title: A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?
abstract: BACKGROUND
  We previously reported, in a study of 608 patients, that the gastric bypass operation (GB) controls type 2 diabetes mellitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible to reduce the mortality from diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This control of diabetes has been ascribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss was really the important factor.
  
  
  METHODS
  Fasting plasma insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 months after surgery versus a control group of six women who did not undergo surgery and were similarly weight-stable. The two groups were matched in age, percentage of fat, body mass index, waist circumference, and aerobic capacity.
  
  
  RESULTS
  Even though the two groups of patients were closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgical group demonstrated significantly lower levels of serum leptin, fasting plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was significantly higher in the surgical group. Finally, self-reported food intake was significantly lower in the surgical group.
  
  
  CONCLUSIONS
  Weight loss is not the reason why GB controls diabetes mellitus. Instead, bypassing the foregut and reducing food intake produce the profound long-term alterations in glucose metabolism and insulin action. These findings suggest that our current paradigms of type 2 diabetes mellitus deserve review. The critical lesion may lie in abnormal signals from the gut.
authors.affiliation: Department of Exercise and Sport Science, Colorado State University, Ft. Collins, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Hickey
authors.forename: W J
authors.initials: WJ
authors.lastname: Pories
authors.forename: K G
authors.initials: KG
authors.lastname: MacDonald
authors.forename: K A
authors.initials: KA
authors.lastname: Cory
authors.forename: G L
authors.initials: GL
authors.lastname: Dohm
authors.forename: M S
authors.initials: MS
authors.lastname: Swanson
authors.forename: R G
authors.initials: RG
authors.lastname: Israel
authors.forename: H A
authors.initials: HA
authors.lastname: Barakat
authors.forename: R V
authors.initials: RV
authors.lastname: Considine
authors.forename: J F
authors.initials: JF
authors.lastname: Caro
authors.forename: J A
authors.initials: JA
authors.lastname: Houmard
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control*; D005260:Female; D015390:Gastric Bypass; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin; D009767:Obesity, Morbid / Q000150:complications / Q000601:surgery; D011506:Proteins / Q000032:analysis
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D020738:Leptin; D011506:Proteins