High sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-6, and vascular cell adhesion molecule-1 levels in Asian Indians with metabolic syndrome and insulin resistance (CURES-105)

Aim

The aim of this study was to assess levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and without MS and among MS subjects with and without insulin resistance (IR).

Methodology

From the population-based Chennai Urban Rural Epidemiology Study, 334 subjects with MS and 342 subjects without MS were selected. Metabolic syndrome was diagnosed based on modified National Cholesterol Education Program criteria. High-sensitivity C-reactive protein, TNF-α, IL-6, and VCAM-1 were measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR) using the following formula: fasting insulin (µIU/ml) × fasting glucose (mmol/liter)/22.5.

Results

Subjects with MS had significantly higher levels of all four inflammatory markers compared to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-α (4.47 vs 3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs 7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047), TNF-α (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r = 0.230, p = .06) were significantly correlated with MS. With increasing quartiles of IR, mean levels of hs-CRP (p for trend <.001) and TNF-α (p for trend <.05) increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001) and TNF-α (p < .05) compared to MS subjects without IR.

Conclusion

In Asian Indians, inflammatory cytokines hs-CRP, TNF-α, IL-6, and VCAM-1 are elevated in subjects with MS while hs-CRP and TNF-α are further elevated in those with MS and IR.     

Reduction of postprandial glycemic excursions in patients with type 1 diabetes: a novel human insulin formulation versus a rapid-acting insulin analog and regular human insulin

Background:

Evaluation of postprandial glycemic excursions in patients with type 1 diabetes with three prandial insulins: VIAject™ (Linjeta™), an ultra-fast insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI).

Methods:

After stabilization of preprandial glycemia, 18 patients received a subcutaneous injection with an individualized insulin dose prior to a meal.

Results:

Injection of UFI resulted in a more rapid insulin absorption than with either LIS or RHI (time to half-maximal insulin levels: 13.1 ± 5.2 vs 25.4 ± 7.6 and 38.4 ± 19.5 min; p = .001 vs LIS and p < .001 vs RHI, LIS vs. RHI p < .001). Maximal postprandial glycemia was lower with UFI (0–180 min; 157 ± 30 mg/dl; p = .002 vs RHI) and LIS (170 ± 42 mg/dl; p = .668 vs RHI) than after RHI (191 ± 46 mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia was smaller with UFI (70 ± 17 mg/dl) than with either RHI (91 ± 33 mg/dl; p = .007 vs UFI) or LIS (89 ± 18 mg/dl; p = .011 vs UFI). Also, the area under the blood glucose profile was lower with UFI than with RHI (0–180 min; 21.8 ± 5.8 vs 28.4 ± 7.6 g·min/dl; p < .001).

Conclusions:

The rapid absorption of UFI results in a reduction of postprandial glycemic excursions.     

Evaluation of cardiovascular risk in patients with Parkinson disease under levodopa treatment

Background Levodopa is the indispensable choice of medial therapy in patients with Parkinson disease (PD). Since L-dopa treatment was shown to increase serum homocysteine levels, a well-known risk factor for cardiovascular disorders, the patients with PD under L-dopa treatment will be at increased risk for future cardiovascular events. The objective of this study is to evaluate cardiovascular risk in patients with PD under levodopa treatment. Methods The study population consisted of 65 patients with idiopathic PD under L-dopa treatment. The control group included 32 age and gender matched individuals who had no cognitive decline. Echocardiographic measurements, serum homocysteine levels and elastic parameters of the aorta were compared between the patients with PD and controls. Results As an expected feature of L-dopa therapy, the Parkinson group had significantly higher homocystein levels (15.1 ± 3.9 μmol/L vs. 11.5 ± 3.2 μmol/L, P = 0.02). Aortic distensibility was significantly lower in the patients with PD when compared to controls (4.8 ± 1.5 dyn/cm² vs. 6.2 ± 1.9 dyn/cm², P = 0.016). Additionally, the patients with PD had higher aortic strain and aortic stiffness index (13.4% ± 6.4% vs. 7.4% ± 3.6%, P < 0.001 and 7.3 ± 1.5 vs. 4.9 ± 1.9, P < 0.001, respectively). Furthermore, serum homocysteine levels were found to be positively correlated with aortic stiffness index and there was a negative correlation between aortic distensibility and levels of serum homocysteine (r = 0.674, P < 0.001; r = -0.602, P < 0.001, respectively). Conclusions The patients with PD under L-dopa treatment have increased aortic stiffness and impaired diastolic function compared to healthy individuals. Elevated serum homocysteine levels may be a possible pathophysiological mechanism.     

