Comparison of coronary artery calcium score and cardiovascular risk-stratification by European Society of Cardiology Guidelines and Steno Type 1 Risk Engine in statin-naïve adults with type 1 diabetes

BackgroundCoronary artery calcium (CAC) is a marker of atherosclerotic cardiovascular disease (CVD). However, for patients with type 1 diabetes (T1D), its relationship with T1D-specific cardiovascular (CV) risk-stratification tools is unknown.AimsAssess prevalence of CAC and evaluate relationship between CAC and T1D-specific CV risk-stratification methods in T1D.MethodsCross-sectional study of adults with T1D age 20–60 years, statin-naïve and no history of CVD. Data was obtained from electronic medical records and by interview. Presence of CAC was assessed using non-contrast cardiac computed tomography and quantified by Agatston Units (AU). CV risk-stratification was assessed using the 2019 European Society of Cardiology (ESC) Guidelines and the Steno T1 Risk Engine (ST1RE).Results85 patients were included with mean age 35.4 ± 10.3 years, HbA1c 8.3 ± 1.5 % and T1D duration 17.0 ± 10.1 years. 67 patients (78.9 %) had a CAC score of 0 AU, 17 (20.0 %) >0–100 AU, and one (1.2 %) >100 AU. Duration of T1D (p = 0.009), body mass index (p = 0.029), neuropathy (p = 0.016) and low-density lipoprotein cholesterol levels (p = 0.016) were independently associated with a positive CAC score on multivariate analysis. Positive predictive value for a positive CAC score was 85.7 % for the ST1RE high risk category and 31.3 % for the 2019 ESC Guidelines very high risk category.ConclusionsOne-fifth of this T1D cohort had a positive CAC score. The ST1RE was superior in identifying positive CAC compared to the 2019 ESC Guidelines. Further studies are required to elucidate the role of CAC in personalising CV risk-stratification and statin initiation in T1D.     

Sodium–glucose cotransporter 2 inhibitors as adjunct therapy for type 1 diabetes and the benefit on cardiovascular and renal disease evaluated by Steno risk engines

AimsSodium–glucose cotransporter inhibitors (SGLTi) have beneficial cardiovascular and renal effects in persons with type 2 diabetes. No studies have shown whether this can be demonstrated in type 1 diabetes (T1D). We aimed to estimate the risk of cardiovascular disease (CVD) and end-stage kidney disease (ESKD) in persons with T1D with and without treatment with SGLTi.MethodsThe study is based on 3660 adults with T1D. The Steno Type 1 Risk Engines were used to calculate 5-year risks of ESKD and 5- and 10-year risk of CVD. The effect of SGLTi was simulated by changing the HbA_1c and systolic blood pressure values in accordance with results from the DEPICT studies with mean (standard deviation (SD)) of -3.6 (0.9) mmol/mol (-2.5 % (2.2)) and -1.12 (2.8) mmHg. eGFR and albuminuria were changed in accordance with results from the Tandem studies; no change in eGFR and mean (SD) %-change in albuminuria of -23.7 (12.9).ResultsWe found a 5-year CVD relative risk reduction of 6.1 % (95%CI 5.9,6.3) and 11.1 % (10.0,12.2) in the subgroup with albuminuria with similar results for the 10-year CVD risk. For the estimated 5-year risk of ESKD, we found a relative risk reduction of 5.3 % (5.1,5.4) with 7.6 % (6.9,8.4) in the subgroup with albuminuria.ConclusionWe found a significant CVD and ESKD risk reduction, especially in the subgroup with albuminuria.     

