Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM). Normally high-density lipoproteins (HDL) protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA-) related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P = 0.088), and significantly in HDL2(P = 0.003) and HDL3(P = 0.005). When the T1DM group were separated according to mean HbA1c (8.34%), serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was <8.34% (P < 0.05). Furthermore, regression analysis illustrated, that for every 1%-unit increase in HbA1c, SAA increased by 20% and 23% in HDL2 and HDL3, respectively, independent of BMI. HsCRP did not differ between groups (P > 0.05). This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk.

Aims/hypothesis The prevalence of atherosclerosis is increased in type 1 diabetes despite normal-to-high HDL-cholesterol levels. The cholesterol efflux capacity (CEC) of HDL is a better predictor of cardiovascular events than static HDL-cholesterol. This cross-sectional study addressed the hypothesis that impaired HDL function contributes to enhanced CVD risk within type 1 diabetes. Methods We compared HDL particle size and concentration (by NMR), total CEC, ATP-binding cassette subfamily A, member 1 (ABCA1)-dependent CEC and ABCA1-independent CEC (by determining [ 3 H]cholesterol efflux from J774-macrophages to ApoB-depleted serum), and carotid intima-media thickness (CIMT) in 100 individuals with type 1 diabetes (37.6 ± 1.2 years; BMI 26.9 ± 0.5 kg/m 2 ) and 100 non-diabetic participants (37.7 ± 1.1 years; 27.1 ± 0.5 kg/m 2 ). Results Compared with non-diabetic participants, total HDL particle concentration was lower (mean ± SD 31.01 ± 8.66 vs 34.33 ± 8.04 μmol/l [mean difference (MD) −3.32 μmol/l]) in participants with type 1 diabetes. However, large HDL particle concentration was greater (9.36 ± 3.98 vs 6.99 ± 4.05 μmol/l [MD +2.37 μmol/l]), resulting in increased mean HDL particle size (9.82 ± 0.57 vs 9.44 ± 0.56 nm [MD +0.38 nm]) (p < 0.05 for all). Total CEC (14.57 ± 2.47%CEC/4 h vs 12.26 ± 3.81%CEC/4 h [MD +2.31%CEC/4 h]) was greater in participants with type 1 diabetes relative to non-diabetic participants. Increased HDL particle size was independently associated with increased total CEC; however, following adjustment for this in multivariable analysis, CEC remained greater in participants with type 1 diabetes. Both components of CEC, ABCA1-dependent (6.10 ± 2.41%CEC/4 h vs 5.22 ± 2.57%CEC/4 h [MD +0.88%CEC/4 h]) and ABCA1-independent (8.47 ± 1.79% CEC/4 h vs 7.05 ± 1.76% CEC/4 h [MD +1.42% CEC/4 h]) CEC, were greater in type 1 diabetes but the increase in ABCA1-dependent CEC was less marked and not statistically significant in multivariable analysis. CIMT was increased in participants with type 1 diabetes but in multivariable analysis it was only associated negatively with age and BMI. Conclusions/interpretation HDL particle size but not HDL-cholesterol level is independently associated with enhanced total CEC. HDL particle size is greater in individuals with type 1 diabetes but even after adjusting for this, total and ABCA1independent CEC are enhanced in type 1 diabetes. Further studies are needed to understand the mechanisms underlying these effects, and whether they help attenuate progression of atherosclerosis in this high-risk group. Keywords HDL particle size . HDL-cholesterol efflux capacity . Type 1 diabetes Mohamad O. Ahmed and Rachel E. Byrne are equal contributors. James Gibney and Fiona C. McGillicuddy share senior authorship.

Background: Adrenal insufficiency (AI) is associated with increased cardiovascular morbidity and mortality and reduced quality of life (QoL).Optimum glucocorticoid (GC) dosing and timing are crucial in the treatment of AI, yet the natural circadian secretion of cortisol is difficult to mimic. The once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may address unmet needs. Methods:An investigator-initiated, prospective, cross-over study in patients with AI. Following baseline assessment of cardiometabolic risk factors and QoL, patients switched from their usual hydrocortisone regimen to a once-daily dose equivalent of DR-HC and were reassessed after 12 weeks of treatment. Results: Fifty-one patients (21 PAI/30 SAI) completed the study. Mean age was 41.6 years (SD 13), and 58% (n=30) were male. The median daily HC dose before study entry was 20mg (IQR 15-20mg). After 3 months on DR-HC, the mean SBP decreased by 5.7mmHg, p=0.0019 and DBP decreased by 4.5mmHg, p=0.0011. There was also a significant reduction in mean body weight (-1.23kg, p=0.006) and BMI (-0.3 kg/m2,p=0.003). In a sub-analysis, there was a greater reduction in SBP observed in patients with SAI when compared to PAI post DR-HC. Patients reported significant improvements in QoL using three validated QoL questionnaires, with a greater improvement in PAI. Conclusion: Dual-release hydrocortisone decreases BP, weight and BMI compared with conventional HC treatment, even at physiological GC replacement doses. Additionally, DR-HC confers significant improvements in QoL compared to immediate-release HC, particularly in patients with PAI, which is also reflected in the patient preference for DR-HC.

In recent years, the short Synacthen test (SS) has become the most widely used test to assess adrenal reserve. Despite its frequent use, there are still several areas related to the short Synacthen test (SST), which have no consensus including the optimum sampling times, that is, whether a 60 min post-Synacthen administration cortisol is necessary or not.MethodologyWe performed a retrospective data analysis of 492 SSTs performed on adult patients in a tertiary referral teaching hospital in Ireland. The SSTs were performed in the inpatient and outpatient setting and included patients across all medical disciplines and not exclusively to the endocrinology department.Results313 patients had 0, 30 and 60 min samples available for analysis. A total of 270/313 (82%) were deemed to pass the test, that is, cortisol ≥500 nmol/L at both 30 and 60 min. Of the 313 patients, 19 (6%) patients had an indeterminate response, cortisol <500 nmol/L at 30 min, but rising to ≥500 nmol/L on the 60 min sample. Of these 19 patients, only 9/19 patients had a serum cortisol level at 30 min <450 nmol/L, requiring clinical treatment with glucocorticoid replacement. All 24/313 (8%) patients who had insufficient responses at 60 min were also insufficient at 30 min sampling. No individuals passed (≥500 nmol/L) at 30 min and then failed (<500 nmol/L) at 60 min.ConclusionUsing the 30 min cortisol sample post-Synacthen administration alone identifies clinically relevant adrenal insufficiency in the majority of cases. A small subset of patients have a suboptimal response at 30 min but have a 60 min cortisol concentration above the threshold for a pass. Data regarding the long-term outcomes and management of such patients are lacking and require further study.

The study was part-funded by the Meath Foundation. The authors have no competing interests.