Assessment of insulin adherence in diabetic outpatients: An observational study.

OBJECTIVES: In the management of diabetic patients on insulin therapy, adherence to medication is a key element for avoiding chronic complications. The purpose of this study was to evaluate diabetic patients' ability to translate glycemic results into an appropriate insulin dose and thus, adherence to insulins. METHODS: This was an observational, retrospective, monocentric pilot study. Diabetic patients on insulin therapy being followed at the metabolic and endocrine diseases department were divided into two groups depending on their mode of glycemic control at home: capillary glycemia (Notebook group) or interstitial glycemia using the FreeStyle Libre® flash system (FSL group). Adherence was assessed based on the rate of compliance in adapting insulin doses to the prescribed protocols (depending on type of insulin, glycemic targets, and patients' characteristics) by a pharmacy resident and a senior diabetologist. Good adherence was defined as a minimum rate of 80% of conforming insulin injections for each patient. RESULTS: A total of 50 patients were included, 35 in the Notebook group and 15 in the FSL group. Two-thirds of patients were non-adherent to insulin. Dose adjustment errors mainly concerned rapid-acting insulin with 51.1% of non- conformities, 10.0% of which were due to underdosing in the Notebook group and 21.7% to overdosing in the FSL group. Hyperglycemia was predominant in both populations with a median time in range of 19.0% in the FSL group and well below recommendations (>70%). CONCLUSIONS: Despite the use of increasingly efficient, easy-to-use devices in diabetes monitoring, insulin non-adherence and glycemic imbalance are unresolved major issues. Diabetic patients require reinforced medical follow-up for optimal insulin management.

Association between ambient air pollution and hospital admissions, length of hospital stay and hospital cost for patients with cardiovascular diseases and comorbid diabetes mellitus: Base on 1,969,755 cases in Beijing, China, 2014-2019.

BACKGROUND: Evidence on the effects of the air pollutants on the hospital admissions, hospital cost and length of stay (LOS) among patients with comorbidities remains limited in China, particularly for patients with cardiovascular diseases and comorbid diabetes mellitus (CVD-DM). METHODS: We collected daily data on CVD-DM patients from 242 hospitals in Beijing between 2014 and 2019. Generalized additive model was employed to quantify the associations between admissions, LOS, and hospital cost for CVD-DM patients and air pollutants. We further evaluated the attributable risk posed by air pollutants to CVD-DM patients, using both Chinese and WHO air quality guidelines as reference. RESULTS: Per 10 ug/m3 increase of particles with an aerodynamic diameter < 2.5 µm (PM2.5), particles with an aerodynamic diameter < 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO) and ozone (O3) corresponded to a 0.64% (95% CI: 0.57 to 0.71), 0.52% (95% CI: 0.46 to 0.57), 0.93% (95% CI: 0.67 to 1.20), 0.98% (95% CI: 0.81 to 1.16), 1.66% (95% CI: 1.18 to 2.14) and 0.53% (95% CI: 0.45 to 0.61) increment for CVD-DM patients' admissions. Among the six pollutants, particulate pollutants (PM2.5 and PM10) in most lag days exhibited adverse effects on LOS and hospital cost. For every 10 ug/m3 increase in PM2.5 and PM10, the absolute increase with LOS will increase 62.08 days (95% CI: 28.93 to 95.23) and 51.77 days (95% CI:22.88 to 80.66), respectively. The absolute increase with hospital cost will increase 105.04 Chinese Yuan (CNY) (95% CI: 49.27 to 160.81) and 81.76 CNY (95% CI: 42.01 to 121.51) in PM2.5 and PM10, respectively. Given WHO 2021 air quality guideline as the reference, PM2.5 had the maximum attributable fraction of 3.34% (95% CI: 2.94% to 3.75%), corresponding to an avoidable of 65,845 (95% CI: 57,953 to 73,812) patients with CVD-DM. CONCLUSION: PM2.5 and PM10 are positively associated with hospital admissions, hospital cost and LOS for patients with CVD-DM. Policy changes to reduce air pollutants exposure may reduce CVD-DM admissions and substantial savings in health care spending and LOS.

