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Smokers are insulin resistant, exhibit several aspects of the insulin resistance syndrome, and are at an increased risk for type 2 diabetes. Prospectively, the increased risk for diabetes in smoking men and women is around 50%. Many patients with type 1 and type 2 diabetes mellitus are at risk for micro- and macrovascular complications. Cigarette smoking increases this risk for diabetic nephropathy, retinopathy, and neuropathy, probably via its metabolic effects in combination with increased inflammation and endothelial dysfunction. This association is strongest in type 1 diabetic patients. The increased risk for macrovascular complications, coronary heart disease (CHD), stroke, and peripheral vascular disease, is most pronounced in type 2 diabetic patients. The development of type 2 diabetes is another possible consequence of cigarette smoking, besides the better-known increased risk for cardiovascular disease. In diabetes care, smoking cessation is of utmost importance to facilitate glycemic control and limit the development of diabetic complications.
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PMID:Cigarette smoking and diabetes. 1270 97

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

In this article, 2 leading physicians debate the strength of outcome data on the efficacy of angiotensin-converting enzyme (ACE) inhibitors versus angiotensin II receptor blockers (ARBs) for reducing the incidence of cardiovascular, cerebrovascular, and renovascular events. Dr. Stephen G. Ball notes that the efficacy of ACE inhibitors for reducing the risk for myocardial infarction independent of their effects on blood pressure is controversial. In the Heart Outcomes Prevention Evaluation (HOPE) study, ramipril treatment in high-risk patients was associated with a 20% reduction in the risk for myocardial infarction; mean reduction in blood pressure was 3 mm Hg for systolic blood pressure and 1 mm Hg for diastolic blood pressure. The HOPE investigators propose that the 20% reduction was much greater than would be expected based on the observed blood pressure reduction. However, a meta-regression analysis of blood pressure reduction in >20 antihypertensive therapy outcome trials found that the reduction in myocardial infarction risk with ramipril observed in HOPE was consistent with the modest blood pressure reduction seen with that agent. Nevertheless, there are convincing data for prevention of myocardial infarction with ACE inhibitors in patients with heart failure, including those with heart failure after myocardial infarction, as well as supportive evidence from studies in patients with diabetes mellitus and concomitant hypertension. On the other hand, Dr. William B. White takes the position that ARBs are well-tolerated antihypertensive agents that specifically antagonize the angiotensin II type 1 (AT(1)) receptor and provide a more complete block of the pathologic effects of angiotensin II-which are mediated via the AT(1) receptor-than ACE inhibitors. The Evaluation of Losartan in the Elderly (ELITE) II study and the Valsartan Heart Failure Trial (ValHeFT) suggest that ARBs reduce the risk for mortality in patients with congestive heart failure. The Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. The Irbesartan in Patients with Diabetes and Microalbuminuria (IRMA) study, the Irbesartan Diabetic Nephropathy Trial (IDNT), and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study demonstrated significant reductions in the rate of progression of renal disease in patients receiving ARBs, independent of effects on blood pressure. These data support the use of ARBs, in addition to the standard of care, in hypertensive patients with heart failure who are intolerant of ACE inhibitors, and also provide compelling evidence for their use in patients with hypertension and type 2 diabetes.
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PMID:Debate: angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers--a gap in evidence-based medicine. 1451 6

