Type 2 Diabetes Mellitus (T2DM) is a significant public health concern with high morbidity and mortality burden. Maladaptive food behaviors contribute to poor glycemic outcomes for persons with Type 2 Diabetes Mellitus (T2DM). Factors which may contribute to poor T2DM dietary behaviors include food addiction (FA; overconsumption to the point there are similar symptoms to substance use addiction) and impulsivity (lack of control in food consumption). FA and impulsivity behaviors can be reflected by differences in brain tissue integrity, but the relationships between FA, impulsivity, and brain tissue changes in persons with T2DM are unclear. To date, little is known about FA and impulsivity in association with A1c levels (indication of poor glycemic control) among T2DM patients. While studies indicate associations between brain injury and A1c levels in T2DM patients, it is also unclear if FA and brain injury can independently predict glycemic control in T2DM. An examination of the brain associated with these behaviors has not been assessed in persons with T2DM. The overarching purpose of this dissertation study is to offer valuable insights into the link between brain tissue integrity, food behaviors, and glycemic control in T2DM patients. Manuscript one compares the relationships between FA, impulsivity, and glycemic outcome (hemoglobin A1c) between 32 T2DM and 32 healthy patients between the ages 40-65 years. Participants completed the Yale Food Addiction Scale 2.0 (YFAS) and Barratt Impulsiveness Scale-11 (BIS) online questionnaires and A1c was measured with a fingerstick test. Between T2DM and healthy patients, there were no group differences in the prevalence of FA diagnosis, YFAS 2.0 scores, BIS-11 scores, or severity classification of FA diagnosis. There were positive correlations between two FA symptomatologies with higher A1c: food tolerance and food use in physically hazardous situations (r= 0.254, r= 0.417, P <0.05). There were no significant correlations between BIS-11 scores and A1c. In this study, two FA symptomatologies were linked to poor A1c suggesting that a subset of questions from YFAS 2.0 could provide clinicians insight into glycemic outcomes (A1c). This was the first study that investigated the associations between FA symptomatologies and A1c among T2DM patients and healthy controls.
In manuscript two, using diffusion tensor imaging data, mean diffusivity (MD) values were calculated, and region-of-interest analyses were performed on various brain areas to examine correlations between brain tissue integrity (measured by MD values) and YFAS 2.0 and BIS scores (partial correlations; covariates, age, and sex). Twenty-one T2DM participants between the ages 40-65 years completed brain magnetic resonance imaging (MRI) scans. There were significant correlations between tissue integrity and YFAS 2.0 scores in brain regions regulating executive decision-making (cortices, precuneus, temporal); memory -visual or auditory (occipital, supramarginal); motor function (putamen); and emotion (cingulum) functions in T2DM patients. While there were no associations between BIS-11 scores and brain tissue integrity, there is now neuroimaging evidence of specific impaired brain sites that mediate FA symptomatologies among T2DM patients in this sample. Manuscript three determined which of the following were independent predictors of A1c status: food tolerance and food use during physically hazardous situations FA symptomatologies (found in manuscript one), and areas of brain damage (that are linked to A1c) in the following regions: areas mediating cognition/executive decision-making (frontal middle-right, frontal medial orbital -right) and emotion (cingulate). Among 32 T2DM patients, only tissue changes in the right medial orbitofrontal cortices (OFC) were an independent predictor of glycemic status, and not the two FA symptomatologies or the other brain regions. Findings from manuscript two and three regarding injury to brain areas regulating cognition (frontal cortices) further corroborate past structural neuroimaging studies that T2DM patients have brain injury in the frontal cortices affecting their decision-making. The dissertation identifies several interventions with the potential to promote neurogenesis or neuroprotection in areas of brain injury (e.g., cognitive brain training, neurofeedback, stem cell therapies, and nutritional supplementation).
This dissertation contributes to T2DM research by shedding light on the crucial role of brain regions in regulating food behaviors and, subsequently, managing A1c. This understanding shifts the focus of interventions from solely addressing physiological or behavioral aspects of T2DM to incorporating brain-based interventions that can improve glycemic outcomes. By highlighting these potential interventions, the dissertation opens new avenues for research and development in T2DM management and ultimately, improved care for T2DM patients.