Increased Arterial Augmentation and Augmentation Index as Surrogate Parameters for Arteriosclerosis in Subjects with Diabetes Mellitus and Nondiabetic Subjects with Cardiovascular Disease

Background

Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to compare these parameters in diabetic subjects and nondiabetic cardiovascular risk subjects with healthy control subjects.

Methods

One hundred sixty-six nonsmoking subjects aged between 35 and 70 years were included in the study, which included 100 subjects with cardiovascular disease but not diabetes (mean age 62.73±8.75 years), 33 subjects with type 2 diabetes (66.58±2.69 years), and 33 healthy controls (51.89±8.91 years). In these subjects, arterial stiffness was measured by the difference between the second and the first systolic peak of the central pressure waveform, and the Aix was calculated as the percentage of Aix from pulse pressure.

Results

Arterial augmentation was increased in subjects with diabetes (DM) with 10.21±6.97 mm Hg and in subjects with cardiovascular disease but not diabetes (CV) with 10.74±5.29 mm Hg in comparison to healthy controls (C) with 6.59±3.97 mm Hg (p < 0.0005 DM vs C; p < 0.00005 CV vs C). Moreover, Aix was increased with 26.00±9.91% in CV subjects compared to healthy controls with 19.84±9.37% (p < 0.02 CV vs C). The augmentation index was increased with 21.12±11.21% in subjects with type 2 diabetes mellitus compared to controls, but failed to be statistically significant. There was no statistical significance in arterial augmentation or the augmentation index between CV and diabetic subjects.

Conclusion

The results of our study revealed a comparable increased augmentation index as a surrogate measure of arterial stiffness and arteriosclerosis in subjects with diabetes mellitus and in nondiabetic subjects with cardiovascular disease.     

Comparison of the Dose Accuracy of Prefilled Insulin Pens

Background

Prefilled insulin pens have become a convenient and accurate way for diabetes patients to inject insulin. Their ease of use has helped to reduce the resistance of patients with type 1 diabetes and type 2 diabetes in the United States and Europe toward initiation of insulin therapy. This study compared the dosing accuracy of two prefilled insulin pens (the SoloStar^® from Sanofi Aventis, Berlin, Germany, and the Next Generation [NG] FlexPen^® from Novo Nordisk, Mainz, Germany).

Methods

The dosing accuracy was tested for both pens with × 24 10 international units of insulin (IU) and 9 × 30 IU injection volumes to investigate whether the pens comply within the acceptable International Organization for Standardization (ISO) limits of 10% (±1 IU) for 10 IU and 5% (±1.5 IU) for 30 IU. The doses were applied each with a new needle strictly according to the instructions for use of the pen manufacturers. A sensitive pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. We used 18 insulin pens (from two different production lots each) for the two volumes, respectively, resulting in a total of 432 doses per pen with 10 IU and 162 doses per pen with 30 IU.

Results

Both pens showed a very good performance, which was better for the 10 IU dose than in comparative previous studies. The NG FlexPen (mean absolute percent deviation 10 IU/30 IU: 1.63 ± 0.84%/1.23 ± 0.76%) was even more accurate than the SoloStar (2.11 ± 0.92%/1.54 ± 0.84%, p < .001/p < .05 versus the NG FlexPen). Only 0.2% of the doses were outside the ISO limit at 10 IU, with the NG FlexPen (0.6% at 30 IU). The corresponding figures for the SoloStar were 0.4% and 1.8%, respectively.

Conclusions

A direct head-to-head comparison of the two prefilled insulin pens with a standardized protocol resulted in a more stable dosing accuracy of both pens as compared to previous investigations. In this investigation, the NG FlexPen was more accurate than the SoloStar at both tested doses.     

Differences in the Dose Accuracy of Insulin Pens

Background

Modern insulin injection pens provide a convenient and accurate way for diabetes patients to inject insulin. They have widespread use among children and adults with type 1 and type 2 diabetes in the U.S. and Europe. This study compared the dosing accuracy of four commonly available insulin pens (OptiClik^® and SoloSTAR^® from sanofi-aventis, FlexPen^® from Novo Nordisk, and HumaPen^® LUXURA™ from Eli Lilly).

