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Metabolic Characterization of Nondiabetic Severely Obese Patients Undergoing Roux-en-Y Gastric Bypass: Preoperative Classification Predicts the Effects of Gastric Bypass on Insulin–Glucose Homeostasis

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Obese individuals may have normal insulin–glucose homeostasis, insulin resistance, or diabetes mellitus. Whereas gastric bypass cures insulin resistance and diabetes mellitus, its effects on normal physiology have not been described. We studied insulin resistance and β-cell function for patients undergoing gastric bypass.

Methods

One hundred thirty-eight patients undergoing gastric bypass had fasting insulin and glucose levels drawn on days 0, 12, 40, 180, and 365. Thirty-one (22%) patients with diabetes mellitus were excluded from this analysis. Homeostatic model of assessment was used to estimate insulin resistance, insulin sensitivity, and β-cell function. Based on this model, patients were categorized as high insulin resistance if their insulin resistance was >2.3.

Results

Body mass index did not correlate with insulin resistance. Forty-seven (34%) patients were categorized as high insulin resistance. Correction of insulin resistance for this group occurred by 12 days postoperatively. Sixty (43%) patients were categorized as low insulin resistance. They demonstrated an increase of β-cell function by 12 days postoperatively, which returned to baseline by 6 months. At 1 year postoperatively, the low insulin resistance group had significantly higher β-cell function per degree of insulin sensitivity.

Conclusions

Adipose mass alone cannot explain insulin resistance. Severely obese individuals can be categorized by degree of insulin resistance, and the effect of gastric bypass depends upon this preoperative physiology.

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Authors and Affiliations

  1. Department of Surgery, University of Massachusetts Medical School, Room H1-758, 55 Lake Avenue N, Worcester, MA, 01655, USA

    Richard A. Perugini, Steven H. Quarfordt, Donald R. Czerniach, Demetrius E. M. Litwin & John J. Kelly

  2. Informatics Unit, Department of Academic Computing, University of Massachusetts Medical School, Worcester, MA, USA

    Stephen Baker

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  1. Richard A. Perugini
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  2. Steven H. Quarfordt
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Correspondence to Richard A. Perugini.

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DISCUSSION

Dr. M. Sarr (Rochester, MN): Dr. Perugini and I have discussed this paper beforehand, and I will have to admit I have had a very, very difficult time understanding several of the concepts of this work.

First, I will remind the audience, these are nondiabetics, some of whom have insulin resistance and some of whom might be considered as having the metabolic X syndrome even though they are not hyperglycemic. That is a new concept for many of us.

Second, the derivation of the HOMA-IR score—that is, the score that defines insulin resistance—is not well-defined. Rich, I think you should tell us how that was done, because you take the fasting insulin concentration in the blood – and, again, these are fasting studies – and the blood glucose concentration and from those two parameters estimate the insulin resistance.

Third, the hypothesis being proposed is that once the nondiabetics that do not have insulin resistance lose weight, they might be the group that has a higher relative amount of insulin secreted than normal for a certain fasting blood glucose, and they may actually be the patients who develop noninsulinoma hyperinsulinemic hypoglycemia postoperatively.

There are, however, several assumptions. One is that postprandial insulin metabolism and homeostasis is the same as what you are estimating from your fasting studies. Maybe you could discuss this point.

Second, just out of interest, were you able to correlate body fat distribution in these nondiabetics with their insulin resistance, according to whether they had central obesity or peripheral obesity?

Dr. Perugini: The homeostasis model of assessment is a computer model generated at Oxford University and first published in the mid-‘80s. The problem is that the gold standard for studying insulin sensitivity and beta cell function is with the insulin and glucose clamp. This particular procedure requires a patient to be on bedrest for up to seven hours and requires two peripheral lines to be started, one of which infuses glucose, and one of which infuses insulin. It is not useful in the clinical setting because it is so cumbersome. Researchers at Oxford performed insulin and glucose clamps on a large body of patients; they then developed a computer program to model the outcomes based on the fasting insulin and the fasting glucose level.

Now, there are a bunch of theoretical presumptions that they made. Suffice it to say, when you compare the results from the HOMA to the results from an insulin and glucose clamp, the correlation coefficient is actually very high; the R is about .7.

Whenever big, broad-based epidemiologic studies examine whether insulin resistance has any impact on cardiovascular morbidity, nobody can use a clamp, for the same pragmatic reasons I just mentioned. These studies typically use calculations to estimate insulin sensitivity; the most common of these is the HOMA.

It is a very simple computer model. You need only plug in is glucose and insulin. It is an on-line, Web-based computer program that anybody has access to.

Dr. Sarr: Was that done in fat people or in others?

Dr. Perugini: There were no restrictions. Indeed, the patient population that I showed you from Europe, where Stern tried to correlate the results of an insulin and glucose clamp with the HOMA, was done on a broad spectrum of the population in Europe. Does it apply to this severely obese patient population? It is not very clear. It probably does.

The final question had to do with whether these patients had central obesity versus peripheral obesity. We don’t measure that, as it is quite difficult to do reproducibly in this patient population. So, no, I have no data to correlate this with waist-to-hip circumference or central versus peripheral obesity.

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Perugini, R.A., Quarfordt, S.H., Baker, S. et al. Metabolic Characterization of Nondiabetic Severely Obese Patients Undergoing Roux-en-Y Gastric Bypass: Preoperative Classification Predicts the Effects of Gastric Bypass on Insulin–Glucose Homeostasis. J Gastrointest Surg 11, 1083–1090 (2007). https://doi.org/10.1007/s11605-007-0158-3

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