Long chain fatty acids metabolism and cardiovascular risk factors in youth with type 1 diabetes

Background and aimsFatty acids (FAs) and their metabolizing enzymes have been associated with several cardiometabolic outcomes. Whether they correlate with cardiovascular risk in type 1 diabetes (T1D), it is unknown. We investigated whether erythrocyte FAs correlated with cardiovascular risk factors and dietary fats in youth with T1D.Methods and resultsWe recruited 154 adolescents with T1D (aged 17.3 ± 2 years, 82 boys) and assessed blood pressure, plasma lipids, HbA1c, estimated insulin sensitivity (eIS) and dietary fats based on a 3-days weighed dietary record. Erythrocyte FAs were measured by gas chromatography and desaturase and elongase activities were estimated as product/precursor ratios. Delta-6-desaturase (D6D) activity correlated inversely with eIS (r = ?0.32,p = 6.6110^?5) and directly with triglycerides (r = 0.24, p = 0.003), adjusted for z-BMI, age and gender. No single erythrocyte FA correlated with eIS. Erythrocyte membrane stearic acid (SA) correlated with HbA1c adjusted for confounders and eIS (r = ?0.26, p = 0.002). We found some weak (r ≤ 0.20) correlations between erythrocyte membrane FAs and dietary fats, which were not retained by correction for multiple testing.ConclusionIn youth with T1D, D6D activity might exert unfavorable effects per se, beyond its role on FAs composition. This is in accordance with previous data associating D6D activity/D6D-enhancing polymorphisms with metabolic syndrome and incident type 2 diabetes, as well as D6D activity with the regulation of cellular red-ox balance. SA was a favorable marker of glycemic control. Future research is needed to clarify the biological pathways linking D6D and SA with the cardiometabolic health of youth with T1D.     

Non-dipping and higher nocturnal blood pressure are associated with risk of mortality and development of kidney disease in type 1 diabetes

AimsPeople with type 1 diabetes have increased risk of cardiovascular (CV) and kidney disease. A 24-hour ambulatory blood pressure (BP) measurement (ABPM) examines diurnal variations in BP. We aimed to determine the prognostic significance of blunted decrease in nocturnal systolic BP of <10 % (non-dipping of nocturnal BP) for CV- and kidney disease and all-cause mortality in type 1 diabetes.MethodsFrom 2009 to 2011, at Steno Diabetes Center Copenhagen, 654 participants with type 1 diabetes had 24-hour ABPM obtained with a tonometric wrist-watch device (BPro, HealthStats, Singapore). In 2017, outcomes (composite CV endpoint; all-cause mortality; decline in estimated glomerular filtration rate (eGFR) ≥30 %; end-stage kidney disease (ESKD); and a composite kidney endpoint including decline in eGFR ≥30 %, ESKD and all-cause mortality) were registered. Hazard Ratios (HR) were calculated using Cox regressions.ResultsParticipants were mean ± SD 55 ± 13 years old and had median (IQR) 35 (24–44) years diabetes duration. Mean daytime and nocturnal systolic BP were 133 ± 16 and 121 ± 16 mmHg while 337 (52 %) participants demonstrated non-dipping. After CV risk factor adjustments, non-dipping was associated with all-cause mortality (HR 2.12 (1.09–4.11), p = 0.03) and the composite kidney endpoint (HR 1.92 (1.23–3.00), p = 0.004).ConclusionsNon-dipping entailed increased risk of all-cause mortality and kidney disease in type 1 diabetes.     

