Health Care Utilization and Burden of Diabetic Ketoacidosis in the U.S. Over the Past Decade: A Nationwide Analysis.

OBJECTIVE: Diabetes is one of the most common chronic diseases and a leading cause of morbidity and mortality in the U.S. Although our ability to treat diabetes and its associated complications has significantly improved, presentation with uncontrolled diabetes leading to ketoacidosis remains a significant problem. RESEARCH DESIGN AND METHODS: We aimed to determine the incidence and costs of hospital admissions associated with diabetic ketoacidosis (DKA). We reviewed the National Inpatient Sample database for all hospitalizations in which DKA (ICD-9 codes 250.10, 250.11, 250.12, and 250.13) was the principal discharge diagnosis during 2003-2014 and calculated the population incidence by using U.S. census data. Patients with ICD-9 codes for diabetic coma were excluded because the codes do not distinguish between hypoglycemic and DKA-related coma. We then analyzed changes in temporal trends of incidence, length of stay, costs, and in-hospital mortality by using the Cochrane-Armitage test. RESULTS: There were 1,760,101 primary admissions for DKA during the study period. In-hospital mortality for the cohort was 0.4% (n = 7,031). The total number of hospital discharges with the principal diagnosis of DKA increased from 118,808 in 2003 to 188,965 in 2014 (P < 0.0001). The length of stay significantly decreased from an average of 3.64 days in 2003 to 3.24 days in 2014 (P < 0.01). During this period, the mean hospital charges increased significantly from $18,987 (after adjusting for inflation) per admission in 2003 to $26,566 per admission in 2014. The resulting aggregate charges (i.e., national bill) for diabetes with ketoacidosis increased dramatically from $2.2 billion (after adjusting for inflation) in 2003 to $ 5.1 billion in 2014 (P < 0.001). However, there was a significant reduction in mortality from 611 (0.51%) in 2003 to 620 (0.3%) in 2014 (P < 0.01). CONCLUSIONS: Our analysis shows that the population incidence for DKA hospitalizations in the U.S. continues to increase, but the mortality from this condition has significantly decreased, indicating advances in early diagnosis and better inpatient care. Despite decreases in the length of stay, the costs of hospitalizations have increased significantly, indicating opportunities for value-based care intervention in this vulnerable population.

No association between hemoglobin A1c and in-hospital mortality in patients with diabetes and acute myocardial infarction.

BACKGROUND: Patients with diabetes have increased in-hospital mortality following acute myocardial infarction (AMI), with studies suggesting higher risk with both hypoglycemia and hyperglycemia. We assessed whether a J-shaped relation exists between hemoglobin A1c (A1C) in patients with diabetes and AMI. METHODS: We assessed the associations between A1C and in-hospital mortality using data from a nationwide sample of AMI patients who had both prior diabetes and measurement of A1C (N = 15,337). RESULTS: When evaluated continuously, we observed no evidence of a J-shaped relation between A1C and in-hospital mortality in multivariable analysis (test for linearity P = .89). Patients with lowest (<5.5%) and highest A1C (≥9.5%) had a crude mortality rate of 4.6% and 2.8%, respectively, compared with 3.8% among those in the referent A1C category (6.5% to <7%). In multivariable regression, we observed no association between low A1C (<5.5%, odds ratio 0.81, 95% CI 0.47-1.39) or high A1C (A1C ≥9.5, odds ratio 1.31, 95% CI 0.94-1.83) and mortality as compared with the referent group. These findings can only be generalized to the subset of patients with diabetes who had A1C assessed during their hospitalization; these patients tended to be healthier than those in whom A1C was not assessed. CONCLUSION: In this large contemporary cohort of patients with diabetes presenting with AMI, we did not observe a J-shaped association between A1C and mortality.

The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study.

