Review
An Update on Hypertension in Children With Type 1 Diabetes

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Abstract

The prevalence of hypertension in children with type 1 diabetes is reported to be between 6% and 16%. This potentially modifiable cardiovascular risk factor may go undiagnosed and undertreated, particularly in children with type 1 diabetes. Recent updated Canadian clinical practice guidelines recommend blood pressure screening every 2 years in children with type 1 diabetes as well as routine use of ambulatory blood pressure monitoring. Risk factors for hypertension in type 1 diabetes include poor glycemic control, overweight and obesity and genetic predisposition for hypertension. In terms of pathophysiology, sustained hyperglycemia, angiotensin I and II and inflammatory cytokines have been implicated. Endothelial and vascular dysfunction, with impaired endothelial-dependent vasodilation and increased carotid artery intima-media thickness, are evident in preclinical and clinical studies of children and not just in adults with type 1 diabetes. Early targeted therapy is critical to the control of hypertension and the development of related morbidity. As with hypertension in adults with type 1 diabetes, lifestyle modifications remain first-line therapy, including diet and glycemic control. Initial antihypertensive therapy should be an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker because of their associated effects of reducing microalbuminuria and improving renovascular outcomes. Pediatric hypertension in type 1 diabetes is an area of evolving study and opinion; identification and appropriate treatment is critical for the prevention of micro- and macrovascular complications in adulthood.

Résumé

La prévalence de l'hypertension chez les enfants atteints de diabète de type 1 est rapportée comme se situant entre 6% et 16%. Ce facteur de risque cardiovasculaire potentiellement variable peut ne pas être diagnostiqué et être mal traité, en particulier chez les enfants atteints de diabète de type 1. Les récentes lignes directrices canadiennes sur la pratique clinique recommandent une mesure de la pression artérielle tous les deux ans chez les enfants atteints de diabète de type 1, ainsi que la mise en place en routine d'un contrôle ambulatoire de la pression artérielle. Les facteurs de risque d'une hypertension dans le diabète de type 1 incluent un mauvais contrôle de la glycémie, un surpoids et une obésité et une prédisposition génétique à l'hypertension. En termes de physiopathologie, une hyperglycémie prolongée, l'angiotensine I et II, et des cytokines inflammatoires ont été montrées comme étant impliquées. Des dysfonctions endothéliales et vasculaires, avec une altération de la vasodilatation endothélium-dépendante et un épaississement accru de l'intima-média de l'artère carotide, sont manifestes dans les études précliniques et cliniques chez l'enfant et pas seulement chez l'adulte atteint de diabète de type 1. Une thérapie ciblée précoce est essentielle au contrôle de l'hypertension et du développement de la morbidité associée. Comme dans le cas de l'hypertension chez les adultes atteints de diabète de type 1, les adaptations du mode de vie demeurent le traitement de première intention, ceci incluant le contrôle du régime alimentaire et de la glycémie. Le traitement anti-hypertenseur initial devrait être un inhibiteur de l'enzyme de conversion de l'angiotensine ou bien un bloqueur du récepteur à l'angiotensine en raison de leurs effets associés sur la réduction de la microalbuminurie et sur l'amélioration de la fonction rénovasculaire. L'hypertension pédiatrique dans le diabète de type 1 est un domaine d'étude et d'opinion en constante évolution; son identification et un traitement approprié demeurent essentiels pour la prévention des complications micro- et macrovasculaires à l'âge adulte.

Introduction

Hypertension is 1 of the leading modifiable risk factors in the development of cardiovascular disease worldwide (1). In patients with diabetes, hypertension is even more prevalent than in the general population, and it has been recognized for decades that cardiovascular disease remains a leading cause of morbidity and mortality in adults with type 1 diabetes mellitus 2, 3. The vascular remodelling in type 1 diabetes begins in childhood and is augmented by the presence of hypertension (4), so the identification and appropriate treatment of hypertension in children with type 1 diabetes is paramount to prevent further micro- and macrovascular complications.

It is alarming that the prevalence of hypertension in children with type 1 diabetes has been reported to be between 6% and 16% 5, 6, 7 and, in a recent study in the United States, children with a single elevated blood pressure (BP) measurement were shown to be at increased risk for developing hypertension when they are adults (8). Despite the existence of Canadian guidelines outlining recommended screening frequency for hypertension in children with type 1 diabetes, as well as treatment strategies (9), hypertension in this setting remains underdiagnosed and undertreated overall (10).

In this review, we discuss what is currently known about the epidemiology, pathophysiology, risk factors and management strategies of hypertension in children with type 1 diabetes.

Section snippets

Definition of Hypertension

The current definition of hypertension in children is based on the normative distribution of BP in healthy children, characterized by sex and height, as outlined in the recently updated clinical practice guidelines (Table 1) (11). The Diabetes Canada clinical practice guidelines dictate that children with type 1 diabetes should be treated according to these normative guidelines (9).

Endothelial and vascular dysfunction in type 1 diabetes

The endothelium is important for maintaining normal vascular tone; it is mediated by the secretion of nitric oxide (a vasodilator) and endothelin-1 (a vasoconstrictor) for angiogenesis via the secretion of vascular endothelial growth factor, and it also modulates innate immunity and the coagulation system (26). Endothelial dysfunction occurs when these normal homeostatic properties are altered (26). The Steno hypothesis suggested that albuminuria represented a marker not only for nephropathy

Management

Prevalence studies have repeatedly shown that hypertension is undertreated in patients with type 1 diabetes; this is believed to be a result of reduced or ineffective screening. ABPM is superior to random BP measurement for the prediction of cardiovascular events (78). One of the first signs of hypertensive load is the loss of dipping, the physiologic drop in BP at night, which is identified by ABPM (79).

Conclusions

Hypertension in children with type 1 diabetes is probably more prevalent than has been realized previously, and there may be subtle patterns that would become apparent only with a 24-hour ABPM, patterns such as inadequate nocturnal dip in BP. The mainstay of therapy at present remains diet and glycemic control with ACE inhibition. Future therapeutic strategies might target the preceding endothelial dysfunction, vascular dysfunction or inflammation.

Author Disclosures

Conflicts of interest: None.

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    The Canadian Diabetes Association is the registered owner of the name Diabetes Canada.

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