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Introduction: Insulin resistance is central to the development of type 2 diabetes (T2D). Association between specific biomarkers of glucose-insulin homeostasis and T2D have been inconsistent. Whether vitamin D or omega-3 fatty acids (n-3 FA) can modify these associations is also unclear. Hypothesis: We hypothesized that higher insulin, C-peptide, insulin resistance score (IRS), and HbA1c are each associated with higher T2D risk, and that these associations would be attenuated among participants who received vitamin D or n-3 FA. Methods: VITAL Diabetes (NCT01633177) was a pre-specified ancillary 2x2 factorial study in the VITAL RCT to assess whether vitamin D (cholecalciferol, 2000 IU/d) or n-3 FA (EPA + DHA, 1 g/d) could prevent T2D. Subjects without baseline reported T2D and with HbA1c Results: Mean age of participants was 66 years, approximately 45% were female, and 16% were African American. Each of the glucose-insulin homeostasis biomarkers was associated with T2D risk ( Table 1 ), aOR (95% CI) per SD increment, insulin: 1.46 (1.10, 1.94), C-peptide: 1.72 (1.28, 2.31), IRS: 1.59 (1.26, 2.01), and HbA1c: 80.43 (25.90, 249.77). Biomarker associations did not differ by randomized treatment ( P interaction >0.05). Conclusions: In VITAL Diabetes, insulin, C-peptide, IRS, and HbA1c were each associated with an increased risk of T2D, independent of other risk factors. Randomization to either vitamin D or n-3 FA did not modify these associations.

Introduction: Dysglycemia and insulin resistance increase cardiovascular disease (CVD) risk. Associations between specific glucose-insulin biomarkers and CVD have been inconsistent. Hypothesis: We hypothesized that higher insulin, C-peptide, insulin resistance score (IRS), and HbA1c are associated with incident CVD and coronary heart disease (CHD) events and that both vitamin D and omega-3 fatty acids (n-3 FA) would improve these biomarkers and attenuate their risks with CVD. Methods: VITAL (NCT01169259) was a 2x2 factorial design RCT testing vitamin D (cholecalciferol, 2000 IU/d) and n-3 FA (EPA+DHA, 1 g/d) for the primary prevention of CVD. Incident CVD cases [non-fatal myocardial infarction (MI), non-fatal stroke, or CV death] were matched 1:1 on age and sex to healthy controls (n=715 CVD pairs including 423 CHD [MI, revascularization, CHD death] pairs). Conditional logistic regression adjusting for demographics, CV risk factors, and randomized treatment was used to assess the adjusted odds ratio (aOR) and 95% CI between baseline levels of insulin, C-peptide, IRS (Insulinх0.0265+C-peptideх0.00511+Creatinineх-3.2641), and HbA1c with risk of CVD and CHD events. In control participants, we examined the randomized effects of vitamin D or n-3 FA on changes in these biomarkers at 1- or 2-years follow-up. Results: Mean age of participants was 71 years, approximately 42% were female, and 12% were African American. Baseline insulin, C-peptide, and IRS were not associated with CVD ( Figure 1 ). HbA1c was associated with CVD risk, aOR (95% CI) per SD increment, 1.17 (1.01, 1.38). Of the 4 biomarkers, only IRS was associated with CHD risk, aOR (95% CI): 1.22 (1.01, 1.46). Randomization to vitamin D or n-3 FA did not modify levels of these biomarkers or their associations. Conclusions: HbA1c was significantly associated with CVD risk, whereas IRS was associated with CHD risk. Neither vitamin D nor n-3 FA appreciably modified these biomarker levels or their risk associations.

Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women&rsquo, s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) &lt, 0.05 in VITAL200, validated (p-values &lt, 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.

