Man With Type 2 Diabetes and Pancreatitis

A 44-year-old man with type 2 diabetes was recently hospitalized for an acuteexacerbation of pancreatitis. This was his seventh admission for the conditionwithin the past several years. Although imaging studies revealed no calcifications,the hospitalist suspected that acute relapsing pancreatitis was evolvinginto chronic pancreatitis.

The patient now comes to your office for evaluation.

HISTORY
The pancreatitis is alcohol-related; the patient has a decades-long historyof alcohol abuse. He consumes about 8 oz daily and drinks more duringbinges (one of which occurred just before his most recent hospitalization).

He has had diabetes for at least 3 years and takes glyburide, 10 mg bid.His glucose control has been problematic at best; he has performed homemonitoring sporadically and reports that glucose levels have ranged between200 and 300 mg/dL. The patient says that the glyburide seemed to work betterwhen he first began therapy. He was given insulin in the hospital; however,glyburide was prescribed at discharge.

LABORATORY STUDIES
Studies performed before his visit disclosed the following values: bilirubin,1.2 mg/dL; creatinine, 1 mg/dL; fasting blood glucose, 212 mg/dL;and glycosylated hemoglobin A (HbA_1c), 9.9%. Elevated transaminase levels(alanine aminotransferase, 300 U/L) prompted a test for hepatitis C virus (HCV)infection, which was positive.

PHYSICAL EXAMINATION
The patient appears older than he is, and his weight is slightly less thannormal for his age and height. However, vital signs are normal, there is nojaundice or spider angiomata, bowel sounds are good, and his abdomen is nontenderand without hepatosplenomegaly.

In addition to dietary measures and alcohol abstinence, which of thefollowing strategies constitutes optimal diabetes management?A. Discontinue glyburide and use metformin as a single agent.
B. Continue glyburide and add metformin.
C. Initiate insulin therapy.
D. Continue glyburide and add troglitazone.
E. Initiate acarbose as a single agent.

CORRECT ANSWER: C
Although this patient has-by definition-"adult-onset," ortype 2, diabetes, his history and laboratory results suggesta somewhat different mechanism of glucose intolerancethan that usually seen in those with type 2 diabetes.

Traditional type 2 diabetes is characterized more byinsulin resistance than by insulin deficiency and is frequentlyassociated with obesity.1 However, in a lean manwhose history strongly suggests that he has evolvingchronic pancreatitis, insulin deficiency is likely to be theprincipal pathophysiology underlying his diabetes.

In this setting, sulfonylureas have limited efficacy.Sulfonylurea failure is common during the course of type2 diabetes; it occurs in about 10% of affected patients eachyear.¹ It is even more likely in patients who have a decreasingnumberof functioningislets because ofchronic pancreatitis.² Thus, tocontinue glyburideas themainstay of therapy(choices Band D) is a suboptimalstrategy.

There arestrong reasonsnot to use eithermetformin ortroglitazone inthis patient. Hisalcohol abuseand HCV infectionwith at leastsporadic evidenceof liverdysfunction areboth documented contraindications to metformin use(choices A and B). In the setting of alcohol abuse (evenbinge drinking without chronic liver damage) or of abnormalhepatic function, metformin can lead to potentiallyfatal episodes of lactic acidosis.¹

Because troglitazone (choice D) has been associatedwith potentially serious drug-induced liver injury, it isalso contraindicated in this man, whose liver function isabnormal.³ Most experts would not recommend troglitazonefor patients with preexisting liver dysfunction.

Acarbose can be used even in patients with liver dysfunction.However, it is unlikely as monotherapy (choiceE) to optimally control glucose levels in this patient. Thedecrease in HbA_1c seen with acarbose is generally lessthan 1%, which would not bring this man's value into thetarget range.⁴

Therefore, the best option for this patient, whosetype 2 diabetes probably stems more from insulin deficiencythan from insulin resistance, is to begin insulintherapy (choice C). Problems can be expected even withthis therapy, because the patient's alcoholism will likelymake compliance difficult. However, in the presence offirm contraindications to alternative therapies, insulinseems the optimal choice here.

Outcome of this case. The patient has adhered toa regimen of twice-daily insulin injections for the past severalmonths. His home glucose readings are in the rangeof 140 to 160 mg/dL, and his HbA_1c level has droppedto 6.6%.

References:

REFERENCES:1. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334:574-578.
2. Steer ML, Waxman I, Freedman S. Chronic pancreatitis. N Engl J Med. 1995;33:1482-1490.
3. Watkins PB, Whitcomb RW. Hepatic dysfunction associated with troglitazone.N Engl J Med. 1998;338:916-917.
4. Yee HS, Fong NT. A review of the safety and efficacy of acarbose in diabetesmellitus. Pharmacotherapy. 1996;16:792-805.