Psychopathology, disordered eating, and impulsivity as predictors of weight loss 24 months after metabolic and bariatric surgery.

BACKGROUND: The relationship between theoretically relevant psychosocial and behavioral variables and outcomes of metabolic and bariatric surgery remains unclear. Some studies have found that the presence of psychopathology, disordered eating, and impulsivity, either before surgery or during the early postoperative period, is associated with suboptimal postoperative weight loss. Other studies have not found these relationships. OBJECTIVE: Examine the relationship between psychopathology, disordered eating, impulsivity, and weight loss 24 months postoperatively. SETTING: Two large, urban university health systems. METHODS: Participant characteristics were collected using validated interviews, patient-reported outcome measures, and computerized assessment methods. Linear mixed effect models were used to test the association of the variables of interest on percent weight loss (%WL). RESULTS: Three hundred participants were enrolled at baseline; weight data at 24 months were available for 227 participants; between 181 and 53 individuals completed other outcome measures. The mean %WL was 23.3 ± 9.9% at 24 months. Patients who underwent Roux-en-Y gastric bypass lost more weight than those who underwent sleeve gastrectomy. The presence of subjective binge episodes at baseline was related to a greater %WL at 24 months; there were no other baseline predictors. The presence of eating disorder diagnoses and disordered eating symptoms after surgery were associated with smaller weight losses over 24 months. Current and lifetime psychopathology and impulsivity were unrelated to %WL at 24 months. CONCLUSION: Disordered eating after bariatric surgery was associated with a smaller %WL at postoperative year 2. Additional monitoring of these symptoms in the early postoperative period is recommended. Psychotherapeutic and/or dietary interventions may promote more optimal weight loss outcomes.

The Impact of Smoking Status and Smoking-Related Comorbidities on Coronavirus Disease 2019 Patient Outcomes: A Causal Mediation Analysis.

INTRODUCTION: Smoking history is a known risk factor for significant chronic diseases as well as pulmonary infections; however, the impact of smoking status on coronavirus disease 2019 (COVID-19) outcomes has not been conclusively characterized. This study aims to evaluate the association of smoking status on COVID-19 outcomes, and to explore the mechanism by which smoking and smoking-related comorbidities relate to COVID-19 outcomes. AIMS AND METHODS: Patients admitted with SARS-CoV-2 infection from November 2020 through January 2021 were included in this study. Causal mediation models investigating the associations between smoking status and the outcomes of mortality, intensive care unit (ICU) admission, advanced respiratory support, mechanical ventilation, ICU length of stay, and hospital length of stay, through mediation via smoking-related comorbidities, were examined. RESULTS: Active smokers did not experience worse COVID-19 outcomes once hospitalized. Former smokers had a higher odds of mortality (total effect OR 1.59, 95% CI 1.07 to 2.38, p = .01; indirect effect OR 1.45, 95% CI 1.09 to 1.93, p < .001), and advanced respiratory support (total effect OR 1.31, 95% CI 1.04 to 1.67, p = .02; indirect effect OR 1.26, 95% CI 1.03 to 1.54, p = .02), which were mediated by smoking-related comorbidities. While there was a nonsignificant increase in the total effect for mechanical ventilation, smoking-related comorbidities were significant mediators for their increased need (total effect OR 1.40, 95% CI 0.92 to 2.14, p = .13; indirect effect OR 1.47, 95% CI 1.10 to 1.87, p < .001). CONCLUSIONS: Although active smokers did not experience worse COVID-19 outcomes compared to never smokers, these results should be interpreted with caution. Compared to never smokers, former smokers had greater odds of mortality, advanced respiratory support, and mechanical ventilation which was significantly mediated through smoking-related comorbidities. IMPLICATIONS: Previous studies have linked smoking status with worse COVID-19 outcomes, and have inferred that smoking-related comorbidities may play a role in these findings. This causal mediation analysis provides statistical evidence supporting this hypothesis, clarifying the risk that smoking-related comorbidities impart on COVID-19 outcomes in those with a smoking history.

Preoperative Depression Status and 5 Year Metabolic and Bariatric Surgery Outcomes in the PCORnet Bariatric Study Cohort.

