Non-albicans Candida Infection as a Rare Cause of Emphysematous Pyelonephritis in an Uncontrolled Diabetic Patient: A Case Report.

The uncommon but dangerous condition known as emphysematous pyelonephritis (EPN) usually affects people with diabetes. This potentially fatal illness is characterized by gas-forming necrosis of the kidneys and surrounding tissues, typically brought on by urinary tract bacteria. Fungal EPN, less prevalent than bacterial EPN, has been reported in a few isolated cases. Cultures of the urine or blood often detect the infection. With an 18% fatality rate, EPN is still a serious illness despite advancements in therapy. High suspicion for EPN is critical in diabetic patients experiencing pyelonephritis. Interestingly, women with uncontrolled diabetes seem to be more susceptible. While Escherichia coli is the usual culprit, rare cases involve Candida species. This case report describes a pathogen that is rarely encountered and causes EPN. A diabetic woman in her sixties without prior hospitalizations presented with a sudden fever and excruciating abdominal pain. The patient also complained of abdominal distension with reduced urine output and breathlessness at rest. Investigations revealed left-sided EPN that was "WAN Type 1." We treated the patient according to culture sensitivity with systemic antifungals, percutaneous nephrostomy (PCN), and ureteral stenting (double J stent or DJ stent). Following successful treatment, the patient recovered and was discharged. This case highlights the importance of considering uncommon causes, even in seemingly typical presentations of EPN. Our case is unique as the patient had an infection with non-albicans Candida with a complication of anuric acute kidney injury and uncontrolled diabetes mellitus.

Role of Insulin Use and Social Determinants of Health on Non-melanoma Skin Cancer: Results From the Behavioral Risk Factor Surveillance System.

BACKGROUND: Non-melanoma skin cancer (NMSC) is a frequent type of malignancy with a steadily increasing incidence rate worldwide. Although NMSC was shown to be associated with diabetes, no studies have addressed the extent to which insulin use influences the risk of NMSC in light of social determinants of health (SDOH). We conducted a quantitative study that examined the interplay between insulin use, SDOH, additional covariates, and NMSC among individuals with diabetes. METHODS: We based our analysis on the 2020 Behavioral Risk Factor Surveillance System (BRFSS), a national survey conducted yearly in the US. We performed weighted chi-squared test, logistic regression, and survival analyses on 8685 eligible participants with diabetes enrolled in the BRFSS. RESULTS: Kaplan Meier survival curves showed higher probability of NMSC event-free survival for participants with diabetes using insulin compared to participants with diabetes not using insulin (log-rank test P < .001). Significant associations were detected between insulin use and reduced odds of NMSC (OR .56; 95% CI: .38-.82), and decreased hazard (HR .36; 95% CI: .21-.62), along with indices of SDOH. CONCLUSIONS: Our findings suggest that socioeconomic differences related to the healthcare system and behavioral patterns are linked to discrepancies in the use of insulin and the development of NMSC.

Insulin Use and The Risk of Hepatocellular Carcinoma: Insights and Implications.

In recent years, the incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide, in the context of an increasing prevalence of non-alcoholic fatty liver disease (NAFLD). In patients with diabetes mellitus, exogenous insulin is commonly prescribed and used in long-term settings. Recent studies suggest that insulin use may elevate the risk of HCC. A substantial body of work seeks to unpack the association between insulin use and the risk of developing HCC, although there may be conflicting evidence. Further validation is necessary to clarify the true relationship between insulin mechanisms and its hepatocarcinogenic effect. Given the burden of diabetic patients developing HCC, diabetologists and hepatologists must collaborate, particularly regarding the prevention and surveillance of HCC in diabetic patients.

Insulin Use During Gestational and Pre-existing Diabetes in Pregnancy: A Systematic Review of Study Design.

