Acute hypoxia improves insulin sensitivity (SI2*) and β cell function in individuals with Type 2 Diabetes

Type 2 diabetes is a multifactorial metabolic disease characterized by defects in β-cells function, insulin sensitivity, glucose effectiveness and endogenous glucose production (1). It is widely accepted that insulin and exercise are potent stimuli for glucose transport (2). Acute exercise is known to promote glucose uptake in skeletal muscle via an intact contraction stimulated mechanism (3), while post-exercise improvements in glucose control are due to insulin-dependant mechanisms (2). Hypoxia is also known to promote glucose uptake in skeletal muscle using the contraction stimulated pathway. This has been shown to occur in vitro via an increase in β-cell function, however data in vivo is lacking. The aim of this study was to examine the effects of acute hypoxia with and without exercise on insulin sensitivity (SI2*), glucose effectiveness (SG2*) and β-cell function in individuals with type 2 diabetes. Following an overnight fast, six type 2 diabetics, afer giving informed written consent, completed 60 min of the following: 1) normoxic rest (Nor Rest); 2) hypoxic rest [Hy Rest; O2 = 14.6 (0.4)%]; 3) normoxic exercise (Nor Ex); 4) hypoxic exercise [Hy Ex; O2 = 14.6 (0.4)%]. Exercise trails were set at 90% of lactate threshold. Each condition was followed by a labelled intravenous glucose tolerance test (IVGTT) to provide estimations of SI2*, SG2* and β-cell function. Values are presented as means (SEM). Two-compartmental minimal model analysis showed SI2* to be higher following Hy Rest when comparisons were made with Nor Rest (P = 0.047). SI2* was also higher following Hy Ex [4.37 (0.48) x10-4 . min-1 (μU/ml)] compared to Nor Ex [3.24 (0.51) x10-4 . min-1 (μU/ml)] (P = 0.048). Acute insulin response to glucose (AIRg) was reduced following Hy Rest vs. Nor Rest (P = 0.014 - Table 1). This study demonstrated that 1) hypoxia has the ability to increase glucose disposal; 2) hypoxic-induced improvements in glucose tolerance in the 4 hr following exposure can be attributed to improvements in peripheral SI2*; 3) resting hypoxic exposure improves β-cell function and 4) exercise and hypoxia have an additive effect on SG2* in type 2 diabetics. These findings suggest a possible use for hypoxia both with and without exercise in the clinical treatment of type 2 diabetes.

Where and how to find data on safety: what do systematic reviews of complementary therapies tell us?

Background: Successfully identifying relevant data for systematic reviews with a focus on safety may require retrieving information from a wider range of sources than for ‘effectiveness’ systematic reviews. Searching for safety data continues to prove a major challenge. Objectives: To examine search methods used in systematic reviews of safety and to investigate indexing. Methods: Systematic reviews focusing on safety of complementary therapies and related interventions were retrieved from comprehensive searches of major databases. Data was extracted on search strategies, sources used and indexing in major databases. Safety related search terms were compared against index terms available on major databases. Data extraction by one researcher using a pre-prepared template was checked for accuracy by a second researcher. Results: Screening of 2563 records resulted in 88 systematic reviews being identified. Information sources used varied with the type of intervention being addressed. Comparison of search terms with available index terms revealed additional potentially relevant terms that could be used in constructing search strategies. Seventy-nine reviews were indexed on PubMed, 84 on EMBASE, 21 on CINAHL, 15 on AMED, 6 on PsycINFO, 2 on BNI and HMIC. The mean number of generic safety-related indexing terms on PubMed records was 2.6. For EMBASE the mean number was 4.8 with at least 61 unique terms being employed. Most frequently used indexing terms and subheadings were adverse effects, side effects, drug interactions and herb-drug interactions. Use of terms specifically referring to safety varied across databases. Conclusions: Investigation of search methods revealed the range of information sources used, a list of which may prove a valuable resource for those planning to conduct systematic reviews of safety. The findings also indicated that there is potential to improve safety-related search strategies. Finally, an insight is provided into indexing of and most effective terms for finding safety studies on major databases.