When planning treatment for patients with hypertension, current guidelines emphasise the importance of risk stratification, based on blood pressure, the presence of end-organ damage and other cardiovascular risk factors. Because the beneficial effect of antihypertensive therapy seems to be linked to the degree of blood pressure reduction, guidelines recommend reducing blood pressure below 140/90mm Hg, with a lower target in patients who are young or who have diabetes mellitus (with or without nephropathy) or non-diabetic nephropathy. Blood pressure reduction can be achieved with several classes of drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists and calcium channel antagonists. Calcium channel antagonists have been shown to reduce the risk of stroke and major cardiovascular events. However, it is still controversial whether different treatment regimens based on different drug classes can offer advantages beyond similar degrees of blood pressure control in preventing cardiovascular morbidity and mortality. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) was a controlled clinical trial aimed at comparing the efficacy of a long-acting calcium channel antagonist, nifedipine gastrointestinal-transport-system (GITS), versus co-amilozide, a combination of the diuretics hydrochlorothiazide (HCTZ) and amiloride, on morbidity and mortality in high-risk hypertensive patients. Nifedipine GITS and HCTZ/amiloride were equally effective at reducing blood pressure and the risk of primary outcomes (a composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction and heart failure). Results from other studies indicate that there may be greater benefits for stroke and smaller benefits for coronary artery disease with calcium channel antagonist-based regimens than with diuretic or beta-blocker-based regimens. However, there is at present insufficient evidence to recommend a specific drug choice based on patient risk profile. Thus, the choice of antihypertensive drug(s) should be according to efficacy and tolerability. In addition to the reductions in cardiovascular risk, two substudies of INSIGHT showed that nifedipine GITS was able to prevent the progression of intima media thickness in the common carotid artery and slow the progression of coronary calcification. The clinical significance of this effect in the prevention of cardiovascular events still remains to be established.
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PMID:Current treatment of patients with hypertension: therapeutic implications of INSIGHT. 1283 62

The presence of long-standing diabetes mellitus leads to the development of a number of typical end organ complications. These complications include coronary heart disease, stroke, peripheral arterial disease, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and diabetic cardiomyopathy. From an epidemiological and clinical standpoint, cardiovascular disease remains the most important complication of diabetes. Cardiovascular complications are the most common causes of morbidity and mortality in diabetics, accounting for up to 85% of the mortality in diabetic patients. The increasing prevalence of obesity and sedentary lifestyle in Western society are leading to an increase in the prevalence in diabetes. As such diabetes is an increasing cause of cardiovascular disease.
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PMID:Diabetic heart dysfunction: is cell transplantation a potential therapy? 1287 29

In type 2 diabetic patients with or without nephropathy, we examined relationships between plasma concentrations of total homocysteine (tHcy) and clinical macroangiopathy, as well as endothelial dysfunction indicated by plasma thrombomodulin (TM) concentrations. We studied 103 type 2 diabetic patients including 26 with macroangiopathy (12 patients with coronary artery disease [CAD], 10 with stroke, and 4 with peripheral vascular disease [PVD]). Plasma tHcy was measured by high-performance liquid chromatography. Plasma TM was determined by enzyme immunoassay. As an index of glomerular filtration rate, creatinine clearance (Ccr) also was determined in a 24-hour urine collection. Considering all diabetic patients, plasma tHcy concentrations were significantly higher in those with macroangiopathy than in those without (10.4 +/- 3.7 v 8.5 +/- 2.8 micromol/L, P=.0077). By univariate and multivariate analyses, plasma tHcy was correlated inversely with Ccr. Plasma tHcy concentrations were significantly higher in the patients with overt albuminuria than in those with normoalbuminuria or microalbuminuria. After exclusion of patients with renal insufficiency (Ccr<60 mL/min), differences in plasma tHcy concentrations between patients with and without macroangiopathy were abolished. By multivariate analysis, total cholesterol, urinary albumin, Ccr, C-peptide, and tHcy retained significant influence on the plasma TM. Even in patients with normal renal function (Ccr > or = 80 mL/min), plasma tHcy was correlated positively with plasma TM. In conclusions, diabetic nephropathy is a main determinant of plasma tHcy elevation in type 2 diabetic patients. Since plasma TM is independently associated with plasma tHcy, in diabetic patients with overt nephropathy, elevation of tHcy reflecting reduced clearance is a likely cause of endothelial dysfunction, resulting in the atherosclerosis underlying development of cardiovascular disease.
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PMID:High plasma homocysteine concentrations are associated with plasma concentrations of thrombomodulin in patients with type 2 diabetes and link diabetic nephropathy to macroangiopathy. 1462 17

