Insulin Resistance and Reward
| Status: | Recruiting |
|---|---|
| Conditions: | Obesity Weight Loss, Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 25 - 60 |
| Updated: | 11/30/2018 |
| Start Date: | November 17, 2014 |
| End Date: | December 31, 2019 |
| Contact: | Julia P Dunn, MD |
| Email: | julia.dunn@va.gov |
Insulin Resistance and Reward Signaling in Obesity
Obesity is a common problem in the Veteran population as at least 1 in 3 Veterans are obese.
When obese people eat food they have less response in areas of the brain that sense pleasure
(reward). Decreased pleasure response to food predicts future weight gain. It is not known if
this poor brain response is reversible or why obese people's brains respond this way. Insulin
in the brain regulates the brain's sensing of pleasure. As people gain weight the function of
insulin becomes impaired. The investigators will study if impaired function of insulin is
related to a poor brain response to food and if this brain response predicts voluntary intake
of food and response to a diet. The investigators will also study if improving the function
of insulin with weight loss improves the brain response. These studies will improve the
understanding as to why weight loss is difficult and inform us if improving insulin signaling
is a potential way to treat obesity.
When obese people eat food they have less response in areas of the brain that sense pleasure
(reward). Decreased pleasure response to food predicts future weight gain. It is not known if
this poor brain response is reversible or why obese people's brains respond this way. Insulin
in the brain regulates the brain's sensing of pleasure. As people gain weight the function of
insulin becomes impaired. The investigators will study if impaired function of insulin is
related to a poor brain response to food and if this brain response predicts voluntary intake
of food and response to a diet. The investigators will also study if improving the function
of insulin with weight loss improves the brain response. These studies will improve the
understanding as to why weight loss is difficult and inform us if improving insulin signaling
is a potential way to treat obesity.
The current research proposal will investigate the relationship of insulin sensitivity to
brain reward signaling. In most obese individuals, insulin signaling is impaired (insulin
resistance). Preclinical animal studies suggest that insulin resistance in brain regions
important for reward contribute to overeating. This proposal aims to test these hypotheses in
humans and to determine if these characteristics are pertinent to clinical outcomes (food
intake and weight loss). In humans increased body mass index (BMI) and weight gain occur with
decreased food consumption-induced neural activation (consummatory reward) in the caudate of
the dorsal striatum. It has been speculated that diminished consummatory reward causes
overeating and prevents weight loss, however, this hypothesis has not been directly tested.
Further, mechanisms for impaired food consumption-induced neural activation in obesity have
not been investigated.
The primary research outcomes of the proposed study are: 1) insulin sensitivity determined by
hyperinsulinemic euglycemic clamp, 2) food consumption-induced neural activation as
determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI)
scanning, 3) caloric intake at a buffet meal, and 4) weight loss during a weight loss
intervention. Based on screening and baseline outcome assessments half of participants will
be enrolled in a weight loss intervention and then repeat outcomes measures after
intervention. Others will only complete baseline outcome measures. Secondary measures of the
study include whole brain activation analyses, neuroendocrine hormone measurement at the time
of imaging, psychometric measures including eating behaviors and personality characteristics,
and measures of reward sensitivity.
brain reward signaling. In most obese individuals, insulin signaling is impaired (insulin
resistance). Preclinical animal studies suggest that insulin resistance in brain regions
important for reward contribute to overeating. This proposal aims to test these hypotheses in
humans and to determine if these characteristics are pertinent to clinical outcomes (food
intake and weight loss). In humans increased body mass index (BMI) and weight gain occur with
decreased food consumption-induced neural activation (consummatory reward) in the caudate of
the dorsal striatum. It has been speculated that diminished consummatory reward causes
overeating and prevents weight loss, however, this hypothesis has not been directly tested.
Further, mechanisms for impaired food consumption-induced neural activation in obesity have
not been investigated.
The primary research outcomes of the proposed study are: 1) insulin sensitivity determined by
hyperinsulinemic euglycemic clamp, 2) food consumption-induced neural activation as
determined by blood-oxygen dependent functional magnetic resonance imaging (BOLD fMRI)
scanning, 3) caloric intake at a buffet meal, and 4) weight loss during a weight loss
intervention. Based on screening and baseline outcome assessments half of participants will
be enrolled in a weight loss intervention and then repeat outcomes measures after
intervention. Others will only complete baseline outcome measures. Secondary measures of the
study include whole brain activation analyses, neuroendocrine hormone measurement at the time
of imaging, psychometric measures including eating behaviors and personality characteristics,
and measures of reward sensitivity.
Inclusion Criteria:
- Age 25-60yoa, inclusive.
- BMI 30.0 and 45.0 kg/m2, inclusive.
- Normal visual acuity with correction.
- Able to travel regularly to the St. Louis VA and Washington University for research
visits.
- Completed signed informed consent form.
Exclusion Criteria:
- Current or history of significant psychiatric disease, including Binge Eating Disorder
(BED).
- Current or history of significant substance abuse or extended use of tobacco.
- Contraindications for MRI (e.g., pregnancy, claustrophobia, pacemaker, circumference >
54 inches, weight > 400 lbs, etc.);
- Significant cardiovascular, pulmonary, renal, liver, neurologic, or metabolic disease.
- Diabetes mellitus.
- Significant anemia.
- Treatment with a medication the affects insulin sensitivity.
- Treatment with centrally acting medications.
- Frequent shift work.
- Significant in-mobility or unable to lay on back still for 1 hour.
- History of bariatric surgery.
- Food allergies/ intolerance that would prevent completing study.
- Symptoms concerning for untreated active mental health disease
We found this trial at
1
site
915 North Grand Boulevard
Saint Louis, Missouri 63106
Saint Louis, Missouri 63106
Principal Investigator: Julia P Dunn, MD
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