Deranged Liver Enzymes In A Case Of Diabetes In Pregnancy: Diagnostic Dilemma

Author Information

Saxena A*, Thunga C**, Madhva Prasad S***, Gupta AS****.

(* First year Resident, ** Senior Resident, *** Assistant Professor, **** Professor, Department of Obstetrics and Gynecology, Seth GS Medical College and KEM Hospital, Mumbai.)

Abstract

A case of a pregnancy with diabetes mellitus and incidental finding of deranged liver enzymes and the diagnostic dilemma associated with such a condition is presented here. A brief discussion of the possibilities is presented.

Introduction

Diabetes in pregnancy can be classified as those known to have diabetes prior to pregnancy, pre gestational or overt diabetes; and those diagnosed during pregnancy, gestational diabetes mellitus. Classification of non pregnant individuals with diabetes is based on the presumed etiopathogenesis and pathological manifestations, broadly as Type 1 diabetes with absolute insulin deficiency and Type 2 diabetes with insulin resistance. Most of the gestational diabetic women are likely to have Type 2 diabetes which had been undiagnosed till pregnancy.[1]

Concern is mainly due to the complications associated with diabetes in pregnancy, both maternal and fetal morbidity and mortality.  Most of them present with deranged blood sugar levels and no symptoms. Some present with complications like ketoacidosis, hypoglycemia, hypertension, infections, pre eclampsia, diabetic nephropathy, neuropathy, and or retinopathy. There are certain unusual manifestations like this case that we are presenting. There was an incidental finding of asymptomatic deranged liver enzymes in a pregnant woman who had diabetes and  no other cause could be found for the same.

Case Report

Twenty nine years old woman, married since 12 years, gravida 4 para 2 abortion 1 living 1, presented to the outpatient department at 31 weeks of gestation. Her pregnancy was complicated by preeclampsia; and the first living issue was a was 3 kg male child, born from a full term lower segment cesarean section, who lived well but died at 4 months of age due to pneumonia. Her second child was a female born from a full term normal delivery, 2.5 kg at birth and is now 8 years old. After this she had a spontaneous abortion at 3 months of amenorrhea, followed by a check curettage.  There was no history of raised blood sugars in any of the previous pregnancies. Her both parents were diabetic.

In this pregnancy, she had registered elsewhere, and presented at 31 weeks with abnormal fasting blood sugars and was admitted for the same.  On examination, she was conscious, oriented, with normal pulse, blood pressure, cardiovascular and respiratory system examinations. On local examination uterus was 30 weeks in size with a live fetus in cephalic presentation and closed cervical os. She had a report of fasting blood sugars measuring 108 mg %. Oral glucose tolerance test was done with 75 gms glucose and the values (all in mg %)  were 216 (fasting), 307 (1 hour), 322 mg (2 hour) and 288 (3 hours).

Endocrinologists advised diabetic diet with self monitoring of blood glucose 6 times a day, and injection Human Insulin [R] 10-10-10-0 U and Human Insulin [N] 22-0-0-26 U, subcutaneously was started. She was given injectable steroids for lung maturation (dexamethasone 6 mg 4 doses 12 hours apart) and insulin values were adjusted accordingly. 

Incidentally, abnormal liver function tests (LFTs) were detected. Ultrasound abdomen was done which was suggestive of normal liver echotexture with no focal lesions but the gall bladder was distended with sludge. All viral markers of hepatitis and HIV were negative. She gave no history suggestive of any liver disorder such as icterus, itching, nausea, vomiting, oedema, or abnormal bleeding. Upon further questioning, she reported use of some homeopathic medications for 6 months that had been discontinued for the last 2 months. Gastroenterologists opined to avoid hepatotoxic drugs and monitor liver function tests every 3rd day.  

