Ed Mason at Large

| May 15, 2013 | 0 Comments

This ongoing column is dedicated to sharing with readers the life and experiences of Dr. Edward Mason.

Column Editor: Tracy Martinez, RN, BSN, CBN
Ms. Martinez is the Program Director for Wittgrove Bariatric Center in La Jolla, California.

This month:

Dr. Mason, Could you talk about the mechanics of sleeve gastrectomy?
-Dr. Girish Juneja, Director Bariatric Programme , International Modern Hospital, Dubai, United Arab Emirates

Dr. Mason: Normal functions of both stomach and duodenum are eliminated by sleeve gastrectomy (SG). Functionally, all that is left is a lesser curvature tube from esophagus to jejunum. This remaining sleeve of stomach is equivalent to a segment of small bowel used to replace the stomach after total gastrectomy. What is swallowed reaches the jejunum without the elaborate regulation of gastric emptying by osmolality and other receptors in the duodenum. Highly concentrated contents reaching the upper small bowel cause an intestinal flush to the distal bowel where the L cells are stimulated by glucose to secrete glucagon-like peptide 1 (GLP-1).

SG has the same effect as total gastrectomy. In a study of total gastrectomy, Miholic et al[1] found a peak GLP-1 secretion occurring 15 minutes after the beginning of a standard meal. There was no difference between Roux-en-Y reconstruction, which bypasses the duodenum, and insertion of a segment of small bowel with passage of contents through the duodenum. This means that when the stomach is converted to a tube, the duodenum also becomes a functionless tube. The duodenal mixing of swallowed contents with bile and pancreatic juice is no longer regulated to provide a diluted solution. The discharge into the upper small bowel is no longer regulated to provide for ideal digestion and absorption for regulation of the body’s optimum concentration of circulating glucose.

Glucose and other stimulants of L cells in a normal digestive tract are absorbed before they reach the ileum after the initial gush. Normally, the peak elevation of plasma GLP-1 is reached in 15 minutes after the beginning of a meal, which was difficult to explain until Brener et al[2] described the initial gastric emptying gush, which provides duodenal feedback and regulates subsequent stomach emptying squirts. Schirra et al[3] demonstrated that there is a glucose threshold for flushing. After SG there is no initial gastric gush, but there is unregulated and more frequent flushing resulting in excessive GLP-1 secretion and improvement of type 2 diabetes (T2D).

In the early days of bariatric surgery, operations were thought to cause weight loss by restricting intake or causing malabsorption or by a combination. Surgeons also observed that T2D no longer required medical treatment after bariatric surgery. These observations were made after intestinal bypass in 1954 and again after gastric bypass in 1966. In 1998, Näslund et al[4] called attention to the importance of GLP-1 in resolving T2D by intestinal bypass. This paper suggested to me that the common denominator between intestinal and gastric bypass was rapid movement of glucose to the ileum. I suggested a study of moving the ileum to a juxta duodenal position.[5] Strader et al[6] performed the ileal transposition in rodents and it increased postprandial GLP-1 secretion. In 2011, Näslund’s group that had demonstrated the importance of GLP-1 in resolving T2D by intestinal bypass provided a similar study and result for gastric bypass.[7] Glucose and other stimulants of GLP-1 secretion, which are normally absorbed in the upper small bowel, were reaching the ileal L cells.
Humans discover the same important relationships at different times according to their experience, study, and problem-solving stress. My experience with gastric dumping prepared me for recognizing the importance of rapid transit. However, I did not know about Brener’s2 study of individuals of normal weight of gush/flush/GLP-1 secretion until I was confronted with the question as to why lean people, who supposedly did not dump, were free of T2D. In fact, those who are lean do dump. If there is no gush and no flush then there is T2DM. If you are having difficulty in following my efforts to make dumping the key to a new paradigm about T2D, you should consult the study by Koopmans et al[8] study on ileal transposition. This prepared me for the recognition of the importance of dumping. My concept of serendipity is a mind prepared with the experiences that need to fall in place in solving a problem. Important pieces of a puzzle need to be provided before they can form a true picture.

An immediate effect of SG is resolution of GLP-1-dependent T2D because it restores dumping. Both intestinal and gastric bypass prevent and cure T2D, which is a failure to secrete sufficient GLP-1. GLP-1 cannot be used to treat T2D because it is too rapidly inactivated by circulating dipeptidyl peptidase 4 (DPP4). Operations that immediately expose the distal bowel to glucose and other stimulants of L-cell secretion have shown us the cause of T2D, which is a failure to secrete adequate amounts of GLP-1. Appropriate medical treatment of T2D should provide a modification of GLP-1 or blockade of DPP4 inactivation of endogenous GLP-1. For T2D in people who are not severely obese, a poorly absorbed oral glucose mimetic taken before beginning each meal could resolve T2D without a surgical operation. There is one hexose that is used as a sweetener in candy and sodas that has been shown to increase plasma GLP-1, but it has not been approved as a nutraceutical or pharmaceutical.

