Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second Edition. Four LA-derived oxylipins were analyzed by ultra-high-pressure-LC/MS, and the 12,13-dihydroxyoctadecamonoenoic acid (12,13-DiHOME) considered the main species of interest. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F1,98 = 7.513, P = 0.007). The CYP450-derived 12(13)-epoxyoctadecamonoenoic acid (12(13)-EpOME) was associated with poorer executive function and verbal memory scores (F1,98 = 7.222, P = 0.008 and F1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent.

Preparing for Colonoscopy in People with Diabetes: A Review with Suggestions for Clinical Practice.

People with diabetes have an increased risk of adverse events during the peri-colonoscopy period, including hypoglycemia, lactic acidosis, diabetic ketoacidosis and acute kidney injury. This is secondary to inadequate dietary modification, the bowel preparation and antihyperglycemic agent modification. With the availability of many new diabetes agents, endoscopists need updated guidance. This review of current literature provides a practical approach to antihyperglycemic agent modification in the context of colonoscopy preparation, as well as guidelines on dietary changes, the bowel preparation itself and glucose monitoring.

An Evaluation of Virtual Care for Gestational Diabetes Using the Quadruple Aim Framework: Assessment of Patient and Provider Experience, Cost, and Clinical Outcomes.

OBJECTIVE: Our aim in this study was to evaluate the impact of virtual care for gestational diabetes mellitus (GDM) in the context of the COVID-19 pandemic. METHODS: This multiple methods program evaluation used the Quadruple Aim Framework. The impact on patient experience, cost, and provider satisfaction was assessed using surveys and interviews. Chi-square and Poisson statistics were used to compare clinical outcomes before (April 2019 to February 2020) and after (May 2020 to March 2021) the shift to virtual care. RESULTS: Patient experience surveys were completed by 85 women. Most of them rated their virtual care experience as good or excellent (93%), with a preference for continued virtual visits in the future (84%). Most respondents felt virtual care saved them money (93%) and time (98%). Six health-care providers at the Diabetes in Pregnancy Clinic were interviewed and all believed the switch to virtual care was largely positive. Overall, interview transcripts revealed that health-care providers were happy with the transition, although nurses initially perceived an increased workload. There were no significant differences in rates of cesarean section procedures, macrosomia, neonatal intensive care unit admissions or the proportion of appointments at which insulin was initiated between in-person and virtual care patient outcomes. There was a decreased proportion of missed appointments after the switch to virtual care (6.15% vs 1.21%, p<0.0001). CONCLUSIONS: There has been high patient and provider satisfaction with virtual GDM care, with no difference in clinical outcomes and fewer missed appointments. Virtual GDM care should remain an option in the future.

Serum soluble epoxide hydrolase related oxylipins and major depression in patients with type 2 diabetes.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) are at increased risk for depression. Both conditions are associated with disturbances in polyunsaturated fatty acids. Omega-3 and omega-6 fatty acids can be converted into bioactive epoxides by cytochrome P450s (CYP450), which play pro-resolving roles in the inflammatory response; however, soluble epoxide hydrolase (sEH) metabolizes epoxides into diols, which lack pro-resolving functions and can be cytotoxic. Here, we survey serum CYP450- and sEH-derived metabolite concentrations in people with T2DM with and without a major depressive episode. METHODS: Sunnybrook Type 2 Diabetes Study (NCT04455867) participants experiencing a major depressive episode (research version of the Structured Clinical Interview for DSM-5 criteria) were matched 1:1 for gender, glycosylated hemoglobin A1c and body mass index to participants without a current depressive episode. Depression severity was assessed using the Beck Depression Inventory 2nd Edition (BDI-II). From fasting morning blood, unesterified serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass spectrometry following solid phase extraction, and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay. RESULTS: Between 20 depressed and 20 non-depressed participants (mean age 58.9 ± 8.5 years, 65% women) with T2DM, several sEH-derived fatty acid diols, but not IL-6, were higher among those with a depressive episode (effect sizes up to d = 0.796 for 17,18-DiHETE, a metabolite of eicosapentaenoic acid [EPA]; t = 2.516, p = 0.016). Among people with a depressive episode, two epoxides were correlated with lower BDI-II scores: 12(13)-EpOME (ρ = -0.541, p = 0.014) and 10(11)-EpDPE (ρ = -0.444, p = 0.049), metabolites of linoleic acid and docosahexaenoic acid (DHA), respectively, while the ratio of 12,13-DiHOME/12(13)-EpOME was correlated with higher BDI-II scores (ρ = 0.513, p = 0.021). CONCLUSIONS: In people with T2DM, major depressive episodes and depressive symptom severity were associated with an oxylipin profile consistent with elimination of pro-resolving lipid mediators by sEH.

