Type 1 diabetes.

Type 1 diabetes is a chronic disease caused by autoimmune destruction of pancreatic ß cells. Individuals with type 1 diabetes are reliant on insulin for survival. Despite enhanced knowledge related to the pathophysiology of the disease, including interactions between genetic, immune, and environmental contributions, and major strides in treatment and management, disease burden remains high. Studies aimed at blocking the immune attack on ß cells in people at risk or individuals with very early onset type 1 diabetes show promise in preserving endogenous insulin production. This Seminar will review the field of type 1 diabetes, highlighting recent progress within the past 5 years, challenges to clinical care, and future directions in research, including strategies to prevent, manage, and cure the disease.

Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes.

BACKGROUND: Type 1 diabetes is an autoimmune disease characterized by progressive loss of pancreatic beta cells. Golimumab is a human monoclonal antibody specific for tumor necrosis factor α that has already been approved for the treatment of several autoimmune conditions in adults and children. Whether golimumab could preserve beta-cell function in youth with newly diagnosed overt (stage 3) type 1 diabetes is unknown. METHODS: In this phase 2, multicenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was endogenous insulin production, as assessed according to the area under the concentration-time curve for C-peptide level in response to a 4-hour mixed-meal tolerance test (4-hour C-peptide AUC) at week 52. Secondary and additional end points included insulin use, the glycated hemoglobin level, the number of hypoglycemic events, the ratio of fasting proinsulin to C-peptide over time, and response profile. RESULTS: A total of 84 participants underwent randomization - 56 were assigned to the golimumab group and 28 to the placebo group. The mean (±SD) 4-hour C-peptide AUC at week 52 differed significantly between the golimumab group and the placebo group (0.64±0.42 pmol per milliliter vs. 0.43±0.39 pmol per milliliter, P<0.001). A treat-to-target approach led to good glycemic control in both groups, and there was no significant difference between the groups in glycated hemoglobin level. Insulin use was lower with golimumab than with placebo. A partial-remission response (defined as an insulin dose-adjusted glycated hemoglobin level score [calculated as the glycated hemoglobin level plus 4 times the insulin dose] of ≤9) was observed in 43% of participants in the golimumab group and in 7% of those in the placebo group (difference, 36 percentage points; 95% CI, 22 to 55). The mean number of hypoglycemic events did not differ between the trial groups. Hypoglycemic events that were recorded as adverse events at the discretion of investigators were reported in 13 participants (23%) in the golimumab group and in 2 (7%) of those in the placebo group. Antibodies to golimumab were detected in 30 participants who received the drug; 29 had antibody titers lower than 1:1000, of whom 12 had positive results for neutralizing antibodies. CONCLUSIONS: Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. (Funded by Janssen Research and Development; T1GER ClinicalTrials.gov number, NCT02846545.).

Calorie restriction, but not Roux-en-Y gastric bypass surgery, increases [3 H] PK11195 binding in a rat model of obesity.

Roux-en-Y gastric bypass surgery (RYGB) remains an effective weight-loss method used to treat obesity. While it is successful in combating obesity, there are many lingering questions related to the changes in the brain following RYGB surgery, one of them being its effects on neuroinflammation. While it is known that chronic high-fat diet (HFD) contributes to obesity and neuroinflammation, it remains to be understood whether bariatric surgery can ameliorate diet-induced inflammatory responses. To examine this, rats were assigned to either a normal diet (ND) or a HFD for 8 weeks. Rats fed a HFD were split into the following groups: sham surgery with ad libitum access to HFD (sham-HF); sham surgery with calorie-restricted HFD (sham-FR); RYGB surgery with ad libitum access to HFD (RYGB). Following sham or RYGB surgeries, rats were maintained on their diets for 9 weeks before being euthanized. [3 H] PK11195 autoradiography was then performed on fresh-frozen brain tissue in order to measure activated microglia. Sham-FR rats showed increased [3 H] PK11195 binding in the amygdala (63%), perirhinal (60%), and ectorhinal cortex (53%) compared with the ND rats. Obese rats who had the RYGB surgery did not show this increased inflammatory effect. Since the sham-FR and RYGB rats were fed the same amount of HFD, the surgery itself seems responsible for this attenuation in [3 H] PK11195 binding. We speculate that calorie restriction following obese conditions may be seen as a stressor and contribute to inflammation in the brain. Further research is needed to verify this mechanism.