Smoking has adverse effects on health, causing ischemic heart disease, stroke, chronic obstructive lung disease and cancers of the respiratory, gastrointestinal, pancreas, kidney and urinary tract. Smoking causes an acute increase in mean arterial pressure and heart rate. Chronic smoking reduces the renal plasma flow. There is clinical evidence that smoking has adverse effects on renal outcome in essential hypertension, diabetic nephropathy, primary glomerular diseases, systemic diseases involving the kidney and renal allograft recipients.
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PMID:Smoking--a renal risk factor. 1471 Sep 79

The goal of antihypertensive therapy is to prevent cardiovascular complications of hypertension, such as heart failure, stroke, end stage renal disease, and death, not just to normalize blood pressure. Recently, several clinical trials investigated the beneficial effects of angiotensin II antagonists (AIIAs) in patients with hypertension, heart failure or diabetic nephropathy utilizing proven clinical outcomes (e.g., all-cause mortality) rather than surrogate outcomes (e.g., blood pressure or proteinuria). The AIIAs may offer therapeutic advantages with respect to particular outcomes in certain types of patients. Evidence is also emerging that losartan may possess beneficial pharmacological properties such as effects on uric acid, platelets, sexual dysfunction, and cognitive function, that may set it apart from other members of the AIIA class. However, further studies are needed to delineate fully these potential pharmacological differences among the AIIAs and their possible clinical relevance. This paper reviews recent AIIA outcomes studies in patients with hypertension, heart failure, or diabetic nephropathy and also examines data suggesting that molecular differences exist within the AIIA class, differences that may assist in explaining the outcomes achieved in these recent trials.
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PMID:AII antagonists in hypertension, heart failure, and diabetic nephropathy: focus on losartan. 1502 37

Candesartan is a novel high-affinity type 1 AT(1)-receptor blocker characterized by prolonged binding to and slow dissociation from the receptor. Pharmacokinetic properties of candesartan explain its pronounced and lengthy (24-36 hours) antihypertensive action which does not depend on patients sex, age and body mass. Long term use of candesartan has been associated with regression of left ventricular hypertrophy, renoprotective effect and lowered risk of stroke. Candesartan is well tolerated. All these features make the drug suitable for wide application in the management of hypertension. Preliminary results suggest that candesartan can be useful in the treatment of diabetic nephropathy.
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PMID:[Candesartan - a novel AT(1)-angiotensin receptor blocker: peculiarities of pharmacology and experience of use in arterial hypertension]. 1502 49

Hypertension frequently coexists with diabetes mellitus, occurring twice as frequently in diabetic as in nondiabetic persons. It accounts for up to 75% of added cardiovascular disease (CVD) risk in people with diabetes, contributing significantly to the overall morbidity and mortality in this high-risk population. Patients with hypertension are two times more prone to have diabetes than are normotensive persons. Hypertension substantially increases the risk for coronary heart disease (CHD), stroke, retinopathy, and nephropathy. In patients with type 2 diabetes, hypertension usually clusters with the other components of the cardiometabolic syndrome, such as microalbuminuria, central obesity, insulin resistance, dyslipidemia, hypercoagulation, increased inflammation, and left ventricular hypertrophy (LVH). In type 1 diabetes, hypertension often occurs subsequent to the development of diabetic nephropathy. Hypertension in people with diabetes is characterized by volume expansion, increased salt sensitivity, isolated systolic blood pressure (BP) elevation, loss of the nocturnal dipping of BP and pulse, and increased propensity toward orthostatic hypotension and albuminuria. Among the treatment strategies tested in hypertensive diabetic persons, low-density lipoprotein (LDL)-cholesterol lowering to less than 100 mg/dL and aggressive BP control to less than 130/80 mm Hg have proven effective in CVD risk reduction. The combination of two or more drugs is usually necessary to achieve the target BP.
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PMID:Diabetes, hypertension, and cardiovascular derangements: pathophysiology and management. 1512 75


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