Je Tooke

Blood flow in the skin of the foot related to posture in diabetes mellitus

Normal healthy subjects show a reflex rise in precapillary resistance in the skin of the foot when they rise from lying to standing. To investigate the integrity of this reflex in patients with diabetes mellitus blood flow in the plantar region of the big toe was measured, using a laser Doppler flowmeter. The responses of diabetic patients with and without peripheral sensory neuropathy and healthy control subjects matched for age and sex were studied, with the foot at heart level and the foot passively lowered to 50 cm below the heart. In normal subjects mean blood flow recorded during the third to fourth minute of dependency fell to 18.1 (SD 11.9)% of the preceding resting flow determined with the foot at heart level. In the diabetic patients without neuropathy blood flow fell to 28.9 (18.6)% of the preceding resting flow. In the diabetic patients with neuropathy blood flow fell to 53.5 (23.7)% of the preceding resting flow, which was significantly different from the value achieved by the diabetics without neuropathy (p less than 0.02) and the healthy controls (p less than 0.002). Six normal subjects were indirectly heated to release sympathetic tone and achieve the same mean skin temperature of the foot as the diabetic patients with neuropathy, and blood flow fell to 38.7 (24.3)% of the preceding resting flow, a value not significantly different from the response seen in the patients with neuropathy. These findings suggest that the postural control of blood flow in the foot is disturbed in patients with diabetic neuropathy, and this disturbance is compatible with a loss of sympathetic vascular tone. The resultant hyperperfusion on dependency may account for the oedema seen in some patients with neuropathy and may also act as a stimulus for the thickening of capillary basement membranes.

Impaired microvascular hyperaemic response to minor skin trauma in type I diabetes

SIR,-Dr G Rayman and colleagues made some interesting observations on the local hyperaemic response to minor skin trauma (needle insertion and warming) in insulin dependent diabetes (17 May, p 1295). However, their literature search may have been incomplete, as they do not mention our reports on the local hyperaemic responses to needle insertion and superficial injection of small volumes of bland liquids in diabetic and nondiabetic subjects. 14 Dr Raymans protocol was similar to our own, except that we used photoelectric plethysmography, a non-invasive optical technique which yields similar results to the laser Doppler flowmetry method used by the authors; the two methods have been compared (1 March, p 620). Injection depth was fixed at 7-8 mm under the centre of the photoelectric plethysmography probe by inserting the needle along an angled track drilled through a perspex block cemented to the side of the probe. Injection of 0-1-0 15 ml of saline or insulin diluent in normal subjects (n=6, mean age 24 years) produced a local hyperaemic flare, which reached a peak representing a 1600/o increase over baseline flow at 2 minutes and had largely faded by 30 minutes. Simple needle insertion without injection produced a response of similar amplitude and duration, suggesting that this acute, transient hyperaemia was a non-specific response to injury. In contrast, there was prolonged and considerable hyperaemia after injection of local vasodilators such as prostaglandin El,l 2nicotinicacid,2aprotinin,3andinsulin.. In stable insulin dependent diabetics (n=7, mean age 22 years, mean duration of diabetes 9years) the response was slightly but not significantly less than in normal subjects, but in severely brittle diabetics with chronic metabolic instability (n= 8, mean age 18 years, mean duration of diabetes 10 years) the hyperaemic flare was significantly flatter and shorter than in both other groups (figure). These findings, unlike those of Dr Rayman and colleagues, therefore suggested that impaired local hyperaemic responses to needle insertion were related to long term metabolic control rather than the presence of diabetes itself; differences in patient selection may explain these divergences. Other points should be mentioned. Firstly, as discussed (1 March, p 620), neither photoelectric plethysmography nor laser Doppler flowmetry can measure absolute units of blood flow, although

Direct measurement of capillary blood flow in the diabetic neuropathic foot

SummaryThe two major components of the microcirculation in the diabetic neuropathic foot have been examined in detail. Nutritive capillary blood flow was measured directly using the non-invasive technique of television microscopy, applied to the toe nailfold. Arteriovenous shunt flow was assessed using the technique of laser Doppler flowmetry, applied to the toe pulp. Fourteen diabetic patients with peripheral and autonomic neuropathy, 11 with no clinical evidence of neuropathy and 14 normal subjects were studied. Laser Doppler flowmetry (predominantly arteriovenous shunt flow) was increased more than three-fold (p<0.01) in the diabetic patients with neuropathy compared to control subjects, (median 3.57, interquartile range 2.00–5.32 volts vs median 0.93, interquartile range 0.47–2.36 volts respectively). There was no evidence of skin capillary closure. The calculated capillary blood flow (erythrocyte flux) was significantly increased in the diabetic neuropathic patients compared to control subjects (median 76.4, interquartile range 34.4–109.8 picolitres/s vs median 23.2, range 8.0–44.8 picolitres/s, p<0.01). This study demonstrates that foot skin capillary blood flow is increased in diabetic patients with neuropathy. There is, therefore, no evidence to support the supposition that capillary ischaemia, either secondary to a “capillary steal phenomenon” or “advanced microangiopathy”, is a feature of diabetic neuropathy under resting conditions.

Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid‐lowering therapy

Aimsu2003 Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes. Although statin therapy improves cardiovascular risk in diabetes, dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy. We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels.

Posturally induced vasoconstriction in diabetes mellitus.

