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  • 1
    Electronic Resource
    Electronic Resource
    Increased plasma endothelin in diabetes: an atherosclerosis marker? (1994)
    Springer
    Diabetologia 37 (1994), S. 333-334 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00398065
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  • 2
    Electronic Resource
    Electronic Resource
    In addition to von Willebrand factor and urinary albumin excretion, plasma endothelin is an indicator of endothelial dysfunction in diabetes mellitus (1993)
    Springer
    Diabetologia 36 (1993), S. 472-473 
    Details
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402288
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of insulin infusion on endothelium-derived vasoactive substances (1996)
    Springer
    Diabetologia 39 (1996), S. 1284-1292 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin ; endothelium ; endothelin ; prostacyclin ; nitric oxide ; vasodilatation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An association between insulin resistance and hypertension has been reported in several studies. In apparent contradiction, insulin infusion in healthy volunteers is associated with vasodilatation. Furthermore, there is evidence that some insulin effects may differ between the sexes. We performed three-step hyperinsulinaemic-euglycaemic clamp studies in six men and six women to test the hypotheses that: 1) insulin might affect the release of vasoactive substances by the endothelium, and 2): this putative effect on vasoactive substances might differ between men and women. Six other women and six men served as control subjects, receiving 154 mmol/l NaCl (saline) infusion. Plasma levels of insulin, immunoreactive endothelin, l-arginine (precursor of nitric oxide), l-citrulline (by-product of nitric oxide synthesis) and cyclic GMP (second messenger of nitric oxide) were measured during infusion of insulin or 154 mmol/l NaCl (saline), respectively. We also assessed urinary excretion of 6-keto PGF-1α (a degradation product of prostacyclin reflecting prostacyclin production). Blood pressure was monitored in all subjects throughout the experiment. In women plasma levels of immunoreactive endothelin decreased from (mean ± SD) 2.58 ± 0.96 to 1.7 ± 0.72 pmol/l during insulin infusion (p 〈 0.01), while remaining constant in female control subjects (p 〈 0.02). No changes in levels of endothelin were observed in men during infusion of insulin or saline. In women levels of cGMP rose and levels of l-arginine decreased significantly during insulin infusion, consistent with an increase in nitric oxide production. Excretion of 6-keto PGF-1α also increased significantly in women during insulin infusion. No such effects were observed in men, or in women during infusion of saline. Blood pressure remained constant in all subjects during hyperinsulinaemia. We conclude that sex differences exist in the effects of insulin on the endothelium. Short-term hyperinsulinaemia in women is associated with a decline in levels of immunoreactive endothelin, and possibly with a rise in production of nitric oxide and prostacyclin. In contrast, levels of vasoactive substances remained constant in men during hyperinsulinaemia. Our findings may partly explain insulin's vasodilatory effects in healthy individuals. It remains to be investigated whether these effects are lost in insulin-resistant states. Our observation that there is a sex difference in insulin effects on the endothelium may help explain why the link between hyperinsulinaemia and cardiovascular disease appears to be clearer in men than in women. [Diabetologia (1996) 39: 1284–1292]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050571
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  • 4
    Electronic Resource
    Electronic Resource
    Heterogeneous nature of microalbuminuria in NIDDM: studies of endothelial function and renal structure (1998)
    Springer
    Diabetologia 41 (1998), S. 233-236 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Non-insulin-dependent diabetes mellitus ; microalbuminuria ; von Willebrand factor ; endothelial function ; renal structure.