INTRODUCTION: Insulin is the first-line pharmacologic therapy for women with diabetes in pregnancy. However, conducting well-designed randomized clinical trials (RCTs) and achieving recommended glycemic targets remains a challenge for this unique population. This systematic literature review (SLR) aimed to understand the evidence for insulin use in pregnancy and the outcome metrics most often used to characterize its effect on glycemic, maternal and fetal outcomes in gestational diabetes mellitus (GDM) and in pregnant women with diabetes. METHODS: An SLR was conducted using electronic databases in Medline, EMBASE via Ovid platform, evidence-based medicine reviews (2010-2020) and conference proceedings (2018-2019). Studies were included if they assessed the effect of insulin treatment on glycemic, maternal or fetal outcomes in women with diabetes in pregnancy. Studies on any type of diabetes other than gestational or pre-existing diabetes as well as non-human studies were excluded. RESULTS: In women diagnosed with GDM or pre-existing diabetes, most studies compared treatment of insulin with metformin (n = 35) followed by diet along with lifestyle intervention (n = 24) and glibenclamide (n = 12). Most studies reporting on glycemic outcomes compared insulin with metformin (n = 22) and glibenclamide (n = 4). Fasting blood glucose was the most reported clinical outcome of interest. Among the studies reporting maternal outcomes, method of delivery and delivery complications were most commonly reported. Large for gestational age, stillbirth and perinatal mortality were the most common fetal outcomes reported. CONCLUSION: This SLR included a total of 108 clinical trials and observational studies with diverse populations and treatment arms. Outcomes varied across the studies, and a lack of consistent outcome measures to manage diabetes in pregnant women was observed. This elucidates a need for global consensus on study design and standardized clinical, maternal and fetal outcomes metrics.

Healthy lifestyle and all-cause and cause-specific dementia in individuals with type 2 diabetes and the roles of diabetes duration and insulin use in UK Biobank cohort.

AIMS: To examine the effect of a healthy lifestyle score derived from seven lifestyle factors recommended by the diabetes management guidelines on all-cause and cause-specific dementia in individuals with type 2 diabetes mellitus (T2DM), and how diabetes duration and insulin use status modify their association. MATERIALS AND METHODS: This study analysed data of 459 840 participants from the UK Biobank. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals for the association of an overall healthy lifestyle score with all-cause and cause-specific dementia of Alzheimer's disease, vascular dementia and non-Alzheimer non-vascular dementia. RESULTS: Using diabetes-free participants who scored 5-7 as the reference group, in diabetes-free participants, we observed higher healthy lifestyle score was related to lower risk of all-cause and cause-specific dementia. However, in people with T2DM, those scored 2-3, 4 and 5-7 all had around the two-time risk of all-cause dementia (HR: 2.20-2.36), while those scored 0-1 had over a three-time risk (HR: 3.14, 95% confidence interval 2.34-4.21). A dose-response trend was observed with vascular dementia (each 2-point increase: 0.75, 0.61-0.93) and no significant association with Alzheimer's disease (0.95, 0.77-1.16). The reduced risk of all-cause and cause-specific dementia with higher lifestyle score was observed in patients with a diabetes duration less than 10 years, or in patients with no insulin use. CONCLUSION: In people with T2DM, higher healthy lifestyle score was associated with lower risk of all-cause dementia. Diabetes duration and insulin use moderated the association between healthy lifestyle score and risk of dementia.

The Association Between Insulin Use and Asthma: An Epidemiological Observational Analysis and Mendelian Randomization Study.

BACKGROUND: Asthma is a common respiratory disease caused by genetic and environmental factors, but the contribution of insulin use to the risk of asthma remains unclear. This study aimed to investigate the association between insulin use and asthma in a large population-based cohort, and further explore their causal relationship by Mendelian randomization (MR) analysis. METHODS: An epidemiological study including 85,887 participants from the National Health and Nutrition Examination Survey (NHANES) 2001-2018 was performed to evaluate the association between insulin use and asthma. Based on the inverse-variance weighted approach, MR analysis were conducted to estimate the causal effect of insulin use on asthma from the UKB and FinnGen datasets, respectively. RESULTS: In the NHANES cohort, we found that insulin use was associated with an increased risk of asthma [odd ratio (OR) 1.38; 95% CI 1.16-1.64; p < 0.001]. For the MR analysis, we found a causal relationship between insulin use and a higher risk of asthma in both Finn (OR 1.10; p < 0.001) and UK Biobank cohorts (OR 1.18; p < 0.001). Meanwhile, there was no causal association between diabetes and asthma. After multivariable adjustment for diabetes in UKB cohort, the insulin use remained significantly associated with an increased risk of asthma (OR 1.17, p < 0.001). CONCLUSIONS: An association between insulin use and an increased risk of asthma was found via the real-world data from the NHANES. In addition, the current study identified a causal effect and provided a genetic evidence of insulin use and asthma. More studies are needed to elucidate the mechanisms underlying the association between insulin use and asthma.

