Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD.</p> <p>Methods</p> <p>We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines.</p> <p>Results</p> <p>IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1-13.2]), respectively (p < 0.001).</p> <p>Conclusions</p> <p>Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR.</p

Correlations between atazanavir Ctrough and hyperbilirubinemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hyperbilirubinemia is a common side effect of the antiretroviral agent atazanavir but is generally reversible upon discontinuation of treatment. We used therapeutic drug monitoring to investigate the occurrence of hyperbilirubinemia in a 49-year-old Hispanic man infected with HIV, following an overdose of ritonavir in ritonavir-boosted atazanavir therapy.</p> <p>Case presentation</p> <p>A 49-year-old Hispanic man with HIV who had received several highly active antiretroviral therapy regimens over a number of years including atazanavir-containing regimens, was diagnosed with hyperbilirubinemia. An inappropriate doubling of ritonavir boosting resulted in a high atazanavir C_troughand an initial rise in bilirubin plasma levels. Bilirubin levels later decreased, probably as a consequence of enzyme induction, while atazanavir plasma concentrations remained elevated.</p> <p>Conclusion</p> <p>This article describes an occurrence of hyperbilirubinemia in a man infected with HIV and supports the importance of therapeutic drug monitoring in investigations of hyperbilirubinemia among patients receiving antiretroviral agents. That the patient tolerated exceptionally high atazanavir levels further strengthens the tolerability profile of this drug.</p

Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentrations (FEC) in patients with diabetes mellitus

<p>Abstract</p> <p>Objective</p> <p>Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus.</p> <p>Methods</p> <p>The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation.</p> <p>Results</p> <p>FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88 patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could not be classified because of lacking information (4.6%).</p> <p>Conclusions</p> <p>Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.</p

Subclinical Inflammation and Diabetic Polyneuropathy: MONICA/KORA Survey F3 (Augsburg, Germany)

Subclinical inflammation represents a risk factor of type 2 diabetes and several diabetes complications, but data on diabetic neuropathies are scarce. Therefore, we investigated whether circulating concentrations of acute-phase proteins, cytokines, and chemokines differ among diabetic patients with or without diabetic polyneuropathy. RESEARCH DESIGN AND METHODS - We measured 10 markers of subclinical inflammation in 227 type 2 diabetic patients with diabetic polyneuropathy who participated in the population-based MONICA/KORA Survey F3 (2004-2005; Augsburg, Germany). Diabetic polyneuropathy was diagnosed using the Michigan Neuropathy Screening Instrument (MNSI). RESULTS - After adjustment for multiple confounders, high levels of C-reactive protein and interleukin (IL)-6 were most consistently associated with diabetic polyneuropathy, high MNSI score, and specific neuropathic deficits, whereas some inverse associations were seen for IL-18. CONCLUSIONS - This study shows that subclinical inflammation is associated with diabetic polyneuropathy and neuropathic impairments. This association appears rather specific because only certain immune mediators and impairments are involved

Limiting esophageal temperature in radiofrequency ablation of left atrial tachyarrhythmias results in low incidence of thermal esophageal lesions

<p>Abstract</p> <p>Background</p> <p>Atrio-esophageal fistula formation following radiofrequency ablation of left atrial tachyarrhythmias is a rare but devastating complication. Esophageal injuries are believed to be precursors of fistula formation and reported to occur in up to 47% of patients. This study investigates the incidence of esophageal lesions when real time esophageal temperature monitoring and temperature limitation is used.</p> <p>Methods</p> <p>184 consecutive patients underwent open irrigated radiofrequency ablation of left atrial tachyarrhythmias. An esophageal temperature probe consisting of three independent thermocouples was used for temperature monitoring. A temperature limit of 40°C was defined to interrupt energy delivery. All patients underwent esophageal endoscopy the next day.</p> <p>Results</p> <p>Endoscopy revealed ulcer formation in 3/184 patients (1.6%). No patient developed atrio-esophageal fistula. Patient and disease characteristics had no influence on ulcer formation. The temperature threshold of 40°C was reached in 157/184 patients. A temperature overshoot after cessation of energy delivery was observed frequently. The mean maximal temperature was 40.8°C. Using a multiple regression analysis creating a box lesion that implies superior- and inferior lines at the posterior wall connecting the right and left encircling was an independent predictor of temperature. Six month follow-up showed an overall success rate of 78% documented as sinus rhythm in seven-day holter ECG.</p> <p>Conclusion</p> <p>Limitation of esophageal temperature to 40°C is associated with the lowest incidence of esophageal lesion formation published so far. This approach may contribute to increase the safety profile of radiofrequency ablation in the left atrium.</p

JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis

This article addresses the criteria for severity assessment and the severity scoring system of the Ministry of Health and Welfare of Japan; now the Japanese Ministry of Health, Labour, and Welfare (the JPN score). It also presents data comparing the JPN score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson score, which are the major measuring scales used in the United States and Europe. The goal of investigating these scoring systems is the achievement of earlier diagnosis and more appropriate and successful treatment of severe or moderate acute pancreatitis, which has a high mortality rate. This article makes the following recommendations in terms of assessing the severity of acute pancreatitis

