Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Examination of the Complex Molecular Landscape in Obesity and Type 2 Diabetes.

The escalating prevalence of metabolic disorders, notably type 2 diabetes (T2D) and obesity, presents a critical global health challenge, necessitating deeper insights into their molecular underpinnings. Our study integrates proteomics and metabolomics analyses to delineate the complex molecular landscapes associated with T2D and obesity. Leveraging data from 130 subjects, including individuals with T2D and obesity as well as healthy controls, we elucidate distinct molecular signatures and identify novel biomarkers indicative of disease progression. Our comprehensive characterization of cardiometabolic proteins and serum metabolites unveils intricate networks of biomolecular interactions and highlights differential protein expression patterns between T2D and obesity cohorts. Pathway enrichment analyses reveal unique mechanisms underlying disease development and progression, while correlation analyses elucidate the interplay between proteomics, metabolomics, and clinical parameters. Furthermore, network analyses underscore the interconnectedness of cardiometabolic proteins and provide insights into their roles in disease pathogenesis. Our findings may help to refine diagnostic strategies and inform the development of personalized interventions, heralding a new era in precision medicine and healthcare innovation. Through the integration of multi-omics approaches and advanced analytics, our study offers a crucial framework for deciphering the intricate molecular underpinnings of metabolic disorders and paving the way for transformative therapeutic strategies.

Imaging with [99mTc]HMPAO - a novel perspective: investigation of [99mTc]HMPAO leg muscle uptake in metabolic diseases.

BACKGROUND: Sensitive imaging modalities in the diagnosis of microcircular complications of the lower extremities induced by metabolic diseases are becoming a focus of interest. PURPOSE: To investigate the [99mTc]HMPAO uptake of the legs in type 2 diabetes mellitus (T2DM) and obesity, and to search for associations with clinical parameters and nerve conducting studies. MATERIAL AND METHODS: A total of 57 patients with controlled T2DM and 46 obese participants without DM were enrolled in the study. [99mTc]HMPAO SPECT/CT examinations were performed to evaluate the radiopharmaceutical accumulation of the legs. For the quantitative assessment of tracer uptake, standardized uptake value (SUVpeak) was measured in fixed spheric volumes of interest placed on both sural muscles on the attenuation-corrected images. Measurement of current perception threshold applying Neurometer (NM-01/CPT) was used to evaluate peripheral nerve dysfunction. Laboratory parameters assessing the glucose homeostasis of the study participants were also measured. RESULTS: In the diabetic group, significantly lower leg SUV values were detected compared to the non-DM obese group (median: 0.517 vs. 0.607; P < 0.001). Body mass index (BMI) (P < 0.0001), age (P = 0.0283), HbA1c (P = 0.0068), and glucose level (P = 0.0044) proved to be significant predictors of muscle tracer uptake. Neurometer studies showed positive correlation with HbA1c levels in the T2DM group (P = 0.0002). CONCLUSION: We assume that [99mTc]HMPAO uptake of leg muscles is associated with microcirculation, so quantitative [99mTc]HMPAO SPECT/CT might be a sensitive method for evaluating lower limb microvascular alterations. BMI, age, HbA1c, and glucose level may be significant predictors of peripheral vascular abnormalities triggered by metabolic disturbances.

Topological dissimilarities of hierarchical resting networks in type 2 diabetes mellitus and obesity.

Type 2 diabetes mellitus (T2DM) is reported to cause widespread changes in brain function, leading to cognitive impairments. Research using resting-state functional magnetic resonance imaging data already aims to understand functional changes in complex brain connectivity systems. However, no previous studies with dynamic causal modelling (DCM) tried to investigate large-scale effective connectivity in diabetes. We aimed to examine the differences in large-scale resting state networks in diabetic and obese patients using combined DCM and graph theory methodologies. With the participation of 70 subjects (43 diabetics, 27 obese), we used cross-spectra DCM to estimate connectivity between 36 regions, subdivided into seven resting networks (RSN) commonly recognized in the literature. We assessed group-wise connectivity of T2DM and obesity, as well as group differences, with parametric empirical Bayes and Bayesian model reduction techniques. We analyzed network connectivity globally, between RSNs, and regionally. We found that average connection strength was higher in T2DM globally and between RSNs, as well. On the network level, the salience network shows stronger total within-network connectivity in diabetes (8.07) than in the obese group (4.02). Regionally, we measured the most significant average decrease in the right middle temporal gyrus (-0.013 Hz) and the right inferior parietal lobule (-0.01 Hz) relative to the obese group. In comparison, connectivity increased most notably in the left anterior prefrontal cortex (0.01 Hz) and the medial dorsal thalamus (0.009 Hz). In conclusion, we find the usage of complex analysis of large-scale networks suitable for diabetes instead of focusing on specific changes in brain function.

Metabolomic Analysis of Serum and Tear Samples from Patients with Obesity and Type 2 Diabetes Mellitus.

Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were collected. The concentration of 23 amino acids and 10 biogenic amines in serum and tear samples was analyzed. Statistical analysis and Pearson correlation analysis along with network analysis were carried out. Compared to controls, changes in the level of 6 analytes in the obese group and of 10 analytes in the T2D group were statistically significant. For obesity, the energy generation, while for T2D, the involvement of NO synthesis and its relation to insulin signaling and inflammation, were characteristic. We found that BCAA and glutamine metabolism, urea cycle, and beta-oxidation make up crucial parts of the metabolic changes in T2D. According to our data, the retromer-mediated retrograde transport, the ethanolamine metabolism, and, consequently, the endocannabinoid signaling and phospholipid metabolism were characteristic of both conditions and can be relevant pathways to understanding and treating insulin resistance. By providing potential therapeutic targets and new starting points for mechanistic studies, our results emphasize the importance of complex data analysis procedures to better understand the pathomechanism of obesity and diabetes.

Homocysteine-related alterations of 18F-FDG brain pattern in metabolic diseases.

Since hyperhomocysteinaemia (HHcys) is implicated as a risk factor for the development of neurodegeneration, and is associated with the development of metabolic diseases,we aimed at analysing the effect of homocysteine (Hcys) on regional fluorine-18-fluorodeoxyglucose (18F-FDG) brain metabolismin 51 controlled type 2 diabetic and in 48 non-DM obese participants. Plasma Hcys levels were measured by an immunoassay. Homocysteine-related 18F-FDG regional brain metabolism was evaluated applying 18F-FDG PET/CT using magnetic resonance imaging (MRI)-based brain template for statistical parametric mapping (SPM) analysis. Homocysteine-related decreased 18F-FDG uptake was shown in the right middle temporal gyrus in the whole population. Diabetics with Hcys above the reference limit expressed decreased glucose metabolismin the left calcarine cortex compared to the obese with HHcys. Regional metabolic alterations evoked on the basis of HHcys draw attention to the potential risk of neurodegeneration caused by metabolic disturbances.

In vivo corneal confocal microscopy and optical coherence tomography on eyes of participants with type 2 diabetes mellitus and obese participants without diabetes.

PURPOSES: To examine corneal nerve and retinal nerve characteristics of participants with type 2 diabetes mellitus (T2DM) compared with obese participants without diabetes to discover potential nerve vulnerabilities. METHODS: All participants underwent a complete medical examination including a physical examination and blood sample tests. The ophthalmologic examination included best-corrected visual acuity, intraocular pressure, Schirmer test, tear film breakup time, slit-lamp examination, dilated fundus photography, in vivo corneal confocal microscopy (IVCCM), and optical coherence tomography (OCT). RESULTS: The study cohort consisted of 83 eyes of 83 individuals: a group of 44 participants with T2DM, and a control group of 39 obese participants with no history of diabetes. Comparing measurements on the two groups, participants with T2DM had lower values with statistical significance for retinal nerve fiber layer (RNFL) nasal superior thickness (p = 0.010) and three corneal nerve (CN) parameters: fiber length (p = 0.025), total branch density (p = 0.013), and fiber area (p = 0.009). There was a borderline significant difference in CN fiber width (p = 0.051) and RNFL nasal inferior thickness (p = 0.056). No other significant differences were observed in the IVCCM and OCT parameters. No statistically significant correlation was found between CN and RNFL parameters. CONCLUSIONS: Progression from a pre-diabetic obese state to a T2DM condition might entail a loss or diminishment of certain corneal nerve fibers or retinal nerve fibers, but not necessarily a loss of both corneal and retinal nerve fibers simultaneously. Using IVCCM and OCT together enables monitoring of both corneal and retinal health of the eye.

Age, BMI and diabetes as independent predictors of brain hypoperfusion.

BACKGROUND: Cerebral blood flow abnormalities are supposed to be potential risk factors for developing cognitive dysfunction in the general population. Aging, obesity and type 2 diabetes mellitus are associated with perfusion abnormalities leading to cognitive impairment, neurodegeneration and future development of dementia. In our study, we aimed at identifying independent factors that contribute to the appearance of regional brain perfusion changes besides those that are already known. MATERIAL AND METHODS: Forty-three type 2 diabetic and twenty-six obese patients were enrolled. After the intravenous administration of 740 MBq 99mTc-hexamethylpropylene amine oxime (HMPAO), all subjects underwent brain perfusion SPECT imaging applying AnyScan S Flex dual-head gamma camera (Mediso, Hungary). Using Philips Achieva 3T scanner brain resting-state functional MRI was also performed. The SPECT and MRI images were co-registered and transformed to the MNI152 atlas space so that data of the following standard volumes of interest (VOIs) could be obtained: frontal lobe, parietal lobe, temporal lobe, occipital lobe, limbic region, cingulate, insