Vascular responses to the multiple overlapped paclitaxel-eluting stents for the treatment of bare-metal in-stent restenotic lesions: angiographic and intravascular ultrasound analysis from the TAXUS-V ISR Trial

BackgroundAlthough effective coverage of coronary diffuse in-stent restenosis (ISR) lesions has warranted the use of multiple drug-eluting stents, the vessel response to paclitaxel-eluting stent (PES) overlap is not fully understood.Methods and materialsIn the TAXUS-V ISR, i.e., comparing PES versus brachytherapy for the treatment of bare-metal ISR, angiographic analyses at 9-month follow-up were available in 184 ISR lesions treated with PES.ResultsIn-stent late loss in entire stented segment of multiple PES (n=50) was 0.45±0.48 mm, whereas that of single PES (n=134) was 0.3±0.47 mm, P=.06. No aneurysm was observed at overlapping PES segments at 9 months. Stent thrombosis up to 9 months was observed in one in each group (single PES, 0.7% vs. multiple PES, 1.8%; P=.47). In a subset of 30 patients, volumetric intravascular ultrasound analysis demonstrated that in-stent net volume obstruction was 12.3±12.4 in single PES (n=20) and 14.9±9.8 in multiple PES (n=10), P=.60. The changes of vessel and lumen at the overlapping PES segment were similar to those of the adjacent 5-mm segments (Δminimum lumen area, mm²: ?1.2±1.0, ?1.1±1.1, ?0.8±0.9, P=.48; Δvessel volume, mm³/mm: ?0.2±1.4, 0.1±1.7, 0.3±1.3, P=.37; proximal, overlap, distal segment, respectively). There was no late incomplete stent apposition at overlapping PES segments.ConclusionsNo in vivo evidence of adverse local vessel response at the site of overlapping PES for the treatment of bare-metal ISR has been demonstrated.     

Gabapentin therapy improves heart rate variability in diabetic patients with peripheral neuropathy

PurposeDiabetic cardiac neuropathy, which is characterized by reduced heart rate variability (HRV), frequently coexists with peripheral neuropathy. Gabapentin has been used for the treatment of diabetic neuropathy. We aimed to evaluate the possible effect of gabapentin treatment on autonomic function in patients with type 2 diabetes via HRV.MethodsThirty patients with type 2 diabetes mellitus and peripheral neuropathy and 28 age- and sex-matched healthy controls were consecutively registered. Each patient underwent HRV measurements, and diabetic patients were administered gabapentin. After 3 months of gabapentin therapy, HRV parameters were measured again.ResultsBaseline HRV parameters were blunted in patients with diabetes mellitus according to the controls [standard deviation of all NN intervals (SDNN, ms): 106.3±29.9 vs. 148.8±36.5, P=.001; power spectrum of the high-frequency band (HF, ms²): 133.6±98.3 to 231.4±197.6, P=.02; power spectrum of the low-frequency band (LF, ms²): 341.8±247.8 to 511.5±409.4, P=.048; LF/HF ratio: 3.3±2.4 to 2.6±1.5, P=.33]. After 3 months of treatment with gabapentin, some HRV parameters showed some improvement. SDNN (106.2±29.8 to 119.4 ± 25, P=.016) and HF (133.6±98.3 to 167.6±118.3, P=.021) increased significantly. LF/HF ratio decreased (from 3.3±2.4 to 2.3±1.9, P=.039) and LF remained unchanged (341.8±247.8 to 352.3±228.9, P=.88).ConclusionsTherapeutic doses of gabapentin not only alleviate neuropathic symptoms but also improve cardiac autonomic function in diabetic patients with peripheral neuropathy.     