Methods

The dosing accuracy was tested for all pens with 24 × 10 IU and 9 × 30 IU injection volumes to investigate whether the pens complied with the acceptable International Organization for Standardization (ISO) limits of 10% (± 1 IU) for 10 IU and 5% (± 1.5 IU) for 30 IU. The doses were each applied with a new needle strictly according to the instructions for use by the pen manufacturers. A pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. Four insulin pens (two each from different production lots) were used for each of the two volumes, resulting in a total of 192 doses per pen with 10 IU, and 72 doses per pen with 30 IU.

Results

FlexPen (mean absolute percent deviation for 10 IU and 30 IU: 1.64 ± 0.84% and 0.83 ± 0.26%, respectively) and HumaPen LUXURA (1.10 ± 0.20% and 0.62 ± 0.19%; not significant versus FlexPen for both doses) were more accurate than the OptiClik (4.78 ± 3.31% and 2.97 ± 2.48%, p <.01) and the SoloSTAR (2.61 ± 0.92% and 1.70 ± 0.84%, p <.05). While 6.8% of doses were outside the ISO limit at 10 IU with OptiClik (13.9% at 30 IU), the corresponding figures were 0.5% and 4.1%, respectively, for SoloSTAR. No doses outside the ISO limits were seen with FlexPen or HumaPen LUXURA at 10 IU and only one 30 IU dose (1.4%) was outside the limit for FlexPen.

Conclusions

A direct head-to-head comparison of four insulin pens with a standardized protocol resulted in a more stable dosing accuracy of the FlexPen and the HumaPen LUXURA in comparison to the OptiClik and SoloSTAR. Even though all insulin delivery systems undergo rigorous testing before being approved for sale, there may be reasons to be attentive to the performance of the devices in practical use.     

Foot Technology, Part 1 of 2: Association between Foot Temperature and Sudomotor Dysfunction in Type 2 Diabetes

Background and Aims

Increased foot skin temperature has been described as a feature of diabetic neuropathy. The aim of this present study was to investigate the association between foot temperature and sudomotor dysfunction in type 2 diabetes mellitus.

Patients and Methods

This study included 51 patients (group A: 25 men, mean age 61.14 ± 6.11 years) without sudomotor dysfunction and 52 patients (group B: 25 men, mean age 59.54 ± 6.18 years) with sudomotor dysfunction. Sudomotor dysfunction was defined as time until complete Neuropad^® color change from blue to pink exceeding 600 s in at least one foot. Time until complete color change of the test was also recorded. Foot skin temperature was measured with a handheld infrared thermometer on the plantar aspect of the foot at the level of the first metatarsal head.

Results

On both feet, temperature was significantly higher in group B than in group A (right foot, group A versus group B, 30.62 ± 1.13 °C versus 32.12 ± 1.06 °C, p < .001; left foot, group A versus group B, 30.65 ± 1.06 °C versus 32.19 ± 1.10 °C, p < .001). There was a significant positive correlation between time to complete Neuropad color change and foot skin temperature (right foot, r = 0.742, p < .001; left foot, r = 0.758, p < .001), which was confirmed in both groups.

Conclusions

Patients with sudomotor dysfunction have significantly higher foot temperature than those without sudomotor dysfunction. Foot temperature is positively correlated with severity of sudomotor dysfunction, as evaluated by the time to complete Neuropad color change.     

Effect of pioglitazone and ramipril on biomarkers of low-grade inflammation and vascular function in nondiabetic patients with increased cardiovascular risk and an activated inflammation: results from the PIOace study

Aims

This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk.

Methods and Results

Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.7 kg/m², duration of hypertension 9 ± 8 years) were treated with either 30/45 mg PIO (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in high-sensitivity C-reactive protein was observed with PIO (−0.89 ± 1.98 mg/liter; -25%) and PIRA (−0.49 ± 2.11 mg/liter; -16%), while an increase was seen with RAM (0.58 ± 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24-hour blood pressure profile showed a small increase with both monotherapies but a decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic systemic inflammation and insulin resistance (IR) were observed in the PIO and PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 ± 1.39 (−29%)/0.15 ± 1.03 (+5%)/ -1.44 ± 2.83 (−40%); adiponectin: 8.51 ± 5.91 (+104%)/ 0.09 ± 2.63 (+1%)/ 8.86 ± 6.37 mg/liter (+107%); matrix metallo-proteinase-9: -48 ± 127 (−12%)/-1 ± 224 (0%)/-60 ± 210 ng/ml (−13%), p < .05 for RAM vs PIO or PIRA in all cases].

Conclusions

Our 3-month study in nondiabetic hypertensive patients showed a decrease in biomarkers of IR and chronic systemic inflammation with the PIO monotherapy and the PIRA combination only, which may help to explain some findings in other cardiovascular outcome trials.     

