Hyperinsulinemic Hypoglycemia with Nesidioblastosis after Gastric-Bypass Surgery

Service, Geoffrey J.; Thompson, Geoffrey B.; Service, F. John; Andrews, James C.; Collazo–Clavell, Maria L.; Lloyd, Ricardo V.

doi:10.1056/nejmoa043690

Cited by 709 publications

(539 citation statements)

References 21 publications

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“…Service and colleagues reported that six patients after Roux-en-Y gastric bypass surgery had postprandial hypoglycemia and neuroglycopenia with elevated insulin levels that led surgeons to perform partial pancreatectomies for control of symptoms (Service et al, 2005). Therefore pancreatic specimens were available for histological evaluation and the patients were diagnosed as having nesidioblastosis and enlarged islets.…”

Section: Potential Glp-1r Effects After Gastric Bypass Surgerymentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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Glucagon-like peptide-1 is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein hydrolysate and/or glucose enters the duodenum. Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past twenty years culminating in a naturally occurring GLP-1 receptor agonist, exendin-4, now being used to treat type 2 diabetes. GLP-1 engages a specific G-protein coupled receptor that is present in tissues other than the pancreas (brain, kidney, lung, heart, major blood vessels). The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion. Upon GLP-1 receptor activation, adenylyl cyclase is activated and cAMP generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the PKA and Epac pathways. As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation and neogenesis. Although these latter effects cannot be currently monitored in humans, there are substantial improvements in glucose tolerance and increases in both first phase and plateau phase insulin secretory responses in type 2 diabetic patients treated with exendin-4. This review we will focus on the effects resulting from GLP-1 receptor activation in islets of Langerhans

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Section: Potential Glp-1r Effects After Gastric Bypass Surgerymentioning

confidence: 99%

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Doyle

Egan

2007

Pharmacology & Therapeutics

583

465

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“…11,30,31 In 2005, Service et al 30 reported in the New England Journal of Medicine 11 the details of six such cases, which these authors deemed adultonset nesidioblastosis, and which were severe enough to require partial pancreatectomy. Several other groups have since reported similar observations.…”

Section: Mechanisms Of Diabetes Improvement Following Bariatric Surgerymentioning

confidence: 99%

“…30,31 Identifying these putative molecules could lead to new medical strategies to reverse the progressive b-cell failure that defines T2DM. Other investigators, however, claimed that pancreas samples from afflicted patients showed no increases in b-cell mass or proliferation beyond those expected from obesity, and therefore that the syndrome must arise from inappropriately increased b-cell function.…”

Section: Mechanisms Of Diabetes Improvement Following Bariatric Surgerymentioning

confidence: 99%

“…25,40 As GLP-1 not only enhances insulin secretion but can also increase proliferation and decrease apoptosis of b cells, 39 it is a candidate mediator of the increase in b-cell mass that is claimed by some investigators to accompany post-RYGB hyperinsulinemic hypoglycemia. 30,31 Further support for the lower intestinal hypothesis comes from experiments involving ileal interposition. In this operation, a segment of L-cell-rich ileum is transplanted into the upper intestine near the duodenum-jejunum boundary, thereby increasing its exposure to ingested nutrients.…”