OBJECTIVE: To examine whether depression status before metabolic and bariatric surgery (MBS) influenced 5-year weight loss, diabetes, and safety/utilization outcomes in the PCORnet Bariatric Study. SUMMARY OF BACKGROUND DATA: Research on the impact of depression on MBS outcomes is inconsistent with few large, long-term studies. METHODS: Data were extracted from 23 health systems on 36,871 patients who underwent sleeve gastrectomy (SG; n=16,158) or gastric bypass (RYGB; n=20,713) from 2005-2015. Patients with and without a depression diagnosis in the year before MBS were evaluated for % total weight loss (%TWL), diabetes outcomes, and postsurgical safety/utilization (reoperations, revisions, endoscopy, hospitalizations, mortality) at 1, 3, and 5 years after MBS. RESULTS: 27.1% of SG and 33.0% of RYGB patients had preoperative depression, and they had more medical and psychiatric comorbidities than those without depression. At 5 years of follow-up, those with depression, versus those without depression, had slightly less %TWL after RYGB, but not after SG (between group difference = 0.42%TWL, P = 0.04). However, patients with depression had slightly larger HbA1c improvements after RYGB but not after SG (between group difference = - 0.19, P = 0.04). Baseline depression did not moderate diabetes remission or relapse, reoperations, revision, or mortality across operations; however, baseline depression did moderate the risk of endoscopy and repeat hospitalization across RYGB versus SG. CONCLUSIONS: Patients with depression undergoing RYGB and SG had similar weight loss, diabetes, and safety/utilization outcomes to those without depression. The effects of depression were clinically small compared to the choice of operation.

Impact of Racial Disparities in Preoperative Cardiovascular Evaluation and Surgical Outcomes in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Cohort Analysis.

Background We investigated preoperative referral patterns, rates of cardiovascular testing, surgical wait times, and postoperative outcomes in White versus Black, Hispanic, or other racial or ethnic groups of patients undergoing metabolic and bariatric surgery. Methods and Results This was a single center retrospective cohort analysis of 797 consecutive patients undergoing metabolic and bariatric surgery from January 2014 to December 2018; 86% (n=682) were Black, Hispanic, or other racial or ethnic groups. White versus Black, Hispanic, or other racial or ethnic groups had similar baseline comorbidities and were referred for preoperative cardiovascular evaluation in similar proportion (65% versus 68%, P=0.529). Black, Hispanic, or other racial or ethnic groups of patients were less likely to undergo preoperative cardiovascular testing (unadjusted odds ratio [OR], 0.56; 95% CI, 0.33-0.95; P=0.031; adjusted for Revised Cardiac Risk Index OR, 0.59; 95% CI, 0.35-0.996; P=0.049). White patients had a shorter wait time for surgery (unadjusted hazard ratio [HR], 0.7; 95% CI, 0.58-0.87; P=0.001; adjusted HR, 0.7; 95% CI, 0.56-0.95; P=0.018). Reduction in body mass index at 6 months was greater in White patients (12.9 kg/m2 versus 12.0 kg/m2, P=0.0289), but equivalent at 1 year (14.9 kg/m2 versus 14.3 kg/m2, P=0.330). Conclusions White versus Black, Hispanic, or other racial or ethnic groups of patients were referred for preoperative cardiovascular evaluation in similar proportion. White patients underwent more preoperative cardiac testing yet had a shorter wait time for surgery. Early weight loss was greater in White patients, but equivalent between groups at 12 months.

Changes in Antihypertensive Medication Following Bariatric Surgery.

Obesity is a leading cause of hypertension (i.e., high blood pressure [BP]). While hypertension can be managed with antihypertensive medication, substantial weight loss can also lower BP, reducing the need for antihypertensive medication. Articles in this review (n = 60) presented data on antihypertensive medication use among adults pre- and postoperatively. Roux-en-Y gastric bypass was the most studied surgical approach followed by Laparoscopic Sleeve Gastrectomy. Antihypertensive medication was discontinued in a large proportion of patients after surgery, and the mean number of antihypertensive medications decreased by approximately one. In almost a third of the studies, over 75% of participants experienced hypertension remission. All articles aside from two reported a decrease in systolic BP, with about 40% reporting a decrease of ≥ 10 mm Hg.

Association between insurance-mandated precertification criteria and inpatient healthcare utilization during 1 year after bariatric surgery.

