view of his age and liver damage Metformin was withdrawn and Glimeperide was reduced to 0.5 mg a day (1/4th of the previous dose).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.

7 Likes

LikeAnswersShare

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!).

Dr Prasad, thank you for indepth analysis of the case. My concern was why he was going into frequent hypos even after withdrawing 0.5 mg of Glimiperide even on 3rd day of hospitalisation. Glimiperide is extensively metabolised in the liver to less active metabolites. In this case as you have aptly said they are blown up, as a result metabolism is hindered resulting in cumulative effect of unmetabolised Glimiperide producing hypos. In this case it took 3 days for normalisation. The other remote possibility was Insulinoma if patient was not to respond to routine line of treatment. I have come across quite a good number of hypoglycaemic episodes in my practice but believe me not the one like this
0

View 2 other replies

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

? HOG.
0

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

Metformin was stopped looking at is age and increased liver enzymes and other parameters. Glimiperide 0.5 mg has also been stopped since 3 days but he is still experiencing hypos. In between these attacks he is walking around taking routine food. He is still in hospital.
0

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.

Nice One Sir Addition to our knowledge broadening our vision for differential diagnosis
0

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

You are partially correct. I will give convincing reply at the end.
0

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

Don't whisk away the expertise of the doctor treating him earlier. As per the history his sugar levels were high metformin was increased to 1500 mg and 2 mg of Glimiperide was added. Later on the patient had liver ailments, & looking at the damage metformin was totally withdrawn and Glimiperide was reduced to a bear minimum of 0.5 from 2 mg a day. While summing up the case I will answer why he was sinking into hypos.
0

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

Plus also go for HBV workup including hbv dna and AFP and other hepatotropic viruses ig M
0
Load more answers

Cases that would interest you