An evaluation of recurrent hypoglycemia across Chicago, Illinois.

AIMS: Recurrent hypoglycemia is understudied. This study evaluates recurrent hypoglycemia, fragmentation of care and mortality in a large urban center. METHODS: The Chicago HealthLNK Data Repository (CHDR), a de-identified electronic health record data set from institutions across Chicago, identified 9741 patients with diabetes (DM) who had hypoglycemia (emergency department (ED) or inpatient admission (IA)) from 2006 to 2012. Recurrence was defined as more than one hypoglycemia encounter, and fragmentation of health care was defined as an ED visit or IA for hypoglycemia at >1 site. RESULTS: 187,644 patients were identified with DM; of 9741 patients with hypoglycemia, 2857 (29.3%) had recurrence. Patients with ≥4 hypoglycemic encounters (n = 1035) represented 10.6%, but accounted for 40.3% hypoglycemic encounters. Of 2857 patients with recurrence, 304 patients (10.6%) had fragmented care. In those with high hypoglycemic encounters (≥4), 22% (N = 226) had ≥10 encounters; race and insurance status differences were associated with number of hypoglycemic encounters. Having hypoglycemia was associated with increased mortality compared to no hypoglycemia (n = 2696, 27.7% vs n = 20,188, 11.4%; p < 0.00001 by chi-square). CONCLUSION: A small subset of patients with hypoglycemia accounted for a large subset of hypoglycemia encounters. Targeted interventions in this high-risk, high mortality group are needed.

Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response.

There is increasing evidence that longevity and stress resistance are connected, but the mechanism is unclear. We report that mitochondria are regulated in response to oxidative stress and calorie restriction through a shared mechanism involving peroxisome proliferator-activated receptor-gamma co-activator 1alpha (PGC-1alpha). We demonstrate that PGC-1alpha subcellular distribution is regulated, and its transcriptional activity is promoted through SIRT1-dependent nuclear accumulation. In addition, the duration of PGC-1alpha activity is regulated by glycogen synthase kinase beta (GSK3beta), which targets PGC-1alpha for intranuclear proteasomal degradation. This mechanism of regulation permits the rapidity and persistence of PGC-1alpha activation to be independently controlled. We provide evidence that this pathway of PGC-1alpha regulation occurs in vivo in mice, both in the oxidative stress response and with calorie restriction. Our data show how mitochondrial function may be adapted in response to external stimuli, and support the concept that such adaptation is critically involved in cellular survival and in lifespan extension by calorie restriction.