BACKGROUND: Insurance-mandated precertification requirements are barriers to bariatric surgery. The value of their prescription, based on insurance type rather that the clinical necessity, is unclear. OBJECTIVES: To determine whether there is an association between insurance-mandated precertification criteria for bariatric surgery and short-term inpatient healthcare utilization. SETTING: Pennsylvania Health Care Cost Containment Council's inpatient care databases for the years 2016-2017. METHODS: The study included 2717 adults who underwent bariatric surgery in Southeastern Pennsylvania in 2016. Postoperative length of stay and rehospitalizations for these individuals were followed using clinical and claims data during the first year after bariatric surgery. RESULTS: The requirements for 3- to 6-month preoperative medical weight management, as well as pulmonology and cardiology examinations, were not associated with the patient length of stay, number of all-cause rehospitalizations, or number of all-cause rehospitalization days after adjusting for patient age, sex, race, ethnicity, the Elixhauser comorbidity score, type of the surgery, facility where the surgery was performed, primary payer type, and the estimated median household income. Among commercially insured individuals (n = 1499), the mean number of all-cause rehospitalizations during the study period was lower in patients with no medical weight management requirement by a factor of .57 (lower by 43.1%; 95% confidence interval, .35-.94, P = .03) and higher in patients with no requirement for preoperative cardiology and pulmonology evaluations by a factor of 2.09 (95% confidence interval 1.09-4.02, P = .03). CONCLUSION: The findings suggest that the precertification requirement for preoperative medical weight management is not associated with a reduction in inpatient healthcare utilization in the first postoperative year.

Role of weight bias and patient-physician communication in the underutilization of bariatric surgery.

A growing body of evidence supports the efficacy and safety of bariatric surgery for clinically severe obesity. Despite this empirical support, bariatric surgery remains profoundly underutilized. The reasons for underutilization are likely multifactorial, including health insurance coverage and benefits design, lack of awareness about bariatric surgery by patients, and anecdotal concerns about safety. We believe that there are two other factors-the occurrence of weight stigma and bias and suboptimal communication between patients and providers-that also serve as barriers to greater utilization. The article reviews the existing literature related to these two factors. The review also highlights the science of shared medical decision-making as a potential strategy to promote appropriate conversations between patients and providers, both surgical and nonsurgical, about the efficacy and safety of bariatric surgery. Shared medical decision-making is used in other areas where complex medical decisions are required. We believe that it has great potential to contribute to the increased utilization for the millions of individuals who could benefit from bariatric surgery.

COVID-19 patients with obesity at risk for worse outcomes despite younger age and fewer inflammatory derangements.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral pulmonary infection that can progress to cytokine storm syndrome because of widespread dysregulated inflammatory response. Many patients at risk for severe COVID-19 manifestation have been identified as those with preexisting conditions of pulmonary origin, as well as conditions that impair appropriate immune response, such as obesity. OBJECTIVES: The aim of this study is to describe the manifestation, clinical course, and inflammatory biomarker milieu of COVID-19 in patients with obesity. SETTING: University Hospital Philadelphia, Pennsylvania. METHODS: In this retrospective cohort study, 600 patients who were positive for COVID-19 were stratified by World Health Organization (WHO) obesity class and their presenting symptoms, disease biomarkers, demographics, and outcomes (intubation rate, intensive care unit [ICU] admission, length of stay [LOS], and mortality) were investigated. RESULTS: Age was inversely related to obesity class; patients of obesity class III presented 12.9 years younger than patients of normal weight (P < .0001). Initial ferritin lab values were negatively correlated with increasing obesity class (P = .0192). Normal or near-normal lymphocyte profile was noted in patients with obesity compared with patients without obesity (P = .0017). Patients with obesity had an increased rate of ICU admission (P = .0215) and increased length of stay (P = .0004), but no differences in intubation rate (P = .3705) or mortality (P = .2486). CONCLUSION: Patients with obesity were more likely to present to the hospital at a younger age, with reduced levels of COVID-19 related biomarker disturbances, and increased LOS and ICU admission rates, although were not at increased risk for mortality.

The effects of the COVID-19 pandemic on patients with obesity undergoing bariatric care.