Femoral neck structural properties are altered in adults with type 1 diabetes

AimsTo determine differences in hip geometry in adults with type 1 diabetes (T1D) compared with healthy adults without diabetes.MethodsIn this cross-sectional study, 43 adults with T1D (mean age 56 years, 84 % female, 92 % White, mean duration of diabetes of 39 years, A1c of 7.8 %) and 40 adults without diabetes (mean age 60 years, 80 % female, 77 % white) who had hip dual-energy x-ray absorptiometry (DXA) scans from previous studies were included. Areal bone mineral density (aBMD) and measures of hip structural properties at the narrow neck, intertrochanteric and femoral shaft regions of the left proximal femur were analyzed between adults with T1D and controls using linear models controlled for age, sex, and body mass index.ResultsThere were no significant differences in DXA-based aBMD at the hip (0.769 ± 0.132 vs. 0.900 ± 0.139 g/cm², p = 0.07) or femoral neck (0.722 ± 0.116 vs. 0.849 ± 0.114 g/cm², p = 0.09) regions between adults with T1D and controls. When controlling for age, sex, and BMI, DXA-based aBMD at the hip (0.880 ± 0.022 vs. 0.943 ± 0.020 g/cm², p = 0.02) and femoral neck (0.750 ± 0.021 vs. 0.812 ± 0.020 g/cm², p = 0.02) regions were significantly lower in adults with T1D than controls. Cortical thickness was significantly lower in all three hip regions in adults with T1D than in controls (narrow-neck: 0.169 ± 0.005 vs. 0.186 ± 0.005 cm, p = 0.011; intertrochanteric: 0.388 ± 0.013 vs. 0.425 ± 0.012 cm, p = 0.017; femoral shaft: 0.529 ± 0.017 vs. 0.586 ± 0.016 cm, p = 0.006). Moreover, adults with T1D had a smaller cross-sectional area at the narrow-neck (3.06 ± 0.09 vs. 3.32 ± 0.08 cm², p = 0.015), a higher femoral shaft endocortical diameter (2.23 ± 0.07 vs. 2.02 ± 0.06 cm, p = 0.011), and higher buckling ratios (an indicator of cortical instability) at the intertrochanteric (9.22 ± 0.34 vs. 8.23 ± 0.32, p = 0.016) and femoral shaft (3.32 ± 0.15 vs. 2.89 ± 0.14, p = 0.016) regions.ConclusionsAdults with T1D have several significant differences in proximal femur morphology compared with controls. These morphological differences may adversely affect the mechanical integrity of the proximal femur, thereby contributing to an increased risk of fracture in the event of a fall.     

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk

Background and aimsPeople with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D.Methods and resultsCross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (¹H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [[7], [8]]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204–0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590–0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495–0.968]; p = 0.032), ¹H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026–1.275]; p = 0.015), and ¹H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019–1.361], p = 0.026) remained associated with atherosclerosis.ConclusionsIn adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.     

A sub-analysis of the SAGE study in Italy indicates good glycemic control in type 1 diabetes

Background and aimsIntensive glycemic control minimizes the risk of micro- and macrovascular complications in patients with type 1 diabetes (T1D). We report glycemic control in Italian participants (age groups: 26–44, 45–64, and ≥65 years) of the global SAGE study.Methods and resultsThe primary endpoint was proportion of participants who achieved an HbA_1c <7% in predefined age groups. In the 523 patients with T1D, mean age was 44.6 years and mean body mass index (BMI) was 25 kg/m². Mean HbA_1c was 7.5% and 29.4% had HbA_1c <7.0%, with the highest percentage in those 26–45 years (31.7%) and the lowest in those ≥65 years (20%). Altogether, 22.9% of patients achieved their physician-established individualized HbA_1c target. Most patients had ≥1 symptomatic hypoglycemic episode in the previous 3 months (≤70 mg/dL 82.5%; ≤54 mg/dL 61%). Severe hypo- and hyperglycemia were experienced by 16.3% and 12% of patients, of which 7.1 and 9.5%, respectively, required hospitalization/emergency visits. More patients achieved HbA_1c <7% with CSII (30%) than with multiple daily insulin injections (27.9%). In multivariate analysis, BMI (OR 0.94, 95% CI 0.89–0.99, p = 0.032) and adherence to diet (OR 0.36, 95% CI 0.18–0.70, p = 0.0028) were significantly associated with HbA_1c <7.0%.ConclusionsGlycemic control can be considered good in the Italian SAGE cohort, especially in younger patients, who more frequently use pumps/continuous glucose monitoring. Greater patient education and use of technology may further support this achievement. Patients should be encouraged to maintain a low BMI and adhere to their diet.     

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange

AimsWe aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry.MethodsDAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010–2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed.ResultsOf the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004).ConclusionsDAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.     