However, in view of increasing trends of liver enzymes (as shown in table 1), a decision to terminate pregnancy was taken (at 30weeks 3 days of gestation). Her coagulation profile was checked and was normal. She was taken up for LSCS in view of breech presentation with worsening of liver function tests. She delivered a female child of 1.862 kg, with Apgar score 0f 9/10, was admitted to NICU where she initially required continuous positive airway pressure ventilation and was gradually weaned off. Injection insulin was discontinued on postpartum day 3 and converted to tablet metformin 500 mg 2-1-2 at discharge. Wound check was healthy, daily blood sugars and liver function tests were monitored (as shown in the table 1). She was discharged on day 5 and was asked to follow up in OPD after 15 days for suture removal and her LFT reports. On 19th post operative day when she came to OPD for follow up her LFTs had come to normal. Her recent fasting sugars were 150 mg% and she was taking medications for the same.

Table 1: Pattern of platelet counts, liver function tests and fasting blood sugars from antenatal to postpartum period during her hospital stay 

	On admission	6 days     prior	3 days prior	1day prior	Day Of LSCS	Day 1 Post op	Day 2 Post op	Day 4 Post op	Day 19 Post op
Hb  (gm%)	10.2		9.1	8.5	8.8	10.1	11.3	10.8
Platelet Count (cmm)	1.15 lakh		1.2 lakh	1.02 lakh	1.1 lakh	1.4 lakh	1.4 lakh	1.6 lakh
Alkaline Phosphatase	536	571	450	427	420	-	-	396	298
SGOT (IU/ml)	195	213	307	317	248	332	76	55	31
SGPT (IU/ml)	136	166	277	299	257	341	211	114	14
FBS (mg%)	274	228	267	197	153	140	132	136

Discussion

Liver has a role in maintaining normal glucose homeostasis. In our patient, both liver enzyme derangement and abnormal blood sugar values were detected at approximately the same time. Whether one preceded the other remote from the time of detection is not known. In such a scenario, any of the possibilities could have existed. That is, liver disease as a consequence of diabetes, diabetes as a complication of liver disorder or liver disorder coincidental with diabetes. This association may explain the pathogenesis behind diabetes and abnormal liver enzymes, or it could be purely coincidental.

One study done in 2011 found an association between insulin resistance and aminotransferases, in the absence of detectable steatosis by ultrasonography. This study indicated that in diabetes, even mild steatosis is sufficient to mediate the derangement of aminotransferases.[2]

The presentation of non-alcoholic steatohepatitis can vary from asymptomatic elevated liver enzymes to full blown fibrosis and nodular regeneration. Hence they can be considered as a cause for chronically elevated liver enzymes in asymptomatic diabetic patients, particularly if they are obese and have hyperlipidemia.[3] This could be one of the differential diagnosis in our case. Our patient had BMI of 31.8 kg/m2 but lipid values were not checked.

Ultrasound abdomen showed a normal liver echotexture with no focal lesions and a distended gall bladder with sludge.  No specific correlation between  pregnancy an non alcoholic steatohepatitis have been reported.  Weight loss upto 10%, good control of blood glucose levels and addition of ursodeoxycholic acid can help in normalizing the liver enzymes in such conditions.[4, 5]

Biliary diseases and diabetes have an association, obesity being a common factor. Although in pregnancy, lithogenicity or the cholesterol saturation index of bile increases due to hyperestrogenemia, the biliary sludge that appears in pregnancy is known to resolve post partum and rarely results in gall stones. Our patient had obesity and gall bladder sludge. However, gallstone disease in pregnancy is extremely rare.[6]

Some studies have shown rare association between the use of oral hypoglycemics and liver injury, mostly with use of sulphonylureas, causing chronic hepatitis and necroinflammatory changes.[6] This possibility is less probable in our case as she was diagnosed with diabetes during antenatal visit and was not on oral hypoglycemics earlier. However, this is relevant in patients who may present with diabetes and raised liver enzymes.[7]

Though we cannot comment on the role of homeopathic medications that she had consumed prior to the ANC visit, literature reports a study of toxic hepatitis or drug induced liver injury in Type 2 diabetic patients treated with Gymnema sylvestre. This is a plant which is known to be a potent antidiabetic, widely used in Ayurveda and Homeopathy medications.[8]

A study done by Frazer and associates found an association between chronic hepatitis C and impaired glucose tolerance, and reported that diabetes is found to be more frequent in patients with hepatitis C than in general population.[9] Our patient was negative for viral markers of hepatitis. 