Section: The Lower Intestinal Hypothesismentioning

confidence: 99%

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Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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Bariatric surgery is currently the most effective method to promote major, sustained weight loss. Roux-en-Y gastric bypass (RYGB), the most commonly performed bariatric operation, ameliorates virtually all obesity-related comorbid conditions, the most impressive being a dramatic resolution of type 2 diabetes mellitus (T2DM). After RYGB, 84% of patients with T2DM experience complete remission of this disease, and virtually all have improved glycemic control. Increasing evidence indicates that the impact of RYGB on T2DM cannot be explained by the effects of weight loss and reduced energy intake alone. Weightindependent antidiabetic actions of RYGB are apparent because of the very rapid resolution of T2DM (before weight loss occurs), the greater improvement of glucose homeostasis after RYGB than after an equivalent weight loss from other means, and the occasional development of very late-onset, pancreatic b-cell hyperfunction. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including enhanced nutrient stimulation of L-cell peptides (for example, GLP-1) from the lower intestine, intriguing but still uncharacterized phenomena related to exclusion of the upper intestine from contact with ingested nutrients, compromised ghrelin secretion, and very probably other effects that have yet to be discovered. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help optimize surgical design and might also reveal novel pharmaceutical targets for diabetes treatment. Keywords: diabetes; gastric bypass; bariatric surgery; ghrelin; GLP-1 Bariatric operations traditionally have been thought to cause weight loss through gastric restriction and/or intestinal malabsorption. Restrictive operations such as adjustable gastric banding (AGB) create a small pouch in the proximal stomach to reduce functional gastric capacity and retard gastric emptying. Malabsorptive procedures such as biliopancreatic diversion (BPD) leave much of the stomach intact but divert ingested food from the stomach to the ileum; thus, only a small segment of the distal bowel can absorb nutrients. The typical proximal Roux-en-Y gastric bypass (RYGB) creates gastric restriction and also causes food to bypass most of the stomach and a short segment of the proximal intestine, primarily the duodenum, leaving enough intact small bowel in digestive continuity to avoid clinically significant malabsorption. RYGB causes weight loss through gastric restriction and additional mechanisms involving changes in gut hormones and other processes under active investigation. 1-14 RYGB and BPD produce the highest and most rapid rates of remission of type 2 diabetes mellitus (T2DM). Remission of diabetes after RYGBAlthough bariatric surgery was designed to facilitate weight loss, anecdotal reports of rapid postoperative remission of T2DM emerged as early as the 1970s. In 1995, Pories et al. 4 reported long term results from 608 severely obese patients who underwent gastric bypass, with a 93% follow-up rate ov...

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“…One mechanism postulated to improve diabetes after gastric bypass is an augmented incretin response; postprandial plasma concentrations of the potent incretin glucagon-like peptide-1 rise after gastric bypass [2]. Recently hyperinsulinaemia and hypoglycaemia have been recognised as new complications of gastric bypass [3,4]. Patients have presented with hypoglycaemia associated with confusion, syncope and seizures attributed to changes in glucose homeostasis [5].…”

Section: Introductionmentioning

confidence: 99%

Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986–2006 in Sweden

et al. 2010

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Aims/hypothesis Symptomatic hypoglycaemia with related confusion, syncope, epilepsy or seizures is a newly recognised complication of gastric bypass surgery for obesity. The incidence of these conditions is not known. We therefore studied the incidence of post-gastric bypass hypoglycaemia and related symptoms in patients who have undergone gastric bypass and a reference cohort from the general population of Sweden. Methods This is a nationwide cohort study based on national registries with 5,040 persons who underwent gastric bypass, vertical banded gastroplasty or gastric banding for obesity in Sweden between 1 January 1986 and 31 December 2006 and a cohort of ten referents per patient matched for sex and age randomly sampled from the general population. The incidence rates of hospitalisation for hypoglycaemia, confusion, syncope, epilepsy or seizures before and after dates of surgery or inclusion in the reference cohort were studied. Results Preoperative incidences of hospitalisation for hypoglycaemia were similar in the surgical and referent cohorts. After gastric bypass surgery, the adjusted hazard ratios were significantly elevated for hypoglycaemia (2.7 [95% CI 1. participants affected by hypoglycaemia were very low (0.2% and 0.04%, respectively). There was no increased risk of hypoglycaemia after vertical banded gastroplasty or gastric banding compared with the referent population. Conclusions/interpretation Obese persons who have undergone gastric bypass have an increased risk of hospitalisation for diagnoses associated with post-gastric bypass hypoglycaemia, although few patients are affected.

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Hyperinsulinemic Hypoglycemia with Nesidioblastosis after Gastric-Bypass Surgery

Cited by 709 publications

References 21 publications

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Mechanisms of action of glucagon-like peptide 1 in the pancreas

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986–2006 in Sweden

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