Cardiovascular risk factor progression in adolescents and young adults with youth-onset type 2 diabetes

AimsYouth-onset type 2 diabetes (T2D) confers a high risk of early adverse cardiovascular morbidity. We describe the cumulative incidence and prevalence of cardiovascular risk factors over time and examine relationships with diabetes progression in young adults with youth-onset T2D from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.MethodsLongitudinal data was used to evaluate the relationships between hypertension, LDL-C dyslipidemia, hypertriglyceridemia, and smoking with risk factors in 677 participants.ResultsBaseline mean age was 14 ± 2 years and mean follow-up 10.2 ± 4.5 years. The 14-year cumulative incidence of hypertension, LDL-C dyslipidemia, and hypertriglyceridemia was 59%, 33%, and 37% respectively. Average prevalence of reported smoking was 23%. Male sex, non-Hispanic white race/ethnicity, obesity, poor glycemic control, lower insulin sensitivity, and reduced beta-cell function were significantly associated with an unfavorable risk profile. At end of follow-up, 54% had ≥2 cardiovascular risk factors in addition to T2D.ConclusionsCardiovascular risk factor incidence and prevalence was high over a decade of follow-up in young adults with youth-onset T2D. Glucose control and management of cardiovascular risk factors is critical in youth with T2D for prevention of cardiovascular morbidity and mortality.     

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

BackgroundMyocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.ObjectivesThis study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.MethodsIn this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block.ResultsOf 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE.ConclusionsThe use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.     

The association of insulin resistance measured through the estimated glucose disposal rate with predictors of micro-and macrovascular complications in patients with type 1 diabetes

Background and aimInsulin resistance (IR) is associated with a higher rate of type 1 diabetes (T1D) complications. We aimed to examine the relationship between estimated glucose disposal rate (eGDR), a readily available marker of IR in clinical practice and early predictor biomarkers of macrovascular and microvascular complications in patients with T1D.DesignA cross-sectional study.MethodsA total of 165 consecutive patients with T1D free of cardiovascular, eye, and renal complications were included in the study from 2016 to 2020. Participants were characterized as insulin resistant if their eGDR value was ≤ 8 mg/kg/min. Pulse wave velocity (PWV) and global longitudinal strain (GLS) were used as surrogates for subclinical atherosclerosis and left ventricular systolic dysfunction (LVSD), respectively. Four previously standardized tests based on the calculation of heart rate variability (HRV) were used to evaluate subclinical cardiac autonomic neuropathy (CAN). Early nephropathy was assessed by assessing urinary albumin to creatinine ratio (ACR).ResultsThe population sample (n = 165) included a majority of female patients (63%) and had a median age of 32 years (24?43), median disease duration of 14 years ( ± 9.5–21.5), a median BMI value of 23.7 kg/m² (21.4–26.6), an HbA1C of 7.2% (6.7–8.2) and median eGDR (lower values indicate higher insulin resistance) of 9.2 mg/kg/min (8.2–9.9), while 21.8% (n = 36) of the participants were characterized as insulin resistant. After adjustment for age, gender, and the duration of diabetes, the presence of IR was significantly associated with higher prevalence of subclinical atherosclerosis (OR:2.59, 95% CI: 1.06–6.30, p = 0.036), CAN (OR:3.07, 95% CI: 1.02–9.32, p = 0.047) and subclinical LVSD (OR: 4.9, 95% CI: 1.94–12.79, p = 0.001). No association was shown with ACR.ConclusionsIn patients with T1D, insulin resistance, as measured by eGDR, correlates well with early CVD predictors and CAN. These associations appear independent of the effects of gender, aging, and disease duration.     

