Comparison of efficacy and safety of once- versus twice-daily insulin detemir added on to oral antidiabetics in insulin-naive type 2 diabetes patients: 24-week,crossover, treat to target trial in a single center

AimTo compare once- versus twice-daily insulin detemir added on OADS therapy in insulin-naive type 2 diabetes patients in terms of efficacy and safety.MethodsAn open-label study performed at a single center, comprised a randomized, crossover 24 week with insulin-naive type 2 diabetes patients. Insulin detemir was initiated with mean 0.12 U/kg in all patients (Group I once-daily, Group II twice-daily) and titrated for 24 week.ResultsA total of 50 patients completed the study (Group I n:25, Group II n:25). With use of once- and twice-daily insulin, HbA1c values were decreased by 1.8% (±2.0) and 1.5% (±1.4) within the first 12 weeks (p < 0.01), whereas increased by 0.21% (±0.7) and 0.14% (±0.8) in the second 12 weeks (p > 0.05). The increases in the insulin doses were found as 0.22 U/kg and 0.35 U/kg with once- and twice-daily insulin use, respectively (p:0.04). Although minor hypoglycemic events were similar in both groups in the first 12 weeks, 2-fold increase was found in the patients shifting from once- to twice-daily dose. Within the first and second periods, the body weight of the patients was observed an increase of 0.4 and 1.6 kg with once-daily dose, whereas a decrease of 0.1 and 2.1 kg in the twice-daily dose, in the same period.ConclusionOnce-daily use of insulin detemir up to 0.4 U/kg was found to have similar efficacy and safety as twice-daily use. Twice dose use of insulin did not provide a prominent glycemic control advantage on 1.5-fold higher use of insulin.     

A comparison of the pharmacodynamic profiles of insulin detemir and insulin glargine: A single dose clamp study in people with type 2 diabetes

AimThe pharmacodynamic properties of a single dose of 0.5 U/kg insulin detemir and insulin glargine were compared during two 24-h isoglycaemic clamps, one week apart.MethodsThe order of treatments was randomised. At approximately 08 30 h, persons with T2DM received subcutaneous administration of a 0.5 U/kg dose of either insulin detemir or insulin glargine into the anterior abdominal wall. Plasma glucose was measured at 10-min intervals throughout the 24-h clamp period and isoglycaemia was maintained by variable infusion of 20% glucose. Glucose infusion rates (GIR) and plasma C-peptide were determined throughout each 24-h period.ResultsEleven persons with type 2 diabetes (8 male) with mean (SD) age 58.5 years (8.5), BMI 30.8 kg/m² (2.8) and HbA_1c 7.5% (0.6) were studied. Plasma glucose remained constant during the clamp (CV: insulin detemir 3.7%; insulin glargine 3.8%). Following injection of insulin detemir, GIR increased, reaching a mean peak of 2.29 mg/kg/min (95% CI 1.64, 2.94) at 11.6 h (range 8.9 to 14.3) compared to 1.71 mg/kg/min (95% CI 1.4, 2.0) at 10.2 h (8.1 to 12.3) for insulin glargine (P = 0.025 for GIR_max). Plasma C-peptide decreased during the study period, remaining significantly lower than the fasting level at the study end after both analogues, insulin detemir (P = 0.01) and insulin glargine (P = 0.02).ConclusionIn persons with T2DM, no difference in duration of action following a single subcutaneous dose of insulin detemir and insulin glargine could be observed. Insulin detemir showed greater between subject variability and achieved a significantly higher maximum GIR than insulin glargine.     

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes

AimsShort-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes.MethodsIn this study, 63 patients (age 59 ± 8.3 years, baseline A1c 6.8 ± 0.7%, diabetes duration 3.0 ± 2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR).ResultsAs expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P = 0.02), decreased HOMA-IR (P < 0.001), and reduced AUC_glucagon (P < 0.001). Of note, however, IIT had no significant impact on AUC_GLP-1 (P = 0.24) and reduced AUC_GIP (P = 0.02).ConclusionDespite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.     

Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH

We studied the weight-sparing effect and treatment satisfaction when switching from NPH to insulin detemir in type 2 diabetes. Mean HbA_1c (P < 0.05) and waist circumference (P < 0.05) were reduced while treatment satisfaction improved (P < 0.03). No weight gain was observed. Detemir improves glycemic control, treatment satisfaction, and may provide additional weight-sparing benefits.     

The relative contributions of insulin resistance and beta cell failure to the transition from normal to impaired glucose tolerance varies in different ethnic groups

AimTo evaluate ethnic differences in the contribution of decline in insulin secretion and insulin sensitivity in impaired glucose tolerance (IGT).MethodsSeven hundred and eighteen subjects of Arab, Japanese and Mexican American decent received oral glucose tolerance test (OGTT) with plasma glucose and insulin measurement every 30 min. The Matsuda index of insulin sensitivity and the relation between incremental increase under plasma insulin to glucose curves during the OGTT (ΔI_0–120/ΔG_0–120) were calculated.ResultsNGT Japanese subjects had highest insulin sensitivity index (7.1 ± 4.6) and lowest insulin secretion index ((ΔI_0–120/ΔG_0–120 = 1.1 ± 0.9). Mexican Americans and Arabs had lower insulin sensitivity (4.1 ± 2.8 and 3.5 ± 2.3, respectively) and higher insulin secretion indices (2.2 ± 2.0 and 2.5 ± 2.5). IGT subjects in all ethnic groups had reduced insulin sensitivity and insulin secretion compared to NTG subjects. However, the reduction in insulin sensitivity was the largest in Mexican American (30%), the smallest in Arabs (11.5%) and intermediate in Japanese (23%). Conversely, the decrease in insulin secretion was the greatest in Arabs (80%), the smallest in Mexican Americans (41%) and intermediate in Japanese (55%).In a multivariate regression analysis model, the decline in insulin secretion was a stronger determinant of 2-h plasma glucose in Arabs than the reduction in insulin sensitivity while the opposite was observed in Mexican Americans and Japanese.ConclusionDifferences in insulin sensitivity and insulin secretion are present amongst different ethnic groups. The relative contributions of reduced insulin action and impaired insulin secretion are likely to contribute differentially to progression from NGT to IGT (and diabetes) in different ethnic groups.     

High fat diet induces central obesity,insulin resistance and microvascular dysfunction in hamsters

Microvascular dysfunction is an early finding in obesity possibly related to co-morbidities like diabetes and hypertension. Therefore we have investigated changes on microvascular function, body composition, glucose and insulin tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD, n = 20) or standard (Control, n = 21) diet during 16 weeks. Total body fat and protein content were determined by carcass analysis, aorta eNOS and iNOS expression by immunoblotting assay and mean blood pressure (MAP) and heart rate (HR) by an arterial catheter. Microvascular reactivity in response to acetylcholine and sodium nitroprusside, functional capillary density (FCD), capillary recruitment induced by a hyperinsulinemic status and macromolecular permeability after 30 min ischemia was assessed on either cheek pouch or cremaster muscle preparations. Compared to Control, HFD animals have shown increased visceral fat (6.0 ± 0.8 vs. 13.8 ± 0.6 g/100 g BW), impaired endothelial dependent vasodilatation, decreased FCD (11.3 ± 1.3 vs. 6.8 ± 1.2/field) and capillary recruitment during hyperinsulinemia and increased macromolecular permeability after ischemia/reperfusion (86.4 ± 5.2 vs.105.2 ± 5.1leaks/cm²), iNOS expression and insulin resistance. MAP, HR, endothelial independent vasodilatation and eNOS expression were not different between groups. Our results have shown that HFD elicits an increase on visceral fat deposition, microvascular dysfunction and insulin resistance in hamsters.     

Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE? study in a cohort of French patients with type 1 or type 2 diabetes

AimPREDICTIVE™ (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n = 1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes.MethodsPatients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA_1c, fasting blood glucose and variability of fasting blood glucose) and weight change.ResultsThe incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P < 0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA_1c, by −0.6% and −0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by −1.4 mmol/L and −1.9 mmol/L respectively; and FBG variability, by −0.8 mmol/L and −0.3 mmol/L, respectively (P < 0.0001 for all).ConclusionPatients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.     

Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo

Background and aimsHyperglycaemia blocks sevoflurane-induced postconditioning, and cardioprotection in hyperglycaemic myocardium can be restored by inhibition of the mitochondrial permeability transition pore (mPTP). We investigated whether sevoflurane-induced postconditioning is also blocked in the prediabetic heart and if so, whether cardioprotection could be restored by inhibiting mPTP.Methods and resultsZucker lean (ZL) and Zucker obese (ZO) rats were assigned to one of seven groups. Animals underwent 25 min of ischaemia and 120 min of reperfusion. Control (ZL-/ZO Con) animals were not further treated. postconditioning groups (ZL-/ZO Sevo-post) received sevoflurane for 5 min starting 1 min prior to the onset of reperfusion. The mPTP inhibitor cyclosporine A (CsA) was administered intravenously in a concentration of 5 (ZO CsA and ZO CsA + Sevo-post) or 10 mg/kg (ZO CsA10 + Sevo-post) 5 min before the onset of reperfusion. At the end of reperfusion, infarct sizes were measured by TTC staining. Blood samples were collected to measure plasma levels of insulin, cholesterol and triglycerides.Sevoflurane postconditioning reduced infarct size in ZL rats to 35 ± 12% (p < 0.05 vs. ZL Con: 60 ± 6%). In ZO rats sevoflurane postconditioning was abolished (ZO Sevo-post: 59 ± 12%, n.s. vs. ZO Con: 58 ± 6%). 5 mg and 10 mg CsA could not restore cardioprotection (ZO CsA + Sevo-post: 59 ± 7%, ZO CsA10 + Sevo-post: 57 ± 14%; n.s. vs. ZO Con). In ZO rats insulin, cholesterol and triglyceride levels were significant higher than in ZL rats (all p < 0.05).ConclusionInhibition of mPTP with CsA failed to restore cardioprotection in the prediabetic but normoglycaemic heart of Zucker obese rats in vivo.     

Initial experience of using intracardiac echocardiography (ICE) for guiding balloon mitral valvuloplasty (BMV)

Background and aimsBMV is an established treatment for rheumatic mitral valve stenosis. The procedure is historically guided by fluoroscopy, and the role of intracardiac echocardiogram (ICE) guidance is not well defined. We report our initial experience of using ICE to guide BMV procedures.MethodsDuring BMV procedure, ICE catheter was inserted into the right atrium from the right femoral vein, and the septal puncture was monitored by ICE, as well as positioning of the balloon in the mitral valve. Comparisons were made between ICE, transthoracic echocardiography (TTE), and catheterization derived hemodynamic measurements (cath).ResultsSeventeen patients with mitral stenosis underwent the procedure. The mean age was 44.4 ± 21 years. The mean MV area increased from 0.9 ± 0.1 cm² to 1.7 ± 0.2 cm², P < 0.0001 and the mean gradient decreased from 12.6 ± 5.8 mmHg to 4.9 ± 1.8 mmHg, P < 0.001. Atrial septum puncture and guidance of the balloon into the MV apparatus were obtained in all patients under ICE guidance. Severe MR developed in one patient and was readily detected by ICE. ICE derived gradient measurements were comparable to those obtained by TTE, and cath.ConclusionICE guidance of BMV is feasible, and useful in monitoring safe septal puncture, optimizing balloon positioning, and in detecting complications. The hemodynamic measurements obtained were comparable to those obtained by TTE, and cath.     

Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes

Aims

This study measured the insulin concentration (Ins_[C]) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R?; in the clear/cloudy phases of unsuspended NPH).

One-year sustained glycemic control and weight reduction in type 2 diabetes after addition of liraglutide to metformin followed by insulin detemir according to HbA1c target

AimTo investigate durability of efficacy and safety over 1 year of the sequence of liraglutide added to metformin followed by add-on insulin detemir if glycated hemoglobin (HbA_1c) remains ≥ 7.0%.MethodsPatients previously uncontrolled on metformin ± sulfonylurea with HbA_1c ≥ 7.0% after 12 weeks of adding liraglutide 1.8 mg to metformin (run-in; sulfonylurea discontinued) were randomized 1:1 to 52 weeks’ open-label add-on detemir (randomized treatment [RT] group; n = 162) or continuation without detemir (randomized control [RC] group; n = 161). Patients with HbA_1c < 7.0% continued 52 weeks’ unchanged treatment (observational group; n = 498).ResultsRun-in HbA_1c improvement from 8.3% to 7.6% (–0.6%) was further enhanced in the RT group (–0.50%) and maintained in the RC group (+ 0.01%) over 52 weeks; estimated treatment difference (ETD)[95%CI]: ? 0.51 [? 0.70;?0.31]; P < 0.0001. More RT (52%) than RC patients (22%) achieved HbA_1c < 7.0% at 52 weeks (P < 0.0001). Run-in weight loss (–3.5 kg) was maintained in the RT (–0.05 kg) and enhanced in the RC group (? 1.02 kg) after 52 weeks; ETD [95%CI]: 0.97 [0.04;1.91]; P = 0.04. No major hypoglycemia occurred; minor hypoglycemia rates were low across groups (0.034–0.228 events/patient-year).ConclusionsSupplementing metformin + liraglutide with detemir for 52 weeks improved glycemic control with sustained weight loss and low hypoglycemia rate.     

Hypoglycaemia and QT interval prolongation in type 1 diabetes – bridging the gap between clamp studies and spontaneous episodes

AimsWe propose a study design with controlled hypoglycaemia induced by subcutaneous injection of insulin and matched control episodes to bridge the gap between clamp studies and studies of spontaneous hypoglycaemia. The observed prolongation of the heart rate corrected QT interval (QTc) during hypoglycaemia varies greatly between studies.MethodsWe studied ten adults with type 1 diabetes (age 41 ± 15 years) without cardiovascular disease or neuropathy. Single-blinded hypoglycaemia was induced by a subcutaneous insulin bolus followed by a control episode on two occasions separated by 4 weeks. QT intervals were measured using the semi-automatic tangent approach, and QTc was derived by Bazett's (QTcB) and Fridericia's (QTcF) formulas.ResultsQTcB increased from baseline to hypoglycaemia (403 ± 20 vs. 433 ± 39 ms, p < 0.001). On the euglycaemia day, QTcB also increased (398 ± 20 vs. 410 ± 27 ms, p < 0.01), but the increase was less than during hypoglycaemia (p < 0.001). The same pattern was seen for QTcF. Plasma adrenaline levels increased significantly during hypoglycaemia compared to euglycaemia (p < 0.01). Serum potassium levels decreased similarly after insulin injection during both hypoglycaemia and euglycaemia.ConclusionsHypoglycaemia as experienced after a subcutaneous injection of insulin may cause QTc prolongation in type 1 diabetes. However, the magnitude of prolongation is less than typically reported during glucose clamp studies, possible because of the study design with focus on minimizing unwanted study effects.     