Obesity has become increasingly prevalent in the United States and diabetes prevalence has increased dramatically. It is estimated that diabetes affects more than 30 million Americans (CDC, 2015). Prediabetes, a condition in which blood sugar or HbA1c levels are elevated but not to levels permitting a diagnosis of type 2 diabetes, is even more prevalent. Prediabetes precedes the development of type 2 diabetes and for this reason, has been identified as a condition at which interventions might be targeted and progression to overt diabetes might be interrupted. The publication of the initial results of the Diabetes Prevention Program (Knowler WC, 2002) demonstrated that lifestyle change and medication could substantially reduce progression to type 2 diabetes. These efforts have stimulated the CDC to implement the National Diabetes Prevention Program. Unfortunately, a substantial proportion of individuals adhering to lifestyle change or medication still progress to overt diabetes and the identification of individuals participating in a DPP at continued risk for the development of type 2 diabetes would be valuable. We designed a protocol to determine whether individuals responding appropriately to a DPP might be distinguished from individuals at continued risk for diabetes progression by sequential assessments of insulin resistance. We recently validated a multiplexed mass spectrometry assay for the measurement of intact insulin and C-peptide (Taylor SW, 2016), used this to model insulin resistance in individuals undergoing formal assessment of insulin resistance using Steady State Plasma glucose (SSPG) measurements (Abbasi F, 2018) and defined an Insulin Resistance Score (IRS) based on this data. To explore the use of this IRS in the context of an established an IRB approved protocol (Quest Testing to Assess Insulin Resistance [Q-TAIR]; Western IRB protocol # 20171395), we enrolled three cohorts totaling 40 individuals. In addition to anthropometric measurements, this protocol permitted assessment of laboratory data for fasting glucose, HbA1c, electrolytes, lipids, and the IRS at baseline, 1, 3, and 6 months, and 1 year. Data collection is complete for cohorts 1 and 2; data collection is still ongoing for cohort 3. Subjects enrolled in the individual cohorts were enrolled in individual participating practices and varied widely in the proportion offered enrollment based on laboratory test results. In keeping with expectations for adherent participants in a DPP, patients lost an average of 11 lbs. In cohorts 1 and 2, initial IRS were top or middle tertile risk in 10 of 17 patients. Importantly, normalization or improvement of laboratory test results at the conclusion of the DPP did not reflect the continued elevation of IRS risk observed in 5 of the 17 patients. These findings suggest the potential utility of the IRS in assessing changes in the degree of insulin resistance in DPP participants.

BACKGROUND The VITamin D and OmegA-3 TriaL (VITAL) is a completed randomized, placebo-controlled trial of vitamin D3 (2000 IU/day) and marine omega-3 (1 g/day) supplements in the primary prevention of cancer and cardiovascular disease. Here we examine baseline and change in 25-hydroxyvitamin D (25(OH)D) and related biomarkers with randomized treatment and by clinical factors. METHODS Baseline 25(OH)D was measured in 15,804 participants (mean age 68 years.; 50.8% women; 15.7% African Americans) and in 1660 1-year follow-up samples using liquid chromatography-tandem mass spectrometry and chemiluminescence. Calcium and parathyroid hormone (iPTH) were measured by chemiluminescence and spectrophotometry respectively. RESULTS Mean baseline total 25(OH)D (ng/mL ± SD) was 30.8 ± 10.0 ng/mL, and correlated inversely with iPTH (r = -0.28), p

The aim of the study was to evaluate the impact of any perioperative parameters on the outcome of treatment for appendicitis.The study included 108 consecutive children with appendicitis. Data were retrieved from files using the codes for appendectomy of the Nordic Classification of Surgical Procedures and the diagnosis codes for appendicitis from the International Classification of Dis-eases (ICD) 10. A non-satisfactory outcome was defined as a post-operative length of stay in hospital ≥ 5 days and/or readmission due to complications.Significantly more patients with a non-satisfactory outcome had complicated appendicitis (73%) compared with those with a satisfactory outcome (25%). A total of 78% of children6 years and 44% of children10 years had a non-satisfactory outcome. The duration of symptoms before operation was mean 2.8 days for children with a non-satisfactory outcome and 2.7 days for those with complicated appendicitis compared with 1.5 days for children with a satisfactory outcome and 1.6 days for those with simple appendicitis. The median difference was two days in the younger patients. Surgical time was significantly shorter in the group of patients with a satisfactory outcome and in those with simple appendicitis than in the other groups.Complicated appendicitis and a non-satisfactory outcome in children after operation are associated with a long preoperative duration of symptoms, young age and long surgical time. A cut-off age has not been established, but young children might benefit from direct referral and access to hospitalization in a regional or tertiary paediatric surgical centre.not relevant.not relevant.