Neointimal response following rotational atherectomy compared to balloon angioplasty in a porcine model of coronary in-stent restenosis

In-stent restenosis remains a clinical therapeutic challenge. Rotational atherectomy (RA) is an attractive treatment option as it may cause less vascular injury than balloon angioplasty (BA) and, therefore, limit further neointimal response. In an animal model of coronary in-stent restenosis, thermal injury and stenting created neointima (old NI). The treatment of in-stent restenosis with either BA (n = 9) or RA (n = 11) also generated neointima (new NI). The average areas (mm²) of old NI in the BA and RA groups were similar (3.77 ± 0.40 vs. 3.67 ± 0.53; P = 0.32). However, new NI formed after treatment of in-stent restenosis was significantly less in the RA as compared to the BA group (0.33 ± 0.12 vs. 0.73 ± 36, P < 0.01). In this porcine coronary artery model of in-stent restenosis, treatment with rotational atherectomy resulted in significantly less recurrent neointimal hyperplasia than balloon angioplasty. This animal study, thus, provides a rationale for the clinical use of rotablation in the treatment of in-stent restenosis. Cathet. Cardiovasc. Diagn. 45:332–336, 1998. © 1998 Wiley-Liss, Inc.     

Effects of bile-acid-binding resin (colestimide) on blood glucose and visceral fat in Japanese patients with type 2 diabetes mellitus and hypercholesterolemia: an open-label, randomized, case-control, crossover study

ObjectiveThe objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients.MethodsThis study was an open-label, randomized, case–control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA_1c), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level.ResultsSerum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA_1c significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 μg/ml to 12.4±9.5 μg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable.ConclusionsColestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.     

雷帕霉素对球囊损伤后血管平滑肌细胞表型及内膜增生的影响

目的建立大鼠腹主动脉球囊损伤模型,研究雷帕霉素对血管平滑肌细胞表型和内膜增生的影响。方法26只大鼠随机分为假手术组、球囊损伤组、羧甲基纤维素钠组和雷帕霉素组。雷帕霉素组行腹主动脉球囊损伤术前3天开始每天肌肉注射雷帕霉素0.5mgkg,术后连续14天每天肌肉注射雷帕霉素0.25mgkg。球囊损伤14天后进行电镜观察、组织学观察和形态学分析。结果假手术组电镜下血管平滑肌细胞呈收缩表型,球囊损伤后血管平滑肌细胞呈合成表型,雷帕霉素干预后血管平滑肌细胞电镜下表现介于两者之间。术后14天雷帕霉素组新生内膜面积比羧甲基纤维素钠组减少36.4%(0.14±0.03mm2比0.23±0.06mm2,P<0.01),内膜中膜比减少28.9%(17.7%±3.37%比28.86%±10.25%,P<0.01)。结论以上提示雷帕霉素可以抑制血管平滑肌细胞表型的改变,减轻球囊损伤后新生内膜的增生程度。     

Twelve-month results of a Paclitaxel Releasing Balloon in Patients Presenting with In-stent Restenosis First-in-Man (PEPPER) trial

BackgroundCoronary in-stent restenosis (ISR) continues to be a therapeutic challenge especially after drug eluting stent (DES) implantation. We studied patients with ISR to investigate safety and efficacy of a novel drug coated balloon (DCB) incorporating paclitaxel into a microcrystalline structure by applying the inert excipient butyryltri-n-hexyl citrate (BTHC) in a prospective First-in-Man trial.Methods and MaterialsEighty-one patients were enrolled at 9 European sites, thereof 43 (53.1%) presenting with bare metal stent (BMS)-ISR and 38 (46.9%) with DES-ISR. The primary study endpoint was in-stent late lumen loss (LLL) independently assessed by a quantitative coronary angiography laboratory at 6 months. A secondary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, non-fatal myocardial infarction, clinically driven target vessel revascularization after 6 and 12 months.ResultsAt 6 months, overall LLL was 0.07±0.31 mm showing differences in BMS-ISR and DES-ISR treatment (? 0.05±0.28 mm vs. 0.19±0.29 mm, respectively, P=.001). Overall MACE rates at 6 and 12 months were 6.5% and 11.8%. At the 12-month follow-up, one myocardial infarction, and no cardiac death nor stent thrombosis had occurred.ConclusionApplication of a novel paclitaxel coated balloon using BTHC as an excipient in patients with ISR is safe and results in very low LLL, revascularization- and MACE-rates at follow-up. (ClinicalTrials.gov:NCT00961181).     

