Therapeutic Options for the Management of Postprandial Glucose in Patients With Type 2 Diabetes on Basal Insulin

In Brief For patients with type 2 diabetes who require add-on therapy to metformin plus basal insulin, GLP-1 receptor agonists may be a favorable option because they effectively manage postprandial glucose, reduce body weight, and have an overall favorable safety profile compared to other agents. Given the wide range of treatment combinations available for type 2 diabetes management, health professionals must partner with patients to determine the best choices based on patients’ individual lifestyle, resources, and treatment goals.Providing patients with optimal strategies for the management of hyperglycemia associated with type 2 diabetes is challenging. This is especially true as type 2 diabetes progresses and patients require two- and three-drug combinations or complex insulin regimens to achieve glycemic targets (1). Current consensus guidelines from the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), as well as the 2015 diabetes management algorithm of the American Association of Clinical Endocrinologists, recognize that many different drug combinations can be used to achieve A1C goals (Figure 1) (1,2). Given this range of available therapeutic options, ADA/EASD guidelines emphasize the importance of individualized, patient-centered care (1). If patients are able to be involved with treatment decisions, health care professionals (HCPs) must use a shared decision-making process to increase patient satisfaction and adherence to treatment (3). HCPs should emphasize treatment outcomes that are also important to the patient (3). Factors to consider in such individualized type 2 diabetes treatment plans include patients’ attitudes and willingness to make lifestyle changes and risk factors for hypoglycemia and other adverse events. HCPs should also consider patients’ body weight, duration of disease, life expectancy, comorbidities, established vascular complications, overall level of support, and economic burdens of treatment (1). All treatment plans should include strategies for controlling obesity, blood pressure, and hyperlipidemia and emphasize smoking cessation, regular exercise, and healthy eating habits (4).Open in a separate windowFIGURE 1.ADA/EASD general recommendations for type 2 diabetes management (1). DPP-4-i, DPP-4 inhibitor; Fx’s, fractures; GLP-1-RA, GLP-1 receptor agonist; HF, heart failure; SU, sulfonylurea.^aConsider beginning at this stage in patients with a very high A1C level (e.g., ≥9%).^bConsider rapid-acting, nonsulfonylurea secretagogues (meglitinides) in patients with irregular meal schedules or who develop late postprandial hypoglycemia on sulfonylureas.^cUsually a basal insulin (NPH, glargine, or detemir) in combination with noninsulin agents.^dCertain noninsulin agents may be continued with insulin. Consider beginning at this stage if patient presents with severe hyperglycemia (≥300−350 mg/dL; A1C level ≥10.0−12.0%) with or without catabolic features (e.g., weight loss or ketosis).     

Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy

There is increasing evidence that terlipressin is useful in patients with cirrhosis and hepatorenal syndrome, but there are no data of its use in patients with acute liver failure (ALF) in whom hepatorenal syndrome is common. Although terlipressin produces systemic vasoconstriction, it produces cerebral vasodilatation and may increase cerebral blood flow (CBF). Increased CBF contributes to intracranial hypertension in patients with ALF. The aim of this study was to evaluate the safety of terlipressin in patients with ALF with respect to cerebral hemodynamics. Six successive patients with ALF were ventilated electively for grade IV hepatic encephalopathy. Patients were monitored invasively and CBF was measured (Kety-Schmidt technique). Measurements were made before and at 1, 3, and 5 hours after intravenous (single bolus) administration of terlipressin (0.005 mg/kg), median, 0.25 mg (range, 0.2-0.3 mg). There was no significant change in heart rate, mean arterial pressure, or cardiac output. CBF and jugular venous oxygen saturation both increased significantly at 1 hour (P = 0.016). Intracranial pressure increased significantly at 1 hour (P = 0.031), returning back to baseline values at 2 hours. In conclusion, administration of terlipressin, at a dose that did not alter systemic hemodynamics, resulted in worsening of cerebral hyperemia and intracranial hypertension in patients with ALF and severe hepatic encephalopathy. These data suggest the need to exercise extreme caution in the use of terlipressin in these patients in view of its potentially deleterious consequences on cerebral hemodynamics.     