Achievement of treatment targets predicts progression of vascular complications in type 1 diabetes

Background and aimTo study the association between achievement of guideline-defined treatment targets on HbA1c, low-density lipoproteins (LDL-C), and blood pressure with the progression of diabetic complications in patients with type 1 diabetes (T1D).MethodsThe study included 355 patients at baseline and 114 patients with follow-up data after 3–5 years. Outcome variables were the progression of diabetic kidney disease, retinopathy, or cardiovascular disease (CVD). We used logistic regression and other machine learning algorithms (MLA) to model the association of achievement of treatment targets and probability of progression of complications.ResultsAchievement of the target blood pressure was associated with 96% lower odds of a new CVD event (0.04 (95% CI 0.00, 0.53), p = 0.016), and 72% lower odds of progression of any complication (0.28 (95% CI 0.09, 0.89), p = 0.027. Achievement of HbA1c target was associated with lower odds of composite complication progression by 82% (0.18 (95% CI 0.04, 0.88), p = 0.034.) None of the patients who achieved HbA1c target progressed in CVD. MLA demonstrated good accuracy for the prediction of progression of CVD (AUC 0.824), and lower accuracy for other complications.ConclusionThe achievement of blood pressure and HbA1c treatment targets is associated with lower odds of vascular complication of T1D in a real life study.     

Novel glycoproteins identify preclinical atherosclerosis among women with previous preeclampsia regardless of type 1 diabetes status

Background and aimsInformation regarding inflammation and cardiovascular disease (CVD) risk in type 1 diabetes (T1D) or preeclampsia (PE) is scarce. We assessed differences in inflammation markers according to the presence of both conditions and their association with atherosclerosis.Methods and resultsWe recruited 112 women without CVD and last pregnancy ≥5 years previously (n = 28 per group): a)T1D and PE; b)T1D without PE; c)PE without T1D; and d)Controls (without T1D or PE). Groups were matched by several CVD risk factors, and diabetes duration and retinopathy in T1D. Carotid intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by ultrasonography. Inflammatory markers included classical variables (leucocytes and high-sensitivity C-reactive protein [hsCRP]) and glycoproteins by nuclear magnetic resonance (¹H-NMR) spectroscopy (GlycA, GlycB, GlycF and the height/width [H/W] ratios of GlycA and GlycB). The age of the participants was 44.9 ± 7.8 years, and 20.5% harbored plaque. There were no differences in inflammatory markers among the four study groups. Overall, in multivariate-adjusted models, all ¹H-NMR-glycoproteins (except GlycB) were positively associated with IMT measures (IMT of bulb and maximum-IMT of any carotid segment; p < 0.05). After dividing the sample according to PE status, previous findings remained largely unchanged. Furthermore, GlycF was independently associated with carotid plaque only in PE group (OR 5.08 [1.03–25.01] per 0.1 log-increments, p = 0.046). Neither leucocytes nor hsCRP were related to atherosclerosis. Regarding T1D status, non-uniform results were observed.ConclusionsHigh ¹H-NMR-glycoprotein concentrations have a negative impact on carotid atherosclerosis among women with preeclampsia, regardless of T1D status.     

Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica

Background and aimsDespite using sensor-augmented pump therapy (SAPT) with predictive low-glucose management (PLGM), hypoglycemia is still an issue in patients with type 1 Diabetes (T1D). Our aim was to determine factors associated with clinically significant hypoglycemia (<54 mg/dl) in persons with T1D treated with PLGM-SAPT.Methodology: This is a multicentric prospective real-life study performed in Colombia, Chile and Spain. Patients with T1D treated with PLGM-SAPT, using sensor ≥70% of time, were included. Data regarding pump and sensor use patterns and carbohydrate intake from 28 consecutive days were collected. A bivariate and multivariate Poisson regression analysis was carried out, to evaluate the association between the number of events of <54 mg/dl with the clinical variables and patterns of sensor and pump use.Results188 subjects were included (41 ± 13.8 years-old, 23 ± 12 years disease duration, A1c 7.2% ± 0.9). The median of events <54 mg/dl was four events/patient/month (IQR 1–10), 77% of these events occurred during day time. Multivariate analysis showed that the number of events of hypoglycemia were higher in patients with previous severe hypoglycemia (IRR1.38; 95% CI 1.19–1.61; p < 0.001), high glycemic variability defined as Coefficient of Variation (CV%) > 36% (IRR 2.09; 95%CI 1.79–2.45; p < 0.001) and hypoglycemia unawareness. A protector effect was identified for adequate sensor calibration (IRR 0.77; 95%CI 0.66–0.90; p:0.001), and the use of bolus wizard >60% (IRR 0.74; 95%CI 0.58–0.95; p:0.017).ConclusionIn spite of using advanced SAPT, clinically significant hypoglycemia is still a non-negligible risk. Only the identification and intervention of modifiable factors could help to prevent and reduce hypoglycemia in clinical practice.     