Assessment of the intracavernosal injection platelet-rich plasma in addition to daily oral tadalafil intake in diabetic patients with erectile dysfunction non-responding to on-demand oral PDE5 inhibitors.

This study aimed to evaluate the effectiveness of ICI of platelet-rich plasma (PRP) in addition to daily oral tadalafil intake in diabetic erectile dysfunction (ED) patients non-responding to PDE5 inhibitors. Overall, 48 patients complaining of ED non-responding to on-demand PDE5 inhibitors were allocated into 2 equal groups, diabetics and non-diabetics that were given a daily dose of 5 mg tadalafil plus vardenafil 20 mg on demand during the study besides being subjected to 3 doses of ICI of PRP, 4 weeks apart. Responses to on-demand PDE5 inhibitors, International index of erectile function-5 (IIEF-5) score, erection hardness scores (EHS) and pharmaco-dynamic duplex studies were assessed. After PRP injections, 33% and 50% of cases were satisfied with on-demand PDE5 inhibitors, respectively, whereas 41% and 66% of them showed improved EHS response. Compared with baseline scores, the mean IIEF-5 scores were significantly improved after PRP therapy in the diabetic ED group (12.1 vs. 8.04, p = 0.003) as well as in the non-diabetic ED group (14.8 vs. 10.2, p = 0.001) linked to pharmaco-penile duplex readings. Both good and fair diabetic control exhibited significant responses to ICI therapy of PRP compared with bad controlled cases. The significant improvement included; the IIEF-5 score increase (86.7%, 126% vs. 16.1%), improved EHS as well as penile duplex readings. Baseline HbA1C demonstrated a significant negative correlation with IIEF-5 score before (p = 0.019) and after PRP therapy (p = 0.002) respectively. It could be concluded that ICI of PRP could be an effective therapy for treating ED patients non-responding to on-demand oral PDE5 treatment.

Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results-Medicare analysis of 5235 patients.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses. Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality. AIM: In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment. METHODS AND RESULTS: Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims (1991-2016), we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ2 tests to compare SSA-treated and SSA-untreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. CONCLUSION: DM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds.

The purpose of this project report is to introduce the European "GOLIATH" project, a new research project which addresses one of the most urgent regulatory needs in the testing of endocrine-disrupting chemicals (EDCs), namely the lack of methods for testing EDCs that disrupt metabolism and metabolic functions. These chemicals collectively referred to as "metabolism disrupting compounds" (MDCs) are natural and anthropogenic chemicals that can promote metabolic changes that can ultimately result in obesity, diabetes, and/or fatty liver in humans. This project report introduces the main approaches of the project and provides a focused review of the evidence of metabolic disruption for selected EDCs. GOLIATH will generate the world's first integrated approach to testing and assessment (IATA) specifically tailored to MDCs. GOLIATH will focus on the main cellular targets of metabolic disruption-hepatocytes, pancreatic endocrine cells, myocytes and adipocytes-and using an adverse outcome pathway (AOP) framework will provide key information on MDC-related mode of action by incorporating multi-omic analyses and translating results from in silico, in vitro, and in vivo models and assays to adverse metabolic health outcomes in humans at real-life exposures. Given the importance of international acceptance of the developed test methods for regulatory use, GOLIATH will link with ongoing initiatives of the Organisation for Economic Development (OECD) for test method (pre-)validation, IATA, and AOP development.

Disease burden attributable to endocrine-disrupting chemicals exposure in China: A case study of phthalates.

