Low Blood Glucose Levels May Complicate Gastric Bypass

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Low Blood Glucose Levels May Complicate Gastric Bypass Surgery,

Study Shows

BOSTON—October 12, 2005—Physicians monitoring patients who have

undergone gastric bypass surgery should be on the alert for a new,

potentially dangerous hypoglycemia (low blood glucose) complication

that, while rare, may require quick treatment, according to a new

study by collaborating researchers at Joslin Diabetes Center, Beth

Israel Deaconess Medical Center (BIDMC), and Brigham and Women's

Hospital (BWH). The paper, recently published online by the journal

Diabetologia and scheduled to be published in the journal's November

print edition, follows on the heels of a Mayo Clinic report on six

similar case studies published in July in the New England Journal of

Medicine. About 160,000 people undergo gastric bypass surgery every

year.

The study details the history of three patients who did not have

diabetes, who suffered such severe hypoglycemia following meals that

they became confused and sometimes blacked out, in two cases causing

automobile collisions. The immediate cause of hypoglycemia was

exceptionally high levels of insulin following meals. All three

patients 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 blood

glucose.

" Severe hypoglycemia is a complication of gastric bypass surgery,

and should be considered if the patient has symptoms such as

confusion, lightheadedness, rapid heart rate, shaking, sweating,

excessive hunger, bad headaches in the morning or bad nightmares, "

says - Patti, M.D., Investigator in Joslin's Research

Section on Cellular and Molecular Physiology and Assistant Professor

of Medicine at Harvard Medical School. " If these symptoms don't

respond to simple changes in diet, such as restricting intake of

simple carbohydrates, patients should be evaluated hormonally,

quickly, " she adds. Dr. Patti and B. Goldfine, M.D., also an

Investigator at Joslin 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

in her 60s and a man in his 40s. All three lost significant amounts

of weight through gastric bypass surgery, putting them in the normal

Body Mass Index (BMI) range. Each, however, developed postprandial

hypoglycemia (low blood glucose after meals) that failed to respond

to dietary or medical intervention. As a result, all patients

required removal of part or all of the pancreas. In all three cases,

it was found that the insulin-producing islet cells in their

pancreases had proliferated abnormally.

A potential cause of this severe hypoglycemia in these patients

is " dumping syndrome, " a constellation of symptoms including

palpitations, lightheadedness, abdominal cramping and diarrhea,

explains Dr. Patti. Dumping syndrome occurs when the small intestine

fills too quickly with undigested food from the stomach, as can

happen following gastric bypass surgery. But the failure to respond

to dietary and medical therapy, and the conditions worsening over

time, suggested that additional pathology was needed to explain the

symptoms' severity, Dr. Patti adds. " The magnitude of the problem

was way beyond what doctors typically call dumping syndrome, " she

says.

Other causes of postprandial hypoglycemia can include overactive

islet cells, sometimes caused by excess numbers of cells, a tumor in

the pancreas that produces too much insulin or familial

hyperinsulinism (hereditary production of too much insulin), which

in severe cases can necessitate removal of the pancreas.

In patients following bariatric surgery, additional mechanisms may

contribute to overproduction of insulin. " First, insulin sensitivity

(responsiveness to insulin) improves after weight loss of any kind,

and can be quite significant after successful gastric surgery, " says

Dr. Patti. " Second, weight gain and obesity are associated with

increased numbers of insulin producing cells in the pancreas, and so

some patients may not reverse this process normally, leaving them

with inappropriately 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

to food intake, since the intestinal tract has been altered. High

levels of GLP1 may stimulate insulin secretion further and cause

increased numbers of insulin-producing cells. " In our patients, the

fact that the post-operative onset of hyperinsulinemia was not

immediate suggests that active expansion of the beta cell mass

contributed to the condition, " 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 Beth

Israel Deaconess Medical Center. Collaborating investigators from

the Brigham and Women's Hospital included R. Arky, M.D., who also is

a Joslin 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 Medical

School. Funding for the study was provided by the National

Institutes of Health, the Henry Fund of BIDMC and the General

Clinical Research Centers.

Besides helping afflicted gastric bypass patients, the research has

hopeful implications for treating people with diabetes, says Dr.

Patti. The gastric bypass patients have what many of those with

diabetes lack – ample insulin – and perhaps an understanding of this

phenomenon could be harnessed to help those with diabetes. " If we

can understand what processes are responsible for too much insulin

production and too many islet cells in these patients, we may be

able to apply this information to stimulate insulin production in

patients with diabetes, who lack sufficient insulin, " Dr. Patti says.