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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of diabetes is increasing in epidemic proportion worldwide. Because of the morbidity and mortality associated with the disease, it is becoming a major burden for the health care system. With a better understanding of the pathogenesis of type 2 diabetes, the concept of primary prevention has emerged. A number of studies demonstrated that both lifestyle modification program and pharmacological interventions in subjects with impaired glucose tolerance (IGT) can prevent or delay the progression to diabetes. The Diabetes Prevention Study (DPS) and the Diabetes Prevention Program (DPP) convincingly showed that an intensive lifestyle modification program is highly effective in decreasing the risk of diabetes in a high risk population (risk reduction of 58%). Four other smaller studies have made similar observations. The DPP study showed that metformin can reduced the risk of diabetes by 31% in subjects with IGT. The STOP-NIDDM trial confirmed the efficacy of acarbose in decreasing the risk of diabetes by 36% in similar high risk population. The TRIPOD study showed that troglitazone can reduce the incidence of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that in very obese population on intensive lifestyle modification program, xenical treatment was associated with a 37% reduced incidence of diabetes compared to placebo. Three studies suggested that bariatric surgery in morbidly obese subjects with or without IGT can reduce the incidence of diabetes to near zero. Eight of 10 studies showed that treatment with inhibitors of the renin-angiotensin aldosterone system in high risk population for cardiovascular disease (CVD) were associated with a significant reduction in the subsequent development of diabetes as a secondary outcome. The WOSCOPS study and the HERS study examined the effect of pravastatin and estrogen/progestin respectively on cardiovascular events and observed that these pharmacological interventions were associated with a 30% and 35% reduction in the incidence of diabetes as secondary outcome. There are 3 major trials currently in progress examining the effect of rosiglitazone/ramipril (the DREAM study), nateglinide/valsartan (the NAVIGATOR study) and pioglitazone (the ACT NOW study) on the development of diabetes in IGT subjects as a primary outcome. We also have 3 studies studying the prevention of diabetes as secondary outcomes: the ONTARGET-TRANSCEND study examining telmisartan with or without ramipril, and the ORIGIN study testing glargine insulin/omega 3. The evidence is overwelming-diabetes can be prevented or delayed in high risk population through lifestyle modification or pharmacological interventions. This new information now has to be translated in the real world into well defined strategies for screening and treating high risk population. Prevention of the disease is our only chance to alleviate the ever growing burden of diabetes mellitus in the world.
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PMID:The prevention of type 2 diabetes: what is the evidence? 1620 7

Cardiovascular disease (CVD) and Type 2 diabetes mellitus (DM2), once conceived as different entities, share common origins and pathways. Increased activity of the renin-angiotensin-aldosterone-system, insulin resistance, chronic low-grade inflammation and oxidative stress collectively contribute to endothelial dysfunction and atherosclerosis, which manifest clinically as CVD. Nowadays, it is possible to identify and intervene in high-risk populations even before the clinical diagnosis of DM2. The control of dietary patterns and increased physical activity is completely feasible, as well as the management of hypertension and dyslipidaemia. Pharmacological interventions targeted at blocking renin-angiotensin-aldosterone-system and sensitising to insulin have a role in the prevention of DM2 and CVD, and are avidly explored worldwide. In the near future, ongoing trials should provide data that will allow us to better treat patients with the cardiometabolic syndrome and diabetes in order to reduce CVD morbidity and mortality.
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PMID:Insights into the emerging cardiometabolic prevention and management of diabetes mellitus. 1621 82

Renal complications resulting from type 2 diabetes mellitus are costly and common. Finding optimal therapy is important for the prevention and management of diabetic nephropathy. Research has focused on antihypertensive agents that modify the renin-angiotensin-aldosterone system. Because of their effects on the glomerulus, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have been studied as interventions at various stages of diabetic nephropathy. The ACE inhibitors may delay the progression to microalbuminuria and then clinical albuminuria. The ARBs decrease albuminuria in patients with microalbuminuria and decrease adverse renal events, specifically the progression to end-stage renal disease in patients with clinical albuminuria and hypertension. Limited data suggest that combination therapy with ACE inhibitors and ARBs may slow the progression of microalbuminuria to clinical albuminuria. Because of the variability in degree of albuminuria evaluated and in study designs (numbers of patients, study duration, drug dosages, and outcomes measured), a detailed review of the available literature about ACE inhibitors and ARBs in the prevention or treatment of diabetic nephropathy may provide insight to clinicians.
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PMID:Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for prevention and treatment of nephropathy associated with type 2 diabetes mellitus. 1623 22