Parents, but not their children, demonstrate greater delay discounting with resource scarcity.

BACKGROUND: Individuals with obesity tend to discount the future (delay discounting), focusing on immediate gratification. Delay discounting is reliably related to indicators of economic scarcity (i.e., insufficient resources), including lower income and decreased educational attainment in adults. It is unclear whether the impact of these factors experienced by parents also influence child delay discounting between the ages of 8 and 12-years in families with obesity. METHODS: The relationship between indices of family income and delay discounting was studied in 452 families with parents and 6-12-year-old children with obesity. Differences in the relationships between parent economic, educational and Medicaid status, and parent and child delay discounting were tested. RESULTS: Results showed lower parent income (p = 0.019) and Medicaid status (p = 0.021) were differentially related to greater parent but not child delay discounting among systematic responders. CONCLUSIONS: These data suggest differences in how indicators of scarcity influence delay discounting for parents and children, indicating that adults with scarce resources may be shaped to focus on immediate needs instead of long-term goals. It is possible that parents can reduce the impact of economic scarcity on their children during preadolescent years. These findings suggest a need for policy change to alleviate the burden of scarce conditions and intervention to modify delay discounting rate and to improve health-related choices and to address weight disparities.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings. Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings. Design, Setting, and Participants: This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021. Interventions: Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress. Main Outcomes and Measures: The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents. Results: Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings). Conclusions and Relevance: Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children. Trial Registration: ClinicalTrials.gov Identifier: NCT02873715.

High Fat Diet Increases [3H] Flunitrazepam Binding in the Mouse Brain that is Dependent on the Expression of the Dopamine D2 Gene.

Dopamine is an important neuromodulator in the brain that binds to dopamine D1-like receptors (D1, D5) as well as dopamine D2-like receptors (D2, D3, D4). The D2 receptor is known to play an integral role in a variety of physiological processes including addictive behaviors, locomotion, motivation, feeding behavior, and more. It was recently reported that dopamine is a direct-acting modulator of mammalian GABA(A) receptors. To this end, we wanted to examine how the expression of the dopamine D2 gene impacts the expression of GABA(A) receptors in the brain under different dietary conditions. Adult female Drd2 wild-type (WT), heterozygous (HT), and knockout (KO) mice were given either normal or high-fat diet for a period of 30 weeks. Following this, their brains were collected for [3H] Flunitrazepam binding in order to assess GABA(A) receptor expression. A high fat diet significantly increased [3H] Flunitrazepam binding in the regions of the somatosensory cortex, striatum, and various other cortical areas within WT mice. In contrast, no effect of diet was observed in HT or KO mice. As such, HT and KO mice displayed reduced [3H] Flunitrazepam binding in these areas relative to WT mice under high-fat dietary conditions. The effect of a high-fat diet on [3H] Flunitrazepam binding is consistent with recent evidence showing increases in GABA neurotransmitter levels following a high-fat diet. We demonstrate for the first time that the expression of the D2 gene plays a prominent role in the ability of a high-fat diet to impact GABA(A) receptors in the mouse brain.

Effects of 6-month episodic future thinking training on delay discounting, weight loss and HbA1c changes in individuals with prediabetes.

People with prediabetes are at risk for type 2 diabetes. They may discount the future delay discounting (DD), and not engage in preventive health behaviors. Episodic future thinking (EFT) can reduce DD when future scenarios are cued, but research is needed to assess long-term effects of EFT and when EFT is not cued. This study tested EFT training compared to control for people with prediabetes enrolled in a 6-month weight loss program on DD, weight, HbA1c, and physical activity. Results showed a reliable EFT effect on reducing DD in cued (p = 0.0035), and uncued DD tasks (p = 0.048), and significant overall changes in weight (p < 0.001), HbA1c (p, 0.001) and physical activity (p = 0.003), but no significant differences in these outcomes by group (p's > 0.05). Sixty-eight percent of the sample ended below the prediabetes HbA1c range. These results suggest that DD can be modified over extended periods, and the effects of EFT can be observed without EFT cues. However, these data do not suggest that changes in weight, HbA1c or physical activity were due to EFT training. The study was initiated before the COVID-19 pandemic which provided the opportunity to compare differences for people treated in-person or remotely. Analyses showed no differences in DD, weight, HBA1c or physical activity outcomes were observed between in-person and remote treatment, suggesting telehealth is a scalable approach to treating prediabetes.

