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Query: UMLS:C0011860 (type 2 diabetes)
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The excess risk of cardiovascular disease in patients with Type 2 diabetes mellitus remains largely unexplained. Arterial stiffness, an early feature of diabetic vasculopathy involving several mechanisms, results in impaired arterial compliance, and has recently been proposed as a powerful independent predictor of cardiovascular disease. Increased arterial stiffness can contribute to the development and progression of hypertension, left ventricular hypertrophy and dysfunction, and to decreased myocardial perfusion, all of which are highly prevalent in Type 2 diabetes mellitus. Large artery stiffening has been demonstrated in Type 2 diabetes using several different methods including measurement of central pulse wave velocity, or estimation of aortic compliance, a technically demanding technique requiring the simultaneous measurement of stroke volume and diastolic pressure decay. Increased arterial stiffness of smaller arteries is also an important contributor to systemic arterial stiffness and cardiovascular risk. Increasing demand by clinical researchers for measurement of arterial stiffness has led to the development and commercial availability of highly practicable techniques. These new techniques, which utilise different aspects of the pulse pressure waveform, are simple, reliable and reflect both large and small vessel stiffness. They offer new tools for identifying patients at increased risk of developing cardiovascular complications including those with established diabetes. In this article we introduce the reader to the concepts of arterial stiffness, the significance of arterial stiffness for diabetes, and the new techniques that may potentially be useful for clinical researchers or practitioners.
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PMID:Measurement and application of arterial stiffness in clinical research: focus on new methodologies and diabetes mellitus. 1276 66

Diabetic patients have a two- to four-fold increase in macrovascular disease compared with non-diabetic subjects, with coronary heart disease (CHD) and stroke being the most common causes of death in type 2 diabetes. Diabetic nephropathy has become the most common single cause of end-stage renal disease in industrialized countries. Risk factors, including hyperglycaemia, high blood lipids and high blood pressure (BP), often co-exist in diabetic subjects. One recent metaanalysis, including more than 90,000 patients with a 12.4-year follow-up, has demonstrated a continuous increase in the relative risks of morbidity and mortality with increasing blood glucose concentration. Both the Multiple Risk Factor Intervention Trial (MRFIT) and the United Kingdom Prospective Diabetes Study (UKPDS) have confirmed in diabetes the close relationship between total cholesterol levels and elevated risk of cardiovascular events. For every 1 mmol/l increase in low-density lipoprotein cholesterol in type 2 diabetes, the relative risk of CHD increases by 1.57. Furthermore, about 40% of newly diagnosed diabetic patients are also hypertensive. Elevated BP is related to the presence of left ventricular hypertrophy (LVH) and, indeed, LVH is observed in more than 70% of diabetic patients with hypertension. Several studies in diabetes have proven treatment benefits when different risk factors are addressed. The need for tighter control of cardiovascular risk factors in diabetic patients is clear. This may include better control of raised BP, hyperlipidaemia and hyperglycaemia as well as closer monitoring for the appearance of LVH and microalbuminuria. There is a clear need to translate the results of clinical trials into everyday clinical practice.
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PMID:The need for tighter control of cardiovascular risk factors in diabetic patients. 1276 60

Even with modern treatment, acromegaly is associated with a 2- to 3-fold increase in mortality, mainly from vascular disease, which is probably a result of the long exposure of tissues to excess GH before diagnosis and treatment. There is accumulating evidence that effective treatment to lower serum GH levels to less than 1-2 ng/ml (glucose suppressed or random, respectively) and normalize IGF-I improves long-term outcome and survival. In addition to recognized cardiovascular risk factors of hypertension, type 2 diabetes mellitus, and dyslipidemia, there is accumulating evidence of specific structural and functional changes in the heart in acromegaly. Along with endothelial dysfunction, these changes may contribute to the increased mortality in this disease. There are specific structural changes in the myocardium with increased myocyte size and interstitial fibrosis of both ventricles. Left ventricular hypertrophy is common even in young patients with short duration of disease. Some of these structural changes can be reversed by effective treatment. Functionally, the main consequence of these changes is impaired left ventricular diastolic function, particularly when exercising, such that exercise tolerance is reduced. Diastolic function improves with treatment, but the effect on exercise tolerance is more variable, and more longitudinal data are required to assess the benefits. What scant data there are on rhythm changes suggest an increase in complex ventricular arrhythmias, possibly as a result of the disordered left ventricular architecture. The functional consequences of these changes are unclear, but they may provide a useful early marker for the ventricular remodeling that occurs in the acromegalic heart. Endothelial dysfunction, especially flow-mediated dilatation, is an early marker of atherosclerosis, and limited data imply that this is impaired in active acromegaly and can be improved with treatment. Similarly, early arterial structural changes, such as thickened intima media layer, appear more common in acromegalics, and there are hints that this may diminish with effective treatment, although more studies are required for a definite conclusion on this topic. In conclusion, impaired cardiac and endothelial structure and function in acromegaly are risk factors for vascular mortality and should be regarded as legitimate therapeutic targets in the overall management of this condition.
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PMID:Cardiovascular function in acromegaly. 1278 99

