Angiogenin Levels and Carotid Intima-Media Thickness in Patients with Type 1 Diabetes and Metabolic Syndrome.

It is well documented that in patients with type 1 diabetes (DM1), decreased levels of angiogenin are associated with the development of overt nephropathy. However, little is known about angiogenin levels and subclinical macrovascular organ damage in patients with DM1 and concomitant metabolic syndrome (MS). Therefore, we analyzed the relationship between angiogenin levels and carotid intima-media thickness (cIMT) in DM1 patients with and without MS. We found that angiogenin concentration was significantly lower in DM1 patients compared to controls, while the cIMT measurements were comparable. Exclusion of patients with MS, patients with hypertension, undergoing treatment, or cigarette smokers did not change these findings. Of note, when comparing the subgroups of DM1 patients with and without MS, there was no significant difference between angiogenin levels. However, we did note a significant difference in these levels after the exclusion of smokers. The comparison of cIMT in these subgroups showed a significant difference between the study subgroups. This difference was no longer observed when the age of the patients was taken into account. In summary, it can be concluded that metabolic syndrome in patients with type 1 diabetes does not appear to impact angiogenin levels or cIMT.

Cognitive Functions Associated with Brain Imaging Markers in Patients with Psoriasis.

Psoriasis is a severe inflammatory disease associated with a higher comorbidity of depression, cognitive dysfunction and brain atrophy. The association between psoriasis, magnetic resonance imaging (MRI) markers and cognitive impairment has rarely been investigated, and the existing results are conflicting. METHODS: This study included 89 subjects (53 patients with psoriasis and 36 healthy controls). The severity of psoriasis was evaluated using the Psoriasis Area and Severity Index (PASI) score; for depression, the Hospital Anxiety and Depression Scale (HADS) scale was used. Neuropsychological tests were also applied, including a Trail Making Test (TMT) as well as Digit Span, Stroop, Verbal Fluency and Rey Auditory Verbal Learning tests. MRI scans were performed using a 1.5 T scanner. Brain volumetry, white matter lesions, grey matter and white matter were evaluated. The extent of these changes was assessed on the Fazekas scale. The differences between groups were evaluated using a Student's t-test and a Mann-Whitney U test, and a Pearson correlation analysis was also performed. RESULTS: Patients with psoriasis presented worse achievements on all the neuropsychological tests and showed more intense changes on MRI compared to healthy controls. The severity of psoriasis as determined by PASI scores was associated with depression, and a greater psychomotor slowness severity of changes in the brain was associated with poorer results on the neurological tests. CONCLUSIONS: Our results indicate the possibility of progressive brain atrophy related to cognitive decline in psoriasis.

Skin oxygenation impairment is associated with increased total cholesterol level in children with short-lasting type 1 diabetes mellitus.

INTRODUCTION: Transcutaneous oxygen pressure (tcPO2) is a non-invasive method of measuring skin oxygenation that may reflect its superficial perfusion. Skin microvasculature may be impaired in patients with late onset of type 1 diabetes (DM1). However, its condition in children has not been fully determined. AIM: To compare tcPO2 in children with short-lasting non-complicated DM1 and age-matched healthy controls with regard to concomitant vascular risk factors. MATERIAL AND METHODS: The study group consisted of 51 paediatric patients aged 14.9 (8.4-18.0) years with short-lasting DM1 without clinical evidence of diabetic micro- or macroangiopathy and 28 control subjects aged 14.8 (11.3-17.7) years. TcPO2 was tested prior, during and after applying post-occlusive reactive hyperaemia (PORH) test in standardized conditions. Biochemical parameters were assessed and then compared between the groups. RESULTS: TcPO2 at maximal ischemia during PORH was higher in the DM1 patients than in healthy controls (2.4 (0.7-18.8) vs. 1.6 (0.4-12.0), p = 0.002). No differences were found regarding the tcPO2 measurements recorded prior to ischemia or after recovery. In DM1, concentrations of total cholesterol, triglycerides, HbA1c and TSH were significantly higher than in healthy controls. The fT4 levels were significantly lower in the DM1 group. After adjusting for lipid levels, no differences in tcPO2 were found, and a multivariate analysis showed the cholesterol levels have a significant impact on tcPO2 response to maximal ischemia. CONCLUSIONS: Our results indicate that increased lipid levels are responsible for the impaired skin response to ischemic stimuli in short-lasting DM1. This supports the importance of aggressive lipid control in prevention of early onset microangiopathy in those patients.

