Insulin-treated Diabetes Research Articles

Insulin Therapy is Associated With Increased Myocardial Interstitial Fibrosis and Cardiomyocyte Apoptosis in a Rodent Model of Experimental Diabetes.

The incidence of diabetes mellitus (DM) is rising. DM is a risk factor for developing left ventricular (LV) dysfunction and adverse cardiovascular outcomes. Insulin, commonly used to treat DM, is associated with further worsening of such outcomes. Yet, the pathophysiology of the adverse properties of insulin on the heart remains poorly defined. Therefore, the objective of this study was to determine the biological effects of insulin on the heart in DM, which we tested in vivo in a diabetic rat model and in vitro on human cardiomyocytes and fibroblasts. Male Wistar rats were divided into 3 groups: controls (n = 17), untreated diabetics (UDM, n = 15), and insulin-treated diabetics (IDM, n = 9). Diabetes was induced with Streptozotocin. Insulin pumps in IDM and saline pumps in UDM and controls were implanted for 4 weeks before tissue collection. Separately, cultures of human cardiomyocytes (AC16) and human cardiac fibroblasts (HCF) were treated with insulin to assess apoptosis and fibrosis, respectively. In rats, insulin partially rescued the DM-associated weight loss while fully restoring euglycemia. However, IDM had 2 × the rate of LV fibrosis (p < 0.0001) compared to UDM, and triple the rate of cardiomyocyte apoptosis compared to controls (p < 0.05). Similarly, in vitro, insulin triggered apoptosis in a dose-dependent fashion in AC16 cells, and it increased fibrosis and upregulated SMAD2 in HCF to levels comparable to Transforming Growth Factor Beta 1. Therefore, we conclude that insulin therapy is associated with increased cardiomyocyte apoptosis and myocardial interstitial fibrosis. Longer studies are needed to explore the long-term effects of insulin on cardiac structure and function.

A telemedicine-based approach with real-time transmission of blood glucose data improves metabolic control in insulin-treated diabetes: the DIAMONDS randomized clinical trial

PurposeTo evaluate if a web-based telemedicine system (the Glucoonline® system) is effective to improve glucose control in insulin-treated patients with type 1 and type 2 diabetes, as compared to standard of care.MethodsThis was a prospective, randomized, controlled trial, carried out at three tertiary referral centers for diabetes in Italy. Adults with insulin-treated type 1 and type 2 diabetes, inadequate glycemic control, and no severe diabetes-related complications and/or comorbidities were eligible for this study. Patients were randomized to either perform telemedicine-assisted (Group A) or standard (Group B) self-monitoring blood glucose (SMBG) for 6 months. In Group A, patients received prompt feedback about their blood glucose levels and therapy suggestions from the study staff via phone/SMS, when appropriate. In Group B, patients had no remote assistance from the study staff between planned visits.Results123 patients were included in the final analysis. After 6 months, patients achieved a significant reduction in HbA1c in Group A (−0.38%, p < 0.05) but not in Group B (+ 0.08%, p = 0.53). A significant difference in the percentage of patients with HbA1c < 7% between Group A and Group B was found after 3 months (28.6% vs 11.1%, p = 0.02). Also, fewer patients (p < 0.05) with HbA1c > 8.5% were found in Group A vs Group B, respectively, after both 3 months (14.3% vs 35.2%) and 6 months (21.8% vs 42.9%).ConclusionsThe use of the Glucoonline™ system resulted in improved metabolic control. Telemedicine services have potential to support diabetes self-management and provide the patients with remote, prompt assistance using affordable technological equipment.Trial registration This study was registered at clinicaltrials.gov (NCT01804803) on March 5, 2013.

Percutaneous coronary intervention in insulin-treated diabetic patients: A meta-analysis.