Sex-specific associations between diabetes and dementia: the role of age at onset of disease, insulin use and complications.

BACKGROUND: Whether the association of type 2 diabetes (T2DM) with dementia was differed by sex remains unclear, and the roles of age at onset of disease, insulin use and diabetes' complications in their association are unknown. METHODS: This study analyzed data of 447 931 participants from the UK Biobank. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between T2DM and incident dementia [all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD)]. The roles of age at onset of disease, insulin use and diabetes' complications in their association were also analyzed. RESULTS: Compared to people with no diabetes at all, people with T2DM had increased risk of all-cause dementia (HR 2.85, 95% CI 2.56-3.17). The HRs between T2DM and AD were higher in women than men, with an RHR (95%CI) of 1.56 (1.20, 2.02). There was a trend that people who experienced T2DM before age 55 had higher risk of VD than those who had T2DM after age 55. In addition, there was a trend that T2DM had higher effect on VD that occurred before age 75 years than events that occurred after age 75. Patients with T2DM using insulin had higher risk of all-cause dementia than those without insulin, with an RHR (95%CI) of 1.54 (1.00-2.37). People with complications had doubled risk of all-cause dementia, AD and VD. CONCLUSIONS: Adopting a sex-sensitive strategy to address the risk of dementia in patients with T2DM is instrumental for a precision medicine approach. Meanwhile, it is warranted to consider patients' age at onset of T2DM, insulin use status and complications conditions.

Cash-Only INcentives to promote insulin DOSE engagement: A protocol paper for the pilot randomized controlled trial of COIN2DOSE.

BACKGROUND: Most adolescents with type 1 diabetes (T1D) do not achieve a glycated hemoglobin (HbA1c) <7.0%, which is the current clinical target. mHealth can offer a scalable and age-appropriate delivery method for behavioral interventions to lower adolescents' HbA1c levels, while applying established behavior change and behavioral economics theories can enhance scientific rigor. METHODS: We aim to conduct a pilot randomized clinical trial of a novel mHealth intervention called Coin2Dose (Cash-Only INcentives To promote insulin DOSE engagement), in a sample of youth with T1D: 1) to obtain measures of feasibility and acceptability and 2) to examine preliminary efficacy versus a standard care control group based on differences in youth's daily BOLUS scores, HbA1c levels, and Time in Range (TIR) at post-intervention and 3-month post-intervention follow-up. This pilot RCT is already registered in http://ClinicalTrials.gov (NCT#05280184). RESULTS: Our pilot will recruit youth with T1D 11-17 years-old who use an insulin pump or Bluetooth connected insulin pen and have an average daily BOLUS score ≤2.5. Youth randomized to Coin2Dose will receive the intervention for 12 weeks followed by a 12-week maintenance period. The pilot is scheduled to start July 2022 and to conclude in 2025. DISCUSSION: At the conclusion of the pilot, we will have information about the feasibility and acceptability of two different behavioral economic incentive structures for improving BOLUS scores. The work is anticipated to progress to final efficacy trial. We will disseminate study results through presentations at local, national, and international conferences and through peer-reviewed diabetes and psychology journals.

Insulin: evolution of insulin formulations and their application in clinical practice over 100 years.

The first preparation of insulin extracted from a pancreas and made suitable for use in humans after purification was achieved 100 years ago in Toronto, an epoch-making achievement, which has ultimately provided a life-giving treatment for millions of people worldwide. The earliest animal-derived formulations were short-acting and contained many impurities that caused adverse reactions, thereby limiting their therapeutic potential. However, since then, insulin production and purification improved with enhanced technologies, along with a full understanding of the insulin molecule structure. The availability of radio-immunoassays contributed to the unravelling of the physiology of glucose homeostasis, ultimately leading to the adoption of rational models of insulin replacement. The introduction of recombinant DNA technologies has since resulted in the era of both rapid- and long-acting human insulin analogues administered via the subcutaneous route which better mimic the physiology of insulin secretion, leading to the modern basal-bolus regimen. These advances, in combination with improved education and technologies for glucose monitoring, enable people with diabetes to better meet individual glycaemic goals with a lower risk of hypoglycaemia. While the prevalence of diabetes continues to rise globally, it is important to recognise the scientific endeavour that has led to insulin remaining the cornerstone of diabetes management, on the centenary of its first successful use in humans.