Improvement of glycaemia control in subjects with type 2 diabetes by self-monitoring of blood glucose: comparison of two management programs adjusting bedtime insulin dosage

Aim: Self‐monitoring of blood glucose (SMBG) is important for patients treated with insulin to detect asymptomatic hypoglycaemia and to guide patients towards reaching blood glucose goal. This study compared two management programs for adjusting bedtime insulin dose: program 1 (performed by study subjects) vs. program 2 (performed by study subjects and reminded by investigators). Methods: This is a prospective, open‐level, 28‐week randomized trial in poorly controlled type 2 diabetic subjects. One hundred subjects treated with oral antidiabetic drugs plus bedtime insulin with glycated haemoglobin A_1C (A1C) >8.0% were screened and received a structure education package in a 4‐week run‐in period. Seventy‐eight subjects were randomized to two treatment programs (adjust insulin dose by themselves with or without investigators’ reminder) and reviewed by the investigators at a 4‐week interval clinical visit. Results: The mean SMBG decreased significantly in both groups, with a greater decrease observed in program 2 vs. program 1 (from 198.7 ± 43.1 to 122.6 ± 21.9 mg/dl vs. from 194.0 ± 42.7 to 151.6 ± 37.7 mg/dl, p < 0.001). Bedtime insulin dose increased in both groups with a greater increase in program 2 (from 14.4 ± 8.7 to 27.4 ± 12.8 IU vs. from 14.3 ± 8.3 to 18.4 ± 6.2 IU, p < 0.001). There was a significant reduction in A1C from 9.54 ± 1.67% to 7.76 ± 1.27%, with a greater decrease (p < 0.001) in program 2 (2.17%) than in program 1 (1.40%). There were more subjects in the program 2 group achieving the treating targets: mean SMBG ≤120 mg/dl (46.9 vs. 17.9%) and A1C ≤7.0% (54.5 vs. 32.2%). There was no significant difference in the incidence of hypoglycaemia and body weight changes. Conclusions: Systematically titrating bedtime insulin dose added to oral therapy, especially combined with health care reminders, can safely improve glycaemic control in type 2 diabetes with poor glycaemic control. This regimen may facilitate safe and effective insulin therapy in routine medical practice and improve achievement of recommended standards of diabetes care.     

Use of Serum c-Peptide Level to Simplify Diabetes Treatment Regimens in Older Adults

BackgroundDiabetes management in older adults is challenging. Poor glycemic control and high risk of hypoglycemia are common in older patients on a complicated insulin regimen. Newer oral hypoglycemic agents have provided an opportunity to simplify regimens in patients with type-2 diabetes on insulin. Serum c-peptide is a test to assess endogenous production of insulin. We analyze the use of serum c-peptide level in simplifying diabetes regimen by decreasing or stopping insulin injection and adding oral hypoglycemic agents in older adults.MethodsOne hundred patients aged over 65 years with either poor glycemic control or difficulty coping with insulin regimen seen at a geriatric diabetes clinic were analyzed for this study. The data on serum c-peptide levels and A1c, along with demographic information, were obtained from medical charts.ResultsSixty-five of 100 patients (aged 79 ± 14 years, duration of diabetes 21 ± 13 years) had detectable serum c-peptide levels. Forty-six of 65 patients were available for simplification of regimen. Eleven of 46 patients had other co-morbidities preventing use of oral hypoglycemic agents. In 35/65 patients, simplification was completed successfully. Nineteen of 35 patients were converted to all-oral regimens (off insulin), while 16/35 had simplification of regimen by addition of oral hypoglycemic agents and lowering the number of insulin injections from an average of 2.7 to 1.5 injections/day (P = .001). Glycemic control improved significantly in patients with a simplified regimen (8.0% ± 1.5% vs 7.4% ± 1.5%; P < .002), and patients reported fewer hypoglycemia episodes.ConclusionsSerum c-peptide level can be used to simplify insulin regimen in older adults with diabetes.     

