Five Minutes with…Joan Carroll, PhD

A New Link: Laparoscopic Gastric Banding and Reduction in Insulin Resistance

Dr. Joan Carroll is an Assistant Professor in the Department of Integrative Physiology at the University of North Texas Health Science Center at Fort Worth. Her research focuses on the cardiovascular and endocrine effects of obesity. As part of the North Texas Healthy Heart Study, she is studying ethnic differences in visceral fat distribution and its relationship to inflammatory risk markers and anthropometric measures of body composition. As part of the DREAMS (Diabetes Research, Education, and Metabolic Studies) project, Dr. Carroll and colleagues studied patients before and for one year after bariatric surgery using the laparoscopic adjustable gastric banding procedure.

What have your study findings thus far reflected regarding laparoscopic gastric banding patients regarding insulin resistance?
As a group, our patients had an approximate 50-percent reduction in insulin resistance six months after laparoscopic adjustable gastric banding surgery (LAGB). We evaluated insulin resistance using the homeostasis model assessment (HOMA) score, which is a simple calculation that combines fasting insulin and glucose concentration measurements. A higher HOMA score indicates greater insulin resistance. In the case of our patients, their initial high HOMA scores were due primarily to high insulin but normal glucose. This represents oversecretion of insulin by the pancreas in order to compensate for insensitivity of peripheral tissues (such as muscle and liver) to the effects of insulin. Basically, more insulin is needed in order to keep glucose levels normal.

Did you find differentiation between any specific subsets of patients?
We did not find that males and females differed in their response, so equal benefits can be obtained regardless of sex. Intuitively one might think that those who were more obese to start with would have the greatest benefit, but we did not find this. Those with a starting BMI of 30 to 40 improved about the same amount as those with a BMI of 40 to 50. The greatest improvements in HOMA score (and in fasting insulin) were in those who, to begin with, had high HOMA scores and high insulin concentrations. In our sample, those with abnormal insulin concentrations prior to surgery had a 58-percent reduction in fasting insulin at six months. But even those with “normal” insulin concentrations to begin with had a 25-percent reduction in fasting insulin at six months.

Were there any differences in insulin resistance levels that correlated with total amount of weight lost in patients studied?
Again, intuitively one would think that the greatest improvements would be in those with the most weight loss. But that does not appear to be the case. If you are overweight or obese, what seems to be the most important thing in improving insulin sensitivity is losing about 5 to 10 percent of your body weight. What this means is that substantial health benefits can occur rather quickly. In our group, the subjects would be still classified as obese by body mass index (BMI) standards six months after surgery (i.e., BMI>30), yet they had greatly improved insulin sensitivity.

We did find that the change in fasting insulin and HOMA was related both to the amount of visceral (intraabdominal) adipose tissue prior to surgery and remarkably also to the loss of visceral adipose tissue. All of the patients had visceral adipose tissue measured by computed tomography (CT) scan before and six months after surgery. Most researchers report data from the CT slice measured at the L4L5 spinal interspace. This slice gives a good measure of central adiposity. In our study, those with higher amounts of L4L5 visceral adipose tissue prior to surgery had a greater drop in fasting insulin, and those who had the greatest loss in L4L5 visceral adipose tissue had the greatest improvements in fasting insulin and HOMA.
Increased amounts of visceral adipose tissue are linked with numerous metabolic aberrations, such as insulin resistance, hypertension, and abnormal blood lipids. Visceral fat is more sensitive to lipolytic stimuli, resulting in increased fatty acids moving into the portal circulation. This may stimulate very low density lipoprotein (VLDL) production in the liver, and therefore contribute to abnormal blood lipid concentrations. So the loss of visceral adipose tissue through diet, exercise, or as the result of surgery is likely to improve metabolic function in numerous ways. It only stands to reason that those who have the most to gain are those with the greatest abnormalities to begin with.

Have you or will you be able to determine further observations regarding other health measures within this patient cohort?
We are following this cohort for 12 months postoperatively, so we will be able to determine if the improvements we see at six months remain stable or further improve as weight loss increases. In the small number of subjects who have completed the 12-month evaluation, we see continued reductions in body weight, BMI, body fat percentage, and waist circumference, as expected. Interestingly, the improvement in insulin resistance at six months appears to level off so that no further improvements occurred at 12 months. However, we will need to complete data collection before we can say this for certain. Although this sounds like it may be discouraging, I think we need to recognize the very fast adjustments and improvements that are made in insulin sensitivity long before the full extent of weight loss is reached.

We also have measures of blood pressure, cholesterol, HDL cholesterol, ApoA and ApoB, triglycerides, homocysteine, and C-reactive protein. These data are currently being analyzed. However, the following preliminary trends at six months post-surgery were noted: 1) The drop in systolic blood pressure (SBP) six months after surgery was very strongly related to the initial SBP—that is, those with the highest SBPs had the greatest reductions. 2) The change in SBP from pre-surgery to six months post-surgery was not related to a change in plasma renin activity (PRA). PRA is a marker of renin-angiotensin system activity, an endocrine system that can contribute to blood pressure control. Our data would suggest that other factors are more important in the reduction of blood pressure. 3) Total cholesterol was not significantly altered (although on average it was not abnormal prior to surgery). But HDL cholesterol (the “good” cholesterol) was increased. 4) Fasting triglycerides were reduced. 5) ApoA was increased (ApoA is the major protein component of HDL, which promotes transfer of cholesterol to the liver for metabolism and excretion). This is consistent with the increase in HDL cholesterol. 6)

There was a significant increase in fasting ghrelin from pre-surgery to six months post-surgery. Ghrelin is a hormone produced primarily in the stomach. Ghrelin concentrations are high before a meal and decrease after eating, so ghrelin is hypothesized to affect eating behavior in an incompletely understood way. Ghrelin is typically reduced in obese persons, and prior to surgery, the fasting ghrelin concentrations were only one-third that seen in the normal-weight controls. However, at six months post-surgery, fasting ghrelin increased 62 percent in the surgery patients and was about two-thirds that seen in normal-weight controls.

Finally, the study also included an evaluation of eating behaviors and other psychological factors that might impact eating and general health. Eating behaviors were evaluated using the Eating Inventory. Preliminary data suggest that prior to surgery, the surgical patients had less cognitive restraint compared with normal weight individuals. They also had greater disinhibition (i.e., the periodic loss of control of eating) and hunger. Six months after surgery, cognitive restraint increased, while disinhibition and hunger decreased. The values were not significantly different than those of normal weight controls. LAGB appeared to normalize eating patterns and consequently provide patients with an effective mechanism for sustained weight loss. This information was presented at the 2007 American Society for Bariatric and Metabolic Surgery.

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