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Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA(R))
CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (NCT01243424) is an ongoing, randomized trial in subjects with early type 2 diabetes and increased cardiovascular risk or established complications that will determine the long-term cardiovascular impact of linagliptin versus the sulphonylurea glimepiride. Eligible patients were sulphonylurea-naïve with HbA1c 6.5%–8.5% or previously exposed to sulphonylurea (in monotherapy or in a combination regimen <5 years) with HbA1c 6.5%–7.5%. Primary outcome is time to first occurrence of cardiovascular death, non-fatal myocardial in...
Source: Diabetes and Vascular Disease Research - April 7, 2015 Category: Endocrinology Authors: Marx, N., Rosenstock, J., Kahn, S. E., Zinman, B., Kastelein, J. J., Lachin, J. M., Espeland, M. A., Bluhmki, E., Mattheus, M., Ryckaert, B., Patel, S., Johansen, O. E., Woerle, H.-J. Tags: Clinical Trial Design Source Type: research

Cardiovascular effects of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes
Cardiovascular (CV) disease is the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). However, improving glycaemic control alone has not decreased CV events. Therapies that improve glycaemic control, CV disease risk factors and CV function are more likely to be successful. Dipeptidyl peptidase-4 (DPP-4) inhibitors prevent breakdown of incretin hormones glucagon-like peptide-1(GLP-1) and glucose-dependent insulinotropic peptide and improve glycaemic control in patients with T2DM. DPP-4 acts on other substrates, many associated with cardioprotection. Thus, inhibition of DPP-4 may lead ...
Source: Diabetes and Vascular Disease Research - April 7, 2015 Category: Endocrinology Authors: Koska, J., Sands, M., Burciu, C., Reaven, P. Tags: Review Article Source Type: research

Pulse pressure does not predict the response of diabetic nephropathy to glucose-lowering therapy
We aimed to study whether pulse pressure (PP) predicts the response of diabetic nephropathy to glucose-lowering treatment. Patients with uncontrolled type 2 diabetes were followed for decrease in albuminuria after insulin/oral-hypoglycemic treatment. A total of 143 patients were followed for a median time of 10.5 months in a cohort study. Fasting blood sugar and HbA1C significantly decreased, while systolic, diastolic and pulse pressures remained constant during intervention. Median albuminuria decreased from 18.4 mg/day [10–40] to 16.4 mg/day [9–28] at the end of study (p-value < 0.005). The number of patie...
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Nakhjavani, M., Nargesi, A. A., Heidari, B., Ghazizadeh, Z., Larry, M., Esteghamati, A. Tags: Letter to the Editor Source Type: research

Prevalence of type 2 diabetes is higher in peripheral artery disease than in coronary artery disease patients
In conclusion, the prevalence of type 2 diabetes mellitus is even higher in peripheral artery disease patients than in coronary artery disease patients. This observation underlines the need to consider impaired glucose regulation in the management of peripheral artery disease. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Silbernagel, G., Rein, P., Saely, C. H., Engelberger, R. P., Willenberg, T., Do, D.-D., Kucher, N., Baumgartner, I., Drexel, H. Tags: Brief Report Source Type: research

The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in childhood diabetes
Conclusion: Serum levels of methylglyoxal-derived hydroimidazolone-1 in diabetes patients are increased and associated with low-grade inflammation, but not yet arterial stiffness or wall thickness. This indicates that methylglyoxal-derived hydroimidazolone-1 may be important in the early phase of the accelerated atherosclerotic process in diabetes. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Heier, M., Margeirsdottir, H. D., Torjesen, P. A., Seljeflot, I., Stensaeth, K. H., Gaarder, M., Brunborg, C., Hanssen, K. F., Dahl-Jorgensen, K. Tags: Original Articles Source Type: research

A genetic variant regulating miR-126 is associated with sight threatening diabetic retinopathy
Conclusion: The A allele of rs4636297, known to be the non-functional allele for post-translational regulation of miR-126, is associated with STDR. This finding suggests that this locus would be a potential therapeutic target for inhibiting the development of DR. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: McAuley, A. K., Dirani, M., Wang, J. J., Connell, P. P., Lamoureux, E. L., Hewitt, A. W. Tags: Original Articles Source Type: research

Guideline treatment results in regression of atherosclerosis in type 2 diabetes mellitus
Conclusions: Guideline treatment arrests atherogenesis in non-diabetes mellitus patients and even decreases vessel wall dimensions in type II diabetes mellitus patients. Baseline body mass index predicts cardiovascular disease prevention efficacy expressed as decrease in total wall volume. These data emphasize the importance of optimal cardiovascular-prevention, particularly in diabetes patients with a high body mass index. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Strang, A. C., van Wijk, D. F., Mutsaerts, H. J., Stroes, E. S., Nederveen, A. J., Rotmans, J. I., Rabelink, T. J., Box, F. M. Tags: Original Articles Source Type: research