Endothelial Function and Arterial Stiffness in Uncomplicated Type 1 Diabetes and Healthy Controls and the Impact of Insulin on These Parameters during an Euglycemic Clamp

Background

In addition to its role in glucose metabolism, insulin has shown to exert numerous vascular effects, and an impaired vascular function of insulin is assumed to be a major contributor in the development of vascular complications. Arterial augmentation (AP) and the augmentation index (Aix) are surrogate parameters of arterial stiffness and are commonly used as predictors for cardiovascular risk. The aim of this study is to investigate the effect of insulin on arterial stiffness and parameters of endothelial function in patients with type 1 diabetes and healthy control subjects.

Methods

Fourteen patients with type 1 diabetes (six male, eight female) with a mean age of 36.6 ± 11.8 years and 14 healthy subjects (seven male, seven female) with a mean age of 27.3 ± 5.5 years were randomized to an euglygemic clamp with either a low (0.25 mU/kg/min) or a high (1.0 mU/kg/min) insulin dose on two different days. The mean HbA1c in the diabetic subjects was 7.3 ± 0.7%. In these subjects, arterial stiffness was measured by pulse wave analysis (SphygmoCor, AtCor Medical, Australia). AP was calculated as the difference between the second and the first systolic shoulders of the central pressure wave curve, and the Aix was expressed as the percentage of AP from total pulse pressure. As parameters of endothelial function, cyclic guanosine monophosphate, nitrotyrosine, and asymmetric dimethylarginine were determined at baseline and after 120 minutes.

Results

Patients with type 1 diabetes showed increased values for AP with 3.5 ± 3.1 mm Hg and Aix with 12.5 ± 12.5% compared to healthy controls with −0.7 ± 2.6 mm Hg for AP and −4.2 ± 10.6% for Aix. This difference was statistically significant (p < 0.01). During the euglycemic clamp, insulin improved, but did not normalize the increased values for AP and Aix in patients with type 1 diabetes. Concerning parameters of endothelial function, patients with type 1 diabetes showed statistically significant increased values for nitrotyrosine compared to healthy controls at baseline [low insulin: diabetes mellitus (DM) 1993.12 ± 1330.85 nmol/liter vs healthy controls 803.7 ± 726.91; high insulin DM: 2208.02 ± 1736.57 nmol/liter vs healthy controls: 750.83 ± 426.03 nmol/liter] (p < 0.05).

Conclusion

Patients with type 1 diabetes mellitus revealed an increased arterial stiffness measured as augmentation and augmentation index and increased nitrotyrosine levels as a marker of oxidative stress compared to healthy control subjects at baseline. Application of insulin improves the arterial elastic properties, but was not able to normalize the vascular function in patients with type 1 diabetes.     

Multicenter user evaluation of ACCU-CHEK® Combo, an integrated system for continuous subcutaneous insulin infusion

Background

The aim of this study was to evaluate a newly developed system for insulin delivery incorporating a multifunctional blood glucose meter and a remotely controlled insulin pump (ACCU-CHEK^® Combo system) in established pump users with type 1 diabetes. The technology was assessed both from device performance and subject usability perspectives.

Method

A multicenter, prospective, single group study was carried out in five centers in the Netherlands and four centers in the United Kingdom for more than 6 months. The study was divided into two phases: Phase 1 (4 weeks) for device validation purposes and phase 2 (22 weeks) to observe the impact of the system on metabolic control, patient satisfaction [using the Diabetes Treatment Satisfaction Questionnaire (DTSQ)] and device safety.

Results

Eighty subjects completed the planned study period. There were no unexpected device errors. Treatment satisfaction was high at baseline and further increased to study end (DTSQ change version: sum score, 10.6 ± 7.2; scale score range, -18 to +18, p < 0.0001). Hemoglobin A1c improved continuously over time, from 7.9% (±0.9%) to 7.7% (±0.8%) at month 3 (p < 0.001) and 7.6% (±0.8%) at month 6 (p < 0.0001). The frequency of severe hypoglycemia was 0.08 per patient years. There was no case of ketoacidosis.

Conclusions

The new system was evaluated by experienced continuous subcutaneous insulin infusion users as safe in daily practice and associated with favorable treatment satisfaction and a modest improvement in glycemic control.     

