Diabetic Mellitus Myth #2: Obesity Causes Insulin Insensitivity

DM.Statistics

Since the middle of 1990’s, diabetes mellitus has become a household disease because of its increasing prevalence globally, especially in those developed and developing countries. [1] In addition, diabetes mellitus continues to be a serious disease. Despite that the all-cause mortality among women and men with diabetes mellitus might have decreased over time, the mortality rate among individuals with diabetes mellitus was still two folds of that among individuals without diabetes mellitus.

Studies have continued to focus on the cause of diabetes mellitus, in hopes that the findings help develop medications for managing the disease. If succeeded, the financial prize for the studies is enormous. Consequently, the number of various hypotheses for the cause of the disease has continued to grow and results in many seemed-breakthrough laboratory findings including those collected in animal studies. However, the validity of these hypotheses and findings remain to be seen. [2, 3]

Because it has been the consensus that during the development of type II diabetes mellitus, the individual may experience stages ranged “from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance”, [4] it seems logical that to halt or avert the situation of insulin resistance prevents the individual from progressing into diabetes mellitus. A majority of experts in diabetes mellitus is convinced that insulin resistance is a result of insulin insensitivity of the insulin receptors of the cells, which cannot use the endogenous insulin for facilitating the utilization of glucose.

Fat has been an ugly word and been blamed for diseases including morbid obesity and diabetes mellitus during the past five decades. To no one’s surprise, researchers have intensively studies fat or obesity and linked it to insulin insensitivity or insulin resistance, thus, blamed it for the development of diabetes mellitus.

In November 1998, Brunzell and Hokanson presented an original article, “Dyslipidemia of Central Obesity and Insulin Resistance.” They pointed out a positive relationship between central obesity and insulin resistance, in addition to dyslipidemia. [5]

In a 2000 issue of Journal of Clinical Investigation, Kahn and Flier wrote a review article, “Obesity and Insulin Resistance.” They carefully analyzed the causative relationship between obesity and insulin resistance from various aspects, namely, insulin action in the adipocyte; insulin resistance in obesity and type 2 diabetes; reduced glucose disposal into adipose tissue in obesity; the significance of the location of body fat for insulin resistance; adipocyte as endocrine cells; lipotoxicity and lipoatrophy: two sides of the same coin; insights from thiazoladinediones and PPARγ. They concluded, “…the complex orchestration of the relationship between adipose tissue, insulin action, and glucose homeostasis evolved out of survival needs to maintain fuel supplies when food was scarce. Now in times of plenty in Western society, obesity with its accompanying morbidities has reached epidemic proportions and the need for scientific advances to identify new therapeutic approaches could not be more acute…” [6] Many more studies were published to affirm that fat or obesity causes insulin resistance, which lead the path to diabetes mellitus. [7, 8, 9, 10, 11]

Having believed that obesity is responsible for insulin insensitivity, diabetes mellitus, and other diseases, weight loss has become a top public health issue and created an industry of 58 billion dollars in the US alone in 2007. [12] The approaches for weight loss include but not limited to dieting, and surgeries. Data have already shown both carbohydrate-restricted diet and calorie-restricted, fat-restricted diet are effective in weight loss. Surgeries include abdominoplasty and gastric by-pass.

Despite that abdominoplasty is a cosmetic surgery for removing excess abdominal fat mass for improving the body contour; the surgery has no benefit in improving insulin sensitivity. The findings doubt the assertion that central obesity causes insulin insensitivity. [13]

Drs. Arnold Kremen and John H. Linner at Mt. Sinai Hospital, Minneapolis, Minnesota performed the first reported gastric bypass surgery on April 9, 1954. Since then, the procedure has been modified. The current approaches are to have the stomach bypass the duodenum and attached to the distal portion of the ileum close to the junction between the small and large intestine.

Aside the issues in terms of surgical complications, safety, and impacts on the postoperative lifestyle, the quick improvement in the patients’ glycemic control as well as insulin sensitivity is astonishing. The patients with type II diabetes mellitus have demonstrated remission of the disease in a matter of few days after surgery and before they began to lose weight, particularly the central fat in these cases. The results have prompted the claim that bariatric surgery is one of the treatments for diabetes mellitus. Validity of the claim requires a careful long-term evaluation. As expected, researchers are scrambling to find new hypothesis or hypotheses for explaining why gastric bypass improves the patients’ glycemic control and insulin sensitivity without weight loss. {14, 15, 16, 17]  Nevertheless, the quick improvement in patient’s glycemic control and insulin sensitivity provides the evidences that central obesity does not cause insulin insensitivity. Rather, central obesity is merely a comorbidity, like diabetes mellitus, of a path of hyperglycemia after meal.

Robert Su, Pharm.B., M.D.