Sex-Specific Risks of Major Cardiovascular and Limb Events in Patients With Symptomatic Peripheral Artery Disease

BackgroundPatients with peripheral artery disease (PAD) have a higher risk of major adverse cardiovascular events (MACE) compared with those without PAD.ObjectivesThe aim of this post hoc analysis was to evaluate sex-specific differences in MACE and limb events in the EUCLID (Examining Use of Ticagrelor in PAD) trial.MethodsCox proportional hazards models were used to compare time-to-event outcomes stratified by sex. Covariates were introduced after adjusted model selection.ResultsEUCLID enrolled 13,885 patients with PAD (28% women [n = 3,888]). PAD severity and medical treatment were comparable between sexes, whereas prior lower extremity revascularization was reported less frequently in women (54.8% vs. 57.3%; p = 0.006). Women were older (mean ± SD age: 67.8 ± 8.9 vs. 66.1 ± 8.2 years; p < 0.001) and more likely to have diabetes mellitus (p = 0.004), hypertension, hyperlipidemia, and chronic kidney disease (all p < 0.001). Over a mean follow-up of 30 months, women had a lower risk of MACE (9.5% vs. 11.2%; adjusted hazard ratio: 0.77; 95% confidence interval: 0.68 to 0.88; p < 0.001) and all-cause-mortality (7.6% vs. 9.7%; adjusted hazard ratio: 0.61; 95% confidence interval: 0.53 to 0.71; p < 0.001). In contrast, risk for major adverse limb events (2.6% vs. 3.0%) and hospitalization for acute limb ischemia (1.6% vs. 1.7%) were not different by sex.ConclusionsAlthough women with PAD are at lower risk for MACE and all-cause mortality, risk for limb events was similar between sexes over a mean follow-up of 30 months. Understanding sex-specific differences and dissociation between baseline cardiovascular risk and subsequent cardiovascular events requires further investigation. (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822)     

Can HDL cholesterol be replaced by paraoxonase 1 activity in the prediction of severe coronary artery disease in patients with type 2 diabetes?

Background and aimsNovel biomarkers are required to improve cardiovascular disease prediction in patients with type 2 diabetes (T2D) as a high-risk population. This study was conducted to examine whether coronary artery disease (CAD) risk assessment can be improved by substituting high-density lipoprotein (HDL)-bound paraoxonase 1 (PON1) activity for HDL cholesterol (HDL-C) concentration in patients with T2D.Methods and resultsIn this study, we studied 139 patients with T2D (mean age 64.12 ± 8.17 years) who underwent coronary angiographic examination. The initial rate of substrate hydrolysis was spectrophotometrically assayed in kinetic mode for measuring PON1 activity. Receiver operating characteristic (ROC) graphs are created by plotting true positivity versus false positivity. In patients with HbA_1c ≥ 7%, PON1 (AUC = 0.7, p = 0.029) and nonHDL-C/PON1 (AUC = 0.75, p = 0.013) were significantly more capable of differentiating patients with CAD from those without CAD compared to HDL-C and nonHDL-C/HDL-C. Also, the predictive power of PON1 (AUC = 0.64, p = 0.029) and nonHDL-C/PON1 (AUC = 0.71, p = 0.004) were significantly higher in comparison with HDL-C and nonHDL-C/HDL-C for CAD characterization in patients aged ≥50 years. Moreover, PON1 and nonHDL-C/PON1 are associated with the incidence of CAD with an AUC of 0.7 (p = 0.026) and AUC of 0.64 (p = 0.087), respectively, among subjects with low HDL-C.ConclusionPON1 and the ratio of nonHDL-C/PON1 significantly improve the prediction of severe CAD in T2D patients and in patients with HbA_1c ≥ 7%, age ≥50 years, or low HDL-C. PON1 activity and lipid ratios using this enzyme may be valuable as substitutes of HDL-C for increasing clinical efficacies in cardiovascular risk assessment.     