Short-term results of thoracoscopic lobectomy and segmentectomy for lung cancer in koo foundation sun yat-sen cancer center

Background

Thoracoscopic lobectomy and segmentectomy have been demonstrated to be safe and technically feasible for curative resection of lung cancer. This minimally invasive surgery is increasingly popular and adopted by the world all over. We report our short-term results of thoracoscopic lobectomy/segmentectomy operations comparing with previous surgical approach for lung cancer resection by muscle-sparing vertical minithoracotomy in Koo Foundation Sun Yat-Sen Cancer Center.

Methods

We performed a retrospective review of 317 consecutive patients who underwent lobectomy or segmentectomy either by thoracoscopic surgery (n=121) or muscle-sparing vertical mini-thoracotomy (n=195) for lung cancer in Koo Foundation Sun Yat-Sen Cancer center between Jan 2000 and Jun 2009. The operative details, postoperative complication, and length of stay were statistically analyzed.

Results

Thoracoscopic lobectomy and segmentectomy were performed successfully in 121 patients. One patient was converted to open thoracotomy during operation due to uncontrolled bleeding. There is no significant difference in age factors (p=0.763), forced expiratory volume in one second (p=0.480) or comorbidities (p=0.549) between these two groups. Thoracoscopic group had a significantly predominant percentage in women, diabetes mellitus, less smoking index and chronic obstructive pulmonary disease incidence. Patients undergoing a thoracoscopic surgery had a shorter length of stay (6.8±3.4 vs. 10.2±9.1 days, p<0.001), longer operative time (3.6±1.0 vs. 3.2±1.2 hours, p=0.004), and less blood loss (102.7±95.7 vs. 140.1±171.2 ml, p<0.029). There was no significant difference in postoperative complication rate between the two groups (18.2% vs. 23.6%, p=0.255). No surgical mortality was found in the thoracoscopic group.

Conclusions

Our findings suggested thoracoscopic surgery for lung cancer would be as safe as muscle-sparing vertical mini-thoracotomy in lobectomy and segmentectomy.     

Deferasirox for up to 3 years leads to continued improvement of myocardial T2* in patients with β-thalassemia major

Background

Prospective data on cardiac iron removal are limited beyond one year and longer-term studies are, therefore, important.

Design and Methods

Seventy-one patients in the EPIC cardiac substudy elected to continue into the 3^rd year, allowing cardiac iron removal to be analyzed over three years.

Results

Mean deferasirox dose during year 3 was 33.6±9.8 mg/kg per day. Myocardial T2*, assessed by cardiovascular magnetic resonance, significantly increased from 12.0 ms ±39.1% at baseline to 17.1 ms ±62.0% at end of study (P<0.001), corresponding to a decrease in cardiac iron concentration (based on ad hoc analysis of T2*) from 2.43±1.2 mg Fe/g dry weight (dw) at baseline to 1.80 ±1.4 mg Fe/g dw at end of study (P<0.001). After three years, 68.1% of patients with baseline T2* 10 to <20 ms normalized (≥20 ms) and 50.0% of patients with baseline T2* >5 to <10 ms improved to 10 to <20 ms. There was no significant variation in left ventricular ejection fraction over the three years. No deaths occurred and the most common investigator-assessed drug-related adverse event in year 3 was increased serum creatinine (n=9, 12.7%).

Conclusions

Three years of deferasirox treatment along with a clinically manageable safety profile significantly reduced cardiac iron overload versus baseline and normalized T2* in 68.1% (32 of 47) of patients with T2* 10 to <20 ms.     

Pancreatic polypeptide administration enhances insulin sensitivity and reduces the insulin requirement of patients on insulin pump therapy

Introduction

The effects of pancreatic polypeptide (PP) infusion were examined in patients on insulin pump therapy to determine whether PP administration can reduce insulin requirements in patients with type 1 diabetes mellitus (T1DM) or type 3c diabetes mellitus (T3cDM; pancreatogenic).

Methods

Ten subjects with long-standing T1DM (n = 7) or T3cDM (n = 3) on insulin pump treatment received a 72 h subcutaneous infusion of 2 pmol/kg/min bovine PP or saline by portable infusion pump in a single-blinded, randomized, crossover design.

Results

Pancreatic polypeptide infusion raised plasma PP levels to 450–700 pmol/liter. Daily insulin infusion requirements (I) fell from 48 ± 6.9 to 40 ± 7.5 U on day 2 (p < .05) and from 46 ± 7.7 to 37 ± 6.6 U on day 3 (p < .05) of PP infusion compared with saline. Corrected for average blood glucose concentration (G), I/G fell in 10/10 subjects during the second 24 h period and in 7/10 subjects during the third 24 h period; sensitivity to insulin, calculated as 1/(I/G), increased 45% ± 12% on day 2 (p < .01) and 34% ± 14% on day 3 (p < .05) of PP infusion. Pancreatic polypeptide responses to a test meal were compared with the change in insulin infusion requirements in 5 subjects; the reduction in insulin requirements seen during PP infusion correlated with the degree of baseline PP deficiency (p < .002).