BackgroundThis meta‐analysis of randomized controlled trials (RCTs) compared long‐term adverse clinical outcomes of percutaneous coronary intervention (PCI) in insulin‐treated diabetes mellitus (ITDM) and non‐ITDM patients.MethodsThis is a meta‐analysis study. The PubMed and Embase databases were searched for articles on long‐term adverse clinical outcomes of PCI in ITDM and non‐ITDM patients. The risk ratios (RR) and 95% confidence intervals (CI) were calculated.ResultsA total of 11 related RCTs involving 8853 DM patients were included. Compared with non‐ITDM patients, ITDM patients had significantly higher all‐cause mortality (ACM) (RR = 1.52, 95% CI: 1.25–1.85, p heterogeneity = .689, I 2 = 0%), major adverse cardiac and cerebrovascular events (MACCE) (RR = 1.35, 95% CI: 1.18–1.55, p heterogeneity = .57, I 2 = 0%), myocardial infarction (MI) (RR = 1.41, 95% CI: 1.16–1.72, p heterogeneity = .962, I 2 = 0%), and stent thrombosis (ST) (RR = 1.75, 95% CI: 1.23–2.48, p heterogeneity = .159, I 2 = 32.4%). No significant difference was found in the target lesion revascularization (TLR) and target vessel revascularization (TVR) between the ITDM and non‐ITDM groups.ConclusionsThe results showed that ITDM patients had significantly higher ACM, MACCE, MI, and ST, compared with non‐ITDM patients.

Previously unrecognized risk factors for severe hypoglycaemia requiring emergency medical care in insulin-treated type 2 diabetes: Results from a real-world nested case-control study.

AimSeveral risk factors for severe hypoglycaemia (SH) are associated with insulin‐treated diabetes. This study explored potential risk factors in adults with insulin‐treated type 2 diabetes mellitus (T2DM).Materials and MethodsIn this case‐control study, adults with T2DM initiating insulin were identified in the IQVIA PharMetrics® Plus database. The index date was the date of the first SH event (cases). Using incidence‐density sampling, controls were selected from those who had been exposed ‘at risk’ of SH for the same amount of time as each case. After exact‐matching on the well‐established factors, previously unreported risk factors were evaluated through conditional logistic regression.ResultsIn 3153 case‐control pairs, pregnancy [odds ratios (OR) = 3.20, p = .0003], alcohol abuse (OR = 2.43, p < .0001), short‐/rapid‐acting insulin (OR = 2.22/1.47, p < .0001), cancer (OR = 1.87, p < .0001), dementia/Alzheimer′s disease (OR = 1.73, p = .0175), peripheral vascular disease (OR = 1.59, p < .0001), antipsychotics (OR = 1.59; p = .0059), anxiolytics (OR = 1.51, p = .0012), paralysis/hemiplegia/paraplegia (OR = 1.51, p = .0416), hepatitis (OR = 1.50, p = .0303), congestive heart failure (OR = 1.47, p = .0002), adrenergic‐corticosteroid combinations (OR = 1.45, p = .0165), β‐adrenoceptor agonists (OR = 1.40, p = .0225), opioids (OR = 1.38, p < .0001), corticosteroids (OR = 1.35, p = .0159), cardiac arrhythmia (OR = 1.29. p = .0065), smoking (OR = 1.28, p = .005), Charlson Comorbidity Index score 2 (OR = 1.28, p = .0026), 3 (OR = 1.41, p = .0016) or ≥4 (OR = 1.57, p = .0002), liver/gallbladder/pancreatic disease (OR = 1.26, p = .0182) and hypertension (OR = 1.19, p = .0164) were independently associated with SH.ConclusionsAlthough all people with insulin‐treated diabetes are at risk of SH, these results have identified some previously unrecognized risk factors and sub‐groups of insulin‐treated adults with T2DM at greater risk. Scrutiny of current therapies and comorbidities are advised as well as additional glucose monitoring and education, when identifying and managing SH in vulnerable populations.

Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study.

Association of maternal polycystic ovary syndrome and diabetes with preterm birth and offspring birth size: a population-based cohort study.

Cost of Severe Hypoglycemia and Budget Impact with Nasal Glucagon in Patients with Diabetes in Spain.