Bleak present, bright future: II. Combined effects of episodic future thinking and scarcity on delay discounting in adults at risk for type 2 diabetes.

The present study sought to determine if episodic future thinking (EFT) can decrease delay discounting (DD) and demand for fast food under simulations of economic scarcity in adults at risk for diabetes (i.e., overweight/obese and with hemoglobin A1c values in, or approaching, the prediabetic range). Across two sessions, participants completed assessments of DD and food demand at baseline and while prompted to: (1) engage in either EFT or control episodic recent thinking, and (2) while reading a brief narrative describing either economic scarcity or neutral income conditions. Results showed that EFT significantly reduced DD, whereas the economic scarcity narrative significantly increased DD; no significant interaction between EFT and scarcity was observed. No significant effect of either EFT or scarcity was observed on food demand. We conclude that EFT decreases DD even when challenged by simulated economic scarcity in adults at risk for diabetes. The absence of a significant interaction between EFT and scarcity suggests that these variables operate independently to influence DD in opposing directions. Effects of EFT and economic scarcity on food demand require further study. The present study was registered on clinicaltrials.gov (NCT03664726).

Delay Discounting, Glycemic Regulation and Health Behaviors in Adults with Prediabetes.

The majority of people with prediabetes transition to type 2 diabetes. Research has suggested that persons with type 2 diabetes are likely to discount the future and focus on immediate rewards. This study was designed to assess whether this process of delay discounting (DD) is associated with glycemic regulation, medication adherence and eating and exercise behaviors in adults with prediabetes. Participants included 81 adults with prediabetes who were also prescribed hypertension or dyslipidemia drugs, which is common for people with prediabetes. Participants completed adjusting amount DD $100 and $1000 tasks, as well assessments of glycemic control (Hemoglobin (Hb) A1c), medication adherence, diet quality, and objectively measured physical activity. Relationships between DD and these variables were assessed. Results showed higher rates of DD were related to higher HbA1c; as well as poorer medication adherence, lower diet quality and lower physical activity. Hierarchical regression showed that the association between minority status, a known risk factor for type 2 diabetes, was moderated by DD, as minorities with higher DD had greater HbA1c values. Delay discounting may represent a novel target to prevent progression from prediabetes to type 2 diabetes.

Does Episodic Future Thinking Repair Immediacy Bias at Home and in the Laboratory in Patients With Prediabetes?

OBJECTIVE: This study aimed to determine if episodic future thinking (EFT) can decrease delay discounting (DD) among adults with prediabetes both in and out of the laboratory. DD measures how much the value of a reinforcer decreases as a function of the delay to receive it. METHODS: Adults with prediabetes (n = 67) completed a three-session study. At session 1, baseline measures (including DD) were collected. At sessions 2 and 3, participants were prompted to engage in either EFT or control episodic thinking (CET) while completing DD and other measures. In addition, between the completion of sessions 2 and 3, participants engaged in EFT or CET at home and completed DD tasks remotely via smartphones or other Internet-connected devices. RESULTS: Results showed significant -1.2759 (-20.24%) reductions in DD in the EFT group compared with a + 0.0287 (+0.46%) DD increase in the CET group (p = .0149) in the laboratory; and -0.4095 (-8.85%) reduction in DD in the EFT group compared with a + 0.2619 (+5.64%) increase in the CET group (p = .011) at home. Working memory (measured by Backwards Corsi and Digit Span) was found to moderate the effects of EFT on some measures of DD. EFT did not change measures from the food purchase task or a food ad libitum procedure. CONCLUSIONS: Results show that EFT decreases DD in and out of the laboratory and supports the further exploration of EFT as an intervention for prediabetes and related chronic diseases. CLINICAL TRIAL REGISTRATION: NCT03664726.