Elevated serum glucose levels and survival after acute heart failure: A population-based perspective
Conclusions: Patients with elevated blood glucose levels at hospital admission are more likely to die acutely. After resolution of the acute illness, patients with previously diagnosed DM need careful monitoring and enhanced treatment. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Helfand, B. K., Maselli, N. J., Lessard, D. M., Yarzebski, J., Gore, J. M., McManus, D. D., Saczynski, J. S., Goldberg, R. J. Tags: Original Articles Source Type: research

Evaluation of body adiposity index as a predictor of aortic stiffness in multi-ethnic Asian population with type 2 diabetes
In conclusion, body adiposity index is a weak predictor of aortic stiffness (when compared with body mass index) in Asians with type 2 diabetes mellitus. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Moh, M. C., Sum, C. F., Lam, B. C. C., Ng, X. W., Su, C., Tavintharan, S., Yeoh, L. Y., Wong, M. D. S., Lee, S. B. M., Tang, W. E., Lim, S. C. Tags: Original Articles Source Type: research

Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor
The sodium-dependent glucose transporter 2 (SGLT2) inhibitors are an important emerging class for the treatment of diabetes. Development of SGLT2 inhibitors has been oriented around a desire for high selectivity for the SGLT2 protein relative to the SGLT1 protein. More recently, genetic and pharmacology research in mice has indicated that gastrointestinal SGLT1 inhibition may also be an appropriate therapeutic target to treat diabetes. Combining SGLT1 and SGLT2 inhibition in a single molecule would provide complementary insulin-independent mechanisms to treat diabetes. Therefore, sotagliflozin (LX4211) has been developed a...
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Lapuerta, P., Zambrowicz, B., Strumph, P., Sands, A. Tags: Feature Articles Source Type: research

SGLT-2 inhibitors and cardiovascular risk: Proposed pathways and review of ongoing outcome trials
Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes mellitus (T2DM), it is likely that interventions to mitigate this risk must address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with apparent multiple effects. Inherent in their mode of action to decrease glucose reabsorption by the kidneys by increasing urinary glucose excretion, these agents improve glycaemic control independent of insulin secretion with a low risk of hypoglycaemia. In this review, we outline those CV risk factors that this class app...
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Inzucchi, S. E., Zinman, B., Wanner, C., Ferrari, R., Fitchett, D., Hantel, S., Espadero, R.-M., Woerle, H.-J., Broedl, U. C., Johansen, O. E. Tags: Feature Articles Source Type: research

Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences
Traditional treatments for type 1 and type 2 diabetes are often associated with side effects, including weight gain and hypoglycaemia that may offset the benefits of blood glucose lowering. The kidneys filter and reabsorb large amounts of glucose, and urine is almost free of glucose in normoglycaemia. The sodium-dependent glucose transporter (SGLT)-2 in the early proximal tubule reabsorbs the majority of filtered glucose. Remaining glucose is reabsorbed by SGLT1 in the late proximal tubule. Diabetes enhances renal glucose reabsorption by increasing the tubular glucose load and the expression of SGLT2 (as shown in mice), wh...
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Gallo, L. A., Wright, E. M., Vallon, V. Tags: Feature Articles Source Type: research

Sodium-glucose co-transporter inhibition in the treatment of diabetes: Sweetening the pot
(Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - February 17, 2015 Category: Endocrinology Authors: Alvarez, C. A., Neeland, I. J., McGuire, D. K. Tags: Guest Editorial Source Type: research

Arterial elasticity in obese adolescents with clinical features of insulin resistance
Conclusion: Obese adolescents with clinical IR have a higher SAEI, which declines with age; this may reflect a pathway to an increased risk of premature cardiovascular disease. (Source: Diabetes and Vascular Disease Research)
Source: Diabetes and Vascular Disease Research - December 9, 2014 Category: Endocrinology Authors: Ho, M., Benitez-Aguirre, P. Z., Donaghue, K. C., Mitchell, P., Baur, L. A., Jenkins, A. J., Craig, M. E., Cowell, C. T., Garnett, S. P. Tags: Original Articles Source Type: research

Decreased platelet aggregation by shear stress-stimulated endothelial cells in vitro: Description of a method and first results in diabetes
The interaction between platelets and endothelium in vivo is a complex phenomenon. Our aim was to develop an in vitro system that mimics the in vivo environment and investigate platelet function in a common pathological condition. Human umbilical vein endothelial cells were used and platelets from 28 type 2 diabetes patients were studied under shear stress conditions. Mean coefficient of variation of platelet aggregation was 10% in dynamic conditions in the presence of endothelium. Endothelial cells increased the concentration of inductor needed to achieve 50% platelet aggregation to adenosine diphosphate from 2.6 ±...
Source: Diabetes and Vascular Disease Research - December 9, 2014 Category: Endocrinology Authors: De Franceschi, M. S., Palange, A. L., Mancuso, A., Grande, L., Muccari, D., Scavelli, F. B., Irace, C., Gnasso, A., Carallo, C. Tags: Original Articles Source Type: research