Hypoglycemia Among Type 1 Diabetes Patients After Insulin Use in Southwest Ethiopia.

Introduction: Glycemic control is a valuable goal for people with diabetes; however, the greatest challenge to achieving tight glycemic control is hypoglycemia. Hypoglycemic events are probably common in type 1 diabetes; however, little is known about hypoglycemia in Ethiopia. Therefore, this study aimed to assess the prevalence and the associated factors of hypoglycemia among type 1 diabetes (T1D) patients after insulin use at Metu Karl Referral Hospital in southwest Ethiopia. Materials and Methods: A hospital-based cross-sectional study was conducted among 242 T1D patients at Metu Karl Referral Hospital in southwest Ethiopia. The prevalence of hypoglycemia was assessed by a structured questionnaire through a face-to-face interview in which all the possible symptoms of hypoglycemia were included. If the patients reported that they had experienced the symptoms at least two times in a month and the symptoms were relieved upon consuming sugar/candy/honey, such cases were considered to have had a hypoglycemic episode. Binary logistic regression analysis was done to identify the factors associated with the occurrence of hypoglycemia. Results: Out of 242 T1D patients interviewed, 114 (47.1%) had self-reported hypoglycemia. The most reported symptom of hypoglycemia was sweating (91.7%), followed by dizziness and hunger and nausea with a prevalence of 24.8 and 14.5%, respectively. The study also found that educational level with reading and writing skills up to primary level [adjusted odds ratio, AOR = 0.41; 95% confidence interval, CI (0.19-0.88)] and secondary level and above [AOR = 0.32, 95% CI (0.14-0.70)], poor knowledge of diabetes [AOR = 2.26, 95% CI (1.06-4.84)], good knowledge of insulin self-administration [AOR = 0.54, 95% CI (0.30-0.99)], and duration of insulin use ≥5 years [AOR = 3.93, 95% CI (1.44-10.7)] were factors associated with hypoglycemia. Conclusions: The prevalence of hypoglycemia was found remarkable. We can conclude that hypoglycemia is of public health importance among T1D patients. Since the study assesses hypoglycemia after insulin injection, this prevalence may be due to the poor practice of insulin injection. Therefore, imparting education on the proper technique of insulin administration should be considered at each follow-up visit.

Evaluation of a telemedicine program managing high-risk pregnant women with pre-existing diabetes in Arkansas's Medicaid program.

OBJECTIVE: We aim to evaluate the effects of the telemedicine program, High-Risk Pregnancy Program at University of Arkansas for Medical Sciences (UAMS), on health services utilization and medical expenditures among pregnant women with pre-existing diabetes and their newborns. RESEARCH DESIGN AND METHODS: The study sample was selected from the Arkansas Medicaid claims linked to infant birth/death certificates and UAMS telemedicine records from 2013 through 2016. We used propensity score matching based on participants' characteristics to create three groups - UAMS telemedicine care, UAMS in-person care, and non-UAMS prenatal care. We compared inpatient and outpatient care services, medication use and caesarean section rates, severe maternal morbidity, infant mortality and preterm birth rates and medical expenditures. RESULTS: The UAMS telemedicine group had fewer inpatient admissions (1.18 vs 1.31; 95% CI: -0.27, 0.00), lower insulin use rates (41.86% vs 59.88%; 95% CI: -29.00%, -7.05%) and lower maternal care expenditures ($7,846 vs $10,644; 95% CI: -$4,089, -$1,507) compared with the UAMS in-person care group. Women receiving UAMS telemedicine had more prenatal care visits (10.45 vs 8.57; 95% CI: -2.96, -0.81), higher insulin use rates (41.86% vs 26.74%: 95% CI: 4.63%, 25.60%) and similar maternal care expenditures ($7,846 vs $7,051), compared with those receiving non-UAMS in-person care. Caesarean section, severe maternal morbidity, and infant mortality rates were similar across the three groups. CONCLUSION: UAMS telemedicine was associated with improved utilization of prenatal care among pregnant women with pre-existing diabetes. Telemedicine services did not differ from usual in-person services in clinical outcomes and medical expenditures.