While it has been acknowledged that exposure to endocrine-disrupting chemicals (EDCs) is associated with human diseases, the overall disease burden attributable to the exposure to a specific EDC has rarely been evaluated. Based on existing models for assessing probabilities of causation and a comprehensive review of available data, we analyzed the burden of three diseases, i.e., male infertility, adult obesity, and diabetes, among the general Chinese population resulting from exposure to phthalates. Our estimation indicates that exposure to phthalates is associated with ~2.50 million cases of the three diseases across China in 2010, causing ~57.2 billion Chinese Yuan (equivalent to ~9 billion US dollars) of health care costs in a year. Male infertility has the largest number of cases, followed by adult obesity and diabetes. Based on these phthalate-specific estimates, we further estimated that the total disease cost due to exposure to the overall EDCs amounted to ~429.43 billion Chinese Yuan in China in 2010, accounting for 1.07% of nationwide gross domestic product (GDP). When comparing our results with an earlier estimate for the European Union (EU) member countries, we find that exposure to phthalates leads to quite a similar disease burden per unit of GDP in both regions. Our study illustrates the considerable socio-economic impact of EDC exposure on human society, implying the imperative need for global risk reduction actions on EDCs, especially in view of the 2030 Sustainable Development Goals.

An open-label pilot study on preventing glucocorticoid-induced diabetes mellitus with linagliptin.

BACKGROUND: Numerous patients develop diabetes in response to glucocorticoid therapy. This study explored the efficacy, safety, and preventive potential of the dipeptidyl peptidase-4 inhibitor, linagliptin (TRADJENTA®), in the development of glucocorticoid-induced diabetes mellitus. METHODS: From December 2014 to November 2015, we recruited non-diabetic Japanese patients scheduled for treatment with daily prednisolone ≥20 mg. Enrolled patients had at least one of following risk factors for glucocorticoid-induced diabetes mellitus: estimated glomerular filtration rate ≤ 60 mL/minute/1.73 m2; age ≥ 65 years; hemoglobin A1c > 6.0%. A daily dose of 5 mg of linagliptin was administered simultaneously with glucocorticoid therapy. The primary outcome was the development of glucocorticoid-induced diabetes mellitus. Additional orally administered hypoglycemic medications and/or insulin injection therapy was initiated according to the blood glucose level. RESULTS: Four of five patients developed glucocorticoid-induced diabetes mellitus within 1 week of glucocorticoid treatment. For 12 weeks, two of the four patients with glucocorticoid-induced diabetes mellitus required orally administered medications, but no patients required insulin. Blood glucose levels before breakfast and lunch tended to decrease with time; the median glucose levels before breakfast were 93 and 79.5 mg/dL at 1 and 3 weeks, respectively. Two patients experienced mild hypoglycemia around 2 weeks. Glucose levels after lunch remained high throughout all 4 weeks despite decreasing the glucocorticoid dosage. CONCLUSIONS: Linagliptin may be insufficient to prevent the development of glucocorticoid-induced diabetes mellitus but has the potential to reduce the requirement for insulin injection therapy. Treatment of glucocorticoid-induced diabetes mellitus was continued for at least 1 month and fasting hypoglycemia in early morning should be monitored after 2 weeks. TRIAL REGISTRATION: This trial was registered 02 November 2014 with UMIN Clinical Trials Registry (no. 000015588 ).

The 2016 global and national burden of diabetes mellitus attributable to PM2·5 air pollution.