Hypertension is a nutritional-hygienic disease. Long-term caloric intake in excess of energy expenditures, chronic supraphysiological intake of dietary sodium, excessive alcohol consumption, and psychosocial stressors all contribute to the development of hypertension throughout the world. Elevated BP, particularly systolic BP, has been linked to multiple adverse clinical outcomes including stroke, heart failure, myocardial infarction, renal insufficiency/failure, peripheral vascular disease, retinopathy, dementia, and premature mortality. These undesirable clinical outcomes are typically, although not invariably, preceded by pressure-related target-organ injury such as left ventricular hypertrophy, renal insufficiency and proteinuria. The relation of BP and CKD and, in turn, the prevention of CKD or forestalling its progression by hypertension treatment, will be the focus of this manuscript. In hypertensive persons with reduced kidney function and/or proteinuria, lowering BP with multidrug therapy that is inclusive of pharmacologic modulators of the renin-angiotensin-aldosterone-kinin system is an effective strategy to forestall the progressive loss of kidney function. The totality of data support low therapeutic BP targets for persons with proteinuria >1 g/d. Nevertheless, in persons with CKD, even those with proteinuria below the dipstick positive level (approximately 300 mg/d or urine protein to creatinine ratio of 0.22), aggressive BP control also may be warranted because of the high risk of nonrenal cardiovascular disease. Multiple antihypertensive drugs will be required in the vast majority of patients with diabetes and/or reduced kidney function to attain BP goal. Renin-angiotensin system (RAS) modulator therapy is indicated among persons with diabetes mellitus and CKD. Available data support the use of angiotensin receptor blockers in persons with type 2 diabetes and overt nephropathy for preservation of kidney function. Among persons with type I diabetes with or without overt nephropathy, type 2 diabetes without overt nephropathy and in nondiabetic CKD, the available clinical data support the use of angiotensin-converting enzyme inhibitors as the RAS modulator of choice. Low therapeutic target BP levels <130/80 mmHg in persons with type 2 diabetes mellitus also appear warranted based on available data mostly for reducing the risk of nonrenal cardiovascular disease and overall mortality.
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PMID:Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. 1281 10

The aim of the present study was to investigate the effect of diet treatment on serum glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein-(HDL) cholesterol, low density lipoprotein-(LDL) cholesterol and very low density lipoprotein-(VLDL) cholesterol levels, systolic and diastolic blood pressure and electrocardiograms (ECGs) in patients with type 2 diabetes mellitus (DM). Twenty healthy subjects (mean age 45.9 +/- 3.7 years) and newly diagnosed patients with type 2 diabetes prior to receiving diet treatment (mean age 47.6 +/- 6.2 years) were included in this study. Diabetic patients were given a standard dietary treatment that was composed of 50% to 55% carbonhydrate and 30% fat (1200 kcal for women and 1600 kcal for men) for 2 months. No diet treatment was applied for control. For both groups serum glucose, TG, TC, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol levels, systolic and diastolic blood pressure and ECGs were measured at the beginning and end of the diet treatment. Although diet treatment decreased the elevated serum glucose in diabetic patients, it still remained higher than that in the controls. Diet treatment also decreased the elevated TG and VLDL-cholesterol in diabetic patients to control values. Although heart rate and systolic blood pressure were higher, diastolic blood pressure was not different in diabetic patients than those in controls. Ventricular hypertrophy was also observed in ECGs of 10% of diabetic patients. Diet treatment normalized all of these findings, except systolic blood pressure. This study showed that diet treatment could not normalize the high systolic blood pressure in type 2 DM. Thus, an effective way of controlling blood pressure should be taken to improve healing in DM.
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PMID:Effects of diet treatment on some biochemical and physiological parameters in patients with type 2 diabetes mellitus. 1286 8