References:

  1. Preis SR et al. “Trends in All-Cause and Cardiovascular Disease Mortality Among Women and Men With and Without Diabetes Mellitus in the Framingham Heart Study, 1950 to 2005.” Circulation. 2009;119:1728-1735.
  2. Crowe S et al. “Pigment Epithelium-Derived Factor Contributes to Insulin Resistance in Obesity.” Cell Metabolism. olume 10, Issue 1, 8 July 2009, Pages 40-47.
  3. DANA-Farber Cancer Institute “Scientists find unsuspected molecular link between obesity and insulin resistance.” July 21, 2010.
  4. American Diabetes Association “Position Statement: Diagnosis and Classification of Diabetes Mellitus.” DIABETES CARE, VOLUME 27, SUPPLEMENT 1, JANUARY 2004.
  5. Brunzell JD & Hokanson JE “Dyslipidemia of Central Obesity and Insulin Resistance.” Diabetes Care. Volume 22 Supplement 3
    Improving Prognosis in Type 1 Diabetes Proceedings from an Official Satellite Symposium of the 16th International Diabetes Federation Congress.
  6. Kahn BB & Flier JS “Obesity and insulin resistance.” Journal of Clinical Investigation. 2000;106(4):473–481.
  7. Kahn SE et al. “Obesity, Body Fat Distribution, Insulin Sensitivity and Islet Beta-Cell Function as Explanations for Metabolic Diversity.” (Journal of Nutrition. 2001;131:354S-360S.)
  8. Kahn SE et al. “Mechanisms linking obesity to insulin resistance and type 2 diabetes.” Nature 444, 840-846 (14 December 2006)
  9. Steinberger J & Daniels SR “Obesity, Insulin Resistance, Diabetes, and Cardiovascular Risk in Children.” Circulation. 2003;107:1448-1453.
  10. Yumuk VD et al. “High prevalence of obesity and diabetes mellitus in Konya, a central Anatolian city in Turkey.” Diabetes Research and Clinical Practice 70 (2005) 151–158.
  11. Cruz ML et al. “Unique Effect of Visceral Fat on Insulin Sensitivity in Obese Hispanic Children With a Family History of Type 2 Diabetes.” Diabetes Care 25:1631–1636, 2002
  12. Armen Hareyan “U.S. Weight Loss Market To Reach 58 Billion in 2007.” EmaxHealth. 2007-04-19.
  13. Martinez-Abundis E et al. “Effect of surgically removing subcutaneous fat by abdominoplasty on leptin concentrations and insulin sensitivity.” Annals of Plastic Surgery. 2007 Apr;58(4):416-9.
  14. Gumbs AA et al. “Changes in insulin resistance following bariatric surgery: role of caloric restriction and weight loss.” Obesity Surgery. 2005 Apr;15(4):462-73.
  15. Wickremesekera K et al. “Loss of Insulin Resistance after Roux-en-Y Gastric Bypass Surgery; a time course study.” Obesity Surgery. 2005 Apr;15(4):474-81
  16. Ballantyne GH et al. “Changes in insulin resistance following bariatric surgery and the adipoinsular axis: role of the adipocytokines, leptin, adiponectin and resistin.” Obesity Surgery. 2005 May;15(5):692-9.
  17. Pournaras  DJ et al. “Remission of Type 2 Diabetes after Gastric Bypass and Banding: Mechanisms and 2 Year Outcomes.” Annals of Surgery. 2010;252(6):966-971.
  • http://diabeticmediterraneandiet.com Steve Parker, M.D.

    Very thought-provoking, Dr. Su!

    I wonder if and how the incretin hormones of the gastrointestinal tract affect insulin resistance.

    At least one of the aricles you reference postulates that incretin hormones explain the rapid improvement in insulin resistance quite soon after bariatric surgery. They suggest adipocytokines mediate the longer-term improvement.

    -Steve

    • http://www.carbohydratescankill.com Robert K. Su MD

      Dr. Parker, I am aware of the hypothesis involving the link between GI tract, Incretin, and insulin. At this point, I am not convinced that this hypothesis can fully explain why the diabetic patient would quickly normalize his BG level and restore the insulin sensitivity. I wonder why the postoperative diet has to insist that the patient avoids sugar and sugary foods, if the intestinal incretin makes the call. It would interesting to have the patient take a glucose tolerance test immediately before and shortly after surgery as long as the patient can tolerate the test after surgery. I love to see if a high concentration of glucose solution would not spike the patient’s BG level.

      • http://www.carbohydratescankill.com Robert K. Su MD

        To add to my earlier reply, I remember an article that might have described the effect on the BG level depending on where the distal ileum be attached to the stomach. Unfortunately, I have not been able to locate the article. However, I have found an article, “Overview of the Epidemiology of Obesity and the Early History of Procedures to Remedy Morbid Obesity“, that describes the effectiveness of the jejunoileal bypass on weight loss is inversely related to the length of the distal ileum where the anastomosis is performed. (page 358). This article unfortunately did not describe the effectiveness of the bypass on the BG level. Nevertheless, with the common knowledge in anatomy and physiology, it is likely the mechanical or anatomical factor (the bypass itself) , not the incretin-insulin factor, helps improve the clinical situations of DM after bariatric surgery. In addition, gastric bypass impacts the BG level even more than that jejunoileal bypass does, because the former denies most of the opportunity to mix the pancreatic amylase with carbohydrate foods.