Cerebral and skin microcirculatory dysfunction in type 1 diabetes.

INTRODUCTION: An increase in cerebral pulsatility index (PI), measured by transcranial Doppler, reflects the presence of cerebral microangiopathy. A decrease in distance between skin capillaries (DISTANCE) and an increase in the ratio between the area of capillaries and total area of examined skin (COVERAGE), revealed by capillaroscopy, reflects skin microangiopathy. However, little is known about the association between the cerebral and skin microvasculature function in patients at risk of microcirculatory dysfunction. AIM: To assess PI of the middle cerebral artery by transcranial Doppler and the DISTANCE and COVERAGE of the nailfold capillaries by quantitative capillaroscopy in patients with type 1 diabetes and control subjects without diabetes, and to investigate relationships between these parameters. MATERIAL AND METHODS: The study group consisted of 51 patients with type 1 diabetes (median age: 37.5 years) and 23 volunteers free from chronic diseases (median age: 37.9 years). RESULTS: Median PI was higher in patients than in control subjects (0.82 vs. 0.75; p < 0.01). Median DISTANCE was lower in patients than in control subjects (220.9 µm vs. 239.7 µm; p = 0.03), while median COVERAGE was higher in patients than in control subjects (20.4% vs. 18.3%; p = 0.01). No correlations between PI and DISTANCE or COVERAGE were found, but PI was correlated with patients' age and diabetes duration. CONCLUSIONS: In spite of simultaneous presence of cerebral and skin microangiopathy, we found no association between cerebral and skin microvasculature dysfunction. This seems to indicate independent progression of microcirculatory injury in cerebral and peripheral vascular beds.

Statin Use and Cognitive Impairment in Patients With Type 1 Diabetes: An Observational Study.

OBJECTIVE: We aimed to assess a wide range of cognitive functions in patients with type 1 diabetes (DM1) compared with healthy control subjects and to evaluate the effects of statins on cognitive functions in DM1 patients. MATERIALS AND METHODS: The sample studied consisted of 55 DM1 patients (80.0% with hyperlipidemia, 20% with statin treatment) and 36 age-matched control subjects (77.8% with hyperlipidemia) without diabetes or statin use. Their cognitive functions (attention, memory, and executive functions) were evaluated with the trail making test, controlled oral word association test (COWAT), Rey-Osterrieth complex figure test, brain damage test (diagnosticum für cerebralschädigung, DCS), Wisconsin card sorting test (WCST), and digit span and block design tests from the revised Wechsler adult intelligence scale. RESULTS: Cognitive performance was impaired in DM1 patients when compared with the control group with regard to semantic verbal fluency (COWAT_animals), visual learning (DCS), conceptual-level responses, executive functions (WCST random errors), and WCST trials to complete the first category. Subgroups of DM1 patients distinguished on the basis of statin therapy did not differ with regard to verbal fluency (COWAT_animals), visual learning (DCS), conceptual-level responses, executive functions (WCST random errors), and WCST trials to complete the first category. Multivariate analysis also does not show the impact of statin therapy on cognitive functioning regardless of the duration of education, microangiopathic evidence, the presence of hyperlipidemia, or antihypertensive therapy. CONCLUSIONS: We find impairment of cognitive functions in DM1 patients when compared with control subjects without diabetes. However, we show neither the effect of statins nor the significant influence of metabolic control, microangiopathic complications, or the presence of hyperlipidemia on cognitive functions in DM1 patients.