Impact of hepatitis virus infection on arterial calcification among incident hemodialysis patients

BackgroundThe impact of hepatitis virus infection on arterial calcification (AC) was not studied.ObjectiveTo study the prevalence, severity and distribution of AC in incident hemodialysis patients with hepatitis B and C viral infection.Cases and methods172 stage 5 CKD adults (98 male and 74 female) were included; 58 of them were seronegative for both hepatitis B and C (SN group), 48 were positive for hepatitis B virus infection (HBV group) and 66 were hepatitis C virus positive (HCV group). Beside histopathology of the obtained arterial samples, all these cases were examined for body mass index (BMI), serum calcium (Ca), phosphorus (P), alkaline phosphatase (AP), serum albumin, uric acid (UA), alanine transaminase (ALT), parathormone (PTH), fibroblast growth factor 23(FGF23), interleukin 6 (IL6), and 25 hydroxy vitamin D (25 (OH) vit D), hemoglobin concentration, and serum ferritin.Results86 (50%) of the cases had AC; 11 of them were in SN group (19%), 9 in HBV group (18.8%) and all the 66 HCV group (100%). In SN group, 4 had intimal calcification, 5 had medial calcification, and 2 had both intimal and medial calcification. In HBV group, 9 had intimal calcification, while no cases were encountered with either medial or both site calcifications. In HCV group, 16 had intimal calcification, 31 had medial calcification, and 19 had both intimal and medial calcification. Calcification was in the form of spots in one case in SN group, and 6 cases in HBV group, a single plaque of calcification in 5 cases of SN group, 3 cases of HBV group, and 16 cases of HCV group, multiple plaques were detected in 4 cases in SN group, and 31 cases in HCV group, and diffuse calcification in one case in SN group, and 19 cases in HCV group.In HBV group, calcification was only detected in patients with high viremia, while all patients with low or moderate viremia were devoid of calcification. In HCV group, all patients with low viremia had intimal solitary plaque of calcification, all patients with moderate viremia had multiple plaques of medial calcification, while all patients with high viremia had diffuse intimal and medial calcification. Both groups of viral hepatitis were significantly different in comparison to SN group in either distribution or calcification score (P < 0.001 in all).HBV group had significantly lower serum P, CaxP and PTH in comparison to SN group (4.6 ± 0.66 vs. 5.45 ± 0.77 mg/dL, 36.4 ± 7.2 vs. 44.1 ± 8.69, and 348 ± 65.4 vs. 405.9 ± 83.2 pg/mL, P < 0.001, <0.001, and 0.035 respectively). On the other hand, HCV group did not show any significant difference in any of the studied parameters compared to SN group.ConclusionHCV positive patients are more prone to develop AC that is more extensive. HBV positive patients were less likely to have arterial medial calcification, probably related to lower serum phosphorus, CaxP product and PTH. HCV infection should be added as risk factor for AC among CKD patients. Further studies are needed to confirm these findings.     

Résultats de la dilatation mitrale percutanée chez la femme enceinte à propos de 12 cas

IntroductionMitral stenosis (MS) is the most common valvular heart disease revealed or exacerbated by pregnancy. Percutaneous mitral balloon commissurotomy (PMC) is currently the treatment of choice when mitral valve morphology is favorable.Aim of the studyThe purpose of this study is to evaluate the immediate, medium and long term results of percutaneous mitral balloon commissurotomy in pregnant women with a severe symptomatic mitral stenosis despite medical treatment.Patients and methodsIt is a retrospective study including 12 pregnant patients diagnosed with severe mitral stenosis and hospitalized in the cardiology department of Habib Thameur hospital between 1994 and 2014. A clinical and ultrasonographic monitoring was performed for over 15 years.ResultsMean patients age was 31.5 ± 4.4 years. All patients were in NYHA class III or IV despite medical treatment. Mitral regurgitation was rated as moderate in four cases. Functional improvement was observed in all cases immediately after the procedure. Mitral valve area increased from 1.02 ± 0.5 cm² averaged to 2 ± 0.35 cm². Mitral regurgitation increased in three cases and appeared in two cases. All patients delivered at term. Newborns were all healthy. Two of them had a low birth weight. On the long term follow-up (95.58 ± 64.1 months), five patients had mitral restenosis: two had a surgical valve replacement and three underwent a second percutaneous mitral balloon commissurotomy.ConclusionThe effectiveness of the percutaneous mitral balloon commissurotomy is clearly documented by clinical and echocardiographic evaluation. In the case of pregnancy, the goal is not so much to obtain an optimal result but to cause hemodynamic improvement authorizing the continuation of pregnancy and childbirth.     