A Tailored Cognitive-Behavioural Intervention Produces Comparable Reductions in Regimen-Related Distress in Adults With Type 2 Diabetes Regardless of Insulin Use: 12-Month Outcomes From the COMRADE Trial.

OBJECTIVES: Our aim in this study was to determine whether a cognitive-behavioural therapy plus small changes lifestyle intervention can produce comparable improvements in insulin users vs patients not using insulin with uncontrolled type 2 diabetes (T2D) and comorbid depressive or regimen-related distress (RRD) symptoms. METHODS: This study is a secondary analysis of Collaborative Care Management for Distress and Depression in Rural Diabetes Study, a randomized, controlled trial of a 16-session, severity-tailored cognitive-behavioural therapy plus small changes lifestyle intervention compared with usual care. Outcomes included glycated hemoglobin (A1C), regimen-related distress, depression, medication adherence and diabetes self-care. Our investigation provides 2 sets of contrasts: 1) insulin users in the intervention group compared with insulin users in the usual-care group and 2) insulin users compared with noninsulin users in the intervention group only. RESULTS: Of the 139 participants, 72 (52%) were using insulin at baseline and had significantly higher levels of A1C (10.2±2.1% vs 8.9±1.6%) and RRD (3.3±1.4 vs 2.8±1.1), and significantly poorer medication adherence (5.2±2.1 days/wk vs 5.5±1.7 days/wk). Intervention patients using insulin exhibited significantly greater reductions in RRD and marginally significant improvements in medication adherence and A1C compared with insulin users in usual care. Within the intervention group, changes in RRD, medication adherence and A1C did not differ significantly by insulin use. CONCLUSIONS: Tailored cognitive-behavioural therapy with a small-changes lifestyle intervention improved elevated RRD and A1C outcomes at least as effectively in insulin users as non‒insulin users. Future powered studies need to address the role of insulin use in uptake and treatment outcomes.

Early administration of glucocorticoid for thyroid storm: analysis of a national administrative database.

BACKGROUND: Thyroid storm is a life-threatening disease with a mortality rate of over 10%. Although glucocorticoids have been recommended as a treatment option for thyroid storm, supportive evidence based on a large-scale clinical research is lacking. The objective of the current study was to evaluate the beneficial effects of glucocorticoids in the treatment of patients with severe thyroid storm. METHODS: A retrospective nationwide cohort study was conducted using a Japanese national administrative claims database. Patients admitted to intensive care units due to severe thyroid storm between the financial years 2013 and 2017 were included in the study. The primary outcome was in-hospital mortality; secondary outcomes were mortality within 30 days and insulin administration during hospitalization. Generalized linear mixed model (GLMM) with maximum likelihood estimation (MLE) and Bayesian estimation using Markov chain Monte Carlo methods (MCMC), in addition to propensity score matching (PSM), were used for statistical analysis. RESULTS: A total of 811 patients were included in the study, of which 600 patients were treated with glucocorticoids, and 211 patients were treated without glucocorticoids. The early administration of glucocorticoids was not associated with a significant improvement in the in-hospital mortality of patients with thyroid storm [adjusted odds ratio (95% confidence interval) = 1.77 (0.95-3.34), 1.44 (1.14-1.93), and 1.46 (0.72-3.00) in the GLMM (MLE), GLMM (MCMC), and PSM, respectively]. The results of mortality within 30 days were almost identical to the results of in-hospital mortality. However, insulin use was significantly higher in the glucocorticoid group. CONCLUSIONS: This analysis of a nationwide administrative database indicates that the administration of glucocorticoids does not improve the survival of patients with thyroid storm.

The effects of clinical decision support systems on insulin use: A systematic review.

BACKGROUND: A clinical decision support system (CDSS) is a computerized system using case-based reasoning to assist clinicians in assessing disease status, in selecting appropriate therapy or in making other clinical decisions. Previous randomized controlled trials (RCTs or trials) have shown that CDSSs have the potential to improve the insulin use, but the evidence was conflicting and uncertain. The purpose of our study was to determine whether a CDSS improves the use of insulin. METHOD: PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from their inception to October 2018. The quality assessment was based on the risk of bias criteria of the Cochrane Handbook. RESULTS: Twenty-four RCTs, involving 7653 participants, were included. Thirteen of those trials (54.2%) used a computerized algorithm or a computer-assisted insulin protocol for insulin dose and therapy adjustment, of which 30.8% (four of 13) found significant changes. Of 10 trials that measured mean blood glucose levels and the 11 trials reported HbA1c, the computerized insulin dose adjustment resulted in lower mean blood glucose levels in 70.0% (seven of 10) and 36.4% (four of 11) of RCTs, respectively. Additionally, a significant reduction of hyperglycaemia events was reported in three of six RCTs. The evidence in a majority of the 24 RCTs was of moderate quality. CONCLUSIONS: CDSSs have the potential to improve the insulin use and blood glucose control in a clinical setting. The methodologies in these studies were of mixed quality. Better designed and longer-term studies are required to ensure a larger and more reliable evidence base on the effects of CDSS intervention on insulin use.

