BOSTON -- Physicians monitoring patients who have undergone gastricbypass surgery should be on the alert for a new, potentially dangeroushypoglycemia (low blood glucose) complication that, while rare, mayrequire quick treatment, according to a new study by collaboratingresearchers at Joslin Diabetes Center, Beth Israel Deaconess MedicalCenter (BIDMC), and Brigham and Women's Hospital (BWH) and published inthe October issue of the journal Diabetologia. The paper follows on theheels of a Mayo Clinic report on six similar case studies published inJuly in the New England Journal of Medicine. About 160,000 peopleundergo gastric bypass surgery every year.
The study details the history of three patients, who did not havediabetes, who suffered such severe hypoglycemia following meals thatthey became confused and sometimes blacked out, in two cases causingautomobile collisions. The immediate cause of hypoglycemia wasexceptionally high levels of insulin following meals. All threepatients in the collaborative study failed to respond to medication,and ultimately required partial or complete removal of the pancreas,the major source of insulin, to prevent dangerous declines in bloodglucose.
"Severe hypoglycemia is a complication of gastric bypasssurgery, and should be considered if the patient has symptoms such asconfusion, lightheadedness, rapid heart rate, shaking, sweating,excessive hunger, bad headaches in the morning or bad nightmares," saysMary-Elizabeth Patti, M.D., Investigator in Joslin's Research Sectionon Cellular and Molecular Physiology and Assistant Professor ofMedicine at Harvard Medical School. "If these symptoms don't respond tosimple changes in diet, such as restricting intake of simplecarbohydrates, patients should be evaluated hormonally, quickly," sheadds. Dr. Patti and Allison B. Goldfine, M.D., also an Investigator atJoslin and Assistant Professor of Medicine at Harvard Medical School,were co-investigators of the study.
The study reported on three patients -- a woman in her 20s, another inher 60s and a man in his 40s. All three lost significant amounts ofweight through gastric bypass surgery, putting them in the normal BodyMass Index (BMI) range. Each, however, developed postprandialhypoglycemia (low blood glucose after meals) that failed to respond todietary or medical intervention. As a result, all patients requiredremoval of part or all of the pancreas. In all three cases, it wasfound that the insulin-producing islet cells in their pancreases hadproliferated abnormally.
A potential cause of this severe hypoglycemia in these patientsis "dumping syndrome," a constellation of symptoms includingpalpitations, lightheadedness, abdominal cramping and diarrhea,explains Dr. Patti. Dumping syndrome occurs when the small intestinefills too quickly with undigested food from the stomach, as can happenfollowing gastric bypass surgery. But the failure to respond to dietaryand medical therapy, and the conditions worsening over time suggestedthat additional pathology was needed to explain the symptoms' severity,Dr. Patti adds. "The magnitude of the problem was way beyond whatdoctors typically call dumping syndrome," she says.
Other causes of postprandial hypoglycemia can include overactive isletcells, sometimes caused by excess numbers of cells, a tumor in thepancreas that produces too much insulin, or familial hyperinsulinism(hereditary production of too much insulin), which in severe cases cannecessitate removal of the pancreas.
In patients following bariatric surgery, additional mechanisms maycontribute to overproduction of insulin. "First, insulin sensitivity(responsiveness to insulin) improves after weight loss of any kind, andcan be quite significant after successful gastric surgery," says Dr.Patti. "Second, weight gain and obesity are associated with increasednumbers of insulin producing cells in the pancreas, and so somepatients may not reverse this process normally, leaving them withinappropriately high numbers of beta cells."
Finally, after gastric bypass surgery, GLP1 (glucagon-like peptide 1)and other hormones are secreted in abnormal patterns in response tofood intake, since the intestinal tract has been altered. High levelsof GLP1 may stimulate insulin secretion further and cause increasednumbers of insulin-producing cells. "In our patients, the fact that thepost-operative onset of hyperinsulinemia was not immediate suggeststhat active expansion of the beta cell mass contributed to thecondition," Dr. Patti adds.
Other researchers participating in the study included S.Bonner-Weir, Ph.D., of Joslin; E.C. Mun, M.D., J.J. Holst, M.D., J.Goldsmith, M.D., D.W. Hanto, M.D., Ph.D., M. Callery, M.D., of BethIsrael Deaconess Medical Center. Collaborating investigators from theBrigham and Women's Hospital included R. Arky, M.D., who also is aJoslin Overseer, G.T. McMahon, M.D., M.M.Sc., A. Bitton, M.D., and V.Nose, M.D. All participants are on faculty at the Harvard MedicalSchool. Funding for the study was provided by the National Institutesof Health, the Julie Henry Fund of BIDMC and the General ClinicalResearch Centers.
Besides helping afflicted gastric bypass patients, the researchhas hopeful implications for treating people with diabetes, says Dr.Patti. The gastric bypass patients have what many of those withdiabetes lack -- ample insulin -- and perhaps an understanding of thisphenomenon could be harnessed to help those with diabetes. "If we canunderstand what processes are responsible for too much insulinproduction and too many islet cells in these patients, we may be ableto apply this information to stimulate insulin production in patientswith diabetes, who lack sufficient insulin," Dr. Patti says.
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