Conclusions

A concurrent subcutaneous infusion of PP enhances insulin sensitivity and reduces insulin requirements in patients with long-standing T1DM and T3cDM on insulin pump therapy. The benefit of PP infusion correlated with the degree of PP deficiency.     

Inhaled Technosphere? Insulin in Comparison to Subcutaneous Regular Human Insulin: Time Action Profile and Variability in Subjects with Type 2 Diabetes

Background

This study assessed time action profile and within- and between-subject variability of inhaled Technosphere® Insulin (TI) compared with subcutaneous regular human insulin (sc RHI).

Methods

Thirteen subjects with type 2 diabetes (age 56 ± 7 years, body mass index 30.4 ± 3.0 kg·m^-2; hemoglobin A1c 6.9 ± 0.9%; mean ± SD) participated in this six-period crossover isoglycemic glucose clamp study. In randomized order, each subject received three single doses of TI and sc RHI on separate study days.

Results

Inhalation of TI resulted in a higher maximum serum insulin concentration (858 vs 438 pmol·liter^-1; p = 0.0001) and shorter intervals to maximum insulin concentration (17 vs 135 minutes; p = 0.0001) than sc RHI. Overall, 48 units of TI and 24 units of sc RHI provided comparable 3-hour insulin exposure (INS area under the curve_{0–3 h} 55.8 vs 60.0 nmol·min·liter^-1, respectively). Time to maximum metabolic effect was shorter (79 vs 293 minutes; p < 0.0001), and percentage of glucose disposal during the first 3 hours was higher for TI compared with sc RHI (59 vs 27%). Within-subject variabilities of insulin exposure following inhalation of TI for 2 and 3 hours and end of study period were 19, 18, and 16% as compared with 27, 25, and 15% after sc RHI injection (p = not significant).

Conclusion

Technosphere Insulin has a more rapid onset of action than sc RHI. About 60% of the glucose-lowering effect of TI occurs during the first 3 hours after application. In contrast, <30% of the glucose-lowering effect of sc RHI occurs in this period. Technosphere Insulin demonstrated a lower intrasubject variability during the 3-hour postprandial period, without reaching statistical significance.     

Effect of diabetes mellitus on outcomes of hyperglycemia in a mixed medical surgical intensive care unit

Background:

Intensive insulin therapy and degree of glycemic control in critically ill patients remains controversial, particularly in patients with diabetes mellitus. We hypothesized that diabetic patients who achieved tight glucose control with continuous insulin therapy would have less morbidity and lower mortality than diabetic patients with uncontrolled blood glucose.

Method:

A retrospective chart review was performed on 395 intensive care unit (ICU) patients that included 235 diabetic patients. All patients received an intravenous insulin protocol targeted to a blood glucose (BG) level of 80–140mg/dl. Outcomes were compared between (a) nondiabetic and diabetic patients, (b) diabetic patients with controlled BG levels (80–140mg/dl) versus uncontrolled levels (>140 mg/dl), and (c) diabetic survivors and nonsurvivors.

Results:

Diabetic patients had a shorter ICU stay compared to nondiabetic patients (10 ± 0.7 vs 13 ± 1.1, p = .01). The mean BG of the diabetic patients was 25% higher on average in the uncontrolled group than in the controlled (166 ± 26 vs 130 ± 9.4 mg/dl, p < .01). There was no difference in ICU and hospital length of stay (LOS) between diabetic patients who were well controlled compared to those who were uncontrolled. Diabetic nonsurvivors had a significantly higher incidence of hypoglycemia (BG <60 mg/dl) compared to diabetic survivors.

Conclusion:

The results showed that a diagnosis of diabetes was not an independent predictor of mortality, and that diabetic patients who were uncontrolled did not have worse outcomes. Diabetic nonsurvivors were associated with a greater amount of hypoglycemic episodes, suggesting these patients may benefit from a more lenient blood glucose protocol.     

A 16-week open-label, multicenter pilot study assessing insulin pump therapy in patients with type 2 diabetes suboptimally controlled with multiple daily injections

Background

We assessed the efficacy, safety, and patient-reported outcomes (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM) who were suboptimally controlled with a multiple daily injection (MDI) regimen.