We recently reported that in subjects with untreated type 2 diabetes mellitus, a 5-week diet of 20:30:50 carbohydrate-protein-fat ratio resulted in a dramatic decrease in 24-hour integrated glucose and total glycohemoglobin compared with a control diet of 55:15:30. Body weight, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and serum ketones were unchanged; insulin and nonesterified fatty acids were decreased. We now present data on other hormones and metabolites considered to be affected by dietary macronutrient changes. The test diet resulted in an elevated fasting plasma total insulin-like growth factor 1, but not growth hormone. Urinary aldosterone was unchanged; free cortisol was increased, although not statistically. Urinary pH and calcium were unchanged. Blood pressure, creatinine clearance, serum vitamin B12, folate, homocysteine, thyroid hormones, and uric acid were unchanged. Serum creatinine was modestly increased. Plasma alpha-amino nitrogen and urea nitrogen were increased. Urea production rate was increased such that a new steady state was present. The calculated urea production rate accounted for 87% of protein ingested on the control diet, but only 67% on the test diet, suggesting net nitrogen retention on the latter. The lack of negative effects, improved glucose control, and a positive nitrogen balance suggest beneficial effects for subjects with type 2 diabetes mellitus at risk for loss of lean body mass.
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PMID:The metabolic response to a high-protein, low-carbohydrate diet in men with type 2 diabetes mellitus. 1642 33

Limited evidence suggests renin-angiotensin-aldosterone system (RAAS) polymorphisms alter the blood pressure (BP) response to aerobic exercise training. We examined if RAAS polymorphisms influenced postexercise hypotension in men with high normal to Stage 1 hypertension. Forty-seven men (44.2+/-1.4 years, 145.1+/-1.6/85.5+/-1.1 mmHg) randomly completed three experiments: seated rest (control) and two cycle exercise bouts at 40% (LITE) and 60% (MOD) of maximal oxygen consumption. Ambulating BP was measured for 14 h after each experiment. RAAS polymorphisms associated with hypertension (i.e. angiotensin converting I enzyme, ACE I/D; angiotensin II type 1 receptor, AT1R A/C; and intron 2 of aldosterone synthase, Int2 W/C) were analyzed using polymerase chain reaction and restriction enzyme digestion. Repeated measure ANOVA tested if BP differed between experimental conditions by RAAS genotypes. Compared to men with 0-2 variant alleles, men with > or =3 combined RAAS variant alleles had lower average systolic BP (SBP) (P=0.030) and lower average diastolic BP (DBP) (P=0.009) for 14 h only after LITE. In contrast, average BP was not different for MOD and control between RAAS variant allele groups over this time period (P> or =0.05). LITE reduced BP in men with > or =3 variant RAAS alleles for 14 h, whereas MOD had no influence on BP in these men. In order to optimally prescribe exercise for its BP lowering benefits in those with hypertension, additional knowledge of how genetic variation affects the BP response to exercise is needed.
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PMID:RAAS polymorphisms alter the acute blood pressure response to aerobic exercise among men with hypertension. 1646 60

