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Aims/Introduction This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy. Materials and Methods This was an exploratory substudy of an open‐label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin, This study shows that patients with type 2 diabetes and insulin resistance undergoing intensive glycemic control with pioglitazone plus exenatide or basal–bolus insulin show blunted small nerve fiber regeneration. Therefore, interventions, such as physical activity and weight reduction, to improve insulin resistance might benefit diabetic neuropathy, and insulin resistance should be considered when assessing the benefits of disease‐modifying therapies for diabetic neuropathy.

Aims/Introduction Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN might influence nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. Materials and Methods This exploratory substudy of an open‐label randomized controlled trial undertook the Douleur Neuropathique en 4 questionnaire and assessment of electrochemical skin conductance, vibration perception threshold and corneal nerve morphology using corneal confocal microscopy in participants with and without pDPN treated with exenatide and pioglitazone or basal–bolus insulin at baseline and 1‐year follow up, and 18 controls at baseline only. Results Participants with type 2 diabetes, with (n = 13) and without (n = 28) pDPN had comparable corneal nerve fiber measures, electrochemical skin conductance and vibration perception threshold at baseline, and pDPN was not associated with the severity of DPN. There was a significant glycated hemoglobin reduction (P, There has been a resurgence of interest in identifying new drug targets or, predictive biomarkers of disease‐modifying therapies in diabetic neuropathy. We show that the presence of painful diabetic neuropathy was associated with greater corneal nerve regeneration and an improvement in painful neuropathic symptoms in patients with type 2 diabetes undergoing intensive glycemic control.

AIM To examine the long-term efficacy of thiazolidinedione plus a glucagon-like peptide-1 receptor agonist versus basal-bolus insulin on glycaemic control and beta-cell function in patients with poorly controlled type 2 diabetes (T2D) on metformin plus sulphonylurea. MATERIALS AND METHODS Three hundred and thirty-one patients with poorly controlled T2D were recruited over 3 years and were followed for an additional year. Subjects received a 75 g oral glucose tolerance test (OGTT) at baseline and at study end. After completing the baseline OGTT, subjects were randomized to receive either pioglitazone plus weekly exenatide (combination therapy) or basal/bolus insulin (insulin therapy) to maintain an HbA1c of less than 7.0%. The primary outcome of the study was the difference in HbA1c at study end between the two treatment groups. RESULTS Both therapies caused a robust decrease in HbA1c. However, combination therapy caused a greater decrement (-1.1%, P

IntroductionTo assess the effect of exenatide and pioglitazone or basal-bolus insulin on diabetic peripheral neuropathy (DPN) in patients with poorly controlled type 2 diabetes (T2D).Research design and methodsThis is a substudy of the Qatar Study, an open-label, randomized controlled trial. 38 subjects with poorly controlled T2D were studied at baseline and 1-year follow-up and 18 control subjects were assessed at baseline only. A combination of exenatide (2 mg/week) and pioglitazone (30 mg/day) or glargine with aspart insulin were randomly assigned to patients to achieve an HbA1c ResultsSubjects with T2D had reduced corneal nerves, but other DPN measures were comparable with the control group. In the combination treatment arm (n=21), HbA1c decreased by 35.2 mmol/mol (3.8 %) (pConclusionsTreatment with exenatide and pioglitazone or basal-bolus insulin results in corneal nerve regeneration, but no change in neuropathic symptoms or sudomotor function over 1 year.

