No abstract

No abstract

SHR controls for background glycemia and is a better biomarker of critical illness than absolute hyperglycemia. SHR identifies patients with relative hyperglycemia at risk of critical illness. Future studies should explore whether basing glucose-lowering therapy on relative, rather than absolute, hyperglycemia improves outcomes in hospitalized patients.

This study evaluated the long-term safety and efficacy of dapagliflozin as an adjunct to adjustable insulin in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) was a randomized (1:1:1), double-blind, placebo-controlled phase 3 study of dapagliflozin 5 mg and 10 mg in patients with type 1 diabetes (HbA 1c 7.5-10.5% [58-91 mmol/mol]) (NCT02268214). The results of the 52-week study, consisting of the 24-week short-term and 28-week extension period, are reported here. RESULTS Of the 833 patients randomized into the study, 708 (85%) completed the 52-week study. Over 52 weeks, dapagliflozin 5 mg and 10 mg led to clinically significant reductions in HbA 1c (difference vs. placebo [95% CI] 20.

No abstract

Prednisolone predominantly causes hyperglycemia in the afternoon and evening. Treatment of prednisolone-induced hyperglycemia should be targeted at this time period.

Objectives: To determine whether relative hyperglycemia was associated with in-hospital mortality in critically ill patients independent of other prognostic variables and whether this association is affected by background glycemia. Design: Prospective observational study. Setting: Mixed medical-surgical ICU in a metropolitan teaching hospital. Patients: From 2,617 admissions to ICU between January 27, 2016, and March 30, 2017, 1,262 consecutive patients who met inclusion and exclusion criteria were studied. Interventions: Glycosylated hemoglobin was used to estimate average glucose concentration over the prior 3 months. Glucose concentration on ICU admission was divided by estimated average glucose concentration to calculate the stress hyperglycemia ratio, an index of relative glycemia. Risk of death score was calculated using data submitted to the Australia and New Zealand Intensive Care Society. Measurements and Main Results: In this study, there were 186 deaths (14.7%). Admission glucose was significantly associated with mortality in univariate analysis (odds ratio = 1.08 per mmol/L glucose increment; p < 0.001) but not after adjustment for risk of death score (odds ratio = 1.01; p = 0.338). In contrast, stress hyperglycemia ratio was significantly associated with mortality both in univariate analysis (odds ratio = 1.09 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and after adjustment for risk of death score (odds ratio = 1.03; p = 0.014). Unlike admission glucose concentration, stress hyperglycemia ratio was significantly associated with mortality in patients with glycosylated hemoglobin less than 6.5% (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p < 0.001) and glycosylated hemoglobin greater than or equal to 6.5% (48 mmol/mol) (odds ratio = 1.08 per 0.1 stress hyperglycemia ratio increment; p = 0.005). Conclusions: Unlike absolute hyperglycemia, relative hyperglycemia, as assessed by the stress hyperglycemia ratio, independently predicts in-hospital mortality in critically ill patients across the glycemic spectrum. Future studies should investigate whether using measures of relative hyperglycemia to determine individualized glycemic treatment targets improves outcomes in ICU.

Hypoglycemia in patients with nonislet cell tumors is often secondary to overexpression of tumor insulin-like growth factor (IGF) II. In these patients the formation of serum complexes between IGFs, IGF binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS) is impaired. An 87-yr-old woman with nonislet cell tumor hypoglycemia resulting from a localized fibrous tumor of the pleura was treated for 97 days with graded doses of prednisolone (30, 10, and 5 mg/day) followed by GH (1, 4, 8, 4, and 2 U/day). Both prednisolone and GH alleviated the hypoglycemia, concomitantly with increases in IGF-I, IGFBP-3, and ALS levels. Pretreatment serum IGFBP-2 and IGFBP-6 levels were greatly elevated, but as glucose normalized with treatment, only IGFBP-2 decreased, showing an inverse correlation with glucose (r = 0.716). IGFBP-1 gave a variable pattern not clearly related to blood glucose. Both treatments caused a redistribution of serum IGFBP-3 from binary- to ternary-complexed forms. However, only prednisolone improved the ability of IGFBP-3 to bind ALS in vitro. Prednisolone also suppressed IGF-II, the effect being confined to pro-IGF-II forms. Compared with normal IGF-II, pro-IGF-II inhibited ALS binding to IGFBP-3 in vitro. Although prednisolone and GH reverse hypoglycemia by different mechanisms, with only prednisolone suppressing tumor IGF-II secretion, both increase the formation of ternary IGF-IGFBP-3 complexes. We conclude that the failure of serum IGFBP-3 and tumor IGF-II to complex with ALS is a primary cause of hypoglycemia in nonislet cell tumor hypoglycemia.