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Does the metabolic syndrome make blood pressure control more difficult in diabetes?

Giunti, Sara; Cooper, Mark

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doi: 10.1097/01.hjh.0000188730.67969.db
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Over the last two decades, evidence indicating the importance of achieving tight blood pressure control in diabetic subjects has been clearly demonstrated. Specifically, it has been shown that hypertension substantially increases the risk of both macrovascular and microvascular complications in diabetes [1,2], and that this risk is significantly decreased by blood pressure reduction, in particular with intensive antihypertensive treatment regimens [3–6]. Furthermore, tight blood pressure control may be more useful than intensified glycemic control [6] and has been reported as the most cost-effective intervention in these patients [7]. Unfortunately, despite strong clinical data on the importance of blood pressure reduction, diabetic subjects continue to achieve the current recommended target of a blood pressure < 130/80 mmHg [8–10] in only a disappointing minority of cases [11,12]. The reasons for inadequate blood pressure control in diabetic subjects remain unknown. It is possible that a lack of detailed understanding of the underlying pathophysiological mechanisms responsible for elevated blood pressure in diabetes means that some individuals are not being treated appropriately with rationally-based therapeutic regimens.

In this issue of the journal, Nilsson et al. [13] have addressed this point by examining which factors appear to be associated with long-term successful blood pressure control (defined as a blood pressure < 135/85 mmHg) in type 2 diabetic subjects from the Swedish National Diabetes register (NDR). Two groups of type 2 diabetic patients with either successful or unsuccessful blood pressure control were compared for the presence of a range of risk factors at both baseline and after 6-year follow-up. The main findings from their study indicated that lower age, a decreased body mass index (BMI) and the absence of microalbuminuria were independently associated with long-term successful blood pressure control. Furthermore, the authors noted that unsuccessful blood pressure control was associated with a significant increase in the prevalence of the metabolic syndrome, as defined according to WHO criteria [14]. Finally, in the successful blood pressure group, there was a calculated lower 10-year risk of coronary heart disease and stroke based on the UKPDS Risk Engine model [15,16]. In another study involving a group of diabetic subjects recruited from primary care clinics in Minnesota [17], a retrospective analysis revealed that poor blood pressure control was also associated with several risk factors, including age, as was the case in the Nilsson study. This strong relationship between age and inadequate blood pressure control, observed in both studies, emphasizes the well-known phenomenon of age being a major factor in modulating the blood pressure response to antihypertensive therapy [18].

The findings from the Swedish NDR study are consistent with the view that the presence of various features of the metabolic syndrome (also known as the insulin resistance syndrome, and including obesity and microalbuminuria [14]) may predict subsequent difficulty in controlling blood pressure. However, in this analysis of the Swedish NDR, where baseline blood pressure data were unavailable before antihypertensive treatment was commenced, some caution is warranted when interpreting the findings obtained. Furthermore, it is possible that, despite subjects primarily originating from medical outpatients and primary health care centres, the exact classification of subjects as having type 2 diabetes may not be totally accurate because no detailed biochemistry or antibody measurements were included to allow appropriate diagnosis among the different types of diabetes and, in particular to exclude individuals with type 1 diabetes or late autoimmune diabetes in adults. Indeed, subjects included in the group characterized by successful blood pressure control were significantly younger, with 47.9% of this group being treated with insulin alone. This suggests that there may have been a significant proportion of type 1 diabetic subjects in the study who do not characteristically have an increased prevalence of the metabolic syndrome, and in whom hypertension often reflects the presence of diabetic nephropathy. Therefore, the association between blood pressure and BMI and microalbuminuria may have been partly driven by the selection of subjects. It is possible that the two groups did not have the same proportion of type 2 diabetic patients.

The association of albuminuria with unsuccessful blood pressure control is not surprising when considering the large body of data linking increased albuminuria to systemic blood pressure [3,19]. This relationship, originally described in the diabetic population, has recently been extended to the non-diabetic population in the Framingham Offspring Study [20]. Indeed, in that study, low-grade albuminuria was associated with progression of blood pressure, and the authors suggested that this biomarker may identify those individuals at high risk for the development of hypertension. Thus, the situation remains where it is difficult to determine whether albuminuria represents a manifestation of blood pressure-related end-organ injury or is itself a predictor of, or even pathogenically linked to, the progression of blood pressure. This is further complicated by the fact that treating blood pressure is generally associated with a decrease in albuminuria [2], making it difficult to fully delineate the relationship between albuminuria and blood pressure.

Increasingly, researchers are now focusing on the metabolic syndrome, although the increased emphasis on this entity remains controversial [21]. Nevertheless, the various components of the metabolic syndrome, including dyslipidemia and obesity, are major therapeutic targets for the population and, in particular, those with type 2 diabetes. There is increasing evidence that the metabolic syndrome is closely linked to albuminuria and other cardiovascular risk factors in type 2 diabetes [22]. Although the relative importance of the various risk factors and potential interactions among risk factors such as hyperglycemia and hypertension remain to be fully determined, it is likely that a multifactorial approach will remain the best way to reduce complications in this population, as demonstrated in the Steno-2 study [23]. Nilsson et al. [13] also suggest this multifactorial approach. However, in the absence of appropriate interventional clinical trials, the epidemiological approach used in this Swedish NDR report can only be considered as supportive, and not definitive, in justifying this treatment strategy. Although they often cannot be considered as having a direct impact on clinical care, such epidemiological studies are helpful in understanding the scope of the problem of diabetes, hypertension and vascular disease and in assisting in the rationale and design of clinical trials. Indeed, the findings by Nilsson et al. [13] provide an impetus for prospective and interventional studies to further explore those factors that ultimately predict successful blood pressure control in type 2 diabetic patients.


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© 2005 Lippincott Williams & Wilkins, Inc.