Diabetic symmetric polyneuropathy is associated with increased aortal stiffening but not cerebral angiopathy in type 1 diabetes.

INTRODUCTION: Diabetic symmetric polyneuropathy (DSP) and cerebral microangiopathy are common complications of type 1 diabetes (T1DM). However, little is known about associations between DSP, cerebral microcirculation and macrovascular injury in T1DM. We aimed to assess relationships between those complications. MATERIAL AND METHODS: We examined 42 patients (25 females; mean age 37.1±5.6years) with T1DM (mean disease duration 20.6±6.1years). DSP was diagnosed with the use of quantitative vibration sensory testing (QVST) and Michigan Neuropathy Screening Instrument (MNSI). Cerebral microvasculature was evaluated with measurements of vasomotor reactivity reserve (VMR) and pulsatility index (PI) of middle cerebral artery, macroangiopathic injury by measuring intima-media complex thickness (IMT) in the common carotid artery and carotid-femoral pulse-wave velocity (PWV). RESULTS: Patients with DSP (33.3%) showed higher PWV than those without DPS (10.5 vs 9.1m/s; P=0.03); no differences concerning VMR, PI or IMT existed. There were correlations between PWV and vibration perception thresholds (VPT) (r=0.44; P=0.004) and MNSI score (r=0.43; P=0.003); VPT showed impact on PWV (beta 0.34; P<0.03). CONCLUSIONS: DSP is associated with systemic macroangiopathy, reflected by increased carotid-femoral PWV, but not with the cerebral macro- and microangiopathy.

Decreased reactivity of skin microcirculation in response to L-arginine in later-onset type 1 diabetes.

OBJECTIVE: The aim of our study was to evaluate the vasodilatory effect of l-arginine infusion on the skin microcirculation and to assess the relationship between this effect and the presence of microangiopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Capillaroscopy was performed before and after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8 ± 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11 men; age, 38.0 ± 6.7 years). The skin microcirculation reactivity, as expressed by the percentage of area covered by capillaries (coverage) and the distance between capillaries (distance), and the relationship between microcirculation reactivity and the presence of microangiopathic complications were assessed. RESULTS: The distance before l-arginine infusion was significantly lower in patients than in controls (221 [153-311] vs. 240 [185-356] µm; P = 0.02) and did not differ after l-arginine infusion (223.5 [127-318] vs. 242.5 [181-341] µm; P = 0.27). The difference between the coverage values obtained before and after l-arginine infusion (Δcoverage) was significantly different from zero in the control group but not in the diabetes group. Patients with later onset of diabetes were characterized by decreased skin microcirculation reactivity when compared with patients with earlier onset of diabetes (-1.18 [-5.07 to 11.60] vs. 1.36 [-6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in patients with earlier onset of diabetes (64% vs. 26%; P = 0.02). CONCLUSIONS: Skin microvascular reactivity is impaired in patients with later onset of type 1 diabetes. Capillaroscopy with l-arginine infusion is useful for the identification of skin microangiopathy in type 1 diabetes.

Angiogenin in middle-aged type 1 diabetes patients.

BACKGROUND: Angiogenin levels are increased in children and adolescent patients with type 1 diabetes, regardless of the extent of diabetic microangiopathy. However, little is known about the angiogenin concentrations in adults with type 1 diabetes. Thus we studied its level in middle aged subjects with the presence of diabetic nephro-, retino and neuropathy. METHODS: We investigated the data of 57 (age 39±6.6 years, 45.6% of males) patients with type 1 diabetes and 38 age-matched control subjects without diabetes (age 37.1±5.9 years, 42.1% of males), including medical histories, evidences of microangiopathy and serum angiogenin concentrations. RESULTS: Serum angiogenin level was lower in patients with type 1 diabetes [384.2(190.4-999.8) ng/ml] compared to controls [460.4(230.6-708.2) ng/ml], p=0.04. In patients with overt diabetic nephropathy the angiogenin level was higher when compared to patients without nephropathy [568.2(269.6-999.8) vs 369.4(190.4-999.8) ng/ml, p=0.01]. There were no differences between angiogenin levels in subgroups of patients distinguished by the presence of other microvascular complications or other concomitant vascular risk factors despite cigarette smoking [smokers: 516.2(294.4-999.8) vs. non-smokers: 372.1(190.4-924.8) ng/ml, p=0.01]. CONCLUSIONS: Regardless of the presence of diabetic microangiopathy, angiogenin level in middle-aged type 1 diabetes patients is lower than in controls. The presence of overt nephropathy and smoking habit in middle-aged patients with type 1 diabetes are associated with higher angiogenin level.