Because of the unique mechanism of action of sodium-glucose co-transport inhibitors (SGLT2i), which is independent of insulin secretion and insulin action, members of this class of drugs effectively lower plasma glucose concentration when used in combination with all other antidiabetic agents, including insulin. Increased plasma ketone concentration has been reported in association with SGLT2i initiation, which, under certain clinical conditions, has developed into diabetic ketoacidosis. The daily insulin dose often is reduced at the time of initiating SGLT2i therapy in insulin-treated patients to avoid hypoglycaemia. However, reduction of insulin dose can increase the risk of ketoacidosis. In the present study, we examined the effect of the addition of dapagliflozin plus pioglitazone on plasma ketone concentration in insulin-treated T2DM patients and compared the results to the effect of dapagliflozin alone. A total of 18 poorly controlled, insulin-treated T2DM participants in the Qatar Study received dapagliflozin (10 mg) plus pioglitazone (30 mg), and 10 poorly controlled non-insulin-treated T2DM patients received dapagliflozin (10 mg) alone for 4 months. Dapagliflozin plus pioglitazone produced a robust decrease in HbA1c (-1.4%) and resulted in a 50% reduction in daily insulin dose, from 133 to 66 units, while dapagliflozin alone caused a 0.8% reduction in HbA1c. Dapagliflozin caused a four-fold increase in fasting plasma ketone concentration, while the combination of pioglitazone plus dapagliflozin was not associated with a significant increase (0.13 vs 0.15 mM) in plasma ketone concentration or in risk of hypoglycaemia. These results demonstrate that the addition of pioglitazone to dapagliflozin prevents the increase in plasma ketone concentration associated with SGLT2i therapy.

Objective To examine the efficacy and safety of combination therapy with exenatide plus pioglitazone vs basal/bolus insulin in patients with poorly controlled type 2 diabetes mellitus (T2DM) with very high hemoglobin A1c (HbA1c) (>10%) receiving sulfonylurea plus metformin and with a long duration of disease. Design and participants Participants (n = 101) in the Qatar Study with very poor glycemic control (HbA1c >10%) and a long duration of diabetes (10.9 years) receiving maximum/near-maximum doses of sulfonylurea plus metformin were randomly assigned to receive pioglitazone plus weekly exenatide (combination therapy), or basal plus prandial insulin (insulin therapy), to maintain HbA1c Results Baseline HbA1c was 11.5% ± 0.2% and 11.2% ± 0.2% (P = not significant) in combination therapy and insulin therapy groups, respectively. At 6 months, combination therapy caused a robust decrease in HbA1c to 6.7% ± 0.1% (∆ = -4.8%) compared with 7.4% ± 0.1% (∆ = -3.8%) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA1c independent of sex, ethnicity, or body mass index. Subjects in the insulin therapy group experienced significantly greater weight gain and a 2.5-fold higher rate of hypoglycemia compared with patients receiving combination therapy. Conclusion Exenatide/pioglitazone combination therapy is an effective and safe therapeutic option in patients with poorly controlled T2DM receiving metformin plus sulfonylurea with very high HbA1c (>10%).

Background: We previously demonstrated that addition of exenatide (EXEN) plus pioglitazone (PIO) in poorly controlled T2DM patients on maximal dose of metformin plus sulfonylurea produced a greater A1c reduction at 1 year than basal-bolus insulin. Here we report the 3-year follow-up data. Methods: 274 poorly controlled T2DM patients (age=56 y; BMI=31; Diabetes duration=11 y, HbA1c=10.1%) on maximal doses of metformin plus SU were randomized to receive: (1) Exenatide once weekly (2 mg) plus pioglitazone (n=142) or (2) basal (glargine)-bolus (aspart) insulin (n=132) to maintain HbA1c below 7%. Results: In subjects receiving EXEN + PIO, A1c decreased to 6.5% at 6 months, and remained at 6.6% after 36 months. With Insulin Therapy, A1c declined to 7.5% at 6 months and remained 7.3 at 36 months (P Conclusion: Addition of EXEN + PIO in poorly controlled T2DM patients on MET/SU produces greater and more durable HbA1c reduction with lower rate of hypoglycemia compared to Insulin Therapy. Disclosure M. Abdul-Ghani: None. O. Migahid: None. A. Megahed: None. M.F. Mohammad: None. R.A. DeFronzo: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca, Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc.. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc.. A. Jayyousi: None.