IntroductionSevere hypoglycemic events (SHE) represent a clinical and economic burden in patients with diabetes. Nasal glucagon (NG) is a novel treatment for SHEs with similar efficacy, but with a usability advantage over injectable glucagon (IG) that may translate to improved economic outcomes. The economic implications of this usability advantage on SHE-related spending in Spain were explored in this analysis.MethodsA cost-offset and budget impact analysis (BIA) was conducted using a decision tree model, adapted for the Spanish setting. The model calculated average costs per SHE over the SHE treatment pathway following a treatment attempt with IG or NG. Analyses were performed separately in three populations with insulin-treated diabetes: children and adolescents (4–17 years) with type 1 diabetes (T1D), adults with T1D and adults with type 2 diabetes (T2D), with respective population estimates applied in BIA. Treatment probabilities were assumed to be equal for IG and NG, except for treatment success following glucagon administration. Epidemiologic and cost data were obtained from Spanish-specific sources. BIA results were presented at a 3-year time horizon.ResultsOn a per SHE level, NG was associated with lower costs compared to IG (children and adolescents with T1D, EUR 820; adults with T1D, EUR 804; adults with T2D, EUR 725). Lower costs were attributed to reduced costs of professional medical assistance in patients treated with NG. After 3 years, BIA showed that relative to IG, the introduction of NG was projected to reduce SHE-related spending by EUR 1,158,969, EUR 142,162,371, and EUR 6,542,585 in children and adolescents with T1D, adults with T1D, and adults with insulin-treated T2D, respectively.ConclusionsIn Spain, the usability advantage of NG over IG translates to potential cost savings per SHE in three populations with insulin-treated diabetes, and the introduction of NG was associated with a lower budget impact versus IG in each group.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01238-8.

Driving with Type 1 Diabetes: Real-World Evidence to Support Starting Glucose Level and Frequency of Monitoring During Journeys.

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n = 436). Thirteen drivers recorded at least one trip (total n = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

Protein Intake Among Patients with Insulin-Treated Diabetes is Linked to Poor Glycemic Control: Findings of NHANES Data.

BackgroundNutrition therapy is considered a key component of diabetes management. Recently, high-protein diets have gained in popularity. Understanding the glycemic effect of dietary protein among patients with diabetes has been of particular interest.MethodsThis study is based on NHANES data of 990 participants aged 40 years and older from the NHANES cohorts of 2011–2012 and 2013–2014 surveys. Glycosylated hemoglobin (HbA1c level) was used as indicator of glycemic control. Patients were categorized into quartiles for daily protein intake. Average protein intakes for patients in quartile 1 to quartile 4 were 35.5 g, 58.7 g, 79.9 g, and 131.6 g, respectively. Covariates included in the analysis were gender, age, race, caloric intake, muscle strength, education, income, smoking, sedentary lifestyle, alcohol consumption, and BMI.ResultsAfter controlling for covariates, patients in quartile 4 of protein intake had 261% increased risk of poor glycemic control compared with those in quartile 1 (95% CI: 1.29–5.30). The association was not attenuated after further control for insulin use (OR = 1.94; 95% CI: 0.89–4.24). In conclusion, higher protein intake seems related to a worse glycemic control in diabetic subjects.

Impact of COVID-19-Related Lockdown on Delivery and Perinatal Outcomes: A Retrospective Cohort Study.