Major bleeding complicating contemporary primary percutaneous coronary interventions—incidence,predictors, and prognostic implications

BackgroundMajor bleeding is one of the most frequent procedural-related complications of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infraction (STEMI). We investigated the incidence, predictors, and prognostic impact of peri-procedural bleeding in a cohort of unselected patients undergoing contemporary primary PCI.MethodsA total of 831 consecutive patients who underwent primary PCI between 1/2001 and 6/2005 were studied. Major bleeding was defined as hemorrhagic stroke, hemoglobin (Hb) drop of >5 g%, or 3–5 g% with a need for blood transfusion. Clinical outcomes were evaluated at 30 days and 6 months.ResultsMajor bleeding occurred in 27 patients (3.5%). Those who experienced major bleeding were older (66±15 vs. 61±13, P=.02), more frequently female gender (48% vs. 27%, P=.0001), presented more often with cardiogenic shock (37% vs. 8%, P=.0001), and had higher CADILLAC score (7.8±4.5 vs. 5.1±4.0, P=.002) and activated clotting time (ACT) levels (284±63 vs. 248±57 s, P=.007). In multivariate analysis, significant predictors of major bleeding were female gender (OR 5.1, 95% CI 1.7–15.2, P=.004), ACT levels >250 s (OR 3.6, 95% CI 1.1–12.1, P=.04), and use of intra-aortic balloon pump (IABP) (OR 3.5, 95% CI 1.0–12.1, P=.047). Major bleeding was associated with increased 6-month mortality rates (37% vs. 10%, P=.0001), which remained significant after adjustment for baseline CADILLAC score (37% vs. 19.4%, P=.05).ConclusionsMajor bleeding complicating primary PCI is associated with increased 6-month mortality. Women and those who need IABP support are at particularly high risk. Tight monitoring of anticoagulation may reduce the risk of bleeding.     

Erythropoietin response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure

AimWe aim to investigate erythropoietin (EPO) response to anemia and its association with autonomic neuropathy in type 2 diabetic patients without advanced renal failure.MethodsA cross-sectional study was conducted on 211 type 2 diabetes mellitus patients without advanced renal failure [estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m²]. The response of EPO to anemia of type 2 diabetic patients without advanced renal failure was compared with those of nondiabetic control subjects. Autonomic nerve function was assessed using three cardiovascular tests (deep breathing, the Valsalva maneuver, and lying-to-standing). The results of each test were scored as 0 if normal, 1 if borderline, and 2 if abnormal. Autonomic neuropathy was diagnosed when a total score of the tests was 2 or more.ResultsFifty-eight patients were anemic; compared with nonanemic patients, they had a longer duration of diabetes (16.69±10.11 vs. 10.67±8.41 years, P<.001), lower eGFR (66.43±16.30 vs. 81.74±19.49 ml/min/1.73 m², P<.001), and higher cardiovascular autonomic neuropathy score (3.17±1.95 vs. 1.79±1.72, P<.001). Serum EPO level was weakly correlated with hemoglobin (Hb) level (r=?.085, P<.001). However, the slopes of regression lines between EPO and Hb levels differed significantly between type 2 diabetic patients and nondiabetic control subjects (?0.0085 vs. ?0.255, P=.008). Multiple linear regression analysis revealed that cardiovascular autonomic neuropathy score was independently related to Hb (P<.001) or EPO level (P=.052).ConclusionsAutonomic neuropathy is associated with a blunted EPO response to anemia in type 2 diabetic patients without advanced renal failure.     

The ischemic etiology of heart failure in diabetics limits reverse left ventricular remodeling after cardiac resynchronization therapy

Aim of the StudyThe aim of this study was to evaluate reverse volumetric left ventricular (LV) remodeling after cardiac resynchronization therapy (CRT) in patients with heart failure (HF) with vs. without diabetes mellitus (DM).MethodsThe study comprised 130 consecutive patients with HF (mean age, 61±12 years) who underwent CRT. Thirty patients (23%) had DM [mean glycated haemoglobin (HbA_1c), 7.2±3.4%; 13 (43%) on insulin therapy]. Echocardiography, including tissue Doppler measurements, was performed before CRT and between 3 and 6 months after CRT. Echocardiographic response was defined as a >15% reduction in LV end-systolic volume (ESV).ResultsPatients with DM had more often hypertension (60% vs. 29%, P<.05) and ischemic HF etiology (87% vs. 51%, P<.05), but similar pre-CRT echocardiographic findings. After CRT, patients with DM had equal reductions in QRS duration and lateral-to-septal mechanical delay, but less improvement in LV ESV, mitral annular tissue velocity, the myocardial performance (or Tei) index and the E/E′ ratio (ratio of early transmitral peak filling velocity to early mitral annular peak diastolic velocity, an indicator of LV filling pressure). Patients without reverse volumetric LV remodeling had more often DM [hazard ratio (HR), 1.897; P=.042] and an ischemic HF etiology (HR, 2.308; P=.006). An ischemic HF etiology (HR, 2.119; P=.018) was the only independent predictor of poor reverse volumetric LV remodeling.ConclusionIschemic etiology of HF is an independent predictor of poor echocardiographic response to CRT. Patients with DM and HF have a relatively poor echocardiographic response to CRT most probably due to a high incidence of ischemic etiology of HF.     