The present study aims to identify predictors for response to combination therapy with pioglitazone plus exenatide vs basal/bolus insulin therapy in T2DM patients who are poorly controlled with maximum/near-maximum doses of metformin plus a sulfonylurea. Participants in the Qatar study received a 75-g OGTT with measurement of plasma glucose, insulin and C-peptide concentration at baseline and were then randomized to receive either treatment with pioglitazone plus exenatide or basal/bolus insulin therapy for one year. Insulin secretion measured with plasma C-peptide concentration during the OGTT was the strongest predictor of response to combination therapy (HbA1c ≤ 7.0%) with pioglitazone plus exenatide. A 54% increase in 2-hour plasma C-peptide concentration above the fasting level identified subjects who achieved the glycaemic goal (HbA1c < 7.0%) with 82% sensitivity and 79% specificity. Only baseline HbA1c was a predictor of response to basal/bolus insulin therapy. Thus, the increment in 2-hour plasma C-peptide concentration above the fasting level provides a useful tool to identify poorly controlled T2DM patients who can achieve glycaemic control without insulin therapy, and thereby, can be used to individualize antihyperglycaemic therapy in poorly controlled T2DM patients.

OBJECTIVE The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS The study randomized 231 patients with poorly controlled (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy) or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c RESULTS After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA1c from 10.0 ± 0.6% (86 ± 5.2 mmol/mol) at baseline to 6.1 ± 0.1% (43 ± 0.7 mmol/mol) compared with 7.1 ± 0.1% (54 ± 0.8 mmol/mol) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA1c independent of sex, ethnicity, BMI, or baseline HbA1c. Subjects in the insulin therapy group experienced significantly greater weight gain and a threefold higher rate of hypoglycemia than patients in the combination therapy group. CONCLUSIONS Combination exenatide/pioglitazone therapy is a very effective and safe therapeutic option in patients with long-standing poorly controlled T2DM on metformin plus a sulfonylurea.

The next generation of microelectronic devices will require better heat management through new technologies such as microchannel heat sinks. The present study focuses on the experimental investigation of onset of boiling and flow boiling heat transfer characteristics in a silicon microchannel heat sink. The microchannel heat sink consists of a rectangular silicon chip in which 45 rectangular microchannels were chemically etched with a depth of 276 μm, width of 225 μm, and a length of 16 mm. Experiments are carried out for mass fluxes ranging from 341 to 531 kg/m2 s and heat fluxes from 55.5 to 154.2 kW/m2 using FC-72 as the working fluid. The present study focuses on the characteristics of boiling incipience in microchannels including the effect of mass and heat fluxes. It provides a first qualitative and quantitative local experimental data on the position of the incipient boiling. The boiling incipience and temperature thermal maps for the heat sink surface are provided from a localized measured data using Un-encapsulated thermochromic liquid crystals (TLC). This measuring technique is also used to determine the local heat transfer coefficient for saturated flow boiling. The heat transfer coefficient decreases sharply at low exit quality and then it remains almost constant as the exit quality increases. Two-phase heat transfer coefficient asymptotic models and correlations in microchannels underpredict the data in the nucleate boiling regime.

This paper experimentally investigates flow boiling characteristics in a cross-linked microchannel heat sink at low mass fluxes and high heat fluxes. The heat sink consists of 45 straight microchannels each with a hydraulic diameter of 248 μm and heated length of 16 mm. Three cross-links, of width 500 μm, are introduced in the present microchannel heat sink to achieve better temperature uniformity and to avoid flow mal-distribution. Flow visualization, flow instability, two-phase pressure drop, and two-phase heat transfer measurements are conducted using the dielectric coolant FC-72 over a range of heat flux from 7.2 to 104.2 kW/m2, mass flux from 99 to 290 kg/m2 s, and exit quality from 0.01 to 0.71. Thermochromic liquid crystals are used in the present study as full-field surface temperature sensors to map the temperature distribution on the heat sink surface. Flow visualization studies indicate that the observed flow regime is primarily slug. Visual observations of flow patterns in the cross-links demonstrate that bubbles nucleate and grow rapidly on the surface of the cross-links and in the tangential direction at the microchannels’ entrance due to the effect of circulations generated in those regions. The two-phase pressure drop strongly increases with the exit quality, at xe,o

