The Medical Student Notebook: Bariatric Physiology

| October 13, 2014 | 0 Comments

This column is written by medical students and is dedicated to reviewing the science behind obesity and bariatric surgery.

Lesson #1 explores topics in gastrointestinal physiology and discusses the implications of gastric bypass surgery for each subject.

Column Editor: Daniel B. Jones, MD, MS, FACS
Professor of Surgery, Harvard Medical School
Vice Chair, Beth Israel Deaconess Medical Center
Boston, Massachusetts

Featured Student: Kyle D. Checchi, MSc
Medical Student, Harvard Medical School, Boston, Massachusetts

This month: Lesson #1: Bariatric Physiology
Part 3: Insulin Physiology and Type 2 Diabetes Mellitus in Bariatric Surgery 
by Kyle D. Checchi, MSc

FUNDING: No funding was provided for this article.
FINANCIAL DISCLOSURES: The author reports no conflicts of interest relevant to the content of this article.

Bariatric Times. 2014;11(10):8–9.

Lesson #1 of The Medical Student Notebook is a five-part series focused on gastrointestinal physiology. Part 1, published in Bariatric Times March 2014, discussed bariatric surgery and B12. In Lesson #1, Part 2, published in Bariatric Times June 2014, we examined bariatric surgery and iron. In Lesson #1, Part 3, we will discuss insulin physiology and type 2 diabetes mellitus (T2DM) in bariatric surgery.

Part 3: Insulin physiology and Type 2 Diabetes Mellitus in Bariatric Surgery
Obesity is a necessary but insufficient justification for pursuing bariatric surgery. In large part, it is obesity’s link to adverse health outcomes, including diabetes, dyslipidemia, hypertension, cardiovascular disease, sleep disturbance and apnea, osteoarthritis, fertility and obstetric issues, and certain cancers1 that favor correcting a patient’s weight.

The cumulative effects of these health problems result in an overall increased mortality associated with obesity.2 Weight loss has been correlated with improvements in diabetes and other intermediate risk factors for cardiovascular disease;[3] however, the net effect of weight loss on mortality is unsettled with many studies finding conflicting effects.[3,4]

In 2007, in recognition of the effects of bariatric surgery on metabolic physiology and pathophysiology, the American Society of Bariatric Surgery changed its name to the American Society of Metabolic and Bariatric Surgery.[5] This segment of the Medical Student Notebook will explore the effect of gastric bypass surgery on a common metabolic disorder—insulin resistance and diabetes.

Insulin is produced, stored, and secreted in the beta cells of the pancreas. Beta cells sense blood sugar levels by transporting glucose from the blood stream into the beta cell through a glucose transporter that is not dependent on insulin (GLUT2). Once in the cell, glucose is phosphorylated by glucokinase in a rate-limiting step that generates adenosine triphosphate (ATP). Therefore, when blood sugar levels are high, ATP levels rise intracellularly, which inhibit an ATP-sensitive K+ channel depolarizing the beta cell and releasing insulin.[6]

Once in the blood stream, insulin binds to insulin receptors leading to receptor autophosphorylation and intracellular signaling that results in GLUT4 expression on the surface of cells with the GLUT4 protein (especially skeletal muscle cells), which facilitates peripheral glucose transport into these cells.[6]

In T2DM, there is uncertainty as to the precise molecular mechanism leading to insulin resistance, but one hypothesis is that defects or down regulation in intracellular signaling result in reduced expression of GLUT4 on the plasma membrane and reduced glucose absorption in these cells resulting in higher blood sugar levels causing the clinical manifestations of T2DM.[6]

While the natural course of T2DM is rarely reversible without weight loss, it has been repeatedly shown that roughly 80 percent of patients with T2DM experience long-lasting remission of their disease and are able to discontinue all diabetic medications following gastric bypass surgery.[7] This effect appears to work through mechanisms separate from weight loss with improvements in T2DM severity occurring within days of the procedure before any weight loss has occurred.[8]

The underlying mechanisms to explain the improvements in diabetes and insulin resistance following gastric bypass surgery are not fully understood. Of the numerous theories to explain this phenomenon, two include the “hindgut hypothesis” and the “foregut hypothesis.” The “hindgut hypothesis” asserts that improved glucose control results from the expedited delivery of nutrient chyme to the distal intestine enhancing GLP-1, a physiologic signal that improves glucose metabolism.[7] GLP-1 exerts proliferative and anti-apoptotic effects on pancreatic beta cells[9] and it has also be associated with improved insulin sensitivity.[10] In the “foregut hypothesis,’’ exclusion of the duodenum and proximal jejunum from the transit of nutrients may reduce secretion of ghrelin, a hormone that promotes insulin resistance. To support this hypothesis it has been observed that ghrelin hinders insulin secretion and action, chronic administration of ghrelin receptor agonists impairs glucose tolerance in humans, and it is known that ghrelin levels decrease after gastric bypass.[7]

This topic illustrates, again, the importance of physiology to bariatric surgery and is another example in a growing list of surgical treatments for traditionally medically managed conditions, in this case obesity and T2DM. While bariatric surgery is not likely to become an isolated treatment in T2DM, it is certainly contributing to increased understanding of the physiology and pathophysiology of insulin resistance, with the potential to improve our understanding of metabolism, obesity, and diabetes, which could lead to future medical therapies for obesity or modifications of surgical technique.

1.    Dixon JB. The effect of obesity on health outcomes. Mol Cell Endocrinol. 2010;316(2):104–108.
2.    Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309(1):71–82.
3.    Sjöström L, Peltonen M, Jacobson, P, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307(1):56–65.
4.    Shea MK, Houston DK, Nicklas BJ, et al. The effect of randomization to weight loss on total mortality in older overweight and obese adults: The ADAPT Study. J Gerontol A Biol Sci Med Sci. 2010;65(5):519.
5.    Frangou C. Bariatric surgery society marks new era with name change. General Surgery News. 2007. Accessed August 24, 2014.
6.    Longo D, Fauci A, Kasper D, Hauser S, et al. Harrison’s Principles of Internal Medicine, 18th Edition. McGraw-Hill Professional. 2011.
7.    Pitombo C, Jones K, Higa K, Pareja J. Obesity Surgery: Principles and Practice. McGraw-Hill Medical. 2008.
8.    Nandagopal R, Brown RJ, Rother KI. Resolution of type 2 diabetes following bariatric surgery: implications for adults and adolescents. Diabetes Technol Ther. 2010;12(8):671–677.
9.    Drucker DJ. Glucagon-like peptide-1 and the islet beta-cell: augmentation of cell proliferation and inhibition of apoptosis. Endocrinology. 2003;144(12):5145–5148.
10.    Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002;359(9309): 824–830.


Category: Medical Methods in Obesity Treatment, Past Articles

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