Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the Western world, given its association with obesity, type 2 diabetes, and dyslipidemia. Medications are widely used in NAFLD to manage comorbid conditions, and there is significant interest in developing new drug therapies to treat the disease. Despite this, little is known about the effects of NAFLD on drug metabolism. We examined the activity and expression of the major drug-metabolizing enzyme subfamily, CYP3A, in subjects with NAFLD as well as in mouse and cellular models. CYP3A activity was determined in healthy volunteers and subjects with biopsy-proven NAFLD by oral midazolam phenotyping and measurement of plasma 4b-hydroxycholesterol, an endogenous metabolic biomarker. CYP3A4 transcriptional activity, metabolic activity, and expression were also assessed in a mouse and cellular model of NAFLD. Subjects with nonalcoholic steatohepatitis (NASH) had 2.4-fold higher plasma midazolam levels compared with controls. Plasma 4b-hydroxycholesterol was 51% and 37% lower than controls in subjects with simple steatosis and NASH, respectively. Fibrosis was associated with 57% lower plasma 4b-hydroxycholesterol levels than controls. Furthermore, hepatic CYP3A4 mRNA expression in NASH was 69% lower than control livers. CYP3A4 gene luciferase activity in the livers of NAFLD mice was 38% lower than that of controls. Lipidloaded Huh7 human hepatoma cells had a 38% reduction in CYP3A4 activity and 80% lower CYP3A4 mRNA expression compared with the control. CYP3A activity is reduced in human NAFLD in addition to mouse and in vitro cell models of the disease.

Objective. Patients with type 2 diabetes often fail to achieve self-management goals. This study tested the impact on glycemic control of a two-way text messaging program that provided behavioral coaching, education, and testing reminders to enrolled individuals with type 2 diabetes in the context of a clinic-based quality improvement initiative. The secondary aim examined patient interaction and satisfaction with the program.Methods. Ninety-three adult patients with poorly controlled type 2 diabetes (A1C >8%) were recruited from 18 primary care clinics in three counties for a 6-month study. Patients were randomized by a computer to one of two arms. Patients in both groups continued with their usual care; patients assigned to the intervention arm also received from one to seven diabetes-related text messages per day depending on the choices they made at enrollment. At 90 and 180 days, A1C data were obtained from the electronic health record and analyzed to determine changes from baseline for both groups. An exit survey was used to assess satisfaction. Enrollment behavior and interaction data were pulled from a Web-based administrative portal maintained by the technology vendor.Results. Patients used the program in a variety of ways. Twenty-nine percent of program users demonstrated frequent engagement (texting responses at least three times per week) for a period of ≥90 days. Survey results indicate very high satisfaction with the program. Both groups’ average A1C decreased from baseline, possibly reflecting a broader quality improvement effort underway in participating clinics. At 90 and 180 days, there was no statistically significant difference between the intervention and control groups in terms of change in A1C (P >0.05).Conclusions. This study demonstrated a practical approach to implementing and monitoring a mobile health intervention for self-management support across a wide range of independent clinic practices.

Background: The expanding role of technology to augment diabetes care and management highlights the need for clinicians to learn about these new tools. As these tools continue to evolve and enhance improved outcomes, it is imperative that clinicians consider the role of telemonitoring, or remote monitoring, in patient care. This article describes a successful telemonitoring project in Utah. Subjects and Methods: This was a nonrandomized prospective observational preintervention-postintervention study, using a convenience sample. Patients with uncontrolled diabetes and/or hypertension from four rural and two urban primary care clinics and one urban stroke center participated in a telemonitoring program. The primary clinical outcome measures were changes in hemoglobin A1C (A1C) and blood pressure. Other outcomes included fasting lipids, weight, patient engagement, diabetes knowledge, hypertension knowledge, medication adherence, and patient perceptions of the usefulness of the telemonitoring program. Results: Mean A1C decreased from 9.73% at baseline to 7.81% at the end of the program (P < 0.0001). Systolic blood pressure also declined significantly, from 130.7 mm Hg at baseline to 122.9 mm Hg at the end (P = 0.0001). Low-density lipoprotein content decreased significantly, from 103.9 mg/dL at baseline to 93.7 mg/ dL at the end (P = 0.0263). Other clinical parameters improved nonsignificantly. Knowledge of diabetes and hypertension increased significantly (P < 0.001 for both). Patient engagement and medication adherence also improved, but not significantly. Per questionnaires at study end, patients felt the telemonitoring program was useful. Conclusions: Telemonitoring improved clinical outcomes and may be a useful tool to help enhance disease management and care of patients with diabetes and/or hypertension.

Our results demonstrate that PON1 does not mediate clopidogrel active metabolite formation or antiplatelet action, while CYP2C19 activity and genotype remains a predictor of clopidogrel pharmacokinetics and antiplatelet response.