BACKGROUND: Patients with obesity are at increased risk of developing severe COVID-19. The pandemic has caused delays in preoperative preparation, progression, and completion of bariatric surgeries. OBJECTIVES: The aim of this study was to evaluate the impact of COVID-19 restrictions on bariatric surgery patients and assess their concern of COVID-19 as they continue the preoperative process. SETTING: Philadelphia, Pennsylvania METHODS: A questionnaire was administered to patients to assess the impact of COVID-19 on their weight loss goals, physical activity, and diet. Time points assessed were initial bariatric consultation (T1), as well as the beginning (T2), and the end (T3) of lockdown restrictions in the region. RESULTS: Seventy-four participants were invited and 50 completed the survey, for a response rate of 67.6%. The average age of participants was 44.1 years. Two-thirds of patients reported significant concern that COVID-19 would affect their weight loss goals. Patients reported significant improvements in their diet from T1 to T2 (P < .01). However, at T3, some patients returned to behaviors held at T1, with snacking behaviors significantly increasing between T2 and T3 (P < .01). Physical activity decreased in 60% of patients between T2 to T3. The vast majority (90%) wanted to have their surgery as soon as possible; 56% reported low levels of concern for COVID-19 infection. CONCLUSION: Bariatric patients were highly motivated to proceed with bariatric surgery despite the risks imposed by the pandemic.

Do Insurance-mandated Precertification Criteria and Insurance Plan Type Determine the Utilization of Bariatric Surgery Among Individuals With Private Insurance?

BACKGROUND: Access to bariatric surgery is restricted by insurers in numerous ways, including by precertification criteria such as 3-6 months preoperative supervised medical weight management and documented 2-year weight history. OBJECTIVES: To investigate if there is an association between the aforementioned precertification criteria, insurance plan type, and the likelihood of undergoing bariatric surgery, after controlling for potential sociodemographic confounders. RESEARCH DESIGN: The study was conducted using the Pennsylvania Health Care Cost Containment Council's data in 5 counties of Pennsylvania in 2016 and records of preoperative insurance requirements maintained by the Temple University Bariatric Surgery Program.Privately insured bariatric surgery patients and individuals who met the eligibility criteria but did not undergo surgery were identified and 1:1 matched by sex, race, age group, and zip code (n=1054). Univariate tests and logistic regression analysis were utilized for data analysis. RESULTS: The insurance requirement for 3-6 months preoperative supervised medical weight management was associated with smaller odds of undergoing surgery [odds ratio (OR)=0.459; 95% confidence interval (CI), 0.253-0.832; P=0.010], after controlling for insurance plan type and the requirement for documented weight history.Preferred provider organization (OR=1.422; 95% CI, 1.063-1.902; P=0.018) and fee-for-service (OR=1.447; 95% CI, 1.021-2.050; P=0.038) plans were associated with greater odds of undergoing surgery, compared with health maintenance organization plans, after controlling for the studied precertification requirements. The documented weight history requirement was not a significant predictor of the odds of undergoing surgery (P=0.132). CONCLUSIONS: There is a need for consideration of insurance benefits design as a determinant of access to bariatric surgery.

Outcomes in conventional laparoscopic versus robotic-assisted primary bariatric surgery: a retrospective, case-controlled study of the MBSAQIP database.

INTRODUCTION: Robotic-assisted bariatric surgery is increasingly performed. There remains controversy about the overall benefit of robotic-assisted (RBS) compared to conventional laparoscopic (LBS) bariatric surgery. In this study, we used a large national risk-stratified bariatric clinical database to compare outcomes between robotic and laparoscopic gastric bypass (RNYGB) and sleeve gastrectomy (SG). METHODS: A retrospective analysis of the 2015 and 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use Data File (PUF) was performed. Primary robotic and laparoscopic RYNGB and SG were analyzed. Descriptive analysis was performed of the unmatched cohorts, followed by 1:3 case-controlled matching. Cases and controls were matched by patient demographics and pre-operative comorbidities, and peri-operative outcomes compared. RESULTS: 77,991 Roux-en-Y gastric bypass (RnYGB) (7.5% robotic-assisted) and 189,503 SG (6.8% robotic-assisted) cases were identified. Operative length was significantly higher in both the robotic-assisted RnYGB and SG cohorts (p < 0.0001). Outcomes were similar between the robotic-assisted and laparoscopic RnYGB cohorts, except a lower mortality rate (p = 0.05), transfusion requirement (p = 0.005), aggregate bleeding (p = 0.04), and surgical site infections (SSI) (p = 0.006) in the robotic-assisted cohort. Outcomes were also similar between robotic-assisted and laparoscopic SG, except for a longer length of stay (p < 0.0001) and higher rates of conversion (p < 0.0001), 30-day intervention (p = 0.01), operative drain present (p < 0.0001), sepsis (p = 0.01), and organ space SSI (p = 0.0002) in the robotic cohort. Bleeding was lower in the robotic SG cohort and mortality was similar. CONCLUSION: Both robotic-assisted and laparoscopic RnYGB and SG are overall very safe. Robotic-assisted gastric bypass is associated with a lower mortality and morbidity; however, a clear benefit for robotic-assisted SG compared to laparoscopic SG was not seen. Given the longer operative and hospital duration, robotic SG is not cost-effective.