Serum osteocalcin is associated with subjective stress in people with depression and type 2 diabetes.

BACKGROUND: Low serum osteocalcin is a risk factor for type 2 diabetes mellitus (T2DM), and osteocalcin release from bone is associated with an acute stress response in mice. Both diabetes and stress are associated with depression. Here, we assess relationships between serum osteocalcin, depression and subjective stress in people with T2DM. METHODS: Participants with T2DM (HbA1c above 6.4 %, impaired fasting glucose or impaired glucose tolerance) were assessed for a major depressive episode using the research version of the Structured Clinical Interview for DSM-5 depression criteria (SCID-5RV). Subjective stress over the past month was assessed using the Perceived Stress Scale (PSS). Serum carboxylated (cOCN) and fully decarboxylated (dcOCN) osteocalcin were assayed from fasting morning blood by commercial enzyme-linked immunosorbent assay. RESULTS: Among 95 participants (mean age 62.4 ± 9.9, 51 % women), 22 % were experiencing a depressive episode (9 men, 12 women). The presence of a depressive episode was not associated with dcOCN or cOCN concentrations; however, higher concentrations of cOCN were associated with higher PSS scores in participants with depression (r = 0.585, p = 0.005). In an analysis of covariance model controlling for age, sex, body mass index, glycemic control (glycosylated hemoglobin), insulin resistance (homeostatic model), depression, and antidepressant use, cOCN was associated with PSS scores (F=10.302, p = 0.002), and this relationship was stronger in those with depression (depression × cOCN interaction F=4.978, p = 0.028). Although associations between dcOCN concentrations and PSS scores did not reach significance, the same trend seen with cOCN concentrations was observed in participants with depression for dcOCN (r=0.365, p=0.10), and for a depression × dcOCN interaction associated with PSS scores in the whole group (F=2.165, p = 0.15). CONCLUSIONS: Osteocalcin is a neuroendocrine marker associated with perceived chronic stress among people with T2DM experiencing a depressive episode.

Determining Root Causes and Designing Change Ideas in a Quality Improvement Project.

In this second article of our diabetes quality improvement primer series, readers will become familiar with various diagnostic tools used to understand the root causes of a quality problem. We discuss change concepts, and specific change ideas are developed to match the root causes. We review the application of a plan-do-study-act cycle from the Model for Improvement quality improvement framework to test 1 change idea and measure for the intended improvements.

Adult Patient Perspectives on Care for Type 1 and Type 2 Diabetes Across the Institute of Medicine's 6 Domains of Quality.

OBJECTIVES: To gather patient perspectives on quality of care provided in diabetes clinics within the framework of the Institute of Medicine's 6 domains of quality. METHODS: A qualitative study including semi-structured interviews was conducted at 5 academic hospital sites. Transcripts were analyzed using a direct content approach for themes and subthemes with saturation of themes achieved. Purposive sampling was conducted at 5 diabetes clinics (n=47 interviews). RESULTS: The median age of participants was 50 years with a mean duration of diabetes of 14 years; 53% of participants were male, 57% had type 2 diabetes and 81% were using insulin. Patients ranked safety as the most important Institute of Medicine domain, followed by the domains effective, patient-centred, timely, equitable and efficient. Their expectations spanned the first 4 Institute of Medicine domains. They expressed a desire for a knowledgeable, caring, available and communicative team that assist with self-management and overall control of diabetes (effective, patient-centred and timely). They wanted to avoid diabetes complications, including hypoglycemia (safe and effective). They wanted to share in care planning and achieve personalized goals (patient-centred). Efficient and equitable care were not prioritized as highly, but many patients expressed concerns about the costs of medications and insulin supplies. CONCLUSION: Patients' views of high-quality diabetes care include all 6 domains of quality with a stronger emphasis on safe, effective and patient-centred care. Future evaluation of diabetes programs should incorporate a comprehensive and patient-informed approach to consideration of what constitutes high-quality care.