Hypoglycemia unawareness in type 1 diabetes patients using intermittent continuous glucose monitoring: Identification of risk factors and glycemic patterns

BackgroundHypoglycemia unawareness designates failure to detect eminent hypoglycemia. Clarke's questionnaire is one of the most used systems to evaluate this problem.AimsTo relate Clarke's questionnaire (QQ) results with continuous glucose monitoring data.MethodsApplication of the questionnaire in a sample of type 1 diabetes mellitus (T1DM) patients using intermittent continuous glucose monitoring (iCGM).Results111 T1DM patients were evaluated, 56.8% female, mean age 35.0 ± 12.4 years and mean disease duration 18.8 ± 10.5 years.According to CQ, 13.5% had unawareness, 76.6% awareness and 9.9% indeterminate awareness to hypoglycemia. Those with unawareness had longer disease duration (25.1 ± 10.4 vs 18.2 ± 10.3 for awareness and 14.9 ± 9.9 for indeterminate awareness, p = 0.047), more time below range (10.3 ± 4.9% vs 6.3 ± 5.1 and 6.3 ± 4.8; p = 0.009) and higher mean duration of hypoglycemia (131.7 ± 38.6 vs 116.6 ± 49.6 and 131.7 ± 38.6; p = 0.008). In multivariate analysis, mean duration of hypoglycemia was an independent predictor of CQ results. In a receiver operating curve (AUC 0.746; p = 0.004) a mean duration of hypoglycemia ≥106.5 min showed 84.6% sensitivity/64.4% specificity for unawareness.ConclusionsOur sample had a significative prevalence of hypoglycemia unawareness which increased with longer diabetes duration. iCGM data can be indicative of this problem, with a mean hypoglycemia duration ≥106.5 min being suggestive, albeit unspecific.     

Evaluating the impact of Ramadan fasting on ambulatory glucose profile among patients with type 1 diabetes using Flash Glucose Monitoring System: A comparative study

Background and aimsEvaluating the impact of Ramadan fasting on Ambulatory Glucose Profile (AGP) among Patients with Type 1 Diabetes (T1D) using Flash Glucose Monitoring (FGM) System.MethodsThe present study is a comparative study, performed using 87 patients with T1D, whose health status permitted them to fast, based on the risk stratification adopted by Diabetes and Ramadan (DAR Guidelines). Besides the demographic data, other data connected with the glycemic profile such as the mean Time in Range (TIR), mean Time Above Range (TAR), mean Time Below Range (TBR), mean glucose level, hemoglobin A1c (HbA1c), Glucose Variability (GV), and Glucose Monitoring Indicator (GMI %), were recorded at three specific periods, namely, pre- (prior to), during and post Ramadan.ResultsThe mean age of the study population was 21.3 ± 8.2 years, and 52.9% of this population was female. Compared to the pre-Ramadan data, no significant alterations (p > 0.05) were noted in terms of the low glucose events, percentage of glucose level below 70 mg/dL, the average duration of hypoglycemic events, and percentage of glucose level below 54 mg/dL, from the values observed during and post-Ramadan. In comparison with the pre-Ramadan data, no significant changes appeared (p > 0.05) concerning the GV, average glucose, GMI, percentage within target, TAR (181–250 mg/dL), and percentage >250 mg/dL), for the periods during and post-Ramadan, except scanning of FreeStyle Libre (p = 0.042) during Ramadan month compared to pre-Ramadan.ConclusionFasting during Ramadan was achievable in patients with T1D who received adequate counseling and support.