A retrospective case control study identifies peripheral blood mononuclear cell albumin RNA expression as a biomarker for non-alcoholic fatty liver disease.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) improves after bariatric surgery. The aim of this study was to determine whether peripheral blood mononuclear cell albumin gene expression was related to NAFLD and whether albumin (ALB) and alpha fetoprotein (AFP) expression could be detected in whole blood and visceral adipose tissue. METHODS: Using a retrospective case control study design, RNA isolated from peripheral blood mononuclear cells from patients prior to undergoing bariatric surgery was used for pooled microarray analysis. Quantitative polymerase chain reaction (QPCR) was used to analyze whole blood and visceral adipose tissue. Liver histology was obtained via intra-operative biopsy and clinical data extracted from the electronic health record. RESULTS: The albumin (ALB) gene was the second most up-regulated found in microarray analysis of peripheral blood mononuclear cell RNA from patients with hepatic lobular inflammation versus normal liver histology. Transcript levels of ALB were significantly different across those with normal (n = 50), steatosis (n = 50), lobular inflammation (n = 50), and peri-sinusoidal fibrosis (n = 50) liver histologies, with lobular inflammation 3.9 times higher than those with normal histology (p < 0.017). Albumin expression levels decreased in 11/13 patients in paired samples obtained prior to and at 1 year after Roux-en-Y gastric bypass surgery. ALB expression could be detected in 23 visceral adipose tissue samples obtained intra-operatively and in 18/19 available paired whole blood samples. No significant correlation was found between ALB expression in visceral adipose tissue and whole blood RNA samples. Alpha fetoprotein expression as a marker of early hepatocytic differentiation was detected in 17/17 available VAT RNA samples, but in only 2/17 whole blood RNA samples. CONCLUSION: Albumin RNA expression from blood cells may serve as a biomarker of NAFLD. Albumin and alpha fetoprotein appear to be ubiquitously expressed in visceral adipose tissue in patients with extreme obesity.

The effect of multilevel upper airway surgery on continuous positive airway pressure therapy in obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: To investigate the effect of multilevel upper airway surgery (USA) on subsequent continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN: Fifty-two patients who underwent multilevel UAS with persistent symptoms of OSAHS represent the cohort for this study. All patients had undergone manual CPAP titrations both pre- and postoperatively. Patients were used as their own controls and were compared pre- and postoperatively with regard to body mass index, full night polysomnography (PSG), optimal CPAP pressure settings, presence of rapid eye-movement (REM) sleep, identification of mouth leakage, and CPAP compliance. RESULTS: Postoperative values for apnea index (AI), apnea hypopnea index (AHI), and minimum oxygen saturation (min SaO(2)) were all significantly decreased from their preoperative levels. Compliance with CPAP therapy significantly increased from a mean 0.02 +/- 0.14 hours per night prior to surgery to a 3.2 +/- 2.6 hours per night following surgery (P < .001). In addition, the optimal CPAP pressure setting decreased significantly for a preoperative value of 10.6 +/- 2.1 cm H(2)O to 9.8 +/- 2.1 cm H(2)O following surgery. Fifty of the 52 patients (96.2%) studied were able to maintain optimal pressure settings without mouth leak, postoperatively. CONCLUSIONS: In this study, most patients who had persistent symptoms of OSAHS after multilevel UAS did not have significant mouth leak that would preclude CPAP therapy. In this cohort of patients, CPAP pressure setting as well as compliance was significantly improved postoperatively.