Objective: The magnitude and direction of effects on pregnancy outcomes of the lockdown imposed during COVID-19 have been uncertain and debated. Therefore, we aimed to quantify delivery and perinatal outcomes during the first nationwide lockdown due to the COVID-19 pandemic compared with the same durations of time for the pre- and post-lockdown periods. Study design: This was a retrospective cohort study of six university hospital maternity units distributed across France, each of which serves as the obstetric care referral unit within its respective perinatal network. Maternal and perinatal outcomes were compared between the lockdown period and same-duration (i.e., 55-day) periods before and after the 2020 lockdown (pre-lockdown: 22 January–16 March; lockdown: 17 March–10 May; post-lockdown: 11 May–4 July). We compared the overall rates of Caesarean delivery (CD), pre-labor CD, labor induction, operative vaginal delivery, severe postpartum hemorrhage (≥1 L), severe perineal tear, maternal transfusion, and neonatal mortality and morbidity (1- and 5-min Apgar scores < 7), hypoxia and anoxia (umbilical arterial pH < 7.20 or <7.10, respectively), and admission to a neonatal intensive care unit before discharge. Adjusted odds ratios were estimated using logistic regression, controlling for region of birth, maternal age category, multiparity, multiple pregnancies, diabetes, and hypertensive disorders. Results: The study sample consisted of 11,929 women who delivered consecutively at one of the six maternity units studied (4093 pre-lockdown, 3829 during lockdown, and 4007 post-lockdown) and their 12,179 neonates (4169 pre-lockdown, 3905 during lockdown, and 4105 post-lockdown). The maternal and obstetric characteristics of the women delivering during the lockdown period were alike those delivering pre- and post-lockdown on maternal age, parity, body mass index, rate of complication by hypertensive disorders or insulin-treated diabetes, and gestational age at delivery. Overall CD rates were similar during the three periods (23.6%, 24.8%, and 24.3% pre-lockdown, lockdown, and post-lockdown, respectively) and no outcome differed significantly during lockdown compared to pre- and post-lockdown. These findings were consistent across maternity units. Conclusion: The maternal and perinatal outcomes are reassuring regarding the performance of the health-care system during the COVID-19 lockdown studied. Such information is crucial, because additional COVID-19-related lockdowns might still be needed. They are also instructive regarding potential future pandemics.

Short- and long-term cardiovascular outcomes in insulin-treated versus non-insulin-treated diabetes mellitus patients after percutaneous coronary intervention: A systematic review and meta-analysis

AimsThis study aims to assess differences in severity of short-term (<1 year) and long-term (≥1 year) adverse CV outcomes after PCI in insulin-treated vs. non-insulin-treated diabetes mellitus (DM) patients. MethodsA systematic search on Pubmed and Embase led to the incorporation of 29 studies that compared post-percutaneous coronary interventional outcomes in insulin-treated and non-insulin-treated diabetes mellitus. Diabetes mellitus (type 2) was defined as fasting blood glucose (FBG) level of >7.0 mmol/L or with an oral glucose tolerance test (OGTT) level of >11.1 mmol/L at least on two separate occasions. Adverse CV outcomes were assessed in insulin-treated and non-insulin-treated DM after the PCI procedure considered for the analyses were mortality, MACE, TLR, TVR, MI, stent thrombosis, target lesion failure (TLF), and need for-post PCI CABG. Data were pooled and analyzed using Review Manager 5.3, and risk ratios (RR) with respective 95% confidence intervals (CI) were calculated.The statistical analyses were carried out by Review Manager v.5.3, and the data were pooled using a random-effects model. Risk ratios (RRs) with 95% confidence intervals (CI) were reported along with forest plots. The chi-square test was performed to assess for differences between the subgroups. Heterogeneity across studies was evaluated using Higgins I2 statistics. Visual inspection of the funnel plot and Begg's regression test were used to assess publication bias. ResultsA total of 40,527 patients (11742 in the Insulin-treated diabetes mellitus group and 28785 in the non-insulin-treated DM group) who underwent PCI were included. The pooled analysis of short-term follow up outcomes preceding PCI demonstrated a significantly higher risk of mortality (RR = 1.75 [1.24,2.47]; p = 0.002), MI (RR = 1.81[1.14,2.87]; p = 0.01], stent thrombosis (RR = 1.63[1.13, 2.35]; p = 0.009) and target lesion revascularization (TLR) (RR = 1.29[1.02,1.63]; p = 0.03) in insulin-treated DM patients. Similarly, analysis of long-term follow-up studies depicted a significantly higher risk mortality (RR = 1.55 [1.22, 1.97]; p = 0.0003), MI (RR = 1.63 [1.35, 1.97]; p=<0.00001), MACE (R = 1.47 [1.31, 1.65]; p=<0.00001), stent thrombosis (RR = 1.54 [1.19,1.99]; p = 0.001), TLR (RR = 1.40 [1.18, 1.66]; p = 0.0001), target vessel revascularization (TVR) (RR = 1.35 [1.11, 1.64]; p = 0.003) in insulin-treated DM group after PCI versus non-insulin-treated DM patients. ConclusionDespite a tremendous technical success rate of multi-vessel stenting, people living with diabetes who were being treated with insulin had higher long-term, and short-term mortality rates, MI, TLR, TVR, and stroke compared to people living with diabetes who were being treated with means other than insulin and are more prone to detrimental cardiovascular outcomes.

