Impairment of gallbladder emptying in diabetes mellitus.

Individuals with diabetes mellitus are reported to have a twofold to threefold increase in the incidence of cholesterol gallstones. A frequently cited but unproven pathophysiologic mechanism for this phenomenon is reduced gallbladder muscle function, which results in stasis and allows for cholesterol gallstone crystal formation and gallstone growth. To date, gallbladder motor function has not been investigated in a well-characterized diabetic population. Therefore, using radionuclide cholescintigraphy, gallbladder filling and subsequent emptying produced in response to an infusion of the octapeptide of cholecystokinin in 30 diabetic patients and 20 control individuals were studied. No difference in any parameter used to assess gallbladder filling was demonstrated in the diabetics when compared with controls. In contrast, gallbladder emptying induced with cholecystokinin-octapeptide (20 ng/kg body wt . h) was reduced in diabetics compared with controls (55% +/- 5% vs. 74% +/- 4%, p less than 0.01). The peak emptying rate in the diabetics was also decreased (5.0% +/- 0.5% per minute) compared with the controls (7.0% +/- 0.6% per minute, p less than 0.02). The observed decreased gallbladder emptying found in diabetics was not related to obesity, type of diabetes, diabetic control, or presence or absence of peripheral neuropathy. The most severe impairment of gallbladder emptying occurred, however, in diabetics with an associated autonomic neuropathy. This subgroup demonstrated a significant reduction in the percentage of gallbladder emptying (40% +/- 8% vs. 62% +/- 5%, p less than 0.04) and the peak ejection rate (3.5% +/- 0.5% per minute vs. 5.6% +/- 0.6%, p less than 0.02) compared with the diabetics without autonomic neuropathy.

Gallbladder function in diabetic patients.

Gallbladder emptying and filling was studied in eight diabetic and six normal control patients. None of the patients had gallstones. Cholescintigraphy was performed using [99mTc]disofenin, and gallbladder emptying was studied using a 45-min i.v. infusion of the octapeptide of cholecystokinin (OP-CCK) 20 ng/kg X hr. The peak filling rate was greater in diabetic than in normal subjects; however, emptying of the gallbladder in response to OP-CCK was significantly less in the diabetic subjects (51.6 +/- 10.4% compared with 77.2 +/- 4.9%). When the diabetic group was subdivided into obese and nonobese diabetics, the obese diabetics had a much lower percentage of emptying than the nonobese diabetics (30.0 +/- 10.4% compared with 73.1 +/- 9.3%). These findings suggest that obese diabetics may have impaired emptying of the gallbladder even in the absence of gallstones. The more rapid rate of gallbladder filling in obesity may indicate hypotonicity of the gallbladder. The combination of these abnormalities may predispose the obese diabetic to the development of gallstones.

Gallbladder function: methods for measuring filling and emptying.

Cholescintigraphy with [99mTc] disofenin was used to determine the optimal dose and method of administration of the octapeptide of cholecystokinin, and to determine the kinetics of gallbladder filling and emptying in 22 patients without disease of the liver or gallbladder. The peak filling rate of the gallbladder occurred at 30 min after injection; filling was complete at 1 hr. A 45-min constant intravenous infusion of the octapeptide 20 ng/kg X hr resulted in progressive emptying of the normal gallbladder; the mean ejection fraction at 45 min was 77.2 +/- 4.9%. A 1-min injection of 20 ng/kg resulted in a rapid, short-lived emptying; the mean ejection fraction was 52.2 +/- 9.3%. Doubling or halving the infusion dose produced no greater response or a smaller response. We conclude that a constant 45-min infusion technique is superior to short injection times, because of more complete emptying, no side effects, and more consistent response.