Discontinuation of hormone replacement therapy in young GH-treated hypopituitary women increases liver enzymes

ObjectiveHypopituitarism, often characterized by hypogonadism, is associated with central obesity, increased cardiovascular and endocrine morbidity and mortality. In Turner syndrome, which is also characterized by hypogonadism liver enzymes are often elevated, but readily suppressed by a short course of hormone replacement therapy (HRT). We investigated the effect of HRT on liver enzymes, lipid levels and measures of insulin sensitivity 26 in hypopituitary women.DesignWe studied 26 hypopituitary women (age 38.8 ± 11.0 (mean ± SD years), BMI 27.4 ± 5.1 kg/m²) during HRT and 28 days off therapy.MethodsWe measured liver enzymes, fasting levels of lipids, insulin and glucose as well as adiponectin and leptin levels. Body composition was assessed by means of anthropometry and bioimpedance.ResultsAlanine transaminase (ALT) and aspartate transaminase (AST) increased after discontinuation of HRT (ALT; treated: 22.3 ± 11.5 vs. untreated: 27.1 ± 11.1 (U/L) (P < 0.02); AST; treated: 20.4 ± 6.1 vs. untreated: 24.6 ± 8.9 (U/L) (P < 0.002)), whereas other liver function tests remained unchanged. Measures of insulin sensitivity and fasting lipids were also unaffected by HRT, whereas leptin levels decreased with cessation of HRT (leptin; treated: 23 (8–71) vs. untreated: 20 (8–64) (μg/L) (P < 0.0005)).ConclusionShort time discontinuation of HRT in young hypopituitary women increased liver enzymes, whereas measures of insulin sensitivity and lipid levels remained unchanged. We speculate that the estrogen component of HRT has beneficial effects on hepatic metabolism through various pathways. Further studies including liver imaging and with a time-dependent design are needed to clarify the role of HRT on liver enzyme levels, metabolic variables and liver fat content.     

Excimer Laser LEsion Modification to Expand Non-dilatable sTents: The ELLEMENT Registry

Background/ObjectivesStent underexpansion is a risk factor for in-stent restenosis and stent thrombosis. Existing techniques to optimize stent expansion are sometimes ineffective. The aim of this study was to evaluate the effectiveness and feasibility of Excimer Laser Coronary Angioplasty (ELCA) in improving stent expansion when high-pressure non-compliant balloon inflation was ineffective.Methods and ResultsECLA ablation was performed at high energy during contrast injection and only within the underexpanded stent. The primary endpoint of successful laser dilatation was defined as an increase of at least 1 mm² in minimal stent cross-sectional area (MSA) on IVUS or an increase of at least 20% in minimal stent diameter (MSD) by QCA, following redilatation with the same non-compliant balloon that had been unsuccessful prior to ELCA. Secondary endpoints were cardiac death, myocardial infarction (MI) and target lesion revascularization. Between June 2009 and November 2011, 28 patients with an underexpanded stent despite high-pressure balloon inflation were included. The mean laser catheter size was 1.2 ± 0.4 (range 0.9-2.0 mm) and a mean of 62 ± 12 mJ/mm² at 62 ± 21hertz were required for optimal expansion. Laser-assisted stent dilatation was successful in 27 cases (96.4%), with an improvement in MSD by QCA (1.6 ± 0.6 mm at baseline to 2.6 ± 0.6 mm post-procedure) and MSA by IVUS (3.5 ± 1.1 mm² to 7.1 ± 1.9 mm²). Periprocedural MI occurred in 7.1%, transient slow-flow in 3.6% and ST elevation in 3.6%. During follow-up, there were no MIs, there was 1 cardiac-death, and TLR occurred in 6.7%.ConclusionsThe ELLEMENT study confirms the feasibility of ELCA with contrast injection to improve stent underexpansion in undilatable stented lesions.     