BACKGROUND: PM2·5 air pollution is associated with increased risk of diabetes; however, a knowledge gap exists to further define and quantify the burden of diabetes attributable to PM2·5 air pollution. Therefore, we aimed to define the relationship between PM2·5 and diabetes. We also aimed to characterise an integrated exposure response function and to provide a quantitative estimate of the global and national burden of diabetes attributable to PM2·5. METHODS: We did a longitudinal cohort study of the association of PM2·5 with diabetes. We built a cohort of US veterans with no previous history of diabetes from various databases. Participants were followed up for a median of 8·5 years, we and used survival models to examine the association between PM2·5 and the risk of diabetes. All models were adjusted for sociodemographic and health characteristics. We tested a positive outcome control (ie, risk of all-cause mortality), negative exposure control (ie, ambient air sodium concentrations), and a negative outcome control (ie, risk of lower limb fracture). Data for the models were reported as hazard ratios (HRs) and 95% CIs. Additionally, we reviewed studies of PM2·5 and the risk of diabetes, and used the estimates to build a non-linear integrated exposure response function to characterise the relationship across all concentrations of PM2·5 exposure. We included studies into the building of the integrated exposure response function if they scored at least a four on the Newcastle-Ottawa Quality Assessment Scale and were only included if the outcome was type 2 diabetes or all types of diabetes. Finally, we used the Global Burden of Disease study data and methodologies to estimate the attributable burden of disease (ABD) and disability-adjusted life-years (DALYs) of diabetes attributable to PM2·5 air pollution globally and in 194 countries and territories. FINDINGS: We examined the relationship of PM2·5 and the risk of incident diabetes in a longitudinal cohort of 1 729 108 participants followed up for a median of 8·5 years (IQR 8·1-8·8). In adjusted models, a 10 µg/m3 increase in PM2·5 was associated with increased risk of diabetes (HR 1·15, 95% CI 1·08-1·22). PM2·5 was associated with increased risk of death as the positive outcome control (HR 1·08, 95% CI 1·03-1·13), but not with lower limb fracture as the negative outcome control (1·00, 0·91-1·09). An IQR increase (0·045 µg/m3) in ambient air sodium concentration as the negative exposure control exhibited no significant association with the risk of diabetes (HR 1·00, 95% CI 0·99-1·00). An integrated exposure response function showed that the risk of diabetes increased substantially above 2·4 µg/m3, and then exhibited a more moderate increase at concentrations above 10 µg/m3. Globally, ambient PM2·5 contributed to about 3·2 million (95% uncertainty interval [UI] 2·2-3·8) incident cases of diabetes, about 8·2 million (95% UI 5·8-11·0) DALYs caused by diabetes, and 206 105 (95% UI 153 408-259 119) deaths from diabetes attributable to PM2·5 exposure. The burden varied substantially among geographies and was more heavily skewed towards low-income and lower-to-middle-income countries. INTERPRETATION: The global toll of diabetes attributable to PM2·5 air pollution is significant. Reduction in exposure will yield substantial health benefits. FUNDING: US Department of Veterans Affairs.

Simulated Effects of Policies to Reduce Diabetes Risk Among Adults With Schizophrenia Receiving Antipsychotics.

OBJECTIVE: Second-generation antipsychotics increase the risk of diabetes and other metabolic conditions among individuals with schizophrenia. Although metabolic testing is recommended to reduce this risk, low testing rates have prompted concerns about negative health consequences and downstream medical costs. This study simulated the effect of increasing metabolic testing rates on ten-year prevalence rates of prediabetes and diabetes (diabetes conditions) and their associated health care costs. METHODS: A microsimulation model (N=21,491 beneficiaries) with a ten-year time horizon was used to quantify the impacts of policies that increased annual testing rates in a Medicaid population with schizophrenia. Data sources included California Medicaid data, National Health and Nutrition Examination Survey data, and the literature. In the model, metabolic testing increased diagnosis of diabetes conditions and diagnosis prompted prescribers to switch patients to lower-risk antipsychotics. Key inputs included observed diagnoses, prescribing rates, annual testing rates, imputed rates of undiagnosed diabetes conditions, and literature-based estimates of policy effectiveness. RESULTS: Compared with 2009 annual testing rates, ten-year outcomes for policies that achieved universal testing reduced exposure to higher-risk antipsychotics by 14%, time to diabetes diagnosis by 57%, and diabetes prevalence by .6%. These policies were associated with higher spending because of testing and earlier treatment. CONCLUSIONS: The model showed that policies promoting metabolic testing provided an effective approach to improve the safety of second-generation antipsychotic prescribing in a Medicaid population with schizophrenia; however, the policies led to additional costs at ten years. Simulation studies are a useful source of information on the potential impacts of these policies.

Assessment of the Prevalence and Risk Factors Associated With Glucocorticoid-Induced Diabetes Mellitus in Pemphigus Vulgaris Patients.