Methods

In this subanalysis of a 16-week multicenter study, 21 insulin-pump-naïve patients [age 57 ± 13 years, hemoglobin A1c (A1C) 8.4 ± 1.0%, body weight 98 ± 20 kg, total daily insulin dose 99 ± 65 U, mean ± standard deviation] treated at baseline with MDI therapy with or without oral antidiabetic agents discontinued all diabetes medications except metformin and initiated insulin pump therapy. Insulin was titrated to achieve the best possible glycemic control with the simplest possible dosing regimen. Outcome measures included A1C, fasting and postprandial glucose, body weight, incidence of hypoglycemia, and PROs.

Results

Glycemic control improved significantly after 16 weeks: A1C 7.3 ± 1.0% (−1.1 ± 1.2%, p < .001), fasting glucose 133 ± 33mg/dl (−32 ± 74 mg/dl, p < .005), and postprandial glucose 153 ± 35 mg/dl (−38 ± 46 mg/dl, p < .001). At week 16, the mean daily basal, bolus, and total insulin doses were 66 ± 36, 56 ± 40, and 122 ± 72 U (1.2 U/kg), respectively, and 90% of patients were treated with two or fewer daily basal rates. Body weight increased by 2.8 ± 2.6 kg (p < .001). Mild hypoglycemia was experienced by 81% of patients at least once during the course of the study with no episodes of severe hypoglycemia. There were significant improvements in PRO measures.

Conclusions

Insulin pump therapy using a relatively simple dosing regimen safely improved glucose control and PROs in patients with T2DM who were unable to achieve glycemic targets with MDI therapy. Controlled trials are needed to further assess the clinical benefits and cost-effectiveness of insulin pumps in this patient population.     

Postprandial glucose monitoring further improved glycemia, lipids, and weight in persons with type 2 diabetes mellitus who had already reached hemoglobin A1c goal

Background

Postprandial hyperglycemia contributes to poor glucose control and is associated with increased cardiovascular risk in type 2 diabetes mellitus (T2DM). The objective of the study was to determine the effect of postprandial self-monitoring of blood glucose (pp-SMBG) on glucose control, lipids, body weight, and cardiovascular events.

Method

Subjects with T2DM hemoglobin A1c (A1C) between 6.5 to 7.0% were randomized into the study group (at least two pp-SMBG a day and dietary modification based on glucose readings) and control group (dietary modification based on glucose readings but no mandatory pp-SMBG) for a 6-month, observational study. Oral antidiabetic drugs or insulin regimen was unchanged in either group if A1C remained less than 7.0% during the study. End points included A1C, lipids, body weight, and cardiovascular events.

Results

One hundred sixty-nine subjects, mean age 63 years, and body weight 88 kg were recruited. Hemoglobin A1c, weight, low-density lipoprotein (LDL), and triglycerides (TGs) were similar in the groups at baseline. By the end of 6 months, A1C (6.7 ± 0.1 to 6.4 ± 0.1%, p < .05), body weight (88.5 ± 7.3 to 85.2 ± 6.3 kg, p < .05), LDL (92.3 ± 2 8.4 to 81.1 ± 22.6 mg/dl, p < .05), and TGs (141 ± 21 to 96 ± 17 mg/dl, p < .05) decreased in the study group, but did not change in the control group. No cardiovascular events were observed in either group during the 6-month study period.

Conclusions

In T2DM subjects who had already reached their A1C goal, pp-SMBG at least twice a day was associated with further improvement in glycemia, lipids, and weight, as well as exercise and dietary habit. We assume that lifestyle modification promoted by postprandial hyperglycemia awareness may underlie these findings. These results substantiate the importance of implementing pp-SMBG into lifestyle modification, and emphasize that pp-SMBG is critical in the control of T2DM.     

Model for end-stage liver disease-based allocation system for liver transplantation in Argentina: does it work outside the United States?

Background

In July 2005, Argentina was the first country after the United States to adopt the MELD system. The purpose of the present study was to analyse the impact of this new system on the adult liver waiting list (WL).

Methods

Between 2005 and 2009, 1773 adult patients were listed for liver transplantation: 150 emergencies and 1623 electives. Elective patients were categorized using the MELD system. A prospective database was used to analyse mortality and probability to be transplanted (PTBT) on the WL.