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microalbuminuria (MA) is associated with microangiopathy (renal and retinal lesions) in insulin-dependent diabetic (IDDM) patients. In contrast MA does not reflect microvascular damage in a substantial number of non-insulin-dependent diabetic (NIDDM) patients. MA predicts cardiovascular disease in NIDDM patients with increased von Willebrand factor (vWF) plasma levels which are hypothesized to reflect endothelial dysfunction. However, it is not known whether MA is consequent to generalised endothelial dysfunction or to renal injury. Thus, this study evaluated vWF plasma levels in relation to renal and retinal structural abnormalities in NIDDM patients with MA. Kidney biopsies, fundoscopy and measures of vWF plasma levels were performed in 32 NIDDM patients with MA. These patients were allocated to two renal structural categories: A) Without renal structural abnormalities (C I, n = 10): normal or near-normal renal structure, and B) With renal structural abnormalities (n = 22), further divided into: C II (n = 12) with typical diabetic nephropathology, predominantly glomerulopathy, and C III (n = 10) with atypical patterns of renal injury (more advanced tubulo-interstitial and arteriolar than glomerular changes). vWF plasma levels were significantly higher in category B (C II: 195 ± 49 % and C III: 161 ± 46 %) than in category A (C I: 119 ± 42 %), (chi-square, p 〈 0.05). Diabetic retinopathy was also related to vWF plasma levels (ANOVA, p 〈 0.05). These data suggest that there are two types of MA in NIDDM: one associated with increased vWF levels, established renal injury and frequently retinopathy, and the other characterized by normal vWF levels, normal renal structure and absent or mild diabetic retinopathy. We propose that vWF plasma levels in NIDDM patients with MA may help to identify patients with important renal structural changes, increased retinopathy risk and, perhaps, generalised endothelial dysfunction. Whether vWF plasma levels predict end-stage renal disease and cardiovascular events deserves longitudinal studies. [Diabetologia (1998) 41: 233–236]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050895
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  • 5
    Electronic Resource
    Electronic Resource
    Arterial compliance and distensibility are modulated by body composition in both men and women but by insulin sensitivity only in women (1999)
    Springer
    Diabetologia 42 (1999), S. 214-221 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin sensitivity ; carotid artery ; femoral artery ; distensibility coefficient ; compliance coefficient ; body composition.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Large artery stiffening could contribute to the development of cardiovascular disease. The aim of this study was to investigate associations between arterial stiffness and diameter with insulin sensitivity and body composition in healthy men and women. In healthy, young (〈 41 years old), non-obese (BMI 〈 27 kg/m2) men (n = 17) and women (n = 17), we measured the arterial diameter, the distension, the distensibility coefficient and the compliance coefficient of the elastic common carotid and muscular femoral arteries with a non-invasive ultrasonographic method. We also assessed glucose uptake (by a euglycaemic hyperinsulinaemic clamp technique), total body fat and lean body mass (by bioelectrical impedance analysis) and abdominal subcutaneous and visceral fat area (by magnetic resonance imaging). In women, but not in men, the distension and distensibility and compliance coefficients of the femoral artery were negatively associated with insulin concentrations (β = –0.62, p = 0.008; β = –0.65, p = 0.005 and β = –0.59, p = 0.01), and positively with glucose uptake (β = 0.59, p = 0.02; β = 0.68, p = 0.005 and β = 0.54, p = 0.04). Associations with glucose uptake were independent of the mean arterial pressure and body composition. In men and women, arterial compliance was positively associated with fat mass variables, which were mediated by a strong association between the femoral artery diameter and lean body mass (β = 0.80, p 〈 0.001) and between the common carotid artery diameter and visceral fat area (β = 0.56, p = 0.001). We found an independent association between insulin resistance and arterial stiffness, which was more pronounced in women than in men. [Diabetologia (1999) 42: 214–221]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051141
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  • 6
    Electronic Resource
    Electronic Resource
    Plasma concentration of C-reactive protein is increased in Type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation (1999)
    Springer