Because of the size of the obesity epidemic, less than one percent of individuals with severe obesity are provided a dumping type operation for treatment of obesity and/or T2D. Today, many millions of kidneys, limbs, eyes, and lives could be saved by changing medical treatment of T2D from insulin to either a GLP-1 mimetic or to an affordable, poorly-absorbed glucose mimetic that would reach the distal bowel at the beginning of a meal or snack. Some of the effects of GLP-1 are prolonged by GLP-1 receptors expressed on the vagal nerve innervating the portal vein where it enters the liver. The ideal medical treatment for T2D in people who are not obese should be stimulation of the secretion of the missing hormone at the beginning of a meal. An epidemic is unlikely to resolve without an appropriate paradigm, plan, and effort.
In the time of the dinosaurs there was a lizard that is still living today. It has a GLP-1 like hormone in its salivary glands. In mammals, such cells must have moved to the distal bowel.[9] These cells need to be stimulated at the beginning of a meal. This is accomplished by flushing of hypertonic intestinal contents to the distal bowel. L-cells are thus stimulated by glucose and other GLP-1 stimulants in the flushed hypertonic contents. Obesity and age block hypertonic gush/flushing.
Current treatment of T2D is available with a GLP-1 mimetic or by blocking DPP4 (the circulating enzyme that inactivates GLP-1). I treat my age-related T2D with DPP4 blocking. I could easily gain enough weight to qualify for a dumping operation if I were younger and desired a surgical procedure. I would rather take an oral glucose mimetic that stimulated secretion of endogenous GLP-1. I encourage you to study the references provided in this and earlier columns and help with the ongoing paradigm-shift. We can all benefit from decreased disease.

Treatment of T2D by dumping has been available since 1885 when Billroth performed his second type of gastrectomy. Dumping occurs in healthy (i.e., nondiabetic) normal-weight people before they are old, after RYGB, and following SG. GLP-1 stimulates growth of beta cells and secretion of insulin. GLP-1 increases satiety. Today, before treatment of patients with dumping surgery, whose body mass index (BMI) is less than 40kg/m2, failure of medical treatment must be demonstrated. If the medical treatment is not GLP-1 related it should not qualify. T2D is not insulin dependent. It is GLP-1 dependent. The effectiveness of treating T2D with dumping type obesity surgery compared with more intensive medical treatment is because the operations used cause rapid transit of GLP-1 secretory stimulants to the distal bowel. SG results in exposure of the upper jejunum to hypertonic contents containing glucose and other stimulants of L-cell secretion.

1.    Miholic J, Orskov C, Holst JJ, et al. Emptying of the gastric substitute, glucagon-like peptide-1, and reactive hypoglycemia after total gastrectomy. Dig Dis Sci. 1991;36(10):1361–1370.
2.    Brener W, Hendrix TR, McHugh PR. Regulation of the gastric emptying of glucose. Gastroenterology. 1983;85:76–82.
3.    Schirra J, Katschinski M, Weidmann C et al. Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest. 1996; 97:92–103.
4.    Näslund E, Backman L, Holst JJ, et al. Importance of small bowel peptides for the improved glucose metabolism 20 years after jejunoileal bypass for obesity. Obes Surg. 1998; 8:253–260.
5.    Mason EE. Ileal transposition and enteroglucagon/GLP-1 in obesity (and diabetic?) surgery. Obes Surg. 1999;9:223–228.
6.    Strader AD, Torsten PV, Ronald JJ, et al. Weight loss through ileal transposition is accompanied by increased ileal hormone secretion and synthesis in rats. Am J Physiol Endocrinol Metab. 2005;288:E447–E453.
7.    Falken Y, Hellstrom PM, Holst JJ, Näslund E. Roux-e-Y gastric bypass surgery for obesity at day three, two months, and one year after surgery: role of gut peptides. J Clin Endocrinol Metab. 2011;96(7):2227–2235.
8.    Koopmans HS, Sclafani A, Fichtner C, et al. The effects of ileal transposition on food intake and body weight loss in VMH-obese rats. Am J Clin Nutr. 1982;35:284–293.
9.    Mason EE. Gila monster’s guide to surgery for obesity and diabetes. J Am Coll Surg. 2008;206:357–360.

Category: Ed Mason at Large, Past Articles

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