Post-bariatric Surgery Hypoglycemia : A Descriptive Analysis Rajasree Nambron, PGY2 Internal Medicine Co-author: Daniel K Short, MD, PhD

Bariatric surgery for obesity- benefits Bariatric surgery for morbid obesity- standard of care after failed medical therapy Weight loss: 61% HTN resolved: 62% OSA resolved: 86% Diabetes resolved: 77% Hyperlipidemia improved: 70%

Bariatric surgery - complications 20%- adverse events Early complications: Bleeding, infections, PE and DVT Late complications: Metabolic and nutritional deficiencies Dumping syndrome Post-bariatric hypoglycemia Failure to lose weight or weight gain

Possible causes of hypoglycemia after bariatric surgery Medications: Hypoglycemic agents if still requiring after surgery Dumping syndrome Post-bariatric hypoglycemia syndrome (PBHS)

PBHS is defined as… Spontaneous and symptomatic blood sugar less than 45 mg/dl in patients with history of gastric bypass Inappropriately elevated insulin and C-peptide levels at the time of confirmed hypoglycemia Exclusion of insulinoma Exclusion of other causes of hypoglycemia (iatrogenic insulin or sulfonylurea use) Subgroup of NIPHS (non insulinoma pancreatogenous hypoglycemia syndrome ) Presents 6 months to 8 years after bypass surgery with neuroglycopenic symptoms occurring 1-3 hours after eating. Exact prevalence or treatment unclear at this time

PBHS Exact prevalence, incidence and treatment of PBHS is unknown Presents 6 months to 8 years after bypass surgery with hypoglycemic or CNS symptoms occurring 1-3 hours after eating Described 5 patients with neuroglycopenic symptoms, hyperinsulinemic hypoglycemia within 4 hours of meal ingestion From endogenous source (not factitious) FJ Service, et al, JCEM 84: 1582-1589

PBHS The mechanism of this process is unclear GLP-1 (increases) and ghrelin (decreases) have both been implicated; but no proof Not simply due to lack of regression of hyperplasia during obesity, since age/weight (pre-procedure) matched controls did not have islet hyperplasia

Pathology : in simple terms new islet cell formation! FJ Service, et al, JCEM 84: 1582-1589

PBHS Treatment approaches tried: Diet- small meals, avoid high carb diet Acarbose and Nifedipine XR Prednisone Octreotide Byetta Reversal of procedure Optimal treatment of the disorder is unknown.  Several approaches have been tried

Our Study To estimate the prevalence of post-bariatric hypoglycemia syndrome in a large community academic center with a large bariatric surgery population Characterize treatments given and their outcome

Methods Retrospective chart review All patients who had bariatric surgery in last 10 years (2001-2011) were included Pre-screened for ‘hypoglycemia’ or symptoms of hypoglycemia

Inclusion Criteria: Significant Hypoglycemia Random blood sugar < 60 mg/dl; AND Exclusion of other known causes of hypoglycemia Use of hypoglycemic agents (insulin or oral) Adrenal insufficiency Alcohol dependency

hypoglycemia syndrome Results N= 1092 Bariatric surgery patients ( 2001- 2011) ↓ N= 407 (37%) Diagnosis of hypoglycemia or symptoms related to hypoglycemia ↓ N= 69(6.9%) Significant Hypoglycemia (BG < 60 mg/dl) with no evidence of other causes ↙ ↘ Post-bariatric hypoglycemia syndrome ( N=5; 0.46%) as BG < 45 mg/ dl Symptomatic C-peptide, insulin elevated Other causes excluded Imaging r/o insulinoma Significant symptomatic hypoglycemia and possible Post-bariatric hypoglycemia ( N= 62) C-peptide, insulin not measured ! D/D for this group other than PBHS : Dumping syndrome, insulinoma N= 67(6.2%) Symptomatic N= 2 (0.18%) Asymptomatic ↙ ↘ N= 6(0.55%) Confirmed Post-bariatric hypoglycemia syndrome N= 61 (5.6%) Unconfirmed (lack of data)

Characteristics of significant symptomatic hypoglycemia group

Therapy in significant symptomatic hypoglycemia group ( N=67) Symptomatic hypoglycemia (N=67) DIET COUNSELING (N=29;43%) DID NOT REQUIRE ANY THERAPY (N=38; 57%) Medications (N=4; 5.9%) None required surgery

Therapy in significant symptomatic hypoglycemia group ( N=67)

Response to therapy in the PBHS group ( N=6)

Response to therapy in the PBHS group ( N=5) Diet Counseling (N=6) Successful Counseling 33.3% (N= 2) Unsuccessful Counseling (66.6%N= 4) Drugs Prednisone (N=1) Acarbose+Nifedipine XR N=2 Acarbose-1

Discussion Prevalence in our cohort: 0.46% (N=5) to 6.2% (N=67) Diet counseling AND medications (acarbose, nifedipine XR, prednisone) can successfully treat this syndrome More than 90% of patients with symptoms compatible with hypoglycemia following surgery not investigated completely SYMPTOMS of hypoglycemia are common after surgery, but severe hypoglycemia requiring further workup was rare.  Since not all of those patients were worked up, it is possible that many more could have been diagnosed with PBHS if they had been evaluated further; however the fact that they did not require further evaluation makes the likelihood that those patients truly had PBHS fairly low.  If any of them DID have PBHS, it must have been fairly mild.  So it may be that our data reflects only severe PBHS.

Take away message.. Symptoms of hypoglycemia are common after bariatric surgery (37%) Confirmed symptomatic hypoglycemia- uncommon Post bariatric hypoglycemia syndrome is very rare (0.46%), but an important diagnosis/entity

Take away message.. Drug therapy + diet counseling successful in improving symptoms in all cases No patient required or desired surgery

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