    Diabetologia 42 (1999), S. 351-357 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I (insulin-dependent) diabetes mellitus ; acute-phase response ; C-reactive protein ; atherosclerosis ; inflammation ; vascular disease ; α1-acid glycoprotein ; fucosylation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Moderately increased plasma concentrations of C-reactive protein are associated with an increased risk of cardiovascular disease. C-reactive protein, its relation to a low degree of inflammatory activation and its association with activation of the endothelium have not been systematically investigated in Type I (insulin-dependent) diabetes mellitus. C-reactive protein concentrations were measured in 40 non-smoking patients with Type I diabetes without symptoms of macrovascular disease and in healthy control subjects, and in a second group of Type I diabetic patients (n = 60) with normo- (n = 20), micro- (n = 20) or macroalbuminuria (n = 20). Differences in glycosylation of α1-acid glycoprotein were assayed by crossed affinity immunoelectrophoresis. Activation of the endothelium was measured with plasma concentrations of endothelial cell markers. The median plasma concentration of C-reactive protein was higher in Type I diabetic patients compared with healthy control subjects [1.20 (0.06–21.64) vs 0.51 (0.04–9.44) mg/l; p 〈 0.02]. The Type I diabetic subjects had a significantly increased relative amount of fucosylated α1-acid glycoprotein (79 ± 12 % vs 69 ± 14 % in the healthy control subjects; p 〈 0.005), indicating a chronic hepatic inflammatory response. In the Type I diabetic group, log(C-reactive protein) correlated significantly with von Willebrand factor (r = 0.439, p 〈 0.005) and vascular cell adhesion molecule-1 (r = 0.384, p 〈 0.02), but not with sE-selectin (r = 0.008, p = 0.96). In the second group of Type I diabetic patients, increased urinary albumin excretion was associated with a significant increase of von Willebrand factor (p 〈 0.0005) and C-reactive protein (p = 0.003), which were strongly correlated (r = 0.53, p 〈 0.0005). Plasma concentrations of C-reactive protein were higher in Type I diabetic patients without (clinical) macroangiopathy than in control subjects, probably due to a chronic hepatic inflammatory response. The correlation of C-reactive protein with markers of endothelial dysfunction suggests a relation between activation of the endothelium and chronic inflammation. [Diabetologia (1999) 42: 351–357]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051162
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  • 7
    Electronic Resource
    Electronic Resource
    von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with Type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion (1992)
    Springer
    Diabetologia 35 (1992), S. 555-559 
    Details
    ISSN: 1432-0428
    Keywords: von Willebrand factor ; endothelial function ; diabetic retinopathy ; blood pressure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A;n=9) or presence (Group B;n=8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123 %, 164 vs 132% and 159 vs 130 % (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9 % and +5 vs +1 % (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150±30 vs 130±12 mmHg,p=0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration. These data do not support the hypothesis that increases in plasma von Willebrand factor concentration reflect retinal endothelial injury in Type 1 diabetic patients with normal urinary albumin excretion. In these patients, high or increasing plasma von Willebrand factor levels may be related to systolic blood pressure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400484
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  • 8
    Electronic Resource
    Electronic Resource
    Microalbuminuria is strongly associated with NIDDM and hypertension, but not with the insulin resistance syndrome: the Hoorn Study (1998)
    Springer
    Diabetologia 41 (1998), S. 694-700 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Microalbuminuria ; insulin resistance syndrome ; non-diabetic subjects ; non-insulin-dependent diabetes mellitus ; hypertension ; population.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Microalbuminuria is a strong predictor of cardiovascular disease. The aim of this study was to investigate whether microalbuminuria is part of a cluster of risk factors, the insulin resistance syndrome (IRS), or whether it is only associated with, and presumably a complication of, hypertension and non-insulin-dependent diabetes mellitus (NIDDM). An age-, sex- and glucose tolerance-stratified random sample from a 50–75 year old general population (n = 622) was investigated. The urinary albumin-to-creatinine ratio was measured in an early morning spot urine sample. Microalbuminuria was defined as an albumin-to-creatinine ratio greater than 2.0 mg/mmol. We considered, as IRS-related variables, fasting hyperinsulinaemia, insulin resistance (IR; calculated from the formula of the homeostasis model assessment), dyslipidaemia, glucose intolerance, hypertension and waist-to-hip ratio (WHR). Dyslipidaemia was defined as levels of HDL-cholesterol in the lowest and / or levels of triglyceride in the highest tertile. Fasting insulin levels, IR and WHR were divided into tertiles; the highest tertiles were compared to the lowest tertiles. Age-, sex- and glucose tolerance-adjusted analyses showed microalbuminuria to be significantly associated with hypertension, NIDDM