Role of delay discounting in predicting change in HBA1c for individuals with prediabetes.

The majority of people with prediabetes transition to type 2 diabetes. Weight gain is a known predictor of increasing the risk of diabetes, but another reason may be a focus on immediate rewards and discounting of the future. Delay discounting (DD: devaluation of future consequences) is related to obesity and poor glycemic control in persons with type 2 diabetes. This study was designed to assess whether changes in DD are associated with HbA1c change beyond BMI change in individuals with prediabetes. Hierarchical regression showed changes in BMI (p = 0.008) and the $1000 DD task (p = 0.04) were associated with HbA1c change beyond demographic characteristics, with the full model accounting for 25.8% of the variance. Those with greater BMI increases and greater increases in discounting of the future showed the greatest increases in HbA1c. DD represents a novel target to prevent progression from prediabetes to type 2 diabetes.

Chronic oral methylphenidate treatment increases microglial activation in rats.

Methylphenidate (MP) is a widely prescribed psychostimulant used to treat attention deficit hyperactivity disorder. Previously, we established a drinking paradigm to deliver MP to rats at doses that result in pharmacokinetic profiles similar to treated patients. In the present study, adolescent male rats were assigned to one of three groups: control (water), low-dose MP (LD; 4/10 mg/kg), and high dose MP (HD; 30/60 mg/kg). Following 3 months of treatment, half of the rats in each group were euthanized, and the remaining rats received only water throughout a 1-month-long abstinence phase. In vitro autoradiography using [3H] PK 11195 was performed to measure microglial activation. HD MP rats showed increased [3H] PK 11195 binding compared to control rats in several cerebral cortical areas: primary somatosensory cortex including jaw (68.6%), upper lip (80.1%), barrel field (88.9%), and trunk (78%) regions, forelimb sensorimotor area (87.3%), secondary somatosensory cortex (72.5%), motor cortices 1 (73.2%) and 2 (69.3%), insular cortex (59.9%); as well as subcortical regions including the thalamus (62.9%), globus pallidus (79.4%) and substantia nigra (22.7%). Additionally, HD MP rats showed greater binding compared to LD MP rats in the hippocampus (60.6%), thalamus (59.6%), substantia nigra (38.5%), and motor 2 cortex (55.3%). Following abstinence, HD MP rats showed no significant differences compared to water controls; however, LD MP rats showed increased binding in pre-limbic cortex (78.1%) and ventromedial caudate putamen (113.8%). These findings indicate that chronic MP results in widespread microglial activation immediately after treatment and following the cessation of treatment in some brain regions.

Exercise Influences the Brain's Metabolic Response to Chronic Cocaine Exposure in Male Rats.

Cocaine use is associated with negative health outcomes: cocaine use disorders, speedballing, and overdose deaths. Currently, treatments for cocaine use disorders and overdose are non-existent when compared to opioid use disorders, and current standard cocaine use disorder treatments have high dropout and recidivism rates. Physical exercise has been shown to attenuate addiction behavior as well as modulate brain activity. This study examined the differential effects of chronic cocaine use between exercised and sedentary rats. The effects of exercise on brain glucose metabolism (BGluM) following chronic cocaine exposure were assessed using Positron Emission Tomography (PET) and [18F]-Fluorodeoxyglucose (FDG). Compared to sedentary animals, exercise decreased metabolism in the SIBF primary somatosensory cortex. Activation occurred in the amygdalopiriform and piriform cortex, trigeminothalamic tract, rhinal and perirhinal cortex, and visual cortex. BGluM changes may help ameliorate various aspects of cocaine abuse and reinstatement. Further investigation is needed into the underlying neuronal circuits involved in BGluM changes and their association with addiction behaviors.

Testosterone concentrations in young pubertal and post-pubertal obese males.