C-peptide concentrations in patients with type 2 diabetes treated with insulin.

AIMS: To determine beta cell reserves of patients with type 2 diabetes who are treated with insulin by using fasting C-peptide concentrations and to investigate the clinical features related to C-peptide concentrations. MATERIALS AND METHODS: Patients with type 2 diabetes, who were using insulin as monotherapy or in combination therapy, were divided into three groups; those with an insufficient beta cell reserve (C-peptide: <0.5 ng/mL), borderline reserve (C-peptide: 0.5-2 ng/mL) and sufficient reserve (C-peptide:> 2 ng/mL). RESULTS: In the 249 patients (mean age, 61.77 ± 9.34 years; 40.6% male), the mean duration of diabetes was 13.9 ± 8.43 years. The mean HbA1c concentrations, fasting glucose and C-peptide concentrations were 8.88 ± 1.87%, 184.29 ± 77.88 mg/dL and 1.95 ± 1.37 ng/mL, respectively. Fifty-seven percent of patients (n = 142) had a borderline beta cell reserve and 37% (n = 92) had high C-peptide concentrations. Only 6% of patients (n = 15) had an insufficient beta cell reserve. C-peptide levels were positively correlated with waist circumference (r: 0.282; p = 0.001), hip circumference (r: 0.251; p = 0.001), body mass index (r: 0.279; p = 0.001), fasting glucose concentrations (r: 0.309; p = 0.001) and triglyceride concentrations (r: 0.358; p = 0.001). CONCLUSION: In this study, almost all patients with type 2 diabetes using insulin were found to have sufficient or borderline beta cell reserves and insulin resistance-related parameters were prominent in those with adequate beta cell reserve. CLINICAL TRIALS NO: NCT04005261.

Predictors of Health-Related Quality of Life Among Patients with Type II Diabetes Mellitus Who Are Insulin Users: A Multidimensional Model.

BACKGROUND: Diabetes Mellitus is a progressive, chronic and multifactorial endocrine disorder characterized by elevated serum glucose levels. It has a direct effect to social and health related quality of life. OBJECTIVE: This study aimed to determine the health-related quality of life among patients with type II diabetes mellitus (T2DM) using insulin therapy. METHODS: Cross-sectional observational study design was used to collect data from Malaysian patients with T2DM. Subjective and objective assessments were made either by using several questionnaires or each patient's specific medication profile registered to care sites. Study participants were recruited from both public hospitals and community health clinics located in Kuala Lumpur, Malaysia. RESULTS: A total of 430 patients with T2DM were recruited in this study with a response rate of 94.7%. The oral antidiabetic medication (OAM) group consisted of 63.0% of the study population and the rest (37.0%) were Insulin users. The body mass index and glycosylated hemoglobin patterns were significantly different between groups (P < 0.011 and P < 0.001). Insulin users showed high percentages of healthy body mass index index (44.7%) compared with OAM users (35.8%) and controlled glycemic index (glycosylated hemoglobin ≤7.5%) was significantly (P = 0.001) better among the insulin-user group compared with the OAM group. The Euro Quality of Life-5 dimension domain analysis indicated significant differences with domains of usual work (P < 0.047), pain and discomfort (P < 0.041), and anxiety and depression (P < 0.001) among insulin users versus OAM users. We also observed a significant difference between the groups regarding diet, monitoring, and disease-specific knowledge. The mean (SD) adherence score showed that insulin users were significantly (P < 0.001) more adherent (6.09 [2.98]) than OAM were nonadherent (4.19 [4.68]). CONCLUSIONS: This study suggests the valuable effect of insulin therapy among patients with T2DM compared with OAMs on health-related quality of life, medication adherence, and health state. Insulin users reported they had better diabetes-related knowledge and treatment adherence characteristics than noninsulin users.