Cerebral vasomotor reactivity and extent of white matter lesions in middle-aged men with arterial hypertension: a pilot study.

BACKGROUND: Cerebrovascular reactivity (CVR) impairment and cerebral white matter lesions (WMLs) are associated in elderly or patients with overt cerebral ischemia. Such association has not been confirmed for asymptomatic middle-aged individuals with risk factors for stroke. We assessed the relationship between the CVR and the presence of WMLs in a middle-aged population-based cohort of hypertensive men. METHODS: Magnetic resonance imaging (MRI) and transcranial Doppler (TCD) examination were performed in 54 hypertensive men, all at 60 years of age, without a history of stroke, neurologic deficits, or carotid stenosis. The CVR of the middle cerebral artery (MCA) was expressed as the vasomotor reactivity reserve (VMRr). RESULTS: WMLs were detected in 22 men (40.7%); all WMLs were classified as mild (first grade of the Fazekas modified scale). The VMRr was lower in patients with WMLs (mean 55%; s.e. 3%) compared to those without WMLs (mean 65%; s.e. 3%; P = 0.03). The lower VMRr in patients with WMLs was consistent after controlling for confounders. A higher pulsatility index (PI) in subjects with WMLs (mean 1.08; s.e. 0.05) compared to those without WMLs (mean 0.90; s.e. 0.05; P = 0.01) was not consistent after controlling for confounders. CONCLUSIONS: The CVR was lower in middle-aged hypertensive men with WMLs compared to those without WMLs indicating that even a low load of WMLs may reflect some functional impairment of the cerebral microvasculature.

Cerebrovascular reactivity, intima-media thickness, and nephropathy presence in patients with type 1 diabetes.

OBJECTIVE: Cerebrovascular reactivity impairment was reported as a marker of cerebral microangiopathy in long-term type 1 diabetes. Intima-media complex thickening reflects early stages of macroangiopathy in type 1 diabetes. The analysis of the relationship between these variables and other microangiopathic complications might serve as a beneficial indicator for early prophylaxis in these patients. RESEARCH DESIGN AND METHODS: Vasomotor reactivity reserve (VMRr) and breath-holding index (BHI) of the middle cerebral artery were measured with transcranial Doppler in 59 patients (median age 32.0 years, range 20-51, 36 females) with type 1 diabetes, without history of cerebrovascular events, and 30 healthy control subjects (median age 31.5 years, range 25-39, 15 females). The relationships between the presence of selected vascular complications of type 1 diabetes and biochemical parameters, intima-media thickness (IMT), and VMRr and BHI in patients were analyzed. RESULTS: VMRr and BHI were lower in patients with type 1 diabetes when compared with healthy subjects (81.5 vs. 100%, P < 0.01, and 1.6 vs. 2.2, P = 0.04, respectively), whereas IMT was significantly higher in patients then in healthy control subjects (0.36 vs. 0.30 mm, P = 0.001). However, no association of IMT with VMRr was found. We found a significant reduction of VMRr and BHI in patients with diabetic nephropathy. CONCLUSIONS: The presence of diabetic nephropathy, but not IMT, can be regarded as an indicator of cerebral microangiopathy severity in patients with type 1 diabetes.