Prognostic value of coronary risk factors, exercise capacity and single photon emission computed tomography in liver transplantation candidates: A 5-year follow-up study

BackgroundAlthough consensus-based guidelines support noninvasive stress testing prior to orthotopic liver transplantation (OLT), the optimal screening strategy for assessment of coronary artery disease in patients with end-stage liver disease (ESLD) is unclear. This study sought to determine the relative predictive value of coronary risk factors, functional capacity, and single photon emission computed tomography (SPECT) on major adverse cardiovascular events and all-cause mortality in liver transplantation candidates. MethodsPrior to listing for transplantation, 404 consecutive ESLD patients were referred to a University hospital for cardiovascular (CV) risk stratification. All subjects met at least one of the following criteria: inability to perform > 4 METs by history (62%), insulin-treated diabetes mellitus (53%), serum creatinine > 1.72 mg/dL (8%), history of MI, PCI or CABG (5%), stable angina (3%), cerebrovascular disease (1%), peripheral vascular disease (1%). Subjects underwent Technetium-99m SPECT with multislice coronary artery calcium scoring (CACS) using exercise treadmill or standard adenosine stress in those unable to achieve 85% maximal heart rate (Siemens Symbia T16). Abnormal perfusion was defined as a summed stress score (SSS) ≥ 4. ResultsOf the 404 patients, 158 (age 59 ± 9 years; male 68%) subsequently underwent transplantation and were included in the primary analysis. Of those, 50 (32%) died after a mean duration follow-up of 5.4 years (maximal 10.9 years). Most deaths (78%) were attributed to noncardiovascular causes (malignancy, sepsis, renal failure). Of the 32 subjects with abnormal perfusion (20%), nine (6%) had a high-risk perfusion abnormality defined as a total perfusion defect size (PDS) ≥ 15% and/or an ischemic PDS ≥ 10%. Kaplan–Meier survival curves demonstrated abnormal perfusion was associated with increased CV mortality (generalized Wilcoxon, P = 0.014) but not all-cause death. Subjects with both abnormal perfusion and an inability to exercise > 4 METs had the lowest survival from all-cause death (P = 0.038). Abnormal perfusion was a strong independent predictor of CV death (adjusted HR 4.2; 95% CI 1.4 to 12.3; P = 0.019) and MACE (adjusted HR 7.7; 95% CI 1.4 to 42.4; P = 0.018) in a multivariate Cox regression model that included age, sex, diabetes, smoking and the ability to exercise > 4 METs. There was no association between CACS and the extent of perfusion abnormality, nor with outcomes. ConclusionsMost deaths following OLT are noncardiovascular. Nonetheless, abnormal perfusion is prevalent in this high-risk population and a stronger predictor of cardiovascular morbidity and mortality than functional status. A combined assessment of functional status and myocardial perfusion identifies those at highest risk of all-cause death. (Exercise Capacity and Single Photon Emission Computed Tomography in Liver Transplantation Candidates [ExSPECT]; ClinicalTrials.gov Identifier: NCT03864497).

Work and diabetes

Work and diabetes

Missed and Mistimed Insulin Doses in People with Diabetes: A Systematic Literature Review.