Early screening for gestational diabetes mellitus is not associated with improved pregnancy outcomes: an observational study including 9795 women

AimsIn addition to screening for hyperglycaemia during pregnancy after 24 weeks of gestation (WG), the current guidelines also suggest screening in early pregnancy and referring women with early gestational diabetes mellitus (eGDM) or overt diabetes (OD) for immediate care. Our aim was to evaluate this strategy.MethodsThis study evaluated, at our hospital (2012–2016), whether the incidence of a predefined composite outcome (preeclampsia, large-for-gestational-age infant, shoulder dystocia) and secondary outcomes was different when women were screened only after 22WG (‘late screening only’) or before 22WG and treated for eGDM or OD if present, with repeat screening after 22WG if absent (‘early ± late screening’).ResultsEarly ± late screening (n = 4605, 47.0%) increased between 2012 and 2016 (P < 0.0001) and was associated with more risk factors for GDM than late screening only. Glycaemic status differed in both groups (early ± late screening: eGDM 10.3%, GDM 12.1%, OD 0.9% vs. late screening only: GDM 16.8%, OD 1.2%; P < 0.001), with a higher rate of insulin therapy (8.9% vs. 6.0%; P < 0.001) and less gestational weight gain (11.1 ± 5.4 kg vs. 11.4 ± 5.5 kg; P = 0.013) in the early ± late screening group. Rates of those meeting the composite criterion were similar in both groups [11.6% vs. 12.0%, respectively; odds ratio (OR): 1.040, 95% confidence interval (CI): 0.920–1.176; P = 0.53] and remained comparable after adjusting for Propensity Scores (OR: 1.046, 95% CI: 0.924–1.185; P = 0.4790). Rates for secondary outcomes were also similar in both groups.ConclusionWhile a strategy including early measurement of fasting plasma glucose during pregnancy increases the incidence and care of hyperglycaemia during pregnancy, it may not significantly improve pregnancy outcomes.     

Therapeutical potential of autologous peripheral blood mononuclear cell transplantation in patients with type 2 diabetic critical limb ischemia

AimThe aim was to evaluate the therapeutic effectiveness of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (PBMNCs) in critical limb ischemia (CLI) of type 2 diabetic patients.MethodForty diabetic patients with CLI were enrolled and randomized to treatment and control groups. In the treatment group, the patients received subcutaneous injections of recombinant human G-CSF (30 MU/day) for 5 days to mobilize stem cells. PBMNCs were collected and transplanted by multiple intramuscular injections of 1 ml in 1–1.5-cm depth into ischemic limbs.ResultsAt the end of 12 weeks of follow-up, the baseline and end point results in transplant group were as follows: Fontaine score improved from 3.8±03 to 3±0.5 (P=.0001), ankle brachial pressure index increased from 0.68±0.24 to 0.87±024 (P=.001), transcutaneous oxygen increased from 33±14 mmHg to 44±10 mmHg (P=.0001), and 6-min walking distance improved from 280±82 m to 338±98 m (P=.0001). Pain score decreased from 8.2±1.3 to 5.63±1.6 (P=.001), and the number of patients with limb ulcers was reduced from 9/20 (45%) to 3/20 (15%) (P=.031). In the control group, Fontaine score, 6-min walking distance, and pain score were improved; ankle brachial pressure index and transcutaneous oxygen pressure were not improved. The number of patients with limb ulcers did not change in the control group. There are improvement in amputation rates, collateral vessel development, and number of limb ulcers healed.ConclusionsThese results indicate that the autologous transplantation of G-CSF that mobilized PBMNCs in CLI diabetic patients is safe and effective in patient compliant reduction and improved perfusion.     

