Vol 44 # 4 December 2012 - Kma.org.kw

275 Bariatric Surgery and Hypoglycemia
December 2012
gastric banding (n = 2,917) for obesity, the relative
risk of severe hypoglycemia was five-fold higher in
the gastric bypass patients compared with controls [12] .
However, it is noteworthy (and reassuring) that the
absolute rate of post-bariatric hypoglycemia was
low (< 1%). Furthermore, the Roux-en-Y gastric
bypass procedure was more frequently associated
with hypoglycemia than other forms of bariatric
surgery, including vertical banding gastroplasty and
gastric banding [12] . The median time from surgery to
hypoglycemic symptoms in the Swedish survey was
2.7 years, consistent with the post-operative latency
of 1 - 5 years reported in other series [5,13-15] . Of note,
the frequency of accidental deaths was higher in postbariatric
surgery patients than in reference cohorts,
which may indicate undiagnosed hypoglycemia and
possible underestimation of the number of patients
with hypoglycemia [12] .
Classically, hypoglycemia in post-gastric
bypass patients occurs postprandially or during
the postabsorptive period (as opposed to during
fasting). Post-gastric bypass hypoglycemia usually is
associated with the concurrence of low serum glucose
levels (typically < 60 mg/dl) and inappropriately
elevated or measurable levels of insulin and C-
peptide. The mechanisms behind post-gastric
bypass hyperinsulinemic hypoglycemia are not
well-understood. In 2005, Service et al reported a
series of six patients with symptomatic postprandial
hyperinsulinemic hypoglycemia that developed on
average 30 months after gastric bypass surgery [16] .
Insulinoma was ruled out using imaging studies and
selective arterial calcium stimulation test [16] . These
patients then underwent either extensive or spleenpreserving
distal pancreatectomy, and islet specimens
were obtained for histological study. The pancreatic
islet sections obtained from the patients reported by
Service et al showed evidence of nesidioblastosis
(hypertrophic beta cells, with enlarged or normalappearing
islets; small scattered clusters of endocrine
cells; and ductuloinsular complexes) [16] . The authors
thus concluded that insulin hypersecretion from
nesidioblasts was responsible for post-gastric bypass
hypoglycemia in their patients [16] . However, reexamination
of the pancreatic histology by Meier
et al raised doubts about the presence of true
nesidioblasts [17] . Instead, evidence of increased beta
cell nuclear diameter was observed in post-gastric
bypass patients compared with controls [17] . Thus, the
hypoglycemia in such patients could have arisen from
a combination of exaggerated “dumping” syndrome
and increased insulin secretion per beta cell.
Another mechanism proposed for the insulin
hypersecretion and possible islet cell proliferation was
enhanced glucagon-like peptide 1 (GLP-1) secretion
from L cells in distal ileum, resulting from the rapid
transit of nutrients following gastric bypass surgery [16] .
Indeed, studies identifiedexaggeratedGLP-1response
and attendant insulinotropic and glucagonostatic
effects as mechanisms for post-gastric bypass
hypoglycemia [18,19] . Since the mechanisms underlying
post-bariatric hypoglycemia are not fully understood,
a standard approach to management has not yet been
developed. Mild hypoglycemia may be evaluated
and treated in an outpatient setting. However severe
hypoglycemia likely requires hospitalization and
evaluation to rule out etiologies such as insulinoma.
Without randomized controlled studies, the
therapeutic approach to severe post-bariatric surgery
hypoglycemia has been empirical. Management
usually begins with dietary modification, including
frequent small meals with low carbohydrate content.
Pharmacological approaches that have had variable
success include diazoxide, acarbose, octreotide, and
calcium channel blockers [6, 13, 20] . For patients with
refractory hypoglycemia, surgical intervention may
be warranted, either to reverse the gastric restriction
procedure or reduce the mass of insulin-secreting
pancreatic tissue [5- 7, 14- 16] .
In summary, severe hyperinsulinemic hypoglycemia
is a rare but serious sequel of gastric bypass surgery.
It usually presents a few years after the surgery and is
accompanied by neuroglycopenic symptoms including
confusion, seizure, syncope or coma. Future studies
should be directed at unraveling the mechanisms,
identifying risk factors, and developing optimal
surveillance and management strategies for post-gastric
bypass hypoglycemia. While awaiting the results of
definitive studies on the subject, clinicians should be
cognizant of the risk of hypoglycemia, educate gastric
bypass patients on the warning symptoms of impending
hypoglycemia and appropriate corrective measures.
REFERENCES
1. Ogden C, Carroll M, Kit B, Flegal K. Prevalence of
obesity in the United States, 2009 - 2010. NCHS Data
Brief 2012; 82:1-7.
2. Haslam DW, James WP. Obesity. Lancet 2005; 366:1197-
1209.
3. Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long
term pharmacotherapy for obesity and overweight:
updated meta-analysis. BMJ 2007; 335:1194-1199.
4. Klein S, Fontana L, Young VL, et al. Absence of an effect
of liposuction on insulin action and risk factors for
coronary heart disease. N Engl J Med 2004; 350:2549-
2557.
5. Ritz P, Hanaire H. Post-bypass hypoglycaemia: a review
of current findings. Diabetes Metab 2011; 37:274-281.
6. Ashrafian H, Athanasiou T, Li JV, et al. Diabetes
resolution and hyperinsulinaemia after metabolic
Roux-en-Y gastric bypass. Obes Rev 2011; 12:257-272.