Glycemic control is impaired in the evening in prediabetes through multiple diurnal rhythms

AimsRecent studies suggest that circadian rhythms regulate glucose metabolism, weight loss, and even drug efficacy. Moreover, molecules targeted at the circadian clock show promise in treating metabolic disease. Therefore, this study set out to better characterize interactions among diurnal rhythms in prediabetes.MethodsTen subjects with prediabetes completed oral glucose tolerance tests at 0700 h and 1900 h on the same day. Lipids and hormones were also measured.ResultsTwo-hour and three-hour glucose tolerances were worse in the evening by 40 ± 52 mg/dl (p = 0.02) and 62 ± 46 mg/dl (p = 0.001), respectively. These impairments were explained by lower insulin sensitivity (OGIS; 5.14 ± 1.02 vs. 4.74 ± 0.77 mg/kg/min; p = 0.03) and 2-hour AUC insulin levels (87.4 ± 37.6 vs. 69.8 ± 40.2 mU∙hr/l; p = 0.02) in the evening. Intriguingly, more insulin resistant subjects had weaker rhythms in insulin sensitivity (r = − 0.66; p = 0.04) but enhanced rhythms in insulin (r = − 0.67; p = 0.03) and cortisol (r = − 0.78; p = 0.008) levels. Importantly, the rhythms in cortisol primarily but also insulin sensitivity drove the declines in evening glucose tolerance (r = 0.86; p = 0.002).ConclusionsGlycemic control is dramatically impaired in the evening in people with prediabetes, particularly when the cortisol rhythm is weak, but is unrelated to the rhythm in insulin levels. Therefore, food intake at dinnertime may need to be curbed in prediabetes.     

Insulin resistance and alanine amino transaminase (ALT) levels in first degree relatives of type 2 diabetes mellitus

IntroductionInsulin resistance is established as an independent predictor of a range of disorders such as obesity, hypertension, dyslipidemia, type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. There is an association of hyperinsulinemia with hypertriglycerdemia, low level of HDL and high level of LDL. In nonalcoholic fatty liver disease, there is an elevation of ALT, raising the possibility that the prospective relationship between ALT and type 2 diabetes may reflect cross-sectional associations with insulin resistance or obesity.Aim and objectiveTo find the significance of insulin resistance and alanine aminotransferase level in first degree relatives of type 2 diabetes mellitus.Materials and methodsThe study included 50 first degree relatives of type 2 diabetes (25 men and 25 women) aged 20–60 years and 30 control of similar age. All cases were taken from SRM Medical College Hospital and Research Centre, Chennai. All the cases were analyzed for HOMA_IR, QUICKI, IR ratio, fasting glucose, insulin (ELISA), lipid profile and alanine aminotransferase. Student's ‘t’ test was applied for statistical analysis.ResultThe data show the significance of insulin resistance (HOMA_IR) (2.76 ± 1.46, 1.35 ± 0.8, p < 0.001) in the first degree relatives of type 2 diabetes mellitus when compared with controls respectively and increased level fasting plasma insulin (12.28 ± 6.16, 6.12 ± 3.04, p < 0.001). In the lipid profile the total cholesterol and TAG are significant. No statistical significance was found in ALT (24.8 ± 9.84, 20.08 ± 11.02).ConclusionResults of the study conclude that there is a high prevalence of insulin resistance in the first degree relatives of type 2 diabetes mellitus. ALT levels in the first degree relatives of type 2 diabetes mellitus had increased levels of insulin resistance, the pathogenesis suggesting increase in ALT levels as seen in insulin resistance condition. In our study, ALT was not statistically significant.