Background: Development of coordinated management approaches is important to facilitate self-care in people with diabetes (PwD). Gaining a better understanding of suboptimal insulin use is key in this endeavor. This review aimed, for the first time, to systematically identify and narratively summarize real-world evidence on the extent of suboptimal insulin use (missed and mistimed insulin) in PwD. Methods: A systematic literature search of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews identified studies reporting on missed and mistimed insulin dosing. Results: From 3305 studies, 37 publications reporting on 30 unique studies that involved 58,617 PwD were included. Studies were conducted across 12 different countries and most employed cross-sectional surveys. Observations regarding missed and mistimed insulin doses were reported in 25 and 10 studies, respectively. PwD reported missing insulin doses, but rates varied due to differences in reporting methods, participant populations, and insulin regimens. The association between missed dosing and glycemic control was evaluated in ten studies in which the authors reported lower glycated hemoglobin (HbA1c) levels in PwD who did not omit insulin. The proportion of PwD reporting mistiming of insulin was in the range of 20-45%, depending on the study; this was associated with higher rates of hypoglycemia and higher HbA1c as reported by study authors. Reasons for suboptimal insulin use were multifactorial, occurring due to disrupted daily routines, social situations, and hypoglycemia avoidance. Conclusions: This review suggests that suboptimal insulin use is widespread and that PwD using insulin may still be struggling with disease management. There is an unmet need for better integrated support in managing the complexities of insulin therapy and for the development of systems (e.g. digital solutions) that empower people to take control of insulin-treated diabetes.

Associations between metabolic syndrome at index PCI and 1-year outcomes

Abstract Background The prevalence of obesity, diabetes and metabolic syndrome is rising, with negative health consequences for the community. Purpose We sought to examine the prevalence and impact of metabolic syndrome (MetS) on 1-year outcomes from an Australian cohort of all-comer PCI patients. Methods We retrospectively analysed the GenesisCare Outcomes multicentre Registry of prospectively collected data in patients undergoing PCI from 2008–2020. Metabolic syndrome was defined as presence of any 3 features including hypertension, diabetes, obesity with body mass index ≥30 kg/m2 and dyslipidaemia. We examined 1-year outcomes for death and MACE (death, MI or TLR), and the adjusted risk after accounting for each of the defining variables. Results During the study period from 2005–2018, 14,405 were included, of which 5480 (38%) had metabolic syndrome. MetS patients were somewhat younger without sex differences (∼76% men). They had greater prevalence of defining characteristics, and smoking and lower prevalence of myocardial infarction presentation compared to non-MetS patients. MetS patients had higher prevalence of B2/C type lesions, restenosis, chronic total occlusions and multivessel disease. At 30-days MetS patients had lower risk of re-infarction (0.1% vs. 0.3%, p=0.011) but from 30-days to 1-year they had greater risk of MI (1.1% vs. 0.5%, p&amp;lt;0.01), TLR (1.5% vs. 1.1%, p=0.03), readmissions (21.8% vs. 19.8%, p=0.008) and MACE (3.6% vs. 2.7%, p=0.03) without differences in mortality (1.3% in both, p=0.88). Unadjusted models showed trend for greater risk of 1-year MACE with MetS, HR 1.15 (95% CI 1.00–1.33), p=0.054. In multivariable models, this risk was lost after adjusting individually for hypertension, dyslipidaemia and insulin-treated diabetes, but not after adjustment for obesity and non-insulin diabetes (See Figure). Conclusions Metabolic syndrome was noted in over one-third of all-comer PCI patients, and was associated with greater risk of 1-year MACE. This risk appeared to be related to hypertension, dyslipidaemia and insulin-treated diabetes but not obesity. Funding Acknowledgement Type of funding sources: None.

A risk predictive model for coronary perforation in patients undergoing percutaneous coronary intervention – APOLLO-XI score

