Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia

Abstract

Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m 2 [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagonlike peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.Gastric bypass (GBP) surgery for the treatment of morbid obesity induces marked weight loss and metabolic effects.Excess BMI loss is typically ;70-80% (1), and almost instant changes occur in glucose homeostasis postsurgery, including frequent remission of diabetes up to 70% (1). After a meal, the rise in glucose and insulin is ;50% higher, reflecting the faster absorption of glucose postsurgery. Incretins are also affected; prandial gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) peak at ;2 and 10 times higher levels after surgery, respectively (2).The sustained weight loss achieved by GBP surgery, superior to that achieved by diet regimens, reflects lowered caloric intake and possibly altered secretion of gastrointestinal peptides (2). Comparing eating habits before and after the GBP surgery, patients lowered the intake with marked reductions in carbohydrate intake in the form of sweets, soda, and milk/ice cream. Fear of dumping was suggested as the main mechanism (3). Dumping can occur within 10-30 min of food intake when, in the absence of a pyloric function, it quickly enters the intestine and produces an osmotic effect. Fluid is shifted from the circulation into the intestine, resulting in a fall of blood pressure and tachycardia. In a rat model, similar food preference adaptations evolved with time, indicating that the preference shift was dependent on learning and dumping (4).In a recent study with continuous glucose monitoring (5), we observed hypoglycemic epis...

Nutrient re-routing and altered gut-islet cell crosstalk may explain early relief of severe postprandial hypoglycaemia after reversal of Roux-en-Y gastric bypass

“…The response of glucagon to hypoglycaemia was attenuated before reversal, which is in accordance with a recent observation of reduced symptoms and counter-regulatory hormonal response to hypoglycaemia after RYGB surgery [10]. All subjective symptoms of hypoglycaemia disappeared, and we observed relief of biochemical hypoglycaemia associated with a 'reversed' hormone profile, with significantly reduced insulin and GLP-1 responses combined with a decreased insulin clearance after reversal.…”

“…Concentrations of GIP and ghrelin were enhanced after reversal. The response of glucagon to hypoglycaemia was attenuated before reversal, which is in accordance with a recent observation of reduced symptoms and counter-regulatory hormonal response to hypoglycaemia after RYGB surgery [10]. Notably, peripheral insulin sensitivity (measured as glucose disposal during hyperinsulinaemic-euglycaemic clamps) remained unchanged despite weight gain.…”

Effect of meal size and texture on gastric pouch emptying and glucagon-like peptide 1 after gastric bypass surgery

“…Therefore, texture had an effect on GLP-1 and on glucose in spite of its absence of effect on insulin. It is possible that the suppression of glucagon release by GLP-1 [35] proportional to the magnitude of the GLP-1 release, and/or a defect in other counter regulatory hormones [36], favored lower blood glucose levels after the liquid meal. However, these counter-regulatory hormones were not measured in this study.…”

Hypoglycemia Following Bariatric Surgery: Our 31-Year Experience

“…Interestingly, we also found that patients with lower blood glucose levels tend to present later. Recent studies suggest that bariatric surgery can lead to an attenuated counter-regulatory hormone response to hypoglycemia and that there are many bariatric surgery patients with asymptomatic hypoglycemia [14, 17]. It is possible that these patients have some level of hypoglycemic unawareness so only developed symptoms at more extreme levels of hypoglycemia, and therefore had delayed presentation of PBSH.…”

“…A 2015 survey-based study found that PBSH may affect up to one third of patients while a nationwide Swedish cohort study showed that only 0.2% of patients undergoing roux-en-Y gastric bypass (RYGB) required hospitalization for PBSH [12, 13]. Early investigators suggested pancreatic nesidioblastosis with resultant hyperinsulinemia as the underlying cause, but further work has shown that PBSH is the result of a multifaceted alteration in glucose homeostasis [11, 14]. Recent studies have identified several risk factors for the development of PBSH such as lower preoperative glycated hemoglobin (A1C) and body mass index (BMI) as well as greater postoperative weight loss [15, 16].…”