Brachial-to-radial systolic blood pressure amplification in patients with type 2 diabetes mellitus.

Brachial-to-radial-systolic blood pressure amplification (Bra-Rad-SBPAmp) can affect central SBP estimated by radial tonometry. Patients with type 2 diabetes mellitus (T2DM) have vascular irregularities that may alter Bra-Rad-SBPAmp. By comparing T2DM with non-diabetic controls, we aimed to determine the (1) magnitude of Bra-Rad-SBPAmp; (2) haemodynamic factors related to Bra-Rad-SBPAmp; and (3) effect of Bra-Rad-SBPAmp on estimated central SBP. Twenty T2DM (64±8 years) and 20 non-diabetic controls (60±8 years; 50% male both) underwent simultaneous cuff deflation and two-dimensional ultrasound imaging of the brachial and radial arteries. The first Korotkoff sound (denoting SBP) was identified from the first inflection point of Doppler flow during cuff deflation. Bra-Rad-SBPAmp was calculated by radial minus brachial SBP. Upper limb and systemic haemodynamics were recorded by tonometry and ultrasound. Radial SBP was higher than brachial SBP for T2DM (136±19 vs 127±17 mm Hg; P<0.001) and non-diabetic controls (135±12 vs 121±11 mm Hg; P<0.001), but Bra-Rad-SBPAmp was significantly lower in T2DM (9±8 vs 14±7 mm Hg; P=0.042). The product of brachial mean flow velocity × brachial diameter was inversely and independently correlated with Bra-Rad-SBPAmp in T2DM (ß=-0.033 95% confidence interval -0.063 to -0.004, P=0.030). When radial waveforms were calibrated using radial, compared with brachial SBP, central SBP was significantly higher in both groups (T2DM, 116±13 vs 125±15 mm Hg; and controls, 112±10 vs 124±11 mm Hg; P<0.001 both) and there was a significant increase in the number of participants classified with 'central hypertension' (SBP⩾130 mm Hg; P=0.004). Compared with non-diabetic controls, Bra-Rad-SBPAmp is significantly lower in T2DM. Regardless of disease status, radial SBP is higher than brachial SBP and this results in underestimation of central SBP using brachial-BP-calibrated radial tonometry.

Exercise aortic stiffness: reproducibility and relation to end-organ damage in men.

Resting aortic stiffness (pulse wave velocity; aortic PWV (aPWV)) independently predicts end-organ damage and mortality. Exercise haemodynamics have been shown to unmask cardiovascular abnormalities, otherwise undetectable at rest, but the response of aPWV to exercise has never been examined. This study aimed to develop a technique to measure exercise aPWV, determine reproducibility and relation to subclinical end-organ damage with aging. Healthy younger (n=17, 30±8 years) and older (n=18, 54±8 years) untreated men underwent cardiovascular assessment at rest and during low intensity semirecumbent cycling. Tonometry was used to assess aPWV and central blood pressure (BP). All participants underwent 24 h ambulatory BP (ABP) monitoring. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Fifteen participants had testing repeated within 28±18 days. Exercise aPWV had good reproducibility (mean difference=-0.35±0.61 m s(-1), intraclass correlations=0.874, P<0.001) and was increased 26% above resting values in younger men (5.8±0.9 vs 7.3±1.6 m s(-1), P<0.001) and 19% above resting values in older men (6.3±1.0 vs 7.4±0.9 m s(-1), P<0.001). Exercise, but not resting, aPWV was significantly correlated with eGFR in older men (r=-0.633, P=0.005), and this was maintained after correction for age, body mass index and daytime systolic ABP (r=-0.656, P=0.008). Conversely, in younger men there was no significant association between eGFR and aPWV either at rest (r=-0.031, P=0.906) or during exercise (r=-0.117, P=0.655). Exercise aPWV is reproducible and significantly associated with kidney function in healthy older men. Further studies to determine the physiology and clinical relevance of raised exercise aPWV are warranted.

Microvascular blood flow responses to muscle contraction are not altered by high-fat feeding in rats.

AIM: Exercise and insulin each increase microvascular blood flow and enhance glucose disposal in skeletal muscle. We have reported that insulin-mediated microvascular recruitment in a diet-induced model of insulin resistance (high-fat feeding for 4 weeks) is markedly impaired; however, the effect of muscle contraction in this model has not been previously explored. METHODS: We fed rats either normal (ND, 10% calories from fat) or high-fat (HFD, 60% calories from fat) diets ad libitum for 4-8 weeks. Animals were then anaesthetized and one hindlimb electrically stimulated to contract at 0.05, 0.1 and 2 Hz (field stimulation, 30 V, 0.1 ms duration) in 15 min stepwise increments. Femoral artery blood flow (Transonic flow probe), muscle microvascular blood flow (hindleg metabolism of 1-methylxanthine and contrast-enhanced ultrasound) and muscle glucose disposal (uptake of radiolabelled 2-deoxy-d-glucose and hindleg glucose disappearance) were measured. RESULTS: Both ND and HFD rats received the same voltage across the leg and consequently developed the same muscle tension. Femoral artery blood flow in the contracting leg increased during 2 Hz contraction, but not during the lower frequencies and these effects were similar between ND and HFD rats. Muscle microvascular blood flow significantly increased in a contraction frequency-dependent manner, and preceded increases in total limb blood flow and these effects were similar between ND and HFD rats. Muscle glucose disposal was markedly elevated during 2 Hz contraction and was comparable between ND and HFD rats. CONCLUSION: Contraction-mediated muscle microvascular recruitment and glucose uptake are not impaired in the HFD insulin resistant rat.

Loss of insulin-mediated microvascular perfusion in skeletal muscle is associated with the development of insulin resistance.

AIM: The aetiology of the development of type 2 diabetes remains unresolved. In the present study, we assessed whether an impairment of insulin-mediated microvascular perfusion occurs early in the onset of insulin resistance. MATERIALS AND METHODS: Hooded Wistar rats were fed either a normal diet (ND) or a high-fat diet (HFD) for 4 weeks. Anaesthetized animals were subjected to an isoglycaemic hyperinsulinaemic clamp (3 or 10 mU/min/kg x 2 h), and measurements were made of glucose infusion rate (GIR), hindleg glucose uptake, muscle glucose uptake by 2-deoxy-d-glucose (R'g), glucose appearance (Ra), glucose disappearance (Rd), femoral blood flow (FBF) and hindleg 1-methylxanthine disappearance (1-MXD, an index of microvascular perfusion). RESULTS: Compared with ND-fed animal, HFD feeding led to a mild increase in fasting plasma glucose and plasma insulin, without an increase in total body weight. During the clamps, HFD rats showed an impairment of insulin-mediated action on GIR, hindleg glucose uptake, R'g, Ra, Rd and FBF, with a greater loss of insulin responsiveness at 3 mU/min/kg than at 10 mU/min/kg. The HFD also impaired insulin-mediated microvascular perfusion as assessed by 1-MXD. Interestingly, 1-MXD was the only measurement that remained unresponsive to the higher dose of 10 mU/min/kg insulin. CONCLUSIONS: We conclude that the early stage of insulin resistance is characterized by an impairment of the insulin-mediated microvascular responses in skeletal muscle. This is likely to cause greater whole body insulin resistance by limiting the delivery of hormones and nutrients to muscle.