Pemphigus vulgaris is a chronic autoimmune disease and glucocorticoids are one of the main treatments. Our study investigates the prevalence and associated factors of glucocorticoid-induced diabetes mellitus in these patients under different glucocorticoid regimens. 36 patients with first diagnosed Pemphigus vulgaris based on pathological and direct immunofluorescence findings who had received different glucocorticoid regimens (1-2 mg/kg oral or 1-2 mg/kg oral with 1g methylprednisolone pulse daily for 3 consecutive days with or without azathioprine) were evaluated during 2014-2016. Our study found that 22.2% of patients had impaired fasting glucose and incidence of corticosteroid-induced diabetes mellitus was 22.2% with no difference between oral and pulse therapy of corticosteroid. The first day after pulse therapy 19 patients of 21 had post bolus hyperglycemia that 36% of them became diabetic after 8 weeks. None of the variables, including age, BMI, HbA1c, LDL, HDL, TG, cholesterol, family history and blood pressure were associated with diabetes. Pretreatment FBS was the factor that would increase the likelihood of glucocorticoid-induced diabetes mellitus, 42.2% of patients with pretreatment FBS 100-126 developed diabetes in comparison with 17.2% in normal pretreatment FBS. Although the group who received azathioprine was associated with increased incidence of diabetes, the overall corticosteroid dose in this group was significantly higher than the other group (P=0.012), and controversy with other studies could be because of difference in corticosteroid dosage and small number of patients. The incidence of diabetes was not different between the group with glucocorticoid pulses and oral prednisolone without pulse therapy. Higher pretreatment FBS can be related to increased incidence of diabetes, but results from this study due to small number of patients are preliminary and multicenter studies are needed.

Correcting hazard ratio estimates for outcome misclassification using multiple imputation with internal validation data.

OBJECTIVE: Outcome misclassification may occur in observational studies using administrative databases. We evaluated a two-step multiple imputation approach based on complementary internal validation data obtained from two subsamples of study participants to reduce bias in hazard ratio (HR) estimates in Cox regressions. METHODS: We illustrated this approach using data from a surveyed sample of 6247 individuals in a study of statin-diabetes association in Quebec. We corrected diabetes status and onset assessed from health administrative data against self-reported diabetes and/or elevated fasting blood glucose (FBG) assessed in subsamples. The association between statin use and new onset diabetes was evaluated using administrative data and the corrected data. By simulation, we assessed the performance of this method varying the true HR, sensitivity, specificity, and the size of validation subsamples. RESULTS: The adjusted HR of new onset diabetes among statin users versus non-users was 1.61 (95% confidence interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when diabetes status and onset were corrected based on self-report and undiagnosed diabetes (FBG ≥ 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report and undiagnosed diabetes/impaired FBG (≥ 6 mmol/L). In simulations, the multiple imputation approach yielded less biased HR estimates and appropriate coverage for both non-differential and differential misclassification. Large variations in the corrected HR estimates were observed using validation subsamples with low participation proportion. The bias correction was sometimes outweighed by the uncertainty introduced by the unknown time of event occurrence. CONCLUSION: Multiple imputation is useful to correct for outcome misclassification in time-to-event analyses if complementary validation data are available from subsamples. Copyright © 2017 John Wiley & Sons, Ltd.

Use of Continuous Exposure Variables when Examining Dose-Dependent Pharmacological Effects - Application to the Association between Exposure to Higher Statin Doses and the Incidence of Diabetes.

BACKGROUND: Many observational studies have found an association between the exposure to statins and the increased risk of diabetes, mostly through the use of intent-to-treat (ITT) like exposure measure (EM). ITT like EM may not adequately reflect the mechanism of action by which statins could cause diabetes. OBJECTIVES: To determine if continuous EMs can more accurately reflect the mechanism of action by which statins and incidence of diabetes would be associated than ITT like EM. METHODS: We obtained a cohort of 404,129 diabetes-free incident statin users from the Québec public drug insurance plan. Patients dispensed with a drug used in the treatment of diabetes or diagnosed with diabetes within 2-years follow-up were defined as cases. Controls were randomly matched to each case on the index date. Three EMs were tested. EM 1: exposure to a high versus low dose statin at baseline (ITT like); EM 2: cumulative standardized statin dose (cSSD) at the index date; and EM 3: cSSD in the 180 days prior to the index date. The optimal EM was selected based upon each model's Akaike's information criterion (AIC). Conditional logistic regressions were used to calculate conditional OR and model AIC. RESULTS: All three EMs identified an increased risk of diabetes among patients exposed to higher statin doses. Model AIC identified EM 3 as the best EM for this association. CONCLUSIONS: Our results indicate that higher statin doses increase the risk of diabetes but favour a cumulative reversible diabetogenic effect of statins.

