Performance Analysis of Finned-Tube Heat Exchanger Charged with Phase Change Material for Space Cooling

The performance of a latent heat storage unit comprised of phase change material (PCM) enclosed in a finned-tube heat exchanger was evaluated experimentally and theoretically to determine its viability to condition a space during summer. The internal and external design conditions of a typical building were selected and analyzed to determine the type of PCM, and the phase change temperature required for space cooling. Subsequently, a PCM of Plus-ice A17 was selected and charged into a small-scale finned-tube heat exchanger. Extensive measurements were conducted on the PCM heat exchanger at different operating conditions. Meanwhile, a three-dimensional computational fluid dynamics model for the PCM heat exchanger was developed and validated with the experimental measurements and thus simulated. When the airflow velocity increases from 1.3 m/s to 6 m/s, the phase change periods decrease by 25% and 13% for the PCM charging and discharging processes respectively. When the PCM thermal conductivity increases from 1 W/(m·K) to 8 W/(m·K), the phase change periods reduce by 36.3% and 47.7% for the PCM charging and discharging processes respectively. In addition, for the same increased range of PCM thermal conductivity, the charging energy efficiency increases by 16.3%, and the discharging energy ratio drops by 7.1%

Does dapagliflozin regress left ventricular hypertrophy in patients with type 2 diabetes?:A prospective, double-blind, randomised, placebo-controlled study

Background: Patients with diabetes have a two to fourfold increased risk for development of and death from cardiovascular disease [CVD]. The current oral hypoglycaemic agents result in limited reduction in this cardiovascular risk. Sodium glucose linked co-transporter type 2 [SGLT2] inhibitors are a relatively new class of antidiabetic agent that have been shown to have potential cardiovascular benefits. In support of this, the EMPA-REG trial showed a striking 38% and 35% reduction in cardiovascular mortality and heart failure [HF] hospitalisation respectively. The exact mechanism (s) responsible for these effects remain (s) unclear. One potential mechanism is regression of Left ventricular hypertrophy (LVH).Methods: The DAPA-LVH trial is a prospective, double-blind, randomised, placebo-controlled 'proof of concept' single-centre study that has been ongoing since January 2017. It is designed specifically to assess whether the SGLT2 inhibitor dapagliflozin regresses left ventricular [LV] mass in patients with diabetes and left ventricular hypertrophy [LVH]. We are utilising cardiac and abdominal magnetic resonance imaging [MRI] and ambulatory blood pressure monitoring to quantify the cardiovascular and systemic effects of dapagliflozin 10 mg once daily against standard care over a 1 year observation period. The primary endpoint is to detect the changes in LV mass. The secondary outcomes are to assess the changes in, LV volumes, blood pressure, weight, visceral and subcutaneous fat.Discussion: This trial will be able to determine if SGLT2 inhibitor therapy reduces LV mass in patient with diabetes and LVH thereby strengthening their position as oral hypoglycaemic agents with cardioprotective benefits.Trial Registration: Clinical Trials.gov: NCT02956811 . Registered November 2016.</p

Dapagliflozin enhances fat oxidation and ketone production in patients with type 2 diabetes

OBJECTIVE Insulin resistance is associatedwithmitochondrial dysfunction and decreased ATP synthesis. Treatment of individuals with type 2 diabetes mellitus (T2DM) with sodium-glucose transporter 2 inhibitors (SGLT2i) improves insulin sensitivity. However, recent reports have demonstrated development of ketoacidosis in subjects with T2DM treated with SGLT2i. The current study examined the effect of improved insulin sensitivity with dapagliflozin on 1) mitochondrial ATP synthesis and 2) substrate oxidation rates and ketone production. RESEARCH DESIGN AND METHODS The study randomized 18 individuals with T2DMto dapagliflozin (n = 9) or placebo (n = 9). Before and after 2 weeks, subjects received an insulin clamp with tritiated glucose, indirect calorimetry, and muscle biopsies. RESULTS Dapagliflozin reduced fasting plasma glucose (167 ± 13 to 128 ± 6 mg/dL) and increased insulin-stimulated glucose disposal by 36% (P < 0.01). Glucose oxidation decreased (1.06 to 0.80 mg/kg · min, P < 0.05), whereas nonoxidative glucose disposal (glycogen synthesis) increased (2.74 to 4.74 mg/kg · min, P = 0.03). Dapagliflozin decreased basal glucose oxidation and increased lipid oxidation and plasma ketone concentration (0.05 to 0.19 mmol/L, P < 0.01) in association with an increase in fasting plasma glucagon (77 ± 8 to 94 ± 13, P < 0.01). Dapagliflozin reduced the ATP synthesis rate, which correlated with an increase in plasma ketone concentration. CONCLUSIONS Dapagliflozin improved insulin sensitivity and caused a shift from glucose to lipid oxidation, which, together with an increase in glucagon-to-insulin ratio, provide the metabolic basis for increased ketone production

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

A randomised study of the impact of the SGLT2 inhibitor dapagliflozin on microvascular and macrovascular circulation

BACKGROUND: The sodium–glucose cotransporter 2 inhibitor, dapagliflozin, has been shown to improve diabetic control and reduce blood pressure in patients with type 2 diabetes mellitus. Its effects on micro- and macrovascular structure and function have not yet been reported. METHODS: This was a prospective, single-centre, placebo-controlled, double-blind, randomised crossover phase IIIb study conducted between March 2014 and February 2015. After a 4-week run-in/washout phase, patients (N = 59) received 6 weeks of either dapagliflozin 10 mg or placebo once daily. They then underwent a 1-week washout before crossing over to the other treatment. Changes in retinal capillary flow (RCF) and arteriole remodelling were evaluated using scanning laser Doppler flowmetry, while micro- and macrovascular parameters in the systemic circulation were assessed using pulse wave analysis. RESULTS: Six weeks of dapagliflozin treatment resulted in improvements in diabetes control, including blood glucose and insulin resistance, and reduced office and 24-h ambulatory blood pressure values. RCF decreased from 324 AU at baseline to 308 AU after treatment with dapagliflozin (p = 0.028), while there was little difference after the placebo (318 AU; p = 0.334). Furthermore, the arteriole remodelling that was seen after the placebo phase was not evident after the dapagliflozin phase. Central systolic and diastolic blood pressure values were significantly lower after 6 weeks of dapagliflozin, by 3.0 and 2.2 mmHg, respectively (p = 0.035 and 0.020, respectively vs. baseline). CONCLUSIONS: Six weeks of dapagliflozin treatment resulted in numerous beneficial effects. In addition to achieving superior diabetes control and blood pressure, parameters associated with the early stages of vascular remodelling were also improved. Trial registration http://www.clinicaltrials.gov (NCT02383238