Interexaminer agreement of Friedman tongue positions for staging of obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: To determine if strong interexaminer agreement exists in identifying Friedman tongue positions (FTPs) for staging of obstructive sleep apnea/hypopnea syndrome (OSAHS). STUDY DESIGN AND METHODS: Twenty-six digital video clips of oropharyngeal examinations were prepared to demonstrate FTPs I through IV. Specific parameters for each FTP were provided to 126 examiners (otolaryngology residents, attendings, and fellows). The video clips were then presented to the examiners to determine the FTP. Kappa statistical analysis was used to evaluate the degree of intergrader agreement or disagreement. RESULTS: A generalized kappa statistic of 0.8 is considered the upper limits of substantial agreement. Thus, the overall kappa value (0.82) as well as all the subgroup kappa values for attendings (0.84), fellows (0.87), and residents (0.84) represented "very good" agreement. CONCLUSION: The strong interexaminer correlation of FTP demonstrated by this study indicates that FTP may be a useful adjunct in describing hypopharyngeal anatomy in patients with OSAHS.

Evaluation of submucosal minimally invasive lingual excision technique for treatment of obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: Submucosal minimally invasive lingual excision (SMILE) is a novel approach to address hypopharyngeal obstruction. This study compares the efficacy, morbidity, and complications of this technique to radiofrequency reduction of the tongue base (RFBOT), the current standard in minimally invasive tongue base reduction. STUDY DESIGN: Retrospective analysis of data extracted from a prospective database. METHODS: Ninety-six patients who underwent SMILE (n=48) or RFBOT (n=48) were studied. Efficacy and safety of the procedures were compared on the basis of polysomnography results, morbidity measures, and complications. RESULTS: Patients in both groups demonstrated a significant reduction in the apnea/hypopnea index. Success rates for SMILE and RFBOT were 64.6 percent and 41.7 percent, respectively (P=0.024). SMILE, however, was associated with increased morbidity and complications. CONCLUSION: In a comparable surgical protocol for obstructive sleep apnea-hypopnea syndrome, SMILE technique for tongue base reduction demonstrated increased efficacy over RFBOT but resulted in more complications. Additional experience with the procedure may reduce complications and increase overall efficacy.

The Ins2Akita mouse as a model of early retinal complications in diabetes.

PURPOSE: This study tested the Ins2(Akita) mouse as an animal model of retinal complications in diabetes. The Ins2(Akita) mutation results in a single amino acid substitution in the insulin 2 gene that causes misfolding of the insulin protein. The mutation arose and is maintained on the C57BL/6J background. Male mice heterozygous for this mutation have progressive loss of beta-cell function, decreased pancreatic beta-cell density, and significant hyperglycemia, as early as 4 weeks of age. METHODS: Heterozygous Ins2(Akita) mice were bred to C57BL/6J mice, and male offspring were monitored for hyperglycemia, beginning at 4.5 weeks of age. After 4 to 36 weeks of hyperglycemia, the retinas were analyzed for vascular permeability, vascular lesions, leukostasis, morphologic changes of micro- and macroglia, apoptosis, retinal degeneration, and insulin receptor kinase activity. RESULTS: The mean blood glucose of Ins2(Akita) mice was significantly elevated, whereas the body weight at death was reduced compared with that of control animals. Compared with sibling control mice, the Ins2(Akita) mice had increased retinal vascular permeability after 12 weeks of hyperglycemia (P < 0.005), a modest increase in acellular capillaries after 36 weeks of hyperglycemia (P < 0.0008), and alterations in the morphology of astrocytes and microglia, but no changes in expression of Muller cell glial fibrillary acidic protein. Increased apoptosis was identified by immunoreactivity for active caspase-3 after 4 weeks of hyperglycemia (P < 0.01). After 22 weeks of hyperglycemia, there was a 16.7% central and 27% peripheral reduction in the thickness of the inner plexiform layer, a 15.6% peripheral reduction in the thickness of the inner nuclear layer (P < 0.001), and a 23.4% reduction in the number of cell bodies in the retinal ganglion cell layer (P < 0.005). In vitro insulin receptor kinase activity was reduced (P < 0.05) after 12 weeks of hyperglycemia. CONCLUSIONS: The retinas of heterozygous male Ins2(Akita) mice exhibit vascular, neural, and glial abnormalities generally consistent with clinical observations and other animal models of diabetes. In light of the relatively early, spontaneous onset of the disease and the popularity of the C57BL/6J inbred strain as a background for the generation and study of other genetic alterations, combining the Ins2(Akita) mutation with other engineered mutations will be of great use for studying the molecular basis of retinal complications of diabetes.