Occupational chemical exposure and diabetes mellitus risk.

Diabetes mellitus (DM) is a group of metabolic diseases that may originate from an interaction between genetic and lifestyle risk factors. However, the possible role of occupational chemical exposures in the disease development and progression remains unclear. Therefore, this review aimed to provide a comprehensive evaluation of the relationship between occupational exposure to specific chemical substances or industrial activities and DM morbidity and mortality outcomes. Although some positive findings may support the diabetogenic role of certain pesticides and dioxins in different workplaces, the variable conditions of exposure, the lack of quantitative environmental or biological monitoring data and the different outcomes evaluated do not allow defining a specific exposure-disease causality. Therefore, further epidemiological studies will be necessary to adequately assess modes of action for different substances, dose-response relationships as well as individual susceptibility factors potentially affecting the exposure-disease continuum. Overall, this appears important to adequately assess, communicate and manage risks in occupational chemical exposure settings with the aim to protect workers and build healthier job conditions for diabetic employees.

ASSESSMENT OF ADVERSE DRUG REACTIONS AS CARDIOVASCULAR RISK FACTORS.

UNLABELLED: A wide range of pharmaceutical substances can induce side-effects expressed as cardiovascular changes or events, adding to other risk factors or worsening preexisting cardiovascular diseases. AIM: Continuous study focused on iatrogenic conditions representing cardiovascular risk factors. METHODS: We developed a descriptive study of patients admitted to the Iasi Vth Internal Medicine and Geriatrics-Gerontology Clinic between 1998-2013, focusing on iatrogenic conditions representing cardiovascular risk factors. RESULTS: We have diagnosed 81 cases of drug-induced hypertension, and 43 patients with hypertensive crises; 72 cases of iatrogenic hyperglycemia; 36 cases of drug-induced hyperuricemia; 50 cases of drug-induced dyslipidemias; and 17 cases of iatrogenic obesity. These iatrogenic diseases were more common in women and the elderly. Twenty-eight patients have developed simultaneous adverse drug reactions induced by the same drug and manifest as different cardiovascular risk factors. CONCLUSIONS: Cardiovascular risk factors can be induced to a significant extent by chronic drug administration. Some medications (e.g., NSAIDs, corticoids, beta-blockers, diuretics, contraceptives) can act on the same patient by multiple pathogenic links. The adverse drug reactions can be cardiovascular risk factors that persist in time, or can be removed (by discontinuing the administration of the implicated drug). The highest importance of their acknowledgment relies on the possibility of their prevention through carefully balancing the benefits and the risk of each new medication.

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes.

Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM.

Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

CONTEXT: Obesity and diabetes are epidemic in the European Union (EU). Exposure to endocrine-disrupting chemicals (EDCs) is increasingly recognized as a contributor, independent of diet and physical activity. OBJECTIVE: The objective was to estimate obesity, diabetes, and associated costs that can be reasonably attributed to EDC exposures in the EU. DESIGN: An expert panel evaluated evidence for probability of causation using weight-of-evidence characterization adapted from that applied by the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and burden of disease. Cost estimation as of 2010 utilized published cost estimates for childhood obesity, adult obesity, and adult diabetes. Setting, Patients and Participants, and Intervention: Cost estimation was performed from the societal perspective. RESULTS: The panel identified a 40% to 69% probability of dichlorodiphenyldichloroethylene causing 1555 cases of overweight at age 10 (sensitivity analysis: 1555-5463) in 2010 with associated costs of €24.6 million (sensitivity analysis: €24.6-86.4 million). A 20% to 39% probability was identified for dichlorodiphenyldichloroethylene causing 28 200 cases of adult diabetes (sensitivity analysis: 28 200-56 400) with associated costs of €835 million (sensitivity analysis: €835 million-16.6 billion). The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs. Prenatal bisphenol A exposure was identified to have a 20% to 69% probability of causing 42 400 cases of childhood obesity, with associated lifetime costs of €1.54 billion. CONCLUSIONS: EDC exposures in the EU contribute substantially to obesity and diabetes, with a moderate probability of >€18 billion costs per year. This is a conservative estimate; the results emphasize the need to control EDC exposures.

