Titrate to diastolic BP Optimal BP Suboptimal BP
< 80 <130/80 < 140/85
<125/75 < 130/80
ABM = Ambulatory blood pressure monitoring.
ABM = Ambulatory blood pressure monitoring.
1 In those with high cardiovascular risk and initial BP 140-159/90-99 mm Hg there could be a case for adopting the targets for diabetic patients (British Hypertension Society 1999).
1970s and has subsequently produced several guidelines, the first in 1975. New guidelines have recently appeared also related to hypertension in diabetes. Several of these new guidelines have a similar approach. There is a clear emphasis on early and effective antihypertensive treatment in patients with diabetes suggesting a lower threshold for the start of the treatment and also a lower goal during treatment. ACE inhibitors are often preferred as initial agents but combination therapy is often warranted. In view of the recent observation that different types of drugs (ACE-I, p-blockers, calcium channel blockers and diuretics) reduce cardiovascular risks in type 2 diabetes, there are different treatment options. In diabetic renal disease, ACE-I is however preferred. We should aim to achieve a BP around 135/85 mmHg during treatment, or lower.
The British Hypertension Society proposes: (1) 'The threshold for antihypertensive treatment in type 1 diabetes is > 140/90 mm Hg. The target BP is <130/80 mmHg, or lower (<125/75 mmHg) when there is proteinuria > 1 g/24 h'. And (2): 'Trials support treatment of all patients with type 2 diabetes and BP > 140/90 mm Hg, aiming for a target BP < 130/80 mm Hg. BPs < 140/85 mm Hg on treatment should be considered suboptimal.' (3) ' Thus there is evidence from outcome trials in hypertensive patients with diabetes for the efficacy and safety of ACE inhibitors, p-blockers, dihydropyrid-ines, and low-dose thiazides. The choice among these drug classes should be made using the criteria set out for nondiabetic patients. BP control will usually require more than one antihypertensive drug, and about 30% of hypertensive patients with diabetes need three or more agents in combination.' A similar approach is seen in table 6.
The problem is that it may be difficult to achieve such BP with patients with proteinuria and overt renal disease and also in others with cardiovascular problems. Therefore, it is strongly advocated to start treatment early, e.g. with development of microalbuminuria, even in patients with normal BP. It has also been proposed to start treatment even before microalbuminuria. Since complications are so closely associated with BP increase (also in the normal range) this could easily be recommended in future guidelines as we now have effective treatment modalites with rather limited side effects.
This chapter clearly documents that excess albuminuria, often accompanied by increased BP, is associated with actual or subsequent organ damage, not only in the kidney but also in other organs, especially in the eyes and in the heart. In the kidney, abnormal albuminuria starting in the microalbumi-nuric range reflects more advanced glomerular structural lesions, although the exact location of the permeability defect has not been defined at an ultrastructural level. BP elevation may not initiate the glomerular permeability defect but high systemic BP aggravates the course of established lesions and clinical disease. Transition from micro- to macroalbuminuria is associated with a reduction in GFR, the key parameter in evaluation of renal function.
Biochemical and hemodynamic hypotheses have been put forward supported by animal models, but these notions are difficult to substantiate in humans, where isolated phenomena cannot be studied, and direct measurement of e.g. glomerular wall charge and intraglomerular pressure is not feasible. A unifying concept would be attractive, comprising biochemical aberrations, such as charge defects, changes in enzymatic activities and glycation phenomena as well as hemodynamic changes such as hyperfiltration with elevated glomerular pressure, aggravated by early systemic BP rise. This may be seen along with vascular and endothelial changes, reflected by increases in von Willebrand factor, circulating prorenin as well as increased transcapillary escape rate of albumin and dyslipidemia. Antioxidant status may also play a role. A common pathway explaining all or most of these abnormalities should be pursued, with the basis in prolonged hyperglycemia and related biochemical changes, characteristic for the diabetic state.
However, when diabetic complications are evolving as a consequence of hyperglycemia, increasing BP remains a decisive factor in promoting organ damage in the kidney, and antihypertensive treatment seems to be the therapeutic cornerstone in ameliorating deterioration in organ function. A low protein diet may also reduce albuminuria and the fall rate in GFR. However, strict antihypertensive therapy may limit the need for any dramatic reduction of the protein content of the diet.
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Carl Erik Mogensen, Medical Department M (Diabetes and Endocrinology), Kommunehospitalet, Arhus University Hospital, DK-8000 Arhus C (Denmark) Tel. +45 89492011, Fax +45 86137852, E-Mail [email protected]
Belfiore F, Mogensen CE (eds): New Concepts in Diabetes and Its Treatment. Basel, Karger, 2000, pp 174-185
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