The role of lifestyle interventions in the prevention of gestational diabetes.

Gestational diabetes is associated with adverse pregnancy outcomes, increased costs, and long-term risk of type 2 diabetes mellitus (T2DM) in the mother. Observational data have shown an association between reduced weight gain, healthy eating, and physical activity and reduced rates of gestational diabetes mellitus (GDM). Despite this, most randomized controlled trials of lifestyle interventions to prevent GDM have been negative. Dietary approaches appear to be more successful than exercise or a combination of diet and exercise at decreasing GDM. Reasons for negative studies may include lack of power, lack of intervention uptake, and severity of placenta mediated insulin resistance. Future studies should be powered for a reduction in GDM, monitor lifestyle changes closely, and include a psychological component in the intervention.

Determinants of quality of life in children with chronic somatic disease: pilot data from the GapS Questionnaire.

PURPOSE: Quality of life (QoL) is a ubiquitous yet poorly defined concept; the precise determinants of QoL are rarely identified. We used pilot data from the GapS Questionnaire to investigate the most important determinants of QoL in children with chronic somatic illness. METHODS: We enrolled 92 participants including 60 parents and 32 of their children. The sample comprised rheumatology, diabetes, epilepsy, gastroenterology, cystic fibrosis, and day unit patients. Trained interviewers administered the GapS Questionnaire to parents, and to children if ≥ 10 years. We determined the relative importance of different items for QoL. RESULTS: Child participants had a mean age of 14.7 years. Children identified "having good friendships", "being happy most days", and "getting along with parents" as most important. Parents ranked most highly "being allowed to do all the things you like doing", "getting told you have done a good job at something", and "being physically able to do everything you enjoy doing". CONCLUSIONS: Physical health items were not as important as social and psychological determinants of QoL in our pilot sample.

Allocation techniques for balance at baseline in cluster randomized trials: a methodological review.

Reviews have repeatedly noted important methodological issues in the conduct and reporting of cluster randomized controlled trials (C-RCTs). These reviews usually focus on whether the intracluster correlation was explicitly considered in the design and analysis of the C-RCT. However, another important aspect requiring special attention in C-RCTs is the risk for imbalance of covariates at baseline. Imbalance of important covariates at baseline decreases statistical power and precision of the results. Imbalance also reduces face validity and credibility of the trial results. The risk of imbalance is elevated in C-RCTs compared to trials randomizing individuals because of the difficulties in recruiting clusters and the nested nature of correlated patient-level data. A variety of restricted randomization methods have been proposed as way to minimize risk of imbalance. However, there is little guidance regarding how to best restrict randomization for any given C-RCT. The advantages and limitations of different allocation techniques, including stratification, matching, minimization, and covariate-constrained randomization are reviewed as they pertain to C-RCTs to provide investigators with guidance for choosing the best allocation technique for their trial.

The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of observational studies.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of young women. First-line treatment is often the oral contraceptive pill (OC), but evidence suggests that OC may worsen metabolic outcomes in this population. We undertook this meta-analysis of observational studies and cohorts from within randomized controlled studies to investigate the association between OC use and dysglycemia, dyslipidemia and insulin resistance (IR) in women with PCOS. METHODS: We searched MEDLINE (1966-April 2010), EMBASE (1980-April 2010) and All EBM Reviews. We included prospective cohorts and RCTs that treated women, aged 13-44, with PCOS with OC for at least 3 months. Blinded quality assessment and data extraction were conducted on 35 included studies by two independent reviewers. We used random effects methods to calculate weighted mean differences as the effect size. We investigated heterogeneity using sequential removal of studies, subgroup analysis and meta-regression. RESULTS: OC use was significantly associated with an increase in high-density lipoprotein cholesterol (HDL-C) (P = 0.004) and triglycerides (P = 0.004). Significant heterogeneity was found in glucose, cholesterol, HDL-C, low-density lipoprotein cholesterol triglycerides, fasting glucose to insulin ratios and homeostatic model assessments-IR. Study characteristics such as mean BMI, mean age and duration of study could explain some of the heterogeneity. CONCLUSIONS: Use of OC was not associated with clinically significant adverse metabolic consequences. Because of limitations of the underlying studies, further research including rigorously designed randomized trials would more definitively confirm our findings.