and WHR. In multiple logistic regression analyses, microalbuminuria showed independent associations with hypertension, NIDDM and WHR, with odds ratios (ORs [95 % confidence interval]) of 3.33 (1.86–5.96), 2.26 (1.14–4.48) and 2.49 (1.09–5.70), respectively. No associations were found with impaired glucose tolerance, hyperinsulinaemia, IR or dyslipidaemia. Multiple logistic regression analyses in diabetic and non-diabetic subjects separately showed that microalbuminuria was independently associated only with hypertension (ORs 4.31 and 2.69). In this Caucasian population, microalbuminuria was associated with hypertension, NIDDM and WHR and not with other variables of the IRS. It is therefore likely that microalbuminuria is a complication of hypertension and NIDDM, and not an integral part of the IRS. [Diabetologia (1998) 41: 694–700]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050970
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  • 9
    Electronic Resource
    Electronic Resource
    Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study (1999)
    Springer
    Diabetologia 42 (1999), S. 926-931 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Glucose ; HbA1 c ; hyperglycaemia ; cardiovascular mortality ; Hoorn population.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The degree of glycaemia has been shown to be associated with all-cause and cardiovascular mortality in diabetic subjects. Whether this association also exists in the general population is still controversial. We studied the predictive value of fasting plasma glucose, 2-hour post-load glucose and HbA1 c in a population-based cohort of 2363 older (50–75 years) subjects, without known diabetes. Methods. Relative risks (RR) of all-cause and cardiovascular mortality were estimated by Cox proportional hazards model, adjusting for age and sex, and additionally for known cardiovascular risk factors. Results. During 8 years of follow-up, 185 subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.1 mmol/l. Post-load glucose and HbA1 c values were, even within the non-diabetic range, associated with an increased risk (p for linear trend 〈 0.05). These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors. After exclusion of subjects with newly diagnosed diabetes or with pre-existent cardiovascular disease (n = 551), a 5.8 mmol/l increase of post-load glucose (corresponding to two standard deviations of the population distribution) was associated with a higher age-adjusted and sex-adjusted risk of all-cause (RR 2.24) and cardiovascular mortality (RR 3.40) (p 〈 0.05). After additional adjustment for known cardiovascular risk factors, these relative risks were still statistically significant, with values of 2.20 and 3.00 respectively (p 〈 0.05). Conclusion/interpretation. High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA1 c values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes. [Diabetologia (1999) 42: 926–931]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051249
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  • 10
    Electronic Resource
    Electronic Resource
    Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed insulin response to glucose (1999)
    Springer
    Diabetologia 42 (1999), S. 177-180 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Impaired glucose tolerance ; insulin ; proinsulin ; hyperglycaemic clamp ; beta-cell function ; insulin sensitivity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown to be predictive for progression to Type II (non-insulin-dependent) diabetes mellitus. These findings are often interpreted as early indicators of an impaired beta-cell function. The aim of our study was to assess the potential determinants of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study group consisted of 110 subjects, 45–74 years of age with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20 % glucose solution, 150 mg/kg) was used to assess the beta-cell function (time needed to reach the insulin peak) and insulin sensitivity (M/I value: glucose metabolised divided by insulin response, 150–180 min). Results showed that the intact-proinsulin:insulin ratio increased with increasing time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin peak ≤ 5 min, 5 to 15 min, 〉 15 min; p 〈 0.05). The split-proinsulin:insulin ratio showed a similar association with the time needed to reach the insulin peak. These associations were independent of age, sex, body mass index and waist:hip ratio. In conclusion, this study shows that relative hyperproinsulinaemia is associated with an impaired beta-cell function in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests. [Diabetologia (1999) 42: 177–180]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051136
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