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Hypoglycaemia post-surgery

Islet cell function contributes to hypoglycaemia post-surgery

Glucagon response to hypoglycaemia is abnormal

Altered islet cell function and reduced insulin clearance contribute to excessive post-meal insulin response in patients experiencing hypoglycaemia following gastric bypass surgery, according to researchers from the University of Cincinnati (UC).

Marzieh Salehi

"For the majority of patients with diabetes, gastric bypass surgery leads to improved glucose control, but a subset of patients develop post-meal hypoglycaemia - associated with too much of an insulin response - several years after surgery,” said study author, Dr Marzieh Salehi, associate professor in the UC division of endocrinology, metabolism and diabetes. "We have shown that meal ingestion after gastric bypass surgery causes an earlier and larger peak of insulin secretion, and this effect is exaggerated in those with hypoglycaemic symptoms following meals.”

The study, which is published in The Journal of Clinical Endocrinology & Metabolism, is part of an ongoing effort by UC researchers to better understand the effect of gastric bypass surgery on glucose metabolism and islet function.

For this study Salehi and colleagues enrolled 65 subjects who had gastric bypass surgery at least two years prior to enrolment. Participants were stratified based on post-meal symptoms of low blood sugar and studied during meal tolerance tests.

Outcomes

The results showed that glucose and insulin responses to meal ingestion were shifted upward and to the left after bypass, with the largest early insulin response and the lowest nadir glucose levels in patients with a history of hypoglycaemia.

Salehi added that the effect was particularly exaggerated in those with neuroglycopenic symptoms (cognitive abnormalities, loss of consciousness, and seizure) rather than autonomic symptoms (fast heart beats, sweating, tingling, fatigue).

They also found that hypoglycaemic bypass patients had lower postprandial insulin clearance rates and higher insulin secretion rates during the glucose decline after the test meal. In addition, meal-induced glucagon was enhanced in all the bypass patients but did not differ between subjects who did and did not develop hypoglycaemia.

According to Salehi and team, this is the largest group of gastric bypass patients with post-meal symptoms of low blood sugar to be reported to date; and among this group, abnormalities in insulin clearance as well as excessive insulin secretion during glucose drops (hyperinsulinemia) were identified.

Moreover, the findings from this study suggest that in addition to excessive insulin secretion, glucagon response to hypoglycaemia is abnormal.

"These abnormalities contributed to elevated insulin response and lower glucose levels in these individuals,” he added.

This study, the authors says, offers a better understanding of mechanisms by which gastric bypass surgery alters glucose metabolism in general, and more specifically in those individuals suffering from hyperinsulinemic hypoglycaemia syndrome.

Although there is no specific therapeutic option available for patients with this condition beyond dietary modification, future studies based on current findings will inform the development of medical and dietary interventions for treatment of this condition, said the researchers.

Co-authors include Dr David D’Alessio, University of Cincinnati and Cincinnati Department of Veterans Affairs Medical Center; and Dr Amalia Gastaldelli, Cardiometabolic Risk Unit, Institute of Clinical Physiology, Pisa, Italy.

This study was funded by grants from the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases and in part by the US Public Health Service, the National Center for Research Resources NIH and the Medical Research Service of the Department of Veterans Affairs.

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