Distribution of metals exposure and associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study".

BACKGROUND: Metals are known endocrine disruptors and have been linked to cardiometabolic diseases via multiple potential mechanisms, yet few human studies have both the exposure variability and biologically-relevant phenotype data available. We sought to examine the distribution of metals exposure and potential associations with cardiometabolic risk factors in the "Modeling the Epidemiologic Transition Study" (METS), a prospective cohort study designed to assess energy balance and change in body weight, diabetes and cardiovascular disease risk in five countries at different stages of social and economic development. METHODS: Young adults (25-45 years) of African descent were enrolled (N = 500 from each site) in: Ghana, South Africa, Seychelles, Jamaica and the U.S.A. We randomly selected 150 blood samples (N = 30 from each site) to determine concentrations of selected metals (arsenic, cadmium, lead, mercury) in a subset of participants at baseline and to examine associations with cardiometabolic risk factors. RESULTS: Median (interquartile range) metal concentrations (µg/L) were: arsenic 8.5 (7.7); cadmium 0.01 (0.8); lead 16.6 (16.1); and mercury 1.5 (5.0). There were significant differences in metals concentrations by: site location, paid employment status, education, marital status, smoking, alcohol use, and fish intake. After adjusting for these covariates plus age and sex, arsenic (OR 4.1, 95% C.I. 1.2, 14.6) and lead (OR 4.0, 95% C.I. 1.6, 9.6) above the median values were significantly associated with elevated fasting glucose. These associations increased when models were further adjusted for percent body fat: arsenic (OR 5.6, 95% C.I. 1.5, 21.2) and lead (OR 5.0, 95% C.I. 2.0, 12.7). Cadmium and mercury were also related with increased odds of elevated fasting glucose, but the associations were not statistically significant. Arsenic was significantly associated with increased odds of low HDL cholesterol both with (OR 8.0, 95% C.I. 1.8, 35.0) and without (OR 5.9, 95% C.I. 1.5, 23.1) adjustment for percent body fat. CONCLUSIONS: While not consistent for all cardiometabolic disease markers, these results are suggestive of potentially important associations between metals exposure and cardiometabolic risk. Future studies will examine these associations in the larger cohort over time.

Adherence to guidelines for glucose assessment in starting second-generation antipsychotics.

OBJECTIVES: In 2003, the US Food and Drug Administration issued warnings about hyperglycemia and diabetes with second-generation antipsychotics (SGAs); guidelines have recommended metabolic screening since 2004. However, little is known of contemporary practices of glucose screening among youth initiating SGAs. Our objective was to evaluate baseline glucose assessment among youth in the Mini-Sentinel Distributed Database starting an SGA. METHODS: The cohort included youth ages 2 through 18 newly initiating SGAs January 1, 2006, through December 31, 2011, across 10 sites. Baseline glucose was defined as fasting/random glucose or hemoglobin A1c (GLU) measurement occurring relative to first SGA dispensing. Differences in GLU assessment were evaluated with χ(2) tests and logistic regression. RESULTS: The cohort included 16,304 youth; 60% boys; mean age 12.8 years. Risperidone was most commonly started (43%). Eleven percent (n = 1858) had GLU assessed between 90 days before and 3 days after first dispensing. Assessment varied across SGAs (olanzapine highest), sites (integrated health care systems higher), ages (16-18 highest), years (2007 highest), and gender (female higher; all P < .001). GLU assessment among those starting olanzapine was more likely than among those starting quetiapine (odds ratio [OR]: 1.72 [95% confidence interval (CI): 1.37-2.18]), aripiprazole (OR: 1.49 [95% CI: 1.18-1.87]), or risperidone (OR: 1.61 [95% CI: 1.28-2.03]). CONCLUSIONS: Few children and adolescents starting SGA have baseline glucose assessed. This is concerning because those at high diabetes risk may not be identified. Further, lack of screening impedes determining the contribution of SGAs to hyperglycemia development.

