Long-term glycaemic control (HbA1c), not admission glucose, predicts hospital re-admission in diabetic patients

Background Diabetic patients are commonly hyperglycaemic on presentation. Admission hyperglycaemia is associated with adverse outcomes, particularly prolonged hospitalisation. Improving inpatient glycaemia may reduce length of hospital stay (LOS) in diabetic patients. Aims To determine whether in-hospital recognition and treatment of admission hyperglycaemia in diabetic patients is associated with reduced LOS. Methods Medical records were reviewed from 1 November 2011 to 31 May 2012 for 162 diabetic patients admitted with a blood glucose level (BGL) ≥11.1mmol/L. In-hospital outcomes were compared. Stepwise multiple regression was used to evaluate factors contributing to LOS. Results Compared to the untreated individuals (n=67), hyperglycaemia treatment (n=95) was associated with a longer LOS (median eight vs. four days, p<0.01), higher HbA1c (9.0 vs. 7.3 per cent, p<0.01), more infections (50 vs. 25 per cent, p<0.01), and more patients with follow-up plans (35 vs. 10 per cent, p<0.01). Higher HbA1c was significantly related to more follow-up (ρs=0.30, n=110, p<0.01) with a trend to lower re-admission in those with follow-up plans (ρs=-1.41, n=162, p=0.07). Conclusion Recognition and treatment of admission hyperglycaemia in diabetic patients was associated with longer LOS than if untreated. Contributory factors to LOS include: illness severity, infections, and higher HbA1c. Although follow-up plans were few (27 per cent) for diabetic patients with hyperglycaemia, it was significantly more likely in those with higher HbA1c. Diabetic patients’ complexities require timely multidisciplinary team involvement. Improved follow-up care, particularly for hospitalised diabetic patients identified to have chronically poor glycaemic control, may help prevent future diabetic patient re-admissions

Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans

Objective Alterations in lipids in muscle and plasma have been documented in insulin-resistant people with obesity. Whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear. Methods Nondiabetic sedentary individuals not treated with lipid-lowering medications were studied (n = 51). Subjects with body mass index (BMI) > 25 kg/m2 (n = 28) were stratified based on median glucose infusion rate during a hyperinsulinemic-euglycemic clamp into insulin-sensitive and insulin-resistant groups (above and below median, obesity/insulin-sensitive and obesity/insulin-resistant, respectively). Lean individuals (n = 23) served as a reference group. Lipidomics was performed in muscle and plasma by liquid chromatography electrospray ionization-tandem mass spectrometry. Pathway analysis of gene array in muscle was performed in a subset (n = 35). Results In muscle, insulin resistance was characterized by higher levels of C18:0 sphingolipids, while in plasma, higher levels of diacylglycerol and cholesterol ester, and lower levels of lysophosphatidylcholine and lysoalkylphosphatidylcholine, indicated insulin resistance, irrespective of overweight/obesity. The sphingolipid metabolism gene pathway was upregulated in muscle in insulin resistance independent of obesity. An overweight/obesity lipidomic signature was only apparent in plasma, predominated by higher triacylglycerol and lower plasmalogen species. Conclusions Muscle C18:0 sphingolipids may play a role in insulin resistance independent of excess adiposity

Longitudinal changes in insulin resistance in normal weight, overweight and obese individuals

Background: Large cohort longitudinal studies have almost unanimously concluded that metabolic health in obesity is a transient phenomenon, diminishing in older age. We aimed to assess the fate of insulin sensitivity per se over time in overweight and obese individuals. Methods: Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 (n = 99) were retrospectively grouped into Lean (body mass index (BMI) < 25 kg/m2) or overweight/obese (BMI ≥ 25 kg/m2), with the latter further divided into insulin-sensitive (ObSen) or insulin-resistant (ObRes), based on median clamp M-value (M/I, separate cut-offs for men and women). Fifty-seven individuals participated in a follow-up study after 5.4 ± 0.1 years. Hyperinsulinaemic-euglycaemic clamp, dual-energy X-ray absorptiometry and circulating cardiovascular markers were measured again at follow-up, using the same protocols used at baseline. Liver fat was measured using computed tomography at baseline and proton magnetic resonance spectroscopy at follow-up with established cut-offs applied for defining fatty liver. Results: In the whole cohort, M/I did not change over time (p = 0.40); it remained significantly higher at follow-up in ObSen compared with ObRes (p = 0.02), and was not different between ObSen and Lean (p = 0.41). While BMI did not change over time (p = 0.24), android and visceral fat increased significantly in this cohort (ptime ≤ 0.0013), driven by ObRes (p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (ptime = 0.0003) driven by ObRes (p = 0.0039). The best correlate of follow-up M/I was baseline M/I (Spearman’s r = 0.76, p = 1.1 × 10-7). Conclusions: The similarity in insulin sensitivity between the ObSen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time

Engineered proteins with sensing and activating modules for automated reprogramming of cellular functions

Protein-based biosensors have been engineered to interrogate cellular signaling and manipulate function. Here the authors demonstrate iSNAP, a tool to detect tyrosine phosphorylation and activate desired protein enzymes allowing the control of phagocytosis in macrophages