The Framingham risk score (FRS), developed in a white cohort aged 30-74 years, is increasingly used in the early risk identification for coronary artery disease (CAD). This study examines the relationship between FRS and carotid artery intima-media thickness (IMT), a surrogate marker of coronary atherosclerosis, in black and white individuals aged 20-37 years. Five hundred seventeen young adults (aged 20-37 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study had carotid artery ultrasonography. Age, gender, systolic blood pressure, total cholesterol to HDL cholesterol ratio, cigarette smoking habit, type 2 diabetes, and left ventricular hypertrophy (LVH) were used to calculate FRS. Results indicated a significant, positive linear relationship between tertiles of FRS and IMT of the common, bulb, and internal carotid segments in blacks and whites alike. In a multivariate analysis including FRS, race, BMI, parental history of CAD, stroke, type 2 diabetes, or hypertension, logtriglycerides, loginsulin, alcohol consumption (ml/week), and regular physical activity, the FRS was independently associated with all three carotid segments. Further, the FRS as a main predictor variable explained relatively more of the variance in the IMT of the carotid bulb (9%) than in the common (5%) or internal (3%) carotid segments. These results support the use of FRS in both white and black young adults and underscore the importance of prevention and control of multiple risk factors in youth.
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PMID:Framingham risk score is related to carotid artery intima-media thickness in both white and black young adults: the Bogalusa Heart Study. 1295 90

Angiotensin-II receptor blockers (ARBs) have been shown to provide stroke, cardiac and renal protection in high-risk hypertensive patients. Telmisartan is a powerful and selective ARB that provides sustained blood pressure reduction for a full 24 h after a single dose and continues to protect against circadian blood pressure surges in the critical early morning hours. The objective of the Programme of Research tO show Telmisartan End-organ proteCTION (PROTECTION) is to measure the end-organ protective effects of telmisartan in patients at high risk of renal, cardiac and vascular damage. An extensive series of clinical trials is being conducted to compare telmisartan with valsartan, losartan, amlodipine and ramipril in patients at increased risk of end-organ damage. Nine clinical studies will examine the effects of telmisartan in about 5000 hypertensive patients with isolated systolic hypertension, type 2 diabetes, obesity, left ventricular hypertrophy or renal disease. All of the studies will be conducted using state-of-the-art technology, including such techniques as ambulatory blood pressure monitoring and magnetic resonance imaging. This programme will also investigate the effects of an ARB on key surrogate markers of organ tissue damage. This series of trials will characterize the end-organ protective effects of telmisartan in hypertensive patient populations at high risk of clinical events.
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PMID:The telmisartan programme of research tO show Telmisartan End-organ proteCTION (PROTECTION) programme. 1451 50

Recent research has demonstrated that ambulatory BP is a superior means to predict cardiovascular outcomes in treated patients with hypertension. Ambulatory blood pressure monitoring has been utilized to evaluate the efficacy of all anti-hypertensive drugs including the angiotensin II receptor blockers (ARBs). This paper reviews the relationship of clinic and ambulatory blood pressures to cardiovascular outcomes and the benefits of ARBs to maximize improvement in clinical end-points in patients with hypertension. Clinical trial evidence has demonstrated that ARBs are a preferred class in patients with electrocardiographic evidence of left ventricular hypertrophy, in patients with type 2 diabetes, patients with chronic kidney disease, and in individuals with heart failure who have clinically relevant intolerability to angiotensin converting enzyme inhibitors. In addition, there is increasing evidence from clinical trials that many of the ARBs provide adequate 24 h blood pressure control alone or in combination with other anti-hypertensive agents. We conclude that the combination of event reduction from large-scale clinical trials, adequate 24 h BP reduction, and improved tolerability compared to most other classes of anti-hypertensive agents, make the ARBs a suitable initial treatment for patients with hypertension.
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PMID:Evaluation of the 24 h effects of the angiotensin II receptor blockers: means to improve cardiovascular outcomes? 1462 72