Abstract Background Coronary perforation (CP) is a rare but potentially life-threatening complication of percutaneous coronary intervention (PCI). Although several variables are associated with the risk of coronary perforation, a cumulative risk predictive model has not been established yet. Purpose To assess an incidence, risk factors and to develop risk predictive model for coronary perforation following PCI. Methods A single center, retrospective study of patients who underwent PCI from March 2010 to December 2019. Multivariate regression analysis was performed to identify independent predictors of CP. A risk predictive model was constructed with incremental weights attributed to each component variable according to their beta coefficients. Results 10,671 PCI procedures were enrolled. The incidence of CP was 0.94%. Adverse in-hospital outcomes were significant higher in CP group, including death (odds ratio [OR]: 3.58), mechanical circulatory support; including IABP and ECMO (OR: 3.79) and urgent revascularization (OR: 7.35). Multivariable analysis identified seven independent risk factors for CP, which were age (OR: 1.02), insulin-treated diabetes (OR: 2.50), prior CABG (OR: 2.03), hydrophilic guidewire (OR: 1.62), rotational atherectomy (OR: 2.60), excimer laser coronary atherectomy (ELCA) (OR: 3.39) and chronic total occlusion PCI (OR: 4.21). Risk predictive model (APOLLO-XI score) was calculated from the total points of each variables as follows: age (1 point per 10-year increase), hydrophilic guidewire (2 points), prior CABG (3 points), insulin-treated diabetes or rotational atherectomy (4 points), ELCA (5 points) and chronic total occlusion PCI (6 points). Cumulative risk score more than 11 points had increased risk for coronary perforation more than 1%. The validation of the risk predictive model (C-statistic) was 0.75 (95% CI: 0.70–0.80). Conclusions Coronary perforation is a rare but lethal complication. Our study demonstrates the risk predictive model which could enhance cardiovascular team to precisely estimate risk of coronary perforation before complex PCI procedure. Funding Acknowledgement Type of funding sources: None. Baseline charecteristicsAPOLLO-XI score

Conversations and Reactions Around Severe Hypoglycaemia (CRASH): Spanish results of a global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers

IntroductionInformation on experience/management of severe hypoglycaemic events (SHEs) among people with insulin-treated diabetes (PWD) and caregivers (CGs) providing care to PWD was sought. Materials and methodsAn online cross-sectional survey was conducted in eight countries. Inclusion criteria: PWD (aged≥18 years; self-reported type 1 [T1D] or insulin-treated type 2 [T2D] diabetes; experienced ≥1 SHE [hypoglycaemia requiring external assistance] in past 3 years); CGs (layperson aged ≥18 years; caring for PWD meeting all criteria above except age [≥4 years]). This descriptive analysis provides data from Spain. SHE-associated data relate to the most recent SHE. ResultsAcross all groups (T1D PWD, n=106; T2D PWD, n=88, T1D CG, n=87; T2D CG, n=96), 76–89% reported that the SHE occurred at home; most common cause was eating less than planned (38–53%). Most usual action during the SHE was to intake carbohydrates (67–84%); glucagon use was low (9–36%). Discussion of the SHE with their healthcare provider (HCP) was reported by 70–75% of PWD. During the SHE, 35–69% of PWD/CGs reported feeling scared, unprepared and/or helpless. ConclusionsMost SHEs occurred outside the healthcare setting; treatment therefore depends greatly on CGs. SHEs have a negative emotional impact on PWD/CGs, underscoring the need for HCPs to discuss SHEs with PWD/CGs, and to provide tools and strategies to prevent and effectively manage SHEs.

Predictors and mid-term outcomes of nosocomial infection in ST-elevation myocardial infarction patients treated by primary angioplasty.

Nosocomial infections (NI) are associated with high morbidity and mortality. Existing data on the impact of NI on patients with ST-elevation myocardial infarction (STEMI) is scarce. Our aim was to determine the incidence, predictors, and prognosis of NI in a contemporary series of STEMI patients. 1131 consecutive STEMI patients treated by primary percutaneous coronary intervention from January 2008 to December 2017 were analyzed. Binary logistic regression and Cox proportional hazard models were used to identify predictors of NI and major adverse cardio-cerebrovascular events (MACCE) at 1-year follow-up, respectively. Of all patients, 126 (11.1%) were diagnosed with NI (>48 hours from admission), mostly of respiratory (50.8%) and urinary (39.7%) tract origin. Insulin-treated diabetics were 3-fold more likely to develop NI. Other independent predictors were peripheral arterial disease, intra-aortic balloon pump insertion, age, lower systolic blood pressure, and higher peak creatine-kinase. Only pre-infarction angina was negatively related to NI. Age, peripheral arterial disease, femoral approach and larger infarct were related to MACCE at 1-year follow-up. NI in isolation was not independently related to MACCE (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.80-1.94; P = 0.34). However, we found a significant interaction between NI and smoking (HR, 2.33; 95% CI, 1.03-5.24; Pinterc = 0.04). Larger infarct size, hemodynamic instability, and co-morbidities were related to both NI and 1-year adverse events. Smokers who developed NI also had a higher 1-year risk of MACCE.