Effect of insulin-metformin combination on hepatic steatosis in patients with type 2 diabetes

ObjectiveHepatic steatosis occurs in up to 78% of patients with type 2 diabetes. Studies evaluating the effect of metformin on hepatic steatosis are conflicting. Insulin is believed to be detrimental due to its lipogenic effect. Since insulin–metformin combination is commonly used for the treatment of diabetes, it is important to assess the effect of this combined therapy on hepatic steatosis. We evaluated the change in hepatic steatosis following the initiation of insulin and metformin in patients with type 2 diabetes.MethodsNewly diagnosed treatment-naïve patients with type 2 diabetes had their hepatic triglyceride (TG) content measured by magnetic resonance spectroscopy at baseline and after 3 months of treatment with BiAsp 30 insulin, in combination with metformin. Insulin was administered twice daily and titrated to achieve normal capillary blood glucose levels. Metformin was titrated during the first month from 500 mg daily to 1000 mg bid.ResultsThe average hepatic TG content in 19 enrolled subjects was 11.83±7.61% (range, 0.93–23.16%) and correlated with body mass index (r=.567). Three months of treatment reduced hepatic steatosis by 45%, with 75% of the study subjects achieving a normal level. The change in hepatic TG content was partially explained by changes in HbA1c (P=.006) and cholesterol (P=.003) levels.ConclusionsThe combined treatment with insulin and metformin significantly reduced hepatic steatosis in patients with newly diagnosed type 2 diabetes.     

Additional stenting promotes intimal proliferation and compromises the results of intravascular radiation therapy: an intravascular ultrasound study

Background

Vascular brachytherapy (VBT) reduces in-stent restenosis (ISR). However, additional stenting at the time of radiation may be associated with a worse outcome.

Methods and results

Intravascular ultrasound (IVUS) was performed after VBT and at 6 months follow-up in 79 native artery ISR patients treated with γ-radiation who participated in the Washington Radiation for In-Stent restenosis Trial (WRIST), Gamma-1, and Angiorad Radiation Technology for In-Stent restenosis Trial in Coronaries (ARTISTIC) trials. Patients were treated with ¹⁹²Ir at 14 or 15 Gy at 2 mm from the source. Additional stents were used to treat the ISR lesions in 45 patients; these patients were then compared with the 34 patients treated without restenting. Paired measurements included stent, lumen, and intimal hyperplasia volumes. After the VBT procedure, intimal hyperplasia volume was smaller in the group treated with additional stents (54 ± 33 mm³ vs 34 ± 33 mm³, P = .012), but minimal lumen area was similar between the 2 groups (4.3 ± 1.5 mm² vs 4.7 ± 1.4 mm² respectively, P = NS). Between the time of the VBT procedure and follow-up, intimal hyperplasia volume increased by 27 ± 19 mm³ in the restented group and by 9 ± 21 mm³ in the group treated without additional stents (P = .014). At 6 months, intimal volume was similar in the 2 groups, but minimal lumen area was slightly smaller in the group treated with additional stents (3.4 ± 1.8 mm² vs 4.2 ± 1.7 mm², P = .053). Patients treated with additional stents had more target lesion revascularizations than the group treated without additional stents (38% vs 15%, P = .02).

Conclusions

Additional stenting reduces intimal hyperplasia within the stents acutely. However, it compromises the benefit of VBT by promoting higher intimal regrowth within months after radiation.     