Misclassification in assessment of diabetogenic risk using electronic health records.

PURPOSE: Suspected diabetogenic effects or drug indication may increase testing for diabetes mellitus (DM), resulting in measurement bias when evaluating diabetogenic drug effects. We sought to evaluate the validity of electronic health record data in determining DM risk. METHODS: We used time-dependent Cox proportional hazard models within a retrospective cohort design to assess associations between use of antihypertensives, statins, atypical antipsychotics, and antidepressants, and two endpoints: (i) DM onset defined as fasting blood glucose (BG) ≥126 mg/dl, random BG ≥200 mg/dl, HbA1c ≥7.0%, or antidiabetic drug initiation; and (ii) first negative DM test. We used Poisson regression to assess the influence of these drugs on DM testing rates. Patients aged 35-64 years enrolled in Kaiser Permanente Northwest between 1997 and 2010 entered the cohort at the first negative BG test after ≥6 months without manifest DM. RESULTS: All drug classes showed significant associations not only with DM onset but also with first negative BG test and with DM testing rates. Antipsychotics had the greatest diabetogenic risk (adjusted hazard ratio [HR] = 1.73 [1.44-2.08]), the greatest propensity for a first negative test (adjusted HR = 1.87 [1.74-2.01]), and the highest testing rate (adjusted rate ratio = 1.76 [1.72-1.81]. Although renin-angiotensin system blockers and calcium channel blockers have shown no diabetogenic risk in clinical trials, both were associated with DM (HR = 1.19 [1.12-1.26] and 1.27 [1.17-1.38]), a negative glucose test (1.38 [1.35-1.41] and 1.24 [1.20-1.28]), and increased testing rates (rate ratio = 1.26 [1.24-1.27] and 1.27 [1.25-1.28]). CONCLUSION: Caution should be used when diabetogenic risk is evaluated using data that rely on DM testing in general practice.

Cost-effectiveness of lurasidone vs aripiprazole among patients with schizophrenia who have previously failed on an atypical antipsychotic: an indirect comparison of outcomes from clinical trial data.

OBJECTIVE: Compare long-term costs and outcomes of lurasidone to aripiprazole among adults with schizophrenia in the US who previously failed ≥1 atypical antipsychotic (olanzapine, risperidone, quetiapine, or ziprasidone) based on an indirect comparison of outcomes data from clinical trials. METHODS: A 5-year Markov cohort model was developed to compare long-term effectiveness of lurasidone to aripiprazole, including total discontinuations, relapse rates, and hospitalization rates. Cost inputs included pharmacy, mental health, and medical costs associated with cardiometabolic risks (diabetes and cardiovascular [CV] events). Effectiveness inputs were derived from an indirect comparison of aripiprazole and lurasidone using common comparators from CATIE. Cardiometabolic risks were derived from claims data analysis for diabetes, weight change and CV events, and Framingham body mass index (BMI) risk equation. Cost inputs were derived from published sources and Red Book. Costs and outcomes were discounted at 3% and tested with sensitivity analyses. RESULTS: Over 5 years, total discounted costs for lurasidone and aripiprazole patients were $86,480 and $90,500, respectively. During this period, the number of relapses per patient, hospitalizations per patient, diabetes rates, and CV events per 1000 patients, respectively, were estimated to be lower for lurasidone (0.442, 0.245, 7.29%, and 37.3) than aripiprazole (0.478, 0.369, 7.36%, and 37.8). Results were sensitive to lurasidone and aripiprazole hospitalization rates. At a willingness-to-pay threshold of $50,000 per hospitalization avoided, lurasidone had a 100% probability of being more cost-effective than aripiprazole. LIMITATIONS: The model was based on results from various comparative clinical trials. Differences in patient population and study methods may change estimates from the model. The model does not account for patient heterogeneity. CONCLUSIONS: Based on this model, when switching from another atypical antipsychotic, lurasidone had fewer relapses and hospitalizations with a lower incidence of diabetes and CV events than aripiprazole. Additionally, lurasidone may be less costly than aripiprazole among adults with schizophrenia.