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110 Diabetic Cardiovascular Autonomic Neuropathy

antidepressants and phenothiazines; eating small, mechanism of action of these agents is the blockade
frequent meals to avoid postprandial hypotension; of vasodilating beta-2 receptors allowing unopposed
and avoiding activities that involve straining, since in- alpha-adrenoceptor–mediated vasoconstriction. To
creased intra-abdominal and intra-thoracic pressure date there is no clear efficacy evidence in diabetic
decrease venous return. Several physical counter DCAN.
manoeuvres, such as leg crossing, squatting, and Clonidine: Clonidine, an alpha-2 antagonist, produces
muscle pumping can help maintain blood pressure a central sympatholytic effect and a consequent de-
during daily activities by inducing increased cardiac crease in blood pressure. Patients with severe DCAN
filling pressures and stroke volume.
have little central sympathetic efferent activity, and
the use of clonidine (0.1– 0.6 mg/day) could result
Pharmacological Treatment in an increase in venous return without a significant
Midodrine: Midodrine, a peripheral-selective alpha increase in peripheral vascular resistance. Its use is
1- adrenoceptor agonist is widelytested agent for limited by the inconsistent hypertensive effect and
the treatment of orthostatic hypotension in doses serious side effects.
of 2.5–10 mg three times/day. It does not cross the
blood-brain barrier, resulting in fewer central side Somatostatin analogs: Somatostatin analogs (25–
effects. The main adverse effects are piloerection, 200 g/day) may attenuate orthostatic hypotension
pruritis, paraesthesia, urinary retention, and supine in patients with DCAN by inhibiting the release of
hypertension. vasoactive gastrointestinal peptides, enhancing car-
diac output, and increasing forearm and splanchnic
Fludrocortisone acetate: Fludrocortisone acetate, a vascular resistance. However, severe cases of hyper-
synthetic mineralocorticoid with a long duration of tension were reported with their use in patients with
action, induces plasma expansion and may enhance DCAN .
29
the sensitivity of blood vessels to circulating cate-
cholamines. The effects usually occur over a 1- to Conclusions
2-week period. Supine hypertension, hypokalaemia, DCAN is one of the most clinically significant compli-
and hypomagnesemia may occur. Caution must be cations of diabetes mellitus (DM), but one of the least
used, particularly in patients with congestive heart frequently diagnosed. It also is one of the most ob-
failure, to avoid fluid overload. Treatment with fludro- scure and controversial topics in current diabetology.
cortisone should begin with 0.05 mg at bedtime and DCAN is an independent predictor of cardiovascular
may be titrated gradually to a maximum of 0.2 mg/ disease mortality. It is associated with a poor prog-
day. Doses up to 0.3– 0.4 mg used in refractory cases nosis and poor quality of life. Conclusive clinical ev-
are associated with high risk for hypokalaemia, ex- idence from randomized prospective trials supports
cessive fluid retention, hypertension, and congestive a central role for hyperglycaemia in the pathogene-
heart failure.
sis of DCAN, although other metabolic and vascular
Erythropoietin: Erythropoietin may improve ortho- factors contribute to the disease state. The clinical
static hypotension, but the mechanism of action for presentation of DCAN comprises a broad constella-
this pressor effect is still unresolved. Possibilities in- tion of symptoms and deficits. Assessment of HRV
clude the increase in red cell mass and central blood is an easily available tool to document the presence
volume, correction of the normochromic normocytic of DCAN. Cardiac scintigraphic imaging with sympa-
anaemia that frequently accompanies severe CAN, thetic analogs offers more sensitive diagnostic al-
and direct or indirect neuro- humoral effects on the ternatives for research use. The treatment of DCAN
vascular wall and vascular tone regulation mediated is challenging. Recent clinical evidence continues to
by the interaction between haemoglobin and the va- prove the benefits of glycemic control, while the ben-
sodilator nitric oxide. Erythropoietin is administered efits of lifestyle and pharmacologic interventions are
subcutaneously or intravenously at doses of 25–75 emerging.
units/kg three times a week until the haematocrit lev-
el approaches normal followed by lower maintenance
doses (25 units/kg three times/week).
Non-selective Beta-blockers: Nonselective be-
ta-blockers, particularly those with intrinsic sym-
pathomimetic activity, may have a limited role in the
treatment of orthostatic hypotension. The suggested

GCDC 2017