Insulin sensitivity in tissues such as a skeletal muscle and fat is closely correlated with insulin action in the vasculature, but the mechanism underlying this is unclear. We investigated the effect ...of dexamethasone on insulin-stimulated glucose disposal and vasodilation in healthy males to test the hypothesis that a reduction in glucose disposal would be accompanied by a reduction in insulin action in the vasculature. We performed a double-blind, placebo-controlled, cross-over trial comparing insulin sensitivity (measured by the euglycemic hyperinsulinemic clamp) and vascular insulin action (measured by small vessel wire myography) in young healthy males allocated to placebo or 1 mg dexamethasone twice daily for 6 d, each in random order. Six days of dexamethasone therapy was associated with a 30% (95% confidence interval, 19.1–40.0%) fall in insulin sensitivity. Despite this, there was no difference in insulin-mediated vasodilation between phases. Dexamethasone had no effect on circulating markers of endothelial function, such as d-dimer, von Willebrand factor, and tissue plasminogen activator. By short-term exposure to high dose dexamethasone we were able to differentially affect the metabolic and vascular actions of insulin. This implies that, using this model, there is physiological uncoupling of the effects of insulin in different tissues.
Objective
To examine some of the potential benefits and risks of water fluoridation for older adults.
Methods
This study used ‘The Irish Longitudinal Study on Ageing’, to access a nationally ...representative sample of 4977 people aged 50 and older. The sample was used to estimate associations between the percentage of households in a respondent's local area with a currently fluoridated water supply and the probability of two binary outcomes: the respondent having all their own teeth and having normal bone density. Past exposure of individuals to fluoridated water was not assessed; the prevalence of fluoridated water in local supplies was obtained from the 2006 Census of Ireland. The Census data indicated that there was considerable variation in the proportion of households with fluoridated water supplies, especially in rural areas. Bone mineral density was estimated from a heel ultrasound of each respondent, and their number of teeth was self‐reported. A range of individual variables, such as educational attainment, housing wealth, age and health behaviours, was controlled for.
Results
It was found that the greater the percentage of households with a fluoridated water supply in an area, the higher the probability that respondents had all their own teeth. There was no significant relationship between the proportion of households with a fluoridated water supply in an area and bone health.
Conclusion
This study suggests that water fluoridation provides a net health gain for older Irish adults, though the effects of fluoridation warrant further investigation.
The aldosterone-to-renin ratio (ARR) is a marker of aldosterone activity in hypertension. We examined the relationship of the ARR to the distribution of two biallelic polymorphisms at the CYP11B2 ...gene locus. One polymorphism affects a putative steroidogenic factor-1 binding site (−344 T/C) in the 5′-regulatory region, whereas the other marker reflects replacement of the intron-2 from CYP11B2 with that from the neighboring gene encoding 11β-hydroxylase (CYP11B1; wild-type/conversion). We studied consecutive referrals to the Tayside hypertension clinic in 1998. Because the specificity of ARR (pmol/liter/ng/ml/h) for hyperaldosteronism increases with its threshold, ARRs of at least 750 and 1000 were used. A total of 375 patients were assessed; 86.9% had complete data. There were significant excesses of steroidogenic factor-1 (T) (ARR ≥ 750, 0.62 vs. 0.51, P = 0.014; ARR ≥ 1000, 0.63 vs. 0.51, P = 0.039) and intron-2 (conversion) (ARR ≥ 750, 0.49 vs. 0.41, P = 0.205; ARR ≥ 1000, 0.54 vs. 0.41, P = 0.029) alleles in patients with a raised ARR. The odds ratio for a raised ARR was 2.27 95% confidence interval, 1.01, 5.09; P < 0.05 comparing patients with a homozygous haplotype for these alleles with those without any such alleles, and this risk increased with age. This study supports the notion that there is a genetic component that regulates aldosterone production and that hyperaldosteronism might develop over time in susceptible individuals.
There is increasing evidence that elevated plasma levels of hemostatic factors fibrinogen, factor VII, von Willebrand factor, fibrin d-dimer, and tissue plasminogen activator (t-PA) antigen are ...independently linked to risk for coronary heart disease (CHD). Women with polycystic ovary syndrome (PCOS) are insulin-resistant and have increased risk for CHD and type 2 diabetes, but there are few data on hemostatic markers in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index (BMI) were recruited. Insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique. Factor VIIc was determined by a clotting assay; fibrinogen was determined by nephelometry; and t-PA, d-dimer, and von Willebrand factor antigens were measured by ELISA techniques. Of these hemostatic markers, only t-PA concentration was significantly (P = 0.013) elevated in women with PCOS relative to controls. t-PA correlated with BMI in both PCOS and controls (r = 0.428, P < 0.1; and r = 0.686, P < 0.01) and inversely with the insulin sensitivity index (r = −0.590, P < 0.05; and r = −0.620, P < 0.05, respectively). After further adjustment for BMI and insulin sensitivity, there remained a significant difference in t-PA between cases and controls (P = 0.017). Together, age and insulin sensitivity explained 39% of the variance in t-PA in women with PCOS (P < 0.05). Total testosterone did not correlate significantly with t-PA in either group. We conclude that women with PCOS have significantly increased t-PA concentrations relative to women with normal menstrual rhythm and normal androgens. We suggest that elevated t-PA and dysfibrinolysis may be a factor in the increased cardiovascular morbidity seen in PCOS.
Aims To determine whether carotid‐radial pulse wave velocity (crPWV), a simple non‐invasive measurement of muscular artery structure and function, is increased in offspring of patients with Type 2 ...diabetes compared with well‐matched controls with no family history of diabetes. Serum levels of intercellular adhesion molecule‐1 (sICAM‐1) were also examined.
Methods Offspring (n = 19, M = 8) were recruited via contact with patients attending clinics. Controls (n = 19, M = 8) were recruited by advertisement. crPWV was measured using COMPLIOR. Blood pressure and heart rate were determined and fasting blood taken for measurement of metabolic and endothelial parameters.
Results Offspring and controls were well matched mean (sd) for age 33.1 (9.6) vs. 32.8 (9.5) years, body mass index 24.8 (4.9) vs. 24.3 (3.4) kg/m2, waist circumference 78.3 (2.3) vs. 76.3 (2.5) cm, and systolic blood pressure 120 (9.3) vs. 119 (14.2) mmHg. crPWV was 10% higher in the offspring 9.94 (1.3) m/s compared with controls 9.01 (1.2) m/s, P = 0.02 despite similar pulse pressure 52 (10.5) vs. 53.5 (9.3) mmHg and resting heart rate 71 (8.7) vs. 69 (14.0) beats/min. They also showed a trend toward higher sICAM‐1 217 (55) vs. 188 (40) ng/ml, P = 0.07 concentrations which were also strongly correlated to crPWV in offspring (r = 0.63, P = 0.004).
Conclusions Vascular dysfunction in the form of increased muscular artery stiffness is present from an early stage in subjects at higher risk of developing diabetes. This may be secondary to impaired activation of endothelial signalling pathways in the context of inherited insulin resistance.
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