OBJECTIVE: Obesity in adult males is associated with hypogonadotropic hypogonadism. We evaluated the effect of obesity on plasma testosterone concentrations in pubertal and post-pubertal young males. DESIGN AND METHODS: Morning fasting blood samples were obtained from 25 obese [body mass index (BMI) ≥95th percentile] and 25 lean (BMI <85th percentile) males between the ages 14-20 years with Tanner staging ≥4. Total (TT) and free testosterone (FT) and estradiol concentrations were measured by liquid chromatography tandem mass spectrometry and equilibrium dialysis. Free testosterone was also calculated using SHBG and albumin. C-reactive protein (CRP), insulin and glucose concentrations were measured and homoeostasis model of insulin resistance (HOMA-IR) was calculated. RESULTS: After controlling for age and Tanner staging, obese males had a significantly lower total testosterone (10·5 vs 21·44 nmol/l), free testosterone (0·22 vs 0·39 nmol/l) and calculated free testosterone (0·26 vs 0·44 nmol/l) concentrations as compared to lean males (P < 0·001 for all). Obese males had higher CRP concentrations (2·8 vs 0·8 mg/l; P < 0·001), and HOMA-IR (3·8 vs 1·1; P < 0·001) than lean males. Free testosterone concentrations were positively related to age and negatively to BMI, HOMA-IR and CRP concentrations. Total and free estradiol concentrations were significantly lower in males with subnormal testosterone concentrations. CONCLUSION: Testosterone concentrations of young obese pubertal and post-pubertal males are 40-50% lower than those with normal BMI. Obesity in young males is associated with low testosterone concentrations, which are not secondary to an increase in estradiol concentrations. Our results need to be confirmed in a larger number of subjects.

Two-Year Follow-up From the T1GER Study: Continued Off-Therapy Metabolic Improvements in Children and Young Adults With New-Onset T1D Treated With Golimumab and Characterization of Responders.

OBJECTIVE: The T1GER (A Study of SIMPONI to Arrest ß-Cell Loss in Type 1 Diabetes) study showed many metabolic benefits of the tumor necrosis factor-α blocker golimumab in children and young adults with type 1 diabetes (T1D). Off-therapy effects are reported. RESEARCH DESIGNS AND METHODS: T1GER was a phase 2, placebo-controlled, randomized trial in which golimumab or placebo was administered for 52 weeks to participants 6-21 years old diagnosed with T1D within 100 days of randomization. Assessments occurred during the 52-week on-therapy and 52-week off-therapy periods. RESULTS: After treatment was stopped, C-peptide area under the curve (AUC) remained greater in the treatment versus control group. At weeks 78 and 104, the golimumab group had lower reductions in the 4-h C-peptide AUC baseline than the placebo group, where specifically the golimumab group had reductions of 0.31 and 0.41 nmol/L, and the placebo group had reductions of 0.64 and 0.74 nmol/L. There were also trends in less insulin use, higher peak C-peptide levels and those in partial remission, and higher peak C-peptide levels in the golimumab group. Golimumab responders, defined as having an increase or minimal loss of C-peptide AUC and/or being in partial remission at week 52, showed even greater improvements in most metabolic parameters on and off therapy and had less hypoglycemia during the off-therapy period versus placebo. Adverse events, including infections, were similar between the groups during all time periods of the study. CONCLUSIONS: In children and young adults with new-onset T1D, golimumab preserved endogenous ß-cell function and resulted in other favorable metabolic parameters on and off therapy. A subpopulation had disease stabilization while on therapy, with improved metabolic parameters off therapy.

Role of Dual-Contingency Management in Family-Based Obesity Therapy and the Effects of Weight Loss on Liver Transient Elastography Parameters in Youth: A Pilot Study.

The pilot study evaluated contingency management (CM) for family-based obesity therapy (FBT). The secondary outcome assessed the association of the hepatic transient electrography (TE) parameters, including the controlled attenuation parameter (CAP) and liver stiffness (LSM), and changes in liver function blood tests and BMI changes in youth involved in intensive FBT. It included youth-parent dyads from an urban pediatric center randomized to weekly behavioral therapy (BT, n= 4) who received fixed financial compensation for attendance, or BT+CM (n= 5) who received an escalating monetary reward for weight loss. At week 30, all youth and parents had weight-loss trends without significant differences between groups. While the TE measures and blood tests were normal in the youth at baseline and week 30, the CAP changes correlated with BMI changes (R2= 0.86, P< 0.001) and LSM changes with alanine aminotransferase changes (R2= 0.79, P=0.005). In conclusion, BT+CM did not significantly add to the BMI improvement seen with BT alone in youth and their parents. However, in youth with obesity and normal liver blood tests, TE may be useful for monitoring changes in fatty liver disease.

Genetic Correlates as a Predictor of Bariatric Surgery Outcomes after 1 Year.

This study analyzed genetic risk assessments in patients undergoing bariatric surgery to serve as a predictive factor for weight loss parameters 1 year after the operation. Thirty (30) patients were assessed for Genetic Addiction Risk Severity (GARS), which analyzes neurogenetic polymorphisms involved in addiction and reward deficiency. Genetic and psychosocial data collected before the operation were correlated with weight loss data, including changes in weight, body mass index (BMI), and percent of expected weight loss (%EWL). Results examined correlations between individual gene risk alleles, 1-year body weight data, and psychosocial trait scores. Spearman's correlations revealed that the OPRM1 (rs1799971) gene polymorphism had significant negative correlation with 1-year weight (rs = -0.4477, p < 0.01) and BMI (rs = -0.4477, p < 0.05). In addition, the DRD2 risk allele (rs1800497) was correlated negatively with BMI at 1 year (rs = -0.4927, p < 0.05), indicating that one risk allele copy was associated with lower BMI. However, this allele was positively correlated with both ∆Weight (rs = 0.4077, p < 0.05) and %EWL (rs = 0.5521, p < 0.05) at 1 year post-surgery. Moreover, the overall GARS score was correlated with %EWL (rs = 0.4236, p < 0.05), ∆Weight (rs = 0.3971, p < 0.05) and ∆BMI (rs = 0.3778, p < 0.05). Lastly, Food Cravings Questionnaire (FCQ) scores were negatively correlated with %EWL (rs = -0.4320, p < 0.05) and ∆Weight at 1 year post-surgery (rs = -0.4294, p < 0.05). This suggests that individuals with a higher genetic addiction risk are more responsive to weight loss treatment, especially in the case of the DRD2 polymorphism. These results should translate clinically to improve positivity and attitude related to weight management by those individuals born with the risk alleles (rs1800497; rs1799971).

The First Exploratory Personalized Medicine Approach to Improve Bariatric Surgery Outcomes Utilizing Psychosocial and Genetic Risk Assessments: Encouraging Clinical Research.

It is predicted that by 2030, globally, an estimated 2.16 billion adults will be overweight, and 1.12 billion will be obese. This study examined genetic data regarding Reward Deficiency Syndrome (RDS) to evaluate their usefulness in counselling patients undergoing bariatric surgery and gathered preliminary data on the potential use in predicting short term (6-month) weight loss outcomes. Methods: Patients undergoing bariatric surgery (n = 34) were examined for Genetic Addiction Risk Severity (GARS) [measures the presence of risk alleles associated with RDS]; as well as their psychosocial traits (questionnaires). BMI changes and sociodemographic data were abstracted from Electronic Health Records. Results: Subjects showed ∆BMI (M = 10.0 ± 1.05 kg/m2) and a mean % excess weight loss (56 ± 13.8%). In addition, 76% of subjects had GARS scores above seven. The homozygote risk alleles for MAO (rs768062321) and DRD1 (rs4532) showed a 38% and 47% prevalence among the subjects. Of the 11 risk alleles identified by GARS, the DRD4 risk allele (rs1800955), was significantly correlated with change in weight and BMI six months post-surgery. We identified correlations with individual risk alleles and psychosocial trait scores. The COMT risk allele (rs4680) showed a negative correlation with EEI scores (r = -0.4983, p < 0.05) and PSQI scores (r = -0.5482, p < 0.05). The GABRB3 risk allele (rs764926719) correlated positively with EEI (r = 0.6161, p < 0.01) and FCQ scores (r = 0.6373, p < 0.01). The OPRM1 risk allele showed a positive correlation with the DERS score (r = 0.5228, p < 0.05). We also identified correlations between DERS and BMI change (r = 0.61; p < 0.01). Conclusions: These data support the potential benefit of a personalized medicinal approach inclusive of genetic testing and psychosocial trait questionnaires when counselling patients with obesity considering bariatric surgery. Future research will explore epigenetic factors that contribute to outcomes of bariatric surgery.