Hypertension continues to be a major public health issue in the world. To combat this problem, many anti-hypertensive drugs have been developed and proven effective at controlling blood pressure in the last half century. In recent decades, antihypertensive drugs have been shown to have cardiovascular benefits beyond the reduction of blood pressure, and the focus has shifted to clarification of these effects. Angiotensin II receptor antagonists and calcium channel blockers are the most widely used antihypertensive drugs in Japan. However, these two classes of drugs have not yet been compared with respect to their efficacy for treating cardiovascular events. The Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial described herein is a prospective, multicenter, randomized, open-label, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration and blinded assessment of endpoints in high-risk hypertensive patients treated with either an angiotensin II receptor antagonist (candesartan cilexetil) or a third-generation calcium channel blocker (amlodipine besilate). The eligibility criteria in this study were 1) age between 20 and 85 years; 2) systolic blood pressure (SBP) > or = 140 mmHg in those below 70 years of age or > or = 160 mmHg in those above 70 years of age or diastolic blood pressure (DBP) > or = 90 mmHg on two consecutive measurements at clinic; and 3) at least one of the following high risk factors for cardiovascular events: a) SBP > or = 2180 mmHg or DBP > or = 110 mmHg on two consecutive visits, b) type 2 diabetes mellitus (fasting blood glucose > or = 126 mg/dl, casual blood glucose > or = 200 mg/dl, HbA1c > or = 6.5%, 2 h blood glucose on 75 g oral glucose tolerance test (OGTT) > or = 200 mg/dl, or current treatment with hypoglycemic therapy), c) history of cerebral hemorrhage, cerebral infarction, or transient ischemic attack until 6 months prior to the screening, d) left ventricular hypertrophy on either echocardiography or ECG, angina pectoris, or history of myocardial infarction until 6 months prior to screening, e) proteinuria or serum creatinine > or = 1.3 mg/dl, and f) symptoms of arteriosclerotic artery obstruction. The therapeutic goals of blood pressure control were set as follows: SBP < 130 mmHg and DBP < 85 mmHg for patients below 60 years of age, SBP < 140 mmHg and DBP < 90 mmHg for those in their 60s, SBP < 150 mmHg and DBP < 90 mmHg for those in their 70s, and SBP < 160 mmHg and DBP < 90 mmHg for those in their 80s. A total of 3,200 patients, equally allocated to each of the two treatment arms, were required based on a two-sided alpha level 0.05 and 90% power. The CASE-J is also the first study to employ the newly developed Automatic Bar Code Data-Capturing/Allocation, Booking & Trial Coding, Data Management (ABCD) system for data collection and management. Enrollment of patients started in September 2001 and ended in December 2002. Follow-up data will be collected every 6 months until December 2005. The CASE-J trial will provide important evidence on the comparative effectiveness of candesartan cilexetil and amlodipine besilate on cardiovascular morbidity and mortality among Japanese. In addition, the use of the ABCD system is expected to contribute to the development of more efficient data management systems for large-scale clinical trials.
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PMID:Candesartan Antihypertensive Survival Evaluation in Japan (CASE-J) trial of cardiovascular events in high-risk hypertensive patients: rationale, design, and methods. 1471 41

Irbesartan (Avapro, Aprovel) is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily administration of irbesartan provided 24-hour control of blood pressure (BP). In patients with mild-to-moderate hypertension irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than valsartan in terms of absolute reduction in BP and response rates. Irbesartan produced a greater reduction in diastolic BP at trough than once-daily losartan, but had a smaller effect than olmesartan; the reduction in systolic BP achieved with irbesartan was similar or greater than that with losartan and similar to that seen with olmesartan. The combination of irbesartan with hydrochlorothiazide produced additive effects on BP reduction. Irbesartan also induced regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy. In two large studies (IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients [IRMA 2] and the Irbesartan Diabetic Nephropathy Trial [IDNT]) irbesartan exerted a renoprotective effect in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. The renoprotective effect was at least partly independent of the BP-lowering effect. In the IRMA 2 trial, the proportion of patients progressing to overt nephropathy was significantly lower for recipients of irbesartan 300mg once daily than placebo. In patients with overt nephropathy in the IDNT, irbesartan 300mg once daily provided significantly greater renoprotection than amlodipine 10mg once daily or placebo. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan is well tolerated in hypertensive patients, including those with type 2 diabetes and incipient or overt nephropathy. The overall incidence of adverse events with irbesartan was similar to that with placebo. Irbesartan was associated with a lower incidence of cough than enalapril and was not associated with ankle oedema or with any clinically significant drug interactions. In conclusion, irbesartan is a well tolerated and effective antihypertensive agent. It also slows the progression of renal disease in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. Thus, irbesartan is a valuable agent in the management of patients with these indications.
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PMID:Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy. 1510 93


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