Different effects of thiazolidinediones on target vessel revascularization with bare metal stents: a meta-analysis

ObjectiveThiazolidinediones (TZDs) are used in patients with Type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on target vessel revascularization. The aim of this meta-analysis is to evaluate the effect of TZDs on repeat target vessel revascularization following percutaneous coronary intervention.Research design and methodsWe searched Medline, EMBASE, Cinahl, and the Cochrane Database from earliest available date through December 2007. Criteria for inclusion in our meta-analysis included the use of randomized control trial and the availability of target vessel revascularization. Relative risks (RRs) with 95% confidence intervals (CIs) of target vessel revascularization (TVR) and restenosis were estimated using a fixed-effects meta-analysis of seven randomized controlled trials (n=347, including 178 receiving pioglitazone and 169 receiving rosiglitazone).ResultsOne hundred seventy-eight patients were treated with pioglitazone, and 169 were treated with rosiglitazone. Pioglitazone is associated with a significantly lower risk of target vessel revascularization or restenosis (TVR: n=37/96 vs. 7/94; RR, 5.91; 95% CI, 3.00–11.7; P<.0001, restenosis: n=42/96 vs. 8/94; RR, 6.48; 95% CI, 3.37–12.4; P<.0001). Rosiglitazone had no effect on target vessel revascularization (n=56/131 vs. 51/124; RR, 1.11; 95% CI, 0.63–1.96; P=.793).ConclusionsPioglitazone is associated with a significantly decreased risk of target vessel revascularization, but rosiglitazone does not reduce the risk of target vessel revascularization following percutaneous coronary intervention.     

Salsalate improves glycemic control in patients with newly diagnosed type 2 diabetes

Chronic inflammation contributes to insulin resistance and type 2 diabetes mellitus (T2DM). We investigated whether treatment with salsalate, an anti-inflammatory medication, improves glycemia in a group of newly diagnosed drug-naïve patients with T2DM. The study was a randomized, double-blind, placebo-controlled trial. Diagnosis of T2DM was made within 2 months of enrollment, and participants had not received any anti-glycemic agent. Sixty adults were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Fasting plasma glucose and insulin, glucose 2 h after 75 g oral glucose, HbA1C, lipid profile, HOMA-IR, and HOMA-B were determined before and after treatment. Salsalate reduced fasting glucose from 6.3 ± 0.2 mmol/l to 5.4 ± 0.2 mmol/l (P < 0.01) and TG from 1.9 ± 0.2 mmol/l to 1.5 ± 0.2 mmol/l (P < 0.03). Fasting insulin levels were increased in the salsalate group from 18.8 ± 1.6 to 21.6 ± 3.9, while they decreased in the placebo group. HbA1c rose in the placebo group from 6.2% ± 0.2 to 7.9% ± 1.1 mmol/mol, but decreased in the intervention group from 6.1% ± 0.5 to 5.6% ± 0.2 mmol/mol (P < 0.04 for between-group comparison). HOMA-IR did not change but HOMA-B increased ~1.7-fold (P = 0.06) in the salsalate group. The results show that salsalate is effective in improving glycemic control in newly diagnosed naïve patients with T2DM. The optimal duration of treatment with salsalate and sustainability of its effect requires further study (IRCT138709011465N1).     

Comparison of inflammatory response after implantation of sirolimus- and paclitaxel-eluting stents in patients on hemodialysis

Because systemic inflammation after coronary intervention places patients at increased risk of subsequent cardiac events, we aimed to compare clinical outcomes and chronic serum inflammation markers of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) in hemodialysis patients. Paclitaxel-eluting stents and SES were implanted in 36 patients with 46 lesions, and 32 patients with 40 lesions, respectively. In addition to 1-year major adverse cardiac event (MACE) rates, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), neopterin, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) were also compared before and 9 months after percutaneous coronary intervention (PCI). The incidence of MACE was significantly lower in the PES group than in the SES group (11.1 vs. 25.0 %, respectively, P = 0.042), mainly due to the reduction of target lesion revascularization in the PES group (6.5 vs. 17.5 %, P = 0.003). The logarithm of hs-CRP as well as IL-6 decreased significantly 9 months post-PCI compared with pre-PCI in the PES group (hs-CRP: 3.65 ± 0.35 vs. 2.91 ± 0.48, P = 0.007; IL-6: 6.73 ± 3.66 vs. 2.61 ± 2.29, P = 0.017) but not in the SES group (hs-CRP: 3.33 ± 0.29 vs. 3.42 ± 0.27, P not significant; IL-6: 6.08 ± 4.97 vs. 5.66 ± 4.29, P not significant). However, neopterin, ICAM-1, and VCAM-1 remained unchanged both pre-PCI and 9 months post-PCI in both groups. Moreover, MACE were less frequent in patients with decreased hs-CRP levels 9 months post-PCI compared with patients without decreased hs-CRP levels (P = 0.002) in all patients. Paclitaxel-eluting stents appear to be more effective than SES in reducing MACE rates, especially target lesion revascularization, and may be able to stabilize local inflammatory changes of target lesions specifically in patients on hemodialysis. Thus PES, which inhibit in-stent restenosis and cardiac events in hemodialysis patients, may play an important role in suppression of chronic inflammatory response in target lesions as compared with SES. Chronic continuous inflammation plays an important role after implantation of both types of stent with regard to in-stent restenosis in patients on hemodialysis.     