Associations of Mortality with Long-Term Exposures to Fine and Ultrafine Particles,Species and Sources: Results from the California Teachers Study Cohort

Background

Although several cohort studies report associations between chronic exposure to fine particles (PM_2.5) and mortality, few have studied the effects of chronic exposure to ultrafine (UF) particles. In addition, few studies have estimated the effects of the constituents of either PM_2.5 or UF particles.

Methods

We used a statewide cohort of > 100,000 women from the California Teachers Study who were followed from 2001 through 2007. Exposure data at the residential level were provided by a chemical transport model that computed pollutant concentrations from > 900 sources in California. Besides particle mass, monthly concentrations of 11 species and 8 sources or primary particles were generated at 4-km grids. We used a Cox proportional hazards model to estimate the association between the pollutants and all-cause, cardiovascular, ischemic heart disease (IHD), and respiratory mortality.

Results

We observed statistically significant (p < 0.05) associations of IHD with PM_2.5 mass, nitrate, elemental carbon (EC), copper (Cu), and secondary organics and the sources gas- and diesel-fueled vehicles, meat cooking, and high-sulfur fuel combustion. The hazard ratio estimate of 1.19 (95% CI: 1.08, 1.31) for IHD in association with a 10-μg/m³ increase in PM_2.5 is consistent with findings from the American Cancer Society cohort. We also observed significant positive associations between IHD and several UF components including EC, Cu, metals, and mobile sources.

Conclusions

Using an emissions-based model with a 4-km spatial scale, we observed significant positive associations between IHD mortality and both fine and ultrafine particle species and sources. Our results suggest that the exposure model effectively measured local exposures and facilitated the examination of the relative toxicity of particle species.

Citation

Ostro B, Hu J, Goldberg D, Reynolds P, Hertz A, Bernstein L, Kleeman MJ. 2015. Associations of mortality with long-term exposures to fine and ultrafine particles, species and sources: results from the California Teachers Study cohort. Environ Health Perspect 123:549–556; http://dx.doi.org/10.1289/ehp.1408565     

Reasons for Distress Among Burn Survivors at 6, 12, and 24 Months Postdischarge: A Burn Injury Model System Investigation

Objective

To identify important sources of distress among burn survivors at discharge and 6, 12, and 24 months postinjury, and to examine if the distress related to these sources changed over time.

HIV Sexual Risk and Syndemics among Women in Three Urban Areas in the United States: Analysis from HVTN 906

Limited data are available on the longitudinal occurrence of syndemic factors among women at risk for HIV infection in the USA and how these factors relate to sexual risk over time. HVTN 906 was a longitudinal study enrolling 799 HIV-uninfected women in three cities. Assessments were done at baseline, 6, 12, and 18 months to assess syndemic factors (low education, low income, unemployment, lack of health insurance, housing instability, substance use, heavy alcohol use, partner violence, incarceration) and sexual risk outcomes. For each sexual risk outcome, a GEE model was fit with syndemic factors or syndemic score (defined as sum of binary syndemics, ranging from 0 to 9), visit, study site, age and race/ethnicity as predictors to examine the multivariable association between syndemic factors and outcomes over time. Odds of unprotected sex while drunk or high were significantly higher when women reported lack of health insurance, substance and heavy alcohol use and partner violence. Housing instability, substance and heavy alcohol use, partner violence and recent incarceration were associated with higher odds of having multiple sexual partners. Odds of sex exchange were significantly higher in the presence of unemployment, housing instability, low education, lack of health insurance, substance and heavy alcohol use, partner violence and incarceration. Housing instability, substance and heavy alcohol use, and partner violence were significantly associated with higher odds of unprotected anal sex. Odds of having a recent STI were significantly higher when women reported housing instability and partner violence. There were significantly higher odds of the reporting of any risk outcomes during follow-up with higher syndemic score. This study highlights a group of women experiencing multiple poor social and health outcomes who need to be the focus of comprehensive interventions.