Risk of insulin-dependent diabetes mellitus in patients undergoing carotid endarterectomy.

OBJECTIVE: There is conflicting evidence regarding the association of diabetes mellitus (DM) and insulin use with outcomes after carotid endarterectomy (CEA). Therefore, we sought to evaluate the risk of insulin-dependent DM (IDDM) and noninsulin-dependent DM (NIDDM) on 30-day outcomes after CEA. METHODS: We identified patients undergoing CEA from the Targeted Vascular module of the National Surgical Quality Improvement Program (2011-2015) and stratified patients on the basis of their preprocedural symptom status. We compared 30-day outcomes between nondiabetics and patients with NIDDM or IDDM, with 30-day stroke/death as the primary end point. RESULTS: Of 16,739 CEA patients, 9784 (58%) were asymptomatic, of whom 6720 (69%) had no diagnosis of DM, 1109 (11%) had IDDM, and 1955 (20%) had NIDDM. Of the 6955 symptomatic patients, 4982 (72%) had no diagnosis of DM, 810 (12%) had IDDM, and 1163 (17%) had NIDDM. Among asymptomatic patients, patients with IDDM experienced higher rates of 30-day stroke/death compared with those without DM (3.4% vs 1.5%; P < .001), whereas those with NIDDM experienced rates similar to those of patients without DM (2.1% vs 1.5%; P = .1). Moreover, asymptomatic patients with IDDM and an anatomic high-risk criterion experienced a 30-day stroke/death rate of 6.6%. After adjustment, IDDM was associated with 30-day stroke/death in asymptomatic patients compared with patients without DM (odds ratio, 2.3; 95% confidence interval, 1.5-3.4; P < .001), but NIDDM was not (odds ratio, 1.4; 95% confidence interval, 1.0-2.1; P = .1). In comparison, among symptomatic patients, those with IDDM and NIDDM experienced similar rates of 30-day stroke/death as patients without DM (4.9% vs 3.6% and 4.0% vs 3.6%; both P > .1). After adjustment, neither IDDM nor NIDDM was associated with 30-day stroke/death in symptomatic patients compared with symptomatic patients without DM. CONCLUSIONS: Rates of 30-day stroke/death after CEA in asymptomatic patients with IDDM exceed international vascular societies' guideline thresholds for acceptable outcomes in asymptomatic patients, especially those with anatomic high-risk criteria. Thus, asymptomatic patients with IDDM may not benefit from CEA, although more data are needed about the natural history of carotid disease in this population.

Blood urea nitrogen and risk of insulin use among people with diabetes.

Laboratory evidence suggests that urea suppresses insulin secretion and sensitivity. Emerging epidemiologic evidence suggests that higher levels of urea are associated with increased risk of incident diabetes mellitus. However, whether elevated levels of blood urea nitrogen are associated with increased risk of insulin use among people with diabetes is unknown. We used the Department of Veterans Affairs databases to assemble a cohort of 197,994 incident users of non-insulin hypoglycaemic agents with an estimated glomerular filtration rate > 60 mL/min per 1.73 m2 and followed them for a median of 4.93 years. Spline analyses suggested that the relationship between blood urea nitrogen and the risk of insulin use was neutral below blood urea nitrogen level of 25 mg/dL and increased exponentially with blood urea nitrogen levels above 25 mg/dL. In survival models, compared to those with blood urea nitrogen ⩽ 25 mg/dL, those with blood urea nitrogen > 25 mg/dL had an increased risk of insulin use (hazard ratio = 1.40; confidence interval = 1.30-1.50). The risk of insulin use was increased in models which accounted for haemoglobin A1c at time zero (hazard ratio = 1.39; confidence interval = 1.28-1.50) and as a time-varying variable (hazard ratio = 1.38; confidence interval = 1.28-1.50). Two-step residual estimation analyses showed that, independent of the impact of estimated glomerular filtration rate, every 10-mg/dL increase in blood urea nitrogen concentration was associated with increased risk of insulin use (hazard ratio = 1.16; confidence interval = 1.12-1.20). Our results suggest that, among people with diabetes, higher levels of blood urea nitrogen are associated with an increased risk of insulin use.