Results

The waiting time increased inversely with the MELD score and PTBT positively correlated with MELD score. With scores ≥ 18 the PTBT remained over 50%. However, the largest MELD subgroup with <10 points (n =433) had the lower PTBT (3%). In contrast, patients with T₂ hepatocellular carcinoma benefited excessively with the highest PTBT (84.2%) and the lowest mortality rate (5.4%). The WL mortality increased after MELD adoption (10% vs. 14.8% vs. P < 0.01). Patients with <10 MELD points had >fourfold probability of dying on the WL than PTBT (14.3% vs. 3%; P < 0.0001).

Conclusions

After MELD implementation, WL mortality increased and most patients who died had a low MELD score. A comprehensive revision of the MELD system must be performed to include cultural and socio-economical variables that could affect each country individually.     

Pioglitazone Improves Metabolic Markers in Patients with Type 2 Diabetes Independently from Physical Activities: Results from the IRIS III Study

Aim

Pioglitazone is an established peroxisome proliferator-activated receptor γ agonist for the treatment of insulin resistance in patients with type 2 diabetes mellitus. This analysis of the observational IRIS III study was performed to evaluate the effects of pioglitazone treatment in relation to the degree of physical exercise activities in a large patient population under daily life conditions.

Methods

A total of 1298 patients out of 2092 enrolled into the IRIS III study who had provided information about their exercise level could be included in the final analysis (622 female, 676 male; age: 63.1 ± 10.4 years, diabetes duration: 6.6 ± 5.0 years, mean ± SD). All patients were glitazone naïve prior to study entry. They received pioglitazone in addition to their previous oral antidiabetic treatment. The patients were stratified according to their physical activity level (never, sometimes, and regularly). Data were evaluated at baseline and after 20 ± 2 weeks of treatment. Observation parameters were fasting blood glucose, lipids, and blood pressure. Hemoglobin A1c (HbA1c) was determined in a central laboratory, and insulin sensitivity was assessed by the IRIS II score.

Results

Glycemic control, blood pressure, and the lipid profile improved independently from the degree of physical activity (e.g., no exercise vs frequent exercise: ΔHbA1c: −0.89 ± 1.2% vs −0.72 ± 1.1%, not significant). A positive impact of exercise on insulin resistance could be observed at baseline, which, however, was further decreased by pioglitazone treatment [IRIS II score (baseline/end point): no exercise vs frequent exercise: 74.0 ± 15.9/62.5 ± 20.2 vs 66.7 ± 19.0/58.0 ± 21.8, p < 0.001/not significant].

Conclusions

These observational results, obtained from a nonselected patient population under daily routine conditions, confirm that the benefits of pioglitazone treatment on glycemic control, lipid metabolism, and blood pressure are independent from physical activity. Exercise has a positive influence on insulin sensitivity, but pioglitazone shows additional favorable effects and is, therefore, recommended for use independently from the activity level of the patients.     

The effect of real-time continuous glucose monitoring on glycemic control in patients with type 2 diabetes mellitus

Background:

Real-time continuous glucose monitoring (RT-CGM) improves hemoglobin A1c (A1C) and hypoglycemia in people with type 1 diabetes mellitus and those with type 2 diabetes mellitus (T2DM) on prandial insulin; however, it has not been tested in people with T2DM not taking prandial insulin. We evaluated the utility of RT-CGM in people with T2DM on a variety of treatment modalities except prandial insulin.

Methods:

We conducted a prospective, 52-week, two-arm, randomized trial comparing RT-CGM (n = 50) versus self-monitoring of blood glucose (SMBG) (n = 50) in people with T2DM not taking prandial insulin. Real-time continuous glucose monitoring was used for four 2-week cycles (2 weeks on/1 week off). All patients were managed by their usual provider. This article reports on changes in A1C 0–12 weeks.

Results:

Mean (±standard deviation) decline in A1C at 12 weeks was 1.0% (±1.1%) in the RT-CGM group and 0.5% (±0.8%) in the SMBG group (p = .006). There were no group differences in the net change in number or dosage of hypoglycemic medications. Those who used the RT-CGM for ≥48 days (per protocol) reduced their A1C by 1.2% (±1.1%) versus 0.6% (±1.1%) in those who used it <48 days (p = .003). Multiple regression analyses statistically adjusting for baseline A1C, an indicator for usage, and known confounders confirmed the observed differences between treatment groups were robust (p = .009). There was no improvement in weight or blood pressure.

Conclusions:

Real-time continuous glucose monitoring significantly improves A1C compared with SMBG in patients with T2DM not taking prandial insulin. This technology might benefit a wider population of people with diabetes than previously thought.