OBJECTIVES: To investigate potential determinants of severe hypoglycaemia, including baseline characteristics, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the association of severe hypoglycaemia with levels of glycated haemoglobin (haemoglobin A(1C)) achieved during therapy. DESIGN: Post hoc epidemiological analysis of a double 2x2 factorial, randomised, controlled trial. SETTING: Diabetes clinics, research clinics, and primary care clinics. PARTICIPANTS: 10 209 of the 10 251 participants enrolled in the ACCORD study with type 2 diabetes, a haemoglobin A(1C) concentration of 7.5% or more during screening, and aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or two or more additional risk factors for cardiovascular disease (dyslipidaemia, hypertension, current smoker, or obese). Interventions Intensive (haemoglobin A(1C) <6.0%) or standard (haemoglobin A(1C) 7.0-7.9%) glucose control. MAIN OUTCOME MEASURES: Severe hypoglycaemia was defined as episodes of "low blood glucose" requiring the assistance of another person and documentation of either a plasma glucose less than 2.8 mmol/l (<50 mg/dl) or symptoms that promptly resolved with oral carbohydrate, intravenous glucose, or glucagon. RESULTS: The annual incidence of hypoglycaemia was 3.14% in the intensive treatment group and 1.03% in the standard glycaemia group. We found significantly increased risks for hypoglycaemia among women (P=0.0300), African-Americans (P<0.0001 compared with non-Hispanic whites), those with less than a high school education (P<0.0500 compared with college graduates), aged participants (P<0.0001 per 1 year increase), and those who used insulin at trial entry (P<0.0001). For every 1% unit decline in the haemoglobin A(1C) concentration from baseline to 4 month visit, there was a 28% (95% CI 19% to 37%) and 14% (4% to 23%) reduced risk of hypoglycaemia requiring medical assistance in the standard and intensive groups, respectively. In both treatment groups, the risk of hypoglycaemia requiring medical assistance increased with each 1% unit increment in the average updated haemoglobin A(1C) concentration (standard arm: hazard ratio 1.76, 95% CI 1.50 to 2.06; intensive arm: hazard ratio 1.15, 95% CI 1.02 to 1.21). CONCLUSIONS: A greater drop in haemoglobin A(1C) concentration from baseline to the 4 month visit was not associated with an increased risk for hypoglycaemia. Patients with poorer glycaemic control had a greater risk of hypoglycaemia, irrespective of treatment group. Identification of baseline subgroups with increased risk for severe hypoglycaemia can provide guidance to clinicians attempting to modify patient therapy on the basis of individual risk. TRIAL REGISTRATION: ClinicalTrials.gov number NCT00000620.

stathmin, a gene enriched in the amygdala, controls both learned and innate fear.

Little is known about the molecular mechanisms of learned and innate fear. We have identified stathmin, an inhibitor of microtubule formation, as highly expressed in the lateral nucleus (LA) of the amygdala as well as in the thalamic and cortical structures that send information to the LA about the conditioned (learned fear) and unconditioned stimuli (innate fear). Whole-cell recordings from amygdala slices that are isolated from stathmin knockout mice show deficits in spike-timing-dependent long-term potentiation (LTP). The knockout mice also exhibit decreased memory in amygdala-dependent fear conditioning and fail to recognize danger in innately aversive environments. By contrast, these mice do not show deficits in the water maze, a spatial task dependent on the hippocampus, where stathmin is not normally expressed. We therefore conclude that stathmin is required for the induction of LTP in afferent inputs to the amygdala and is essential in regulating both innate and learned fear.

Stathmin-deficient mice develop an age-dependent axonopathy of the central and peripheral nervous systems.

Stathmin is a cytosolic protein that binds tubulin and destabilizes cellular microtubules, an activity regulated by phosphorylation. Despite its abundant expression in the developing mammalian nervous system and despite its high degree of evolutionary conservation, stathmin-deficient mice do not exhibit a developmental phenotype.(1) Here we report that aging stathmin(-/-) mice develop an axonopathy of the central and peripheral nervous systems. The pathological hallmark of the early axonal lesions was a highly irregular axoplasm predominantly affecting large, heavily myelinated axons in motor tracts. As the lesions progressed, degeneration of axons, dysmyelination, and an unusual glial reaction were observed. At the functional level, electrophysiology recordings demonstrated a significant reduction of motor nerve conduction velocity in stathmin(-/-) mice. At the molecular level, increased gene expression of SCG 10-like protein, a stathmin-related gene with microtubule destabilizing activity, was detected in the central nervous system of aging stathmin(-/-) mice. Together, these findings suggest that stathmin plays an essential role in the maintenance of axonal integrity.