Basal insulin or premix analogue therapy in type 2 diabetes patients

BackgroundWe sought to compare the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) given twice daily with once-daily insulin glargine in patients with type 2 diabetes beginning insulin therapy and who did not use thiazolidinediones, which are contraindicated with insulin in the European Union, in a subpopulation (N = 157) of the INITIATE study.MethodsAt baseline, HbA_1c was ≥ 8.0% on ≥ 1000 mg/day metformin alone or in combination with other oral antidiabetic drugs (OADs; e.g. sulphonylurea or alpha-glucosidase inhibitors). Metformin was adjusted up to 2550 mg/day and other OADs were discontinued. Starting insulin doses were subsequently adjusted weekly for 26 weeks by algorithm-directed titration.ResultsThe proportion of patients achieving a HbA_1c below 7.0% at 28 weeks was greater with BIAsp 30 than with insulin glargine (65% vs 41%, P = 0.003). The mean reduction in HbA_1c was greater for BIAsp 30 than for insulin glargine: − 2.89 ± 1.6% vs − 2.46 ± 1.6%, respectively (P = 0.035). Postprandial glucose increments were lower for the BIAsp 30 group after breakfast (P = 0.003) and dinner (P = 0.033); post-lunch values were not significantly different. No major hypoglycemic episodes were recorded. Nocturnal hypoglycemia was reported by 25% of subjects in the BIAsp 30 group and by 10% in the insulin glargine group (P = 0.021). Weight gain was 5.6 ± 4.6 and 3.0 ± 4.3 kg (P = 0.0004) for BIAsp 30 and insulin glargine, respectively.ConclusionsBIAsp 30, given twice daily in combination with metformin, was more effective than insulin glargine, given once daily in combination with metformin, at controlling blood glucose in insulin-naïve patients with type 2 diabetes, but was associated with increased weight gain and minor hypoglycemic events.     

Effect of insulin on renal sodium handling and renal haemodynamics in insulin-dependent (type 1) diabetes mellitus patients

The effects of insulin on renal haemodynamics and renal sodium handling were studied in eight insulindependent (type 1) diabetic patients (aged 30±3 years). Seven healthy men (aged 38±4 years) served as controls. The type 1 diabetic patients were resistant to insulin-stimulated glucose disposal as estimated by a 45% lower metabolic (P<0.01) clearance of glucose as compared with controls. However, type 1 diabetic patients were still sensitive to the distal tubular antinatriuretic effect of insulin, as indicated by an increase in distal sodium reabsorption (95.5%±0.5% to 96.9%±0.4%;P<0.05) during insulin infusion compared with controls (95.5%±0.6% to 97.4%±0.3%;P<0.05). In control subjects insulin infusion was associated with 9% increases (P<0.05) in lithium clearance and in renal plasma flow, whereas no significant increases in lithium clearance and in renal plasma flow were observed in the type 1 diabetic patients. In both groups, the changes in renal plasma flow in response to insulin infusion were positively correlated with that in lithium clearance (r=0.80 andr=0.90, respectively;P<0.05?0.01). In conclusion, the present result demonstrates an intact distal tubular sodium retaining effect in conjunction with a blunted decrease in proximal tubular sodium reabsorption following insulin infusion, which could be the result of an impaired renal vasodilation in type 1 diabetes mellitus.