Pancreatitis and pancreatic cancer in two large pooled case–control studies

The association between duration of pancreatitis and pancreatic cancer has not been well characterized in large population-based studies. We conducted detailed analyses to determine the association between pancreatitis onset and pancreatic cancer risk. Data from two case–control studies of pancreatic cancer (n = 4515) in the San Francisco Bay Area and the M.D. Anderson Cancer Center were pooled for analysis (1,663 cases, 2,852 frequency-matched controls). Adjusted odds ratios (OR) were estimated using a random-effects model. In the pooled multivariable model, history of pancreatitis was associated with a 7.2-fold increased risk estimate for pancreatic cancer [95% confidence interval (CI): 4.0, 13]. The risk estimate was nearly 10-fold in participants aged &lt;55 years (OR = 9.9, 95% CI: 3.5, 28). A shorter temporal history of pancreatitis was more closely associated with pancreatic cancer than was a longer temporal history: &lt;3 years (OR = 29, 95% CI: 12, 71), 3–10 years (OR = 2.6, 95% CI: 1.5, 5.6), and &gt;10 years (OR = 1.8, 95% CI: 0.7, 4.5, p trend &lt; 0.001). A short temporal history of pancreatitis was highly associated with pancreatic cancer, suggesting that pancreatitis may be an early manifestation of pancreatic cancer in some individuals. Pancreatic cancer should be considered in the differential diagnosis of individuals with an episode of pancreatitis

Variation in the human soluble epoxide hydrolase gene and risk of restenosis after percutaneous coronary intervention

<p>Abstract</p> <p>Background</p> <p>Restenosis represents the major limiting factor for the long-term efficacy of percutaneous coronary intervention (PCI). Several genetic factors involved in the regulation of the vascular system have been described to play a role in the pathogenesis of restenosis. We investigated whether the <it>EPHX2 K55R </it>polymorphism, previously linked to significantly higher risk for coronary heart disease (CHD), was associated with the occurrence of restenosis after PCI. The association with incident CHD should have been confirmed and a potential correlation of the <it>EPHX2 K55R </it>variant to an increased risk of hypertension was analysed.</p> <p>Methods</p> <p>An overall cohort of 706 patients was studied: This cohort comprised of 435 CHD patients who had undergone successful PCI. Follow-up coronary angiography in all patients was performed 6 months after intervention. Another 271 patients in whom CHD had been excluded by coronary angiography served as controls. From each patient EDTA-blood was drawn at the baseline ward round. Genomic DNA was extracted from these samples and genotyping was performed by real-time PCR and subsequent melting curve analysis.</p> <p>Results</p> <p>In CHD patients 6 month follow-up coronary angiography revealed a restenosis rate of 29.4%, classified as late lumen loss as well as lumen re-narrowing ≥ 50%.</p> <p>Statistical analysis showed an equal genotype distribution in restenosis patients and non-restenosis patients (A/A 82.0% and A/G + G/G 18.0% versus A/A 82.1% and A/G + G/G 17.9%). Moreover, neither a significant difference in the genotype distribution of CHD patients and controls nor an association with increased risk of hypertension was found.</p> <p>Conclusion</p> <p>The results of the present study indicate that the <it>EPHX2 K55R </it>polymorphism is not associated with restenosis after PCI, with incidence of CHD, or with an increased risk of hypertension and therefore, can not serve as a predictor for risk of CHD or restenosis after PCI.</p

Basal plus basal-bolus approach in type 2 diabetes

This is a copy of an article published in the Diabetes Technology and Therapeutics © 2011 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology and Therapeutics is available online at: http://online.liebertpub.com.[EN] Type 2 diabetes is characterized by insulin resistance and progressive b-cell deterioration. As b-cell function declines, most patients with type 2 diabetes treated with oral agents, in monotherapy or combination, will require insulin therapy. Addition of basal insulin (glargine, detemir, or NPH/neutral protamine lispro insulin) to previous treatment is accepted as the simplest way to start insulin therapy in those patients. But even when basal insulin is adequately titrated, some patients will also need prandial insulin to achieve or maintain individual glycemic targets over time. Starting with premixed insulin is an effective option, but it is frequently associated with increased hypoglycemia risk, ¿xed meal schedules, and weight gain. As an alternative, a novel approached known as ``basal plus strategy¿¿ has been developed. This approach considers the addition of increasing injections of prandial insulin, beginning with the meal that has the major impact on postprandial glucose values. Finally, if this is not enough intensi¿cation to basal¿bolus will be necessary. In reducing hyperglycemia, this modality still remains the most effective option, even in people with type 2 diabetes. This article will review the currently evidence on the basal plus strategy and also its progression to basal¿bolus therapy. In addition, practical recommendations to start and adjust basal plus therapy will be provided.F.J.A.-B. has received honoraria as speaker and/or consultant from Abbott, AstraZeneca, Bristol-Myers Squibb, Glaxo-SmithKline, LifeScan, Lilly, Madaus, MannKind Corp., Medtronic, Menarini, Merch Farma y Quimica, SA, MSD, Novartis, Novo Nordisk, Pfizer, Roche, sanofi-aventis, Schering-Plough, and Solvay. In addition, F.J.A.-B. has participated in clinical trials supported totally or partially by AstraZeneca, Glaxo-SmithKline, LifeScan, Lilly, MSD, Novo Nordisk, Pfizer, sanofi-aventis, and Servier. P. R. has no potential conflicts of interest to declare. J.F.A. has received honoraria as speaker and/or consultant form AstraZeneca, Ferrer, Glaxo-SmithKline, Laboratorios Dr. Esteve, Lilly, MSD, and Solvay.Ampudia-Blasco, J.; Rossetti ., P.; Ascaso, JF. (2011). Basal plus basal-bolus approach in type 2 diabetes. Diabetes Technology & Therapeutics. 13:75-83. doi:10.1089/dia.2011.0001S75831