Blood pressure and cardiac autonomic function in relation to risk factors and treatment perspectives in Type 1 diabetes

Abstract

The cumulative incidence of diabetic nephropathy in Type 1 diabetes mellitus is in the order of 25 30%. The recognition that elevated blood pressure (BP) is a major factor in the progression of these patients to end-stage renal failure has led to the widespread use of antihypertensive therapy in order to preserve glomerular filtration rate and ultimately to reduce mortality. The routine measurement of microalbuminuria allows early identification of the subgroup of patients at increased risk of developing clinical nephropathy. Microalbuminuric Type 1 diabetic patients show a number of characteristic pathological abnormalities. In addition to elevated BP and abnormal circadian rhythm, there are also associated abnormalities of vagal function, lipid profile and endothelial function, as well as an increased prevalence of retinopathy. The first section of this two-part review focusses on the early changes associated with renal involvement in Type 1 diabetes. It addresses the associations between urinary albumin excretion, glycaemic control, smoking, BP, circadian BP variation, QT interval abnormalities and autonomic function in three groups of patients; those with normoalbuminuria, those progressing towards microalbuminuria and those with established low-grade microalbuminuria.

Cardiac Autonomic Neuropathy and Early Progressive Renal Decline in Patients with Nonmacroalbuminuric Type 1 Diabetes

“…In young patients with type 1 diabetes, SNS activity causes early, preclinical BP changes that are in turn associated with increased glomerular basement membrane thickness and mesangial matrix expansion (38). Autonomic dysfunction also correlates with higher-range normoalbuminuria in patients with type 1 diabetes, suggesting a possible role for SNS activation in the transition from normo-to microalbuminuria (39) and activation of intrarenal RAAS, intraglomerular hypertension, and hyperfiltration in animals and in humans with type 1 diabetes (40)(41)(42). Therapeutic interventions using pharmacologic SNS blockade in type 1 diabetes resulted in lower BP and improved HRV (43).…”

“…First, we cannot confirmdespite conditioning on confounding variables-the independent causal role of cardiac autonomic neuropathy. Specifically, subclinical renal disease may instead lead to autonomic dysfunction (39). Ultimately, pharmacologic approaches or blockade of the SNS will be required to elucidate the role of cardiac autonomic neuropathy in the initiation and progression of DN.…”

Review: Early renal involvement in Type 1 diabetes mellitus — Part 2: ACE inhibitor intervention in Type 1 diabetes with low grade microalbuminuria

“…46 The odds ratio of progression to macroalbuminuria on ACE-I treatment was approximately one third compared with the placebo-treated patients. Conversely, regression to normoalbuminuria was three times greater in the ACE-I group compared with the placebo group.Apparently, the impact of ACE inhibition on UAE change was attenuated by duration of follow-up: those with the longest follow-up had the smallest treatment effect.…”

“…As discussed fully in reference 46 in early studies, Spacelabs 90202 monitors were used with readings at 20-minute intervals during the day and hourly from 24.00 to 6.00. In later studies, Spacelabs 90207 was used, with readings at 20-minute intervals throughout 24 hours.…”

“…44 In a number of clinical trials encompassing microalbuminuric Type 1 diabetic patients, antihypertensive treatment in particular with ACE inhibitors (ACE-I), has been shown to reduce albuminuria. 45,46 Importantly, data suggesting positive effects on harder endpoints such as GFR 25 and glomerulopathy 26 are now emerging. At present, the consensus calls for antihypertensive treatment in most patients with microalbuminuria, regardless of BP.…”