Within the entrance region of a closed channel, the effects on flowfield and heat transfer mechanisms are significant. Where microchannels and microdevices are concerned, there are limited heat transfer studies into this region, and those available are for laminar flows. In the turbulent regime, where the hydraulic resistance is conventionally increased, higher pumping powers are required. However, future microscale applications may have a need for turbulent flow data in microchannels. There is currently no heat transfer data available on the turbulent entrance region of microchannels. An experimental investigation has been carried out to explore turbulent convection heat transfer in the entrance region of uniformly heated microtubes. The measurement of local wall temperatures is achieved through the use of unencapsulated thermochromic liquid crystals, a state-of-the-art, nonintrusive thermal-measurement technique. Heat transfer data was obtained for two stainless steel microtubes, with nominal inner diameters of 1.067 and 0.508 mm, over a Reynolds number range of 4000 to 9000. The working fluid is FC-72, and adequate tube entry length is provided for hydrodynamic flow development before heating. Local temperature data and Nusselt values are obtained in the thermal entrance region of the microchannels. The thermal turbulent entrance length is found to remain relatively constant for the Reynolds number range considered for both microtube diameters. This is in good agreement with conventional thermal turbulent entrance studies for pipes.

The rapid development of two-phase microfluidic devices has triggered the demand for a detailed understanding of the flow characteristics inside microchannel heat sinks to advance the cooling process of micro-electronics. The present study focuses on the experimental investigation of pressure drop characteristics and flow visualization of a two-phase flow in a silicon microchannel heat sink. The microchannel heat sink consists of a rectangular silicon chip in which 45 rectangular microchannels were chemically etched with a depth of 276 μm, width of 225 μm, and a length of 16 mm. Experiments are carried out for mass fluxes ranging from 341 to 531 kg/m2 s and heat fluxes from 60.4 to 130.6 kW/m2 using FC-72 as the working fluid. Bubble growth and flow regimes are observed using high speed visualization. Three major flow regimes are identified: bubbly, slug, and annular. The frictional two-phase pressure drop increases with exit quality for a constant mass flux. An assessment of various pressure drop correlations reported in the literature is conducted for validation. A new general correlation is developed to predict the two-phase pressure drop in microchannel heat sinks for five different refrigerants. The experimental pressure drops for laminar-liquid laminar-vapor and laminar-liquid turbulent-vapor flow conditions are predicted by the new correlation with mean absolute errors of 10.4% and 14.5%, respectively.

In the above-mentioned article, Fig. 1 A was corrected (the colors in the panel were switched) to …

The present study investigates the effect of cross-links on flow boiling heat transfer characteristics in rectangular microchannel heat sinks, using FC-72 as the working fluid. The silicon test section consists of 45 cross-linked microchannels, measuring 16 mm in length, with a hydraulic diameter of 248 μm. The parameters investigated include mass flux, heat flux, and exit quality, ranging from 99–275 kg/m2 s, 7.2–88.8 kW/m2 , and 0.01–0.71, respectively. Thermochromatic liquid crystals have been used in the present study as full-field surface temperature sensors to map the temperature distribution on the heat sink surface. The flow boiling heat transfer coefficient shows a different trend in the cross-linked design relative to the straight microchannel design. The flow boiling heat transfer coefficient increases with increasing exit quality at a constant mass flux, which is caused by the domination of the nucleation boiling mechanism in the cross-link region. The predictions obtained from the existing heat transfer correlations found in the literature significantly under-estimate the present heat transfer measurements, except for the Yu et al. (2002) correlation.Copyright © 2009 by ASME

The present study focuses on the experimental investigation of boiling heat transfer characteristics and pressure drop in a silicon microchannel heat sink. The microchannel heat sink consists of a rectangular silicon chip in which 45 rectangular microchannels were chemically etched with a depth of 295 μm, width of 254 μm, and a length of 16 mm. Un-encapsulated Thermochromic liquid Crystals (TLC) are used in the present work to enable nonintrusive and high spatial resolution temperature measurements. This measuring technique is used to provide accurate full and local surface-temperature and heat transfer coefficient measurements. Experiments are carried out for mass velocities ranging between 290 to 457 kg/m2 .s and heat fluxes from 6.04 to 13.06 W/cm2 using FC-72 as the working fluid. Experimental results show that the pressure drop increases as the exit quality and the flow rate increase. High values of heat transfer coefficient can be obtained at low exit quality (xe < 0.2). However, the heat transfer coefficient decreases sharply and remains almost constant as the quality increases for an exit quality higher than 0.2.Copyright © 2008 by ASME