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© 2004 by the American Diabetes Association, Inc.
Letters: Observations |
Improper Insulin Compliance May Lead to Hepatomegaly and Elevated Hepatic Enzymes in Type 1 Diabetic Patients
From the Section of Endocrinology, Children’s Mercy Hospital, University of Missouri at Kansas City School of Medicine, Kansas City, Missouri
Address correspondence to Miles Yu, Section of Endocrinology, Children’s Mercy Hospital, 2401 Gillham Rd., Kansas City, MO 64108. E-mail: milesyu{at}cmh.edu
We have encountered hepatomegaly and pronounced elevation of liver enzymes AST and ALT in four patients with type 1 diabetes. These patients shared similar clinical features. They were all female (aged 11–14 years) with poor glycemic control. All had frequent hyperglycemia and intermittent hypoglycemia related to their history of poor compliance. Most of them had multiple hospital admissions for severe hyperglycemia and/or diabetic ketoacidosis. In addition to their high daily doses of insulin (1.3–2.2 units · kg-1 · day-1), most were receiving extra doses of insulin to correct their frequent hyperglycemia. A1C levels were all higher than normal (ranging from 9.2 to 14.5%). Their initial AST and ALT levels were at least 30- and 14-fold higher than the normal limits, respectively, but the other liver function tests, such as alkaline phosphatase, prothrombin/partial prothrombintime, and total bilirubin, were normal except for one patient who had a minimal increase in alkaline phosphatase and total billirubin. The degree of hepatomegaly did not correlate with the liver enzyme levels, nor did it correlate with glycemic control or HbA1c levels.
Upon admission to the hospital, proper insulin dosing was established. Three of the four patients were able to lower their insulin dose to 0.9–1.2 units · kg-1 · day-1 and achieve normal glycemic control. The AST and ALT levels were quickly decreased in just a few days after the patients obtained better glycemic control during hospitalization. Except for one patient, who was admitted for diabetic ketoacidosis, the patients had no apparent symptoms of liver disease before the admission. Their hepatomegaly was an incidental finding. Other than poorly controlled diabetes, the investigations did not reveal any other causes for hepatomegaly and increased liver enzymes. The normal creatine phosphokinase level and negative myoglobinuria from one patient ruled out the possibility of rhabdomyolysis. The liver biopsy obtained in one patient revealed abundant glycogen deposits in hepatocytes that were consistent with the abdominal computed tomography finding of "fatty" appearance of those enlarged livers in all four patients. There were also some features that these patients did not share. One patient with the most profound hepatomegaly had significant delay in growth and puberty consistent with Mauriac syndrome as previously described (1), whereas the other three patients had normal growth and puberty. One patient, who was found to have hepatomegaly and elevated hepatic enzymes during one of her admissions to the hospital for diabetic ketoacidosis, had some nonspecific gastrointestinal symptoms that might have been related to her diabetic ketoacidosis rather than the hepatic disorder. Although all of our cases were girls, similar cases have been identified in boys (2).
Hepatomegaly and elevated hepatic enzymes, reported in both adult and pediatric patients with type 1 diabetes (2,3), could be relatively common but may be under-recognized or misidentified as the more common nonalcoholic steatohepatitis (NASH) because of similar clinical features. NASH is commonly seen in obese type 2 diabetic patients with insulin resistance. The hepatic enzyme elevation is slow to resolve. Our patients, however, were all nonobese type 1 diabetic patients. Their pronounced elevation of hepatic enzymes was resolved in just a few days once they achieved reasonable glycemic control at insulin dosages that were lower than what they were prescribed at home. Though the mild hepatomegaly and abnormal liver enzymes were believed to be associated with liver steatic change in NASH, whether the pronounced elevation of the liver enzymes was directly caused by liver glycogen deposit is not known. The pathogenesis for these problems has not been well studied. Nevertheless, both the increased hepatic enzymes and glycogen deposits may be related to poor glycemic control. Most of our patients received relatively high doses of insulin at home. We question the possible role of insulin over-treatment that might contribute to the pathogenesis of hepatomegaly because insulin is clearly a promoting agent for glycogenesis. Similar cases of hepatomegaly and elevated hepatic enzymes have been reported in children and adolescents who were chronically over-treated with insulin (4,5).
We therefore advocate the high vigilance in promoting patient compliance to insulin dosing rather than simply increasing insulin dosage in response to hyperglycemia. The swift reduction of hepatic enzymes in our cases after achieving reasonable glycemic control suggests that liver biopsy and other extensive work-up may be unnecessary in managing similar patients.
References
- Lee RGG, Bode HH: Stunted growth and hepatomegaly in diabetes mellitus. J Peds 91:82–84, 1977[Medline]
- Chatila R, West AB: Hepatomagely and abnormal liver tests due to glycogenesis in adults with diabetes. Medicine 75:327–333, 1996[Medline]
- Olssen R, Wesslau C, William-Olsen T, Zettergren L: Elevated aminotransferases and alkaline phosphatases in unstable diabetes mellitus without ketoacidosis or hypoglycemia. J Clin Gastroenterol 11:541–545, 1989[Medline]
- Asherov J, Mimouni M, Varsano I, Lubin E, Laron Z: Hepatomegaly due to self-induced hyperinsulinism. Arch Dis Child 54:148–149, 1979[Abstract]
- Rosenbloom AL, Giordano BP: Chronic overtreatment with insulin in children and adolescents. Am J Dis Child 131:881–885, 1977[Abstract]
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  D. Iafusco, A. Zanfardino, L. D'Alessandro, and F. Prisco Improper Insulin Compliance May Lead to Hepatomegaly and Elevated Hepatic Enzymes in Type 1 Diabetic Patients: Response to Yu and Howard Diabetes Care, August 1, 2004; 27(8): 2094 - 2095. [Full Text] [PDF]
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