D Mawson

Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide

Aims/hypothesisHydrogen sulphide is a recently identified endogenous endothelium-dependent vasodilator. Animal models of diabetes have shown that low plasma H2S levels are associated with marked endothelial dysfunction and insulin resistance. However, human studies on H2S and vascular function in health and disease are lacking.MethodsPlasma was obtained from male patients with type 2 diabetes (n = 11), overweight (n = 16) and lean (n = 11) volunteers. H2S levels were determined by zinc trap spectrophotometry. Anthropometric measurements (BMI/waist:hip ratio), lipid profile, systemic blood pressure, biochemical indices of diabetes (fasting glucose, insulin sensitivity, Hb1Ac) and microvascular function (minimum vascular resistance) were determined.ResultsMedian plasma H2S levels (25th, 75th percentiles) in age-matched lean, overweight and type 2 diabetes individuals were 38.9 (29.7, 45.1) µmol/l, 22.0 (18.6, 26.7) µmol/l and 10.5 (4.8, 22.0) µmol/l, respectively. Median plasma H2S levels were significantly lower in patients with type 2 diabetes compared with lean (p = 0.001, Mann–Whitney) and overweight participants (p = 0.008). Median plasma H2S levels in overweight participants were significantly lower than in lean controls (p = 0.003). Waist circumference was an independent predictor of plasma H2S (R2 = 0.423, standardised beta: −0.650, p < 0.001). This relationship was independent of diabetes, which only contributed a further 5% to the model (R2 = 0.477). Waist circumference or other measures of adiposity (waist:hip ratio/BMI) remained independent predictors of plasma H2S after adjustment for systolic blood pressure, microvascular function, insulin sensitivity, glycaemic control and lipid profile.Conclusions/interpretationPlasma H2S levels are reduced in overweight participants and patients with type 2 diabetes. Increasing adiposity is a major determinant of plasma H2S levels.

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

Aims  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.

Older Type 2 diabetic males do not exhibit abnormal pulmonary oxygen uptake and muscle oxygen utilization dynamics during submaximal cycling exercise

There are reports of abnormal pulmonary oxygen uptake (Vo(2)) and deoxygenated hemoglobin ([HHb]) kinetics in individuals with Type 2 diabetes (T2D) below 50 yr of age with disease durations of <5 yr. We examined the Vo(2) and muscle [HHb] kinetics in 12 older T2D patients with extended disease durations (age: 65 ± 5 years; disease duration 9.3 ± 3.8 years) and 12 healthy age-matched control participants (CON; age: 62 ± 6 years). Maximal oxygen uptake (Vo(2max)) was determined via a ramp incremental cycle test and Vo(2) and [HHb] kinetics were determined during subsequent submaximal step exercise. The Vo(2max) was significantly reduced (P < 0.05) in individuals with T2D compared with CON (1.98 ± 0.43 vs. 2.72 ± 0.40 l/min, respectively) but, surprisingly, Vo(2) kinetics was not different in T2D compared with CON (phase II time constant: 43 ± 17 vs. 41 ± 12 s, respectively). The Δ[HHb]/ΔVo(2) was significantly higher in T2D compared with CON (235 ± 99 vs. 135 ± 33 AU·l(-1)·min(-1); P < 0.05). Despite a lower Vo(2max), Vo(2) kinetics is not different in older T2D compared with healthy age-matched control participants. The elevated Δ[HHb]/ΔVo(2) in T2D individuals possibly indicates a compromised muscle blood flow that mandates a greater O(2) extraction during exercise. Longer disease duration may result in adaptations in the O(2) extraction capabilities of individuals with T2D, thereby mitigating the expected age-related slowing of Vo(2) kinetics.

Comparison of CapiFlow and frame by frame analysis for the assessment of capillary red blood cell velocity

CapiFlow (CF), a new fully computerized system for the measurement of capillary blood velocity (CBV) was compared to manual frame by frame analysis (a) in a model system, and (b) in finger nailfold capillaries recorded on video tape. In the model the overall agreement between the two methods was very good (figure 1), with no significant differences being noted between the two sets of results and the calculated velocities. However, when comparing frame by frame and CapiFlow directly, CapiFlow read on average 4.50 +/- 5.21% higher than frame by frame analysis (figure 2). The in vivo results obtained by the two methods showed similar dynamic changes although some differences between the overall mean CBVs were noted (capillary 1, manual 0.13 +/- 0.59 mm s-1 versus CF 0.12 +/- 0.02 mm s-1, (mean +/- SD), p = 0.354; capillary 2, manual 0.66 +/- 0.23 mm s-1 versus CF 0.47 +/- 0.09 mm s-1, p < 0.001; capillary 3, manual 2.53 +/- 0.73 mm s-1 versus CF 2.35 +/- 0.34 mm s-1, p = 0.062). Further analyses established the optimum settings of delta limit and cross correlation. Investigations into the effects of changes in window size, window distance or video settings on CBV results obtained by CapiFlow, indicated that only settings radically different from the optimum had a significant effect on the results obtained.

Are Features of the Metabolic Syndrome Associated with Macular Thickness in Individuals without Diabetes Mellitus

Background: Maculopathy is a common feature at diagnosis of type 2 diabetes. However, it is not known whether macular thickening, a potential preclinical sign of macular oedema, occurs in individuals with risk factors for diabetes. Purposes: To examine whether macular thickness is increased in individuals with features of the metabolic syndrome, namely waist circumference, blood pressure, and fasting levels of triglycerides, HDL-cholesterol and glucose in non-diabetic individuals. Methods: 50 non-diabetic Caucasian individuals were recruited (25 males, age range: 26-78 years, BMI range: 20-46 kg/m 2 ). Macular thickness, divided into fovea and the inner and outer temporal, nasal, superior and inferior quadrants, was assessed by Optical Coherence Tomography. Additional assessments included: arterial blood pressure, fasting glucose and lipid profile (including triglycerides and HDL-cholesterol), BMI and waist circumference. Features of the metabolic syndrome were collectively entered into a forced regression model to examine their relationship with thickness in the macular subdivisions. Results: Fovea thickness was within the normal range for all participants. Features of the metabolic syndrome were not collectively associated with macular thickness. However, mean arterial blood pressure (MAP) was independently associated with macular thickness in all regions (standardized beta>0.381, p<0.05) except for the outer nasal quadrant (standardized beta=0.346, p=0.071) and a vascular fovea region (standardized beta=0.105, p=0.591). Conclusions: MAP, independent of other features of the metabolic syndrome, is associated with thickness in the inner and outer quadrants of the macular. Further research is needed to fully elucidate this relationship. However, potential explanations include altered pressure autoregulation (pressure or metabolic induced) and microvascular rarefaction.