female, 25-75 years old, no pregnancy, with/out Hormone replacement therapy T2DM, HbA1c > 7% with metformin mono-therapy

25-75 years, T2DM, HbA1c > 7% with metformin mono-therapy

Type 2 Diabetes Mellitus

Cardiovascular Risk

Endothelial Dysfunction

Medical University of Viemma

Influence of DPP-4 on Inflammatory Parameters in Diabetics: Gender Aspects

Influence of a Modern Oral Anti-diabetic Medication on Endothelial Dysfunction and Cardiovascular Risk in Diabetic Women and Men: Gender Aspects

ENST, a 20-kDa C-terminal fragment derived from type XVIII collagen, is an endogenous protein that blocks the formation of blood vessels. It inhibits endothelial cell proliferation, migration and angiogenesis. There is evidence for several functions of neovascularisation in plaque growth that maintain perfusion beyond limits of diffusion from the artery lumen and outer adventitial vasa vasorum, deposit pro-atherogenic plasma molecules, recruit immune cells and progenitors, and promote intraplaque hemorrhage . ENST, as an angiostatic factor, might be the weapon of choice to battle these effects

Catecholamines are released by the adrenal gland in situations of stress such as psychological stress, physical stress or low blood sugar levels . They are water-soluble and 50 % bound to plasma proteins. The three major catecholamines that circulate in the blood are epinephrine, norepinephrine and dopamine. They are mainly produced from the adrenal medulla and the postganglionic fibers of the sympathetic nervous system. The measurement of the catecholamines serves as control parameter for the applied stress situations.

Brain natriuretic peptide (BNP), a 32-amino acid peptide synthesized predominantly in the left ventricle of the heart as the 108-amino acid prohormone, is a potent vasodilator and a natriuretic factor regulating salt and water homeostasis.. Increased secretion of BNP and Nt-proBNP occurs mainly with increased tension in the ventricular walls, decreased oxygen supply, acute myocardial infarction, chronic cardiac heart failure, and in hypertrophy of the heart.
The Nt-proBNP level was shown to be significantly elevated in the cohort of patients with diabetes.

IMT is a measurement of the thickness of artery walls, usually by external ultrasound, to detect the presence and to track the progression of atherosclerotic lesions. Cross-sectional associations between common carotid artery IMT and cardiovascular risk factors have been demonstrated in several studies

Total testosterone concentrations in the low-normal range predict diabetes and the development of the metabolic syndrome as defined by the NCEP in middle-aged men, independently of BMI and other factors related to insulin resistance. Hyperandrogenicity in women is closely associated with insulin resistance and presents a risk factor for CVD and T2DM. Hormone replacement therapy improves glucose homeostasis and lipoprotein profile. T2DM abolishes the female-gender related differences in the risk of CVD, and diabetic women have rates of ischemic heart disease mortality approaching those of men.

Plasminogen activator inhibitor 1 (PAI-1) is the primary physiological inhibitor of plasminogen activation in vivo. Circulating PAI-1 levels are elevated in patients with coronary heart disease and may play an important role in the development of atherothrombosis by decreasing fibrin degradation. Increased PAI-1 expression can also directly influence vessel wall remodelling. The insulin resistance syndrome, which is characterized partly by obesity with visceral fat accumulation, is considered as a major regulator of PAI-1 expression

Adrenomedullin (AM) has multi-functional properties, of which the vasodilatory hypotensive effect is the most characteristic. AM secretion, especially in cardiovascular tissues, is regulated mainly by mechanical stressors (shear stress, inflammatory and metabolic factors). Elevation of plasma AM due to overproduction in response to one or more of these stimuli in pathological conditions may explain the raised plasma AM levels present in cardiovascular diseases such as myocardial infarction, hypertension, stroke and diabetes mellitus

Endothelial activation and acute-phase reaction correlate with insulin resistance and obesity in T2DM patients. Prospective studies have shown that ultra sensitive C-reactive protein (usCRP) can be used to predict risk of future cardiovascular events

Increased plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is associated with endothelial dysfunction, insulin resistance, and atherosclerosis and might, thus, serve as a marker for cardiovascular morbidity. In T2DM, the release and/or bioavailibility of nitric oxide are diminished. This endogenous nitric oxide synthase inhibitor, ADMA, has recently emerged as a key factor in nitric oxide biosynthesis.

Adiponectin is a hormone secreted by visceral adipose tissue beside others like leptin, angiotensin and resistin and exhibits antiinflammatory and insulin-sensitizing properties. Low plasma adiponectin concentrations have been suggested to promote atherosclerosis and have been found to be associated with early CVD onset and multiple atherosclerotic lesions in coronary arteries. Thus, adiponectin concentrations may influence risk of CVD and might serve as one of the screening tests facilitating early intervention

Apelin, a newly discovered adipocytokine and inotropic agent, is produced by white adipose tissue and is also expressed in the kidney and heart. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. Plasma apelin is reduced in newly diagnosed and untreated patients with T2DM. Regulation of circulating apelin and adiponectin seems to be in the same manner in patients with T2DM. Dysregulation of apelin might be involved in the mechanism of establishment of overt diabetes mellitus as well as associated atherosclerotic complications.

The Homeostasis model assessment of insulin resistance (HOMA-IR) is calculated by multiplying fasting insulin (μU/ml) and fasting blood sugar (mg/dl) divided through 19 (Version 1.2. vom 08.12.2008)
. A HOMA-IR below 1 is regarded as normal whereas a value over 2 is a hint for insulin resistance. The HOMA-IR has been suggested as a method to assess insulin resistance and secretion from the fasting glucose and insulin concentrations. T2DM is characterized by high HOMA IR. The HOMA-IR is an independent predictor of CVD in T2DM.

Jeanette Strametz-Juranek, MD

Medical University of Vienna

Chinese in origin
Healthy
No medication at least two weeks before the study

Plasma samples retained, with no potential for DNA extraction from any retained samples. The retained samples will be destroyed after the results published.

Healthy

Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital

A Pilot Study to Evaluate the Glucagon-Like Peptide 1 Response to the Challenge of Mixed Meals in Chinese Subjects

vghtpe user

Attending physician

Taipei Veterans General Hospital, Taiwan

Type 1 Diabetes

Pramlintide will be started at 15 mcg (2.5 units) subcutaneously immediately prior to major meals and it will be increased by 15mcg every 3 days as tolerated (i.e. nausea, vomiting, upset stomach) to a maximum dose of 60 mcg (10 units) before meals. If significant nausea persists at 45 or 60 mcg level, the dose should be decreased to 30 mcg (5 units) before meals. If the 30 mcg dose is not tolerated, investigator will evaluate for possibility of withdrawing the pramlintide. The dose of preprandial short acting insulin (eg: Novolog/Humalog) will be reduced by 30 to 50% at the start of pramlintide 15 mcg (2.5 units) and then will be adjusted every time the dose of pramlintide is increased by 15 mcg (2.5 units) as needed based on blood glucose readings.

acidic peptide/obezita

Influence of DPP-4 on Inflammatory Parameters in Diabetics: Gender Aspects

A Pilot Study to Evaluate the Glucagon-Like Peptide 1 Response to the Challenge of Mixed Meals in Chinese Subjects

Efficacy of Pramlintide on Prevention of Weight Gain Early Onset of Type 1 Diabetes

Prader-Willi Syndrome and Appetite

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