In healthy subjects, standing elicits a reduction in blood flow to the skin of the foot. In adults with insulin dependent diabetes this posturally induced response is deficient, resulting in capillary hypertension when the foot is in the dependent position (that is, below heart level). Such functional abnormalities of the microcirculation in diabetes may precede any evidence of clinically detectable microangiopathy. This study investigates the posturally induced change in blood flow to the skin of the foot in prepubertal and postpubertal patients with insulin dependent diabetes. Laser Doppler fluximetry was used to assess the postural change in blood flow at the pulp of the great toe. Postural vasoconstriction (dependent flux value/supine flux value x 100) was greater after puberty in normal subjects (median (range) 60.4 (7.0-164.9)% prepubertal v 20.5 (5.9-101.0)% postpubertal). Prepubertal children with diabetes did not differ from their healthy peers (69.8 (7.2-192.7)% with diabetes v 60.4 (7.0-164.9)% controls); however postpubertal children with diabetes had a significantly impaired postural vasoconstriction (40.6 (7.9-140.2)% with diabetes v 20.5 (5.9-101.7)% controls). Abnormalities in the normal reduction of blood flow on standing occurred in young postpubertal children with diabetes, most of whom were free of complications.

Capillary filtration coefficient and urinary albumin leak at altitude

Rapid ascent to altitude risks the development of acute mountain sickness. This study demonstrates changes in peripheral capillary filtration coefficient and renal protein loss in subjects suffering from various degrees of mountain sickness after passive ascent to 4559u2003m. Capillary filtration coefficient of the calf capillary bed, measured by computer‐based multistep strain gauge plethysmography, increased significantly after 23.5u2003h at altitude when symptoms were most severe: 4.45 (2.76–6.03) to 6.31 (3.86–11.07) mlu2003min–1 per 100u2003g of tissueu2003mmHg–1, median (range) (Pu2003<0.02). Urinary albumin excretion was increased after one night at altitude from 1.1 (0.6–1.5) to 2.45 (1.0–6.8) mg of albumin per mmol of creatinine (Pu2003<0.05). These results demonstrate simultaneous leakage of a peripheral capillary bed to fluid measured by strain gauge plethysmography, and renal albumin leak, and suggest a systemic process of increased capillary leakage for different‐sized molecules caused by rapid exposure to hypobaric hypoxia.

The effect of insulin infusion on capillary blood flow in the diabetic neuropathic foot

The effect of a short‐term improvement in glycaemic control induced by insulin infusion on foot skin capillary blood flow was previously unknown. In seven Type 2 (non‐insulin‐dependent) diabetic subjects with neuropathy capillary blood flow was measured in the great toe nailfold by television microscopy. An estimate of arteriovenous shunt flow was obtained simultaneously in the pulp of the great toe by laser Doppler flowmetry. After omission of oral hypoglycaemic therapy for 24 h mean blood glucose was 15.7 ± 0.7 (SEM) mmol I−1. A priming infusion of 0.1 U kg−1 of insulin was given intravenously over 15 min, followed by a variable rate insulin infusion adjusted to steadily reduce blood glucose avoiding hypoglycaemia. At the end of the study blood glucose was reduced to 6.9 ± 0.7 mmol I−1 (p < 0.001). During the insulin infusion, capillary blood velocity increased by 28.8% (p < 0.05), and the diameter of the capillary erythrocyte column increased from 7.6 ± 0.2 to 9.2 ± 0.3 μm (p < 0.01). Thus during the insulin infusion, the calculated capillary flow increased to 226 ± 36% above basal values (p < 0.01). Laser Doppler flow did not change significantly, suggesting that during insulin infusion skin blood flow is redistributed with an increase in capillary flow relative to arteriovenous shunt flow.

A study of factors governing fluid filtration in the diabetic foot

Abstract. The effect of lowering the foot on the factors governing fluid filtration in the foot were studied in 12 male insulin‐dependent diabetic subjects and 10 controls. Toe skin blood flow, measured by laser Doppler flowmetry, was significantly higher during dependency in the diabetic group. In the control subjects, the colloid osmotic pressure of venous blood sampled from the foot rose to 47·7 mmHg (range 45·1–53·8) after 50 min of foot dependency. In the diabetic group, colloid osmotic pressure failed to rise to the same extent (median 36·7 mmHg; range 28·6–43·0; P < 0·001). Capillary pressure, measured directly by the Landis microinjection technique, was significantly higher in the diabetic group (85·3±1·7 (n= 6) vs. 92·2±4·6 cm H2O (n= 6); P < 0·007), as was foot swelling rate determined by mercury strain gauge plethysmography (0·069±0·022 vs. 0·099±0·025 ml min‐1 100ml‐1; P < 0·02). These results suggest an impairment of the oedema‐preventing mechanisms in diabetic subjects which may contribute to the risks of ulceration in the diabetic foot.

Insulin and lysophosphatidylcholine synergistically stimulate NO‐dependent cGMP production in human endothelial cells

Aimsu2003 Nitric oxide (NO) is an important regulator of cardiovascular homeostasis. Lysophosphatidylcholine (lyso‐PC), a major constituent of oxidized low density lipoproteins (oxLDL), has been reported to impair nitric oxide‐dependent vasodilatation. This study investigated the possible mechanism of the lyso‐PC effect on insulin‐stimulated NO‐dependent of cyclic guanosine 3′,5′‐monophosphate (cGMP) generation in human endothelial cells.

Effect of venesection on calf blood flow in polycythaemia.

Calf blood flow at rest and during postocclusive reactive hyperaemia was measured using an electrocardiogram-triggered plethysmograph in 14 patients with polycythaemia (nine with primary disease and five with polycythaemia secondary to cyanotic heart disease) before and after a course of venesection. The mean packed cell volume was reduced from 0.57 to 0.47, and whole-blood viscosity fell by 50% at low shear rates. Venesection did not affect rest flow, but peak flow was increased by 18%. The increase in peak flow failed to compensate for the reduced haemoglobin content of the blood, calculated haemoglobin delivery being reduced by 23% at rest and 10% during reactive hyperaemia. These results indicate that while venesection improves blood viscosity, this does not necessarily lead to improved delivery of oxygen to the tissues.