In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining ␤-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual ␤-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: Յ0.03, 0.04 -0.20, 0.21-0.50 nmol/l at entry, and 0.21-0.50 nmol/l at entry and at least 1 year later (sustained C-peptide secretion). Uniformly in the intensive and partially in the conventional DCCT treatment groups, any C-peptide secretion, but especially at higher and sustained levels of stimulated C-peptide, was associated with reduced incidences of retinopathy (both a single three-step change and a repeated three-step change on the Early Treatment of Diabetic Retinopathy Study [ETDRS] scale at the next 6 month visit) and nephropathy (both albuminuria Ͼ40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia (ϳ65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level Ͼ0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of ϳ30%. Therefore, even modest levels of ␤-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).

Background Potentially inappropriate medications (PIM) are widely used in institutionalized older adults, yet the key determinants that drive their use are incompletely characterized. Methods We systematically searched published literature within MEDLINE® and Embase® from January 1998 to March 2017. We searched for studies conducted in the United States that described determinants of PIM use in adults ≥60 years of age in a nursing home or residential care facility, in the Emergency Department (ED), or in the hospital. Paired reviewers independently screened abstracts and full text articles, assessed quality and extracted data. Results Among 30 included articles, 12 examined PIM use in the nursing home or residential care settings, 4 in the ED, 12 in acute-care hospitals, and 2 across settings. The Beers criteria were most frequently used to identify PIM use, which ranged from 3.6 to 92%. Across all settings, the most common determinants of PIM use were medication burden and geographic region. In the nursing home, the most common additional determinants were younger age, and diagnoses of depression or diabetes. In both the ED and hospital, patients receiving care in the West, Midwest, and South, relative to the Northeast, were at greater risk of receiving a PIM. Very few studies examined clinician determinants of PIM use; geriatricians used fewer PIMs in the hospital than other clinicians. Conclusions Among older adults, those who are on many medications are at increased risk for PIM use across multiple settings. We propose that careful testing of interventions that target modifiable determinants are indicated to assess their impact on PIM use.

Objectives Potentially inappropriate medication (PIM) use in older adults is a prevalent problem associated with poor health outcomes. Understanding drivers of PIM use is essential for targeting interventions. This study systematically reviews the literature about the patient, clinician and environmental/system factors associated with PIM use in community‐dwelling older adults in the United States. Methods PRISMA guidelines were followed when completing this review. PubMed and EMBASE were queried from January 2006 to September 2017. Our search was limited to English‐language studies conducted in the United States that assessed factors associated with PIM use in adults ≥65 years who were community‐dwelling. Two independent reviewers screened titles and abstracts. Reviewers abstracted data sequentially and assessed risk of bias independently. Key findings Twenty‐two studies were included. Nineteen examined patient factors associated with PIM use. The most common statistically significant factors associated with PIM use were taking more medications, female sex, and higher outpatient and emergency department utilization. Only three studies examined clinician factors, and few were statistically significant. Fifteen studies examined system‐level factors such as geographic region and health insurance. The most common statistically significant association was the south and west geographic region relative to the northeast United States. Conclusions Amongst older adults, women and persons on more medications are at higher risk of PIM use. There is evidence that increased healthcare use is also associated with PIM use. Future studies are needed exploring clinician factors, such as specialty, and their association with PIM prescribing.

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