Autoimmune hepatitis is another progressive liver disease that can manifest at any time of life, including pregnancy and postpartum. Pregnancy is a period of immune tolerance hence the disease activity of autoimmune conditions attenuates during antenatal period but worsens during postpartum period. Hence post pregnancy is a better time to evaluate presence of autoantibodies.[10] This is not applicable to our study as her LFTs normalized after delivery.

Considering the liver diseases unique to pregnancy, HELLP syndrome which is a complication occurring as a sequel to severe pre eclampsia must be considered here. It is also known that there is a high risk for a diabetic mother to develop chronic or gestational hypertension,  specially pre eclampsia. A study by Yanit and colleagues in 2012, reported that pre eclampsia developed three or four times more often in women with overt diabetes.[11]

Another possible explanation for our case could be atypical HELLP syndrome with normal blood pressure in a diabetic pregnant woman. HELLP syndrome comprises of hemolysis, elevated liver enzymes and low platelet count, as a complication in a patient with severe pre eclampsia. Literature study reveals some atypical presentations of this condition where no other etiology could be considered.[12] After delivery the liver enzymes level began to reduce, with improvement in haemoglobin levels and platelet count. 

To conclude, diabetes in pregnancy and liver disease could coexist in a patient with various manifestations and possible conditions are discussed above. The condition is discussed because sometimes decisions to terminate pregnancy need to be taken even without a specific diagnosis, and many a time extensive evaluation in postpartum period may be required for accurate diagnosis.  

References

1. Feig DS, Palda VA. Type 2 diabetes in pregnancy: a growing concern.Lancet. 2002;359(9318):1690-2.
2. Esteghamati A, Noshad S, Khalilzadeh O, Khalili M, Zandieh A, Nakhjavani M. Insulin resistance is independently associated with liver aminotransferases in diabetic patients without ultrasound signs of nonalcoholic fatty liver disease. Metab Syndr Relat Disord. 2011;9(2):111-7. 
3. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann Intern Med. 1997; 126(2):137-45.
4. Palmer M, Schaffner F. Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology. 1990;99(5):1408-13.
5. Laurin J, Lindor KD, Crippin JS, Gossard A, Gores GJ, Ludwig J, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study.Hepatology. 1996;23(6):1464-7.
6. Kolbeinsson HM, Hardardottir H, Birgisson G, Moller PH. Gallstone disease during pregnancy at Landspitali University Hospital 1990-2010. Laeknabladid. 2016; 102(12):538-542.
7. Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, et al. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015; 11(4): 840–848.
8. Shiyovich A, Sztarkier I, Nesher L. Toxic hepatitis induced by Gymnema sylvestre, a natural remedy for type 2 diabetes mellitus. Am J Med Sci 2010;340 (6): 514-7.
9. Fraser GM, Harman I, Meller N, Niv Y, Porath A. Diabetes mellitus is associated with chronic hepatitis C but not chronic hepatitis B infection. Isr J Med Sci 1996; 32(7):526-30.
10. Mehta V, Prasad M, Gupta AS. Autoimmune Hepatitis in Pregnancy. JPGO 2016;3(8). Available from: http://www.jpgo.org/2016/08/autoimmune-hepatitis-in-pregnancy.htm
11. Yanit KE, Snowden JM, Cheng YM, Caughey AB. The impact of chronic hypertension and pregestational diabetes on pregnancy outcomes Am J Obstet Gynecol 2012; 207(4): 333
12. Garrido MF, Carvajal JA. Normotensive HELLP syndrome: report of one case. Rev Med Chil. 2013; 141(11):1470-4.

Citation

Saxena A, Thunga C, Madhva Prasad S, Gupta AS. Deranged Liver Enzymes In A Case Of Diabetes In Pregnancy:  Diagnostic Dilemma.  JPGO 2017. Volume 4 No.10. Available from: http://www.jpgo.org/2017/10/deranged-liver-enzymes-in-case-of.html