The American journal of medicine
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The renin-angiotensin-aldosterone system regulates renal vasomotor activity, maintains optimal salt and water homeostasis, and controls tissue growth in the kidney. However, pathologic consequences can result from overactivity of this cascade, involving it in the pathophysiology of kidney disease. An activated renin-angiotensin-aldosterone system promotes both systemic and glomerular capillary hypertension, which can induce hemodynamic injury to the vascular endothelium and glomerulus. ⋯ An understanding of this system is important to appreciate that inhibitors of this cascade can reduce the progression of chronic kidney disease in proteinuric disease states. Pharmacologic agents that can interfere with this cascade include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone receptor antagonists. This paper will provide an overview of the renin-angiotensin system, review its role in kidney disease, examine the renal effects of inhibition of this cascade in experimental animal models, and review clinical studies utilizing renin-angiotensin-aldosterone inhibitors in patients with diabetic and nondiabetic nephropathies.
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Recognition of the basal and postprandial components of hyperglycemia, in tandem with the development of new insulins and other clinical research, has led to a reassessment of type 2 diabetes mellitus treatment. In the future, insulin will be used earlier, treatment will intensify as the disease progresses, and combination therapy will be routine. Hyperglycemia can be controlled initially with sulfonylureas and metformin, agents that mainly improve control of fasting and preprandial glucose. ⋯ Although the traditional approach has been to introduce insulin therapy only after very high glucose values have persisted, despite prolonged use of oral agents alone, a more desirable strategy would be to prevent patients from ever experiencing the loss of glycemic control associated with hemoglobin A(1c) (HbA(1c)) elevations >7%. This goal could be achieved by diagnosing type 2 diabetes earlier in its course and by adding basal insulin to oral therapy much earlier. To maintain the recommended <7% HbA(1c) target level of control, treatments that target postprandial hyperglycemia will have to be added to basal insulin later on, as endogenous insulin continues to decline.
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Review
Treatment of patients with severe insulin deficiency; what we have learned over the past 2 years.
The initial injection in 1922 of a pancreatic extract, or insulin as it came to be known, into a patient with diabetes mellitus has since been followed by the successive introduction of longer-acting insulins, more highly purified insulins, and insulins that have been modified to more closely match insulin activity to patients' physiologic requirements. The recently introduced rapid-acting insulin analogues lispro and aspart and the long-acting analogue glargine are further refinements of insulin therapy. Current treatment strategies for severe insulin deficiency are based on the need to provide 2 components of insulin replacement: basal and postprandial. ⋯ Experience and observations since 2001 indicate that insulin therapy should be introduced earlier in patients with type 2 diabetes to control blood glucose levels. More importantly, the greatest benefit of insulin glargine has been to change positively the way physicians and patients think about insulin therapy. Newer insulin analogues, improved devices for home glucose monitoring, and pulmonary inhaled insulin are other innovations that promise improvement of hemoglobin A(1c) levels.
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The burden of type 2 diabetes mellitus will become even greater in coming decades as more young people present with the disease and patients live longer with the devastating complications of chronic hyperglycemia. Conventional and largely ineffectual treatment strategies consisting of lifestyle measures and long-term oral therapy are being challenged by studies showing that the early addition of insulin to oral agents can significantly improve glycemic control in patients with type 2 diabetes. ⋯ This simple treat-to-target strategy may be readily adopted in general practice through a widely translatable algorithm moving from oral pharmacotherapy to early addition of basal insulin glargine if glycemic targets are not met. The once-daily flexible dosing of insulin glargine and its smooth, flat profile, associated with fewer episodes of nocturnal hypoglycemia, make it among the safest and most practical tools to date for transforming the paradigm of type 2 diabetes management.
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This paper reviews the current literature pertaining to calcium channel blockers, including their classification, properties, and therapeutic indications, in light of several recent trials that have addressed their safety. Calcium channel blockers are a structurally and functionally heterogeneous group of medications that are used widely to control blood pressure and manage symptoms of angina. They are classified as dihydropyridines or nondihydropyridines. ⋯ Even so, the use of these agents has been linked with an increased risk of heart failure. Thus, long-acting calcium channel blockers may be safely used in the management of hypertension and angina. However, as a class, they are not as protective as other antihypertensive agents against heart failure.