Greater plaque burden and cholesterol content may explain an increased incidence of non-culprit events in diabetic patients: a Lipid-Rich Plaque substudy.

Diabetes mellitus (DM) is associated with increased cardiovascular morbidity and mortality. The multicentre, prospective Lipid-Rich Plaque trial (LRP) examined non-culprit (NC) non-obstructive coronary segments with a combined near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) catheter. This study assessed the differences in NC plaque characteristics and their influence on major adverse cardiac events (MACE) in diabetic and non-diabetic patients. Patients with known DM status were divided into no diabetes, diabetes not treated with insulin (non-ITDM), and insulin-treated diabetes (ITDM). The association between presence and type of DM and NC-MACE was assessed at both the patient and coronary segment levels by Cox proportional regression modelling. Out of 1552 patients enrolled, 1266 who had their diabetes status recorded were followed through 24 months. Female sex, hypertension, chronic kidney disease, peripheral vascular disease, and high body mass index were significantly more frequent in diabetic patients. The ITDM group had more diseased vessels, at least one NC segment with a maxLCBI4 mm ≥400 in 46.2% of patients, and maxLCBI4 mm ≥400 in nearly one out of six Ware segments (15.2%, 125/824 segments). The average maxLCBI4 mm significantly increased from non-diabetic patients (NoDM) to non-insulin-treated diabetic patients (non-ITDM) to insulin-treated diabetic patients (ITDM; 137.7 ± 161.9, 154.8 ± 173.6, 182.9 ± 193.2, P < 0.001, respectively). In patients assigned to follow-up (692 ± 129 days), ITDM doubled the incidence of NC-MACE compared with the absence of diabetes (15.7% vs. 6.9%, P = 0.0008). The presence of maxLCBI4 mm>400 further increased the NC-MACE rate to 21.6% (Kaplan-Meier estimate). Cholesterol-rich NC plaques detected by NIRS-IVUS were significantly more frequent in diabetic patients, especially those who were insulin-treated, and were associated with an increased NC-MACE during follow-up.

Increased mortality in very old patients treated by continuous subcutaneous insulin infusion (CSII)

To compare glycemic control, safety and health burden in ambulatory elderly patients with diabetes treated by continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). Adults ( n = 68) > 75 years of age (mean age 80 ± 4) with insulin-treated diabetes (mean duration 31 ± 13 years, BMI 27 ± 6 kg/m 2 and HbA1 C 9.0 ± 1.6%) treated by CSII or MDI were recruited in a systematic retrospective study. Efficacy was assessed with composite criteria : adjusted for frailty HbA1 C target without occurrence of severe or frequent hypoglycemia. Safety was assessed by frequency of severe hypoglycemia, diabetes ketoacidosis, major cardiovascular events or death. Health burden was considered through hospitalization duration per year. Thirty CSII subjects and 38 MDI subjects were analyzed. The most frequent reason to initiate CSII was mostly instable blood glucose control in TD1 whereas it was insufficient blood glucose control in TD2. A lower HbA1 C was decreased in both groups (7.7 ± 0.9% vs. 7.8 ± 1.1% CSII vs. MDI). Number of severe hypoglycemia, diabetic ketoacidosis and patient's hospitalizations for uncontrolled diabetes/year were similar in both group ns. More deaths occurred in the CSII group than in the MDI group (9 vs. 2, OR adjusted 0.118 IC [0.017–0.520], P 0.011). In very elderly patients with insulin-treated diabetes both CSII and MDI achieved optimal glycemic control. However, more deaths occurred in the CSII group. The improvement in blood control obtained by CSII does not compensate the increased frailty in these patients.

Outcomes of Participants With Diabetes in the ISCHEMIA Trials.

Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.