Hypertension is a major risk factor for stroke and coronary events in elderly people and clinical trials have shown that treatment of hypertension with various drugs can result in a substantial reduction in cerebrovascular and cardiovascular events. The angiotensin II type 1 (AT1) receptor antagonists are the newest class of antihypertensive agents to be used widely in clinical practice. AT1 receptor antagonists can generally be given once-daily. They are also extremely well tolerated with minimal first-dose hypotension and an incidence of adverse effects similar to that seen with placebo. Adverse event rates are significantly lower than with other classes of antihypertensive drugs including ACE inhibitors. These factors result in improved compliance and increased rates of continuance on therapy. AT1 receptor antagonists show similar efficacy in lowering blood pressure to other classes of antihypertensive agents and their antihypertensive effect is potentiated when they are given concomitantly with low-dose thiazide diuretics. AT1 receptor antagonists are eliminated predominantly by the hepatic route but most are not subject to extensive metabolism and interactions with other drugs are uncommon. This is an advantage in the elderly, who are often receiving multiple medications which increases the risk for adverse drug interactions. Dose adjustments are not usually required in the elderly unless there is plasma volume depletion. Although plasma AT1 receptor antagonist concentrations are generally higher in the elderly than in younger subjects, this pharmacokinetic difference may be balanced by decreased activation of the circulating renin-angiotensin-aldosterone system in the elderly. Recent clinical studies in high-risk hypertensive patients with left ventricular hypertrophy or in patients with diabetic nephropathy or heart failure have demonstrated that AT1 receptor antagonists can improve clinical outcomes to a similar or sometimes greater extent than other antihypertensive agents. Many of these studies have included large numbers of older patients and have confirmed the excellent tolerability profile of these drugs. Thus, AT1 receptor antagonists should be considered as a possible first-line treatment or as a component of combination therapy in patients with type 2 diabetes mellitus and microalbuminuria or nephropathy and as an alternative or additional treatment to ACE inhibitors in patients with heart failure or left ventricular dysfunction. AT1 receptor antagonists also appear to reduce the onset of new diabetes compared with some other antihypertensive drugs. The benefits in terms of organ protection have mainly been seen in studies using higher doses of particular AT1 receptor antagonists and it is not certain at present whether these results can be extrapolated to other members of the class. As the elderly are more likely to have developed organ damage related to hypertension or to have heart failure or diabetes as concomitant conditions, AT1 receptor antagonists represent an appropriate option for many elderly patients. The main disadvantage of these drugs is the cost of the medication but this may be offset by their improved tolerability with fewer adverse reactions and thus increased compliance, resulting in better blood pressure control and fewer clinical events. Overall, AT1 receptor antagonists are well tolerated and efficacious for blood pressure-lowering when given as a single daily dose in elderly patients and have many potential benefits in high-risk hypertensive subjects.
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PMID:The role of angiotensin II type 1 receptor antagonists in elderly patients with hypertension. 1653 36

Management of hypertension is the mainstay of prevention and treatment of diabetic renal disease; evidence suggests that tight blood pressure control slows renal disease progression in established diabetic nephropathy. Inhibition of the renin-angiotensin-aldosterone system (RAAS) has renoprotective effects over and above those achieved by lowering systemic blood pressure. To date, however, no long-term study using hard end points has directly compared current mechanisms for RAAS inhibition, angiotensin II receptor blockade (ARB) and angiotensin-converting enzyme (ACE) inhibition. This issue was addressed in the recently published Diabetics Exposed to Telmisartan and Enalapril (DETAIL) study, a head-to-head comparison of telmisartan and enalapril in 250 patients with hypertension and type 2 diabetes mellitus and early-stage nephropathy. After 5 years' treatment, change in glomerular filtration rate (GFR), the primary efficacy end point, was equivalent in the 2 treatment groups, as were all secondary end points. The expected steep decline in GFR in the first year was followed by a lesser decrease in the second year and then almost complete stabilization of renal function at > or =3 years. Over 5 years, no patient went into end-stage renal disease or required dialysis. There were also no increases in albumin excretion rate, nor was there an increase in creatinine beyond 200 mumol/L. Incidence of cardiovascular morbidity and mortality was extremely low in both treatment groups, a remarkable outcome given that almost 50% of patients had evidence of cardiovascular disease at randomization. Inhibition of the RAAS should play a major part in management of patients with type 2 diabetes with nephropathy, for which both telmisartan and enalapril provide long-term renoprotection.
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PMID:Prevention of loss of renal function over time in patients with diabetic nephropathy. 1656 47

The life expectancy of patients with type 2 diabetes and diabetic nephropathy is reduced; the main cause of death is cardiovascular disease. The majority of patients with renal replacement therapy are type 2 diabetics. Inhibition of the renin-aldosterone-angiotensin system is beneficial in diabetes mellitus. It reduces the incidence and slows the progression of nephropathy. ACE inhibitors are the accepted standard of care for nephropathy in type-1 diabetics; the role of ACE inhibitors versus angiotensin-receptor-blockers in type 2 diabetes is less clear. Large studies from the last 15 years and meta-analyses show a reduction of mortality of about 20% with ACE inhibitors in type 2 diabetic nephropathy; angiotensin-receptor-blockers have no documented effect on mortality yet, but do also slow the progression of nephropathy in type 2 diabetics. From these data and because of economic considerations, ACE inhibitors should be first choice therapy for diabetic nephropathy in type 2 diabetes mellitus.
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PMID:[Diabetic nephropathy and ACE inhibitors]. 1659 56

We recently reported that in subjects with untreated type 2 diabetes a 5-wk diet of 30:30:40 carbohydrate/protein/fat ratio resulted in a significant decrease in 24-h integrated glucose, total %glycohemoglobin, and total cholesterol compared with a control diet of 55:15:30 carbohydrate/protein/fat given at the beginning of the 5-wk period. Body weight was stable and insulin was unchanged. We now present data on other hormones and metabolites considered to be affected by dietary macronutrient changes. The test diet resulted in an elevated fasting plasma total IGF-I, but not growth hormone. Urinary free cortisol was increased. Serum renin and urinary aldosterone remained unchanged. Blood pressure was stable. Serum creatinine and uric acid were increased. Urinary microalbumin was decreased. Creatinine clearance, serum B(12), folate, homocysteine, TSH, and free thyroxine were unchanged. Total triiodothyronine was decreased. Plasma alpha-amino nitrogen, urea nitrogen, and serum albumin were increased. Urea production rate was increased such that a new steady state was present. The calculated urea production rate accounted for 84% of protein ingested on the control diet but only 68% on the test diet, suggesting net nitrogen retention on the latter. Overall, the lack of negative effects, the improved glucose control, and the positive nitrogen balance suggest such a diet will be beneficial for older subjects with type 2 diabetes. Nevertheless, the long-term effects and general applicability of the diet remain to be determined.
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PMID:Metabolic effect of a LoBAG30 diet in men with type 2 diabetes. 1672 Jun 31

The increasing prevalence of diabetes is reaching epidemic proportion worldwide. Because of the associated morbidity and mortality, it is exerting major pressure on the healthcare system. With a better understanding of the pathophysiology of type-2 diabetes, the concept of primary prevention has emerged. A number of studies have confirmed that intensive lifestyle modification was very effective in the prevention of diabetes in the impaired glucose tolerance (IGT) population. However, maintaining long-term lifestyle modification is a major challenge. It is, therefore, important to have other strategies, either pharmacological or surgical, that can be used as an adjunct or alternative to lifestyle modification. The Chinese study showed that metformin and acarbose could reduce the risk of diabetes by 65 and 83%, respectively, in IGT subjects. The efficacy of metformin was confirmed by the Diabetes Prevention Program (31% risk reduction) and that of acarbose by the STOP-NIDDM trial (36% risk reduction) in a similar high-risk population. The TRIPOD study showed that troglitazone could reduce the risk of diabetes by 55% in Hispanic women with a history of gestational diabetes. And more recently, the XENDOS study showed that orlistat could reduced the risk of diabetes by 37% in obese subjects when used as an adjunct to an intensive lifestyle program. Three studies have suggested that bariatric surgery in morbidly obese subjects could reduce the risk of diabetes to near zero. Furthermore, a number of studies have examined the effect of a renin angiotensin aldosterone system inhibitor, as well as statin and hormone replacement therapy on the prevention of type-2 diabetes in high-risk subjects as secondary outcomes and have suggested that they could be of potential benefit. The accumulating evidence is now overwhelming. Yes, diabetes can be prevented or delayed in high-risk populations. With this new information, we need to design new strategies to screen high-risk populations and to implement the new treatments that have proven effective in the prevention of type-2 diabetes.
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PMID:Pharmacological and surgical intervention for the prevention of diabetes. 1682 Jul 29


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