A new paradigm for type 2 diabetes mellitus: Could it be a disease of the foregut?

Matthew S. Hickey, Walter J. Pories, Kenneth G. MacDonald, Kelly A. Cory, G. Lynis Dohm, Melvin S. Swanson, Richard G. Israel, Hisham A. Barakat, Robert Considine, Jose F. Caro, Joseph A. Houmard

Research output: Contribution to journalArticle

224 Citations (Scopus)

Abstract

Summary Background Data: 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.

Original languageEnglish (US)
Pages (from-to)637-644
Number of pages8
JournalAnnals of Surgery
Volume227
Issue number5
DOIs
StatePublished - May 1998
Externally publishedYes

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Gastric Bypass
Type 2 Diabetes Mellitus
Fasting
Weights and Measures
Weight Loss
Insulin
Leptin
Glucose
Insulin Resistance
Eating
Control Groups
Fat Body
Waist Circumference
Diabetes Mellitus
Body Mass Index
Research Design
Fats
Mortality
Serum
Therapeutics

ASJC Scopus subject areas

  • Surgery

Cite this

Hickey, M. S., Pories, W. J., MacDonald, K. G., Cory, K. A., Dohm, G. L., Swanson, M. S., ... Houmard, J. A. (1998). A new paradigm for type 2 diabetes mellitus: Could it be a disease of the foregut? Annals of Surgery, 227(5), 637-644. https://doi.org/10.1097/00000658-199805000-00004

A new paradigm for type 2 diabetes mellitus : Could it be a disease of the foregut? / Hickey, Matthew S.; Pories, Walter J.; MacDonald, Kenneth G.; Cory, Kelly A.; Dohm, G. Lynis; Swanson, Melvin S.; Israel, Richard G.; Barakat, Hisham A.; Considine, Robert; Caro, Jose F.; Houmard, Joseph A.

In: Annals of Surgery, Vol. 227, No. 5, 05.1998, p. 637-644.

Research output: Contribution to journalArticle

Hickey, MS, Pories, WJ, MacDonald, KG, Cory, KA, Dohm, GL, Swanson, MS, Israel, RG, Barakat, HA, Considine, R, Caro, JF & Houmard, JA 1998, 'A new paradigm for type 2 diabetes mellitus: Could it be a disease of the foregut?', Annals of Surgery, vol. 227, no. 5, pp. 637-644. https://doi.org/10.1097/00000658-199805000-00004
Hickey MS, Pories WJ, MacDonald KG, Cory KA, Dohm GL, Swanson MS et al. A new paradigm for type 2 diabetes mellitus: Could it be a disease of the foregut? Annals of Surgery. 1998 May;227(5):637-644. https://doi.org/10.1097/00000658-199805000-00004
Hickey, Matthew S. ; Pories, Walter J. ; MacDonald, Kenneth G. ; Cory, Kelly A. ; Dohm, G. Lynis ; Swanson, Melvin S. ; Israel, Richard G. ; Barakat, Hisham A. ; Considine, Robert ; Caro, Jose F. ; Houmard, Joseph A. / A new paradigm for type 2 diabetes mellitus : Could it be a disease of the foregut?. In: Annals of Surgery. 1998 ; Vol. 227, No. 5. pp. 637-644.
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abstract = "Summary Background Data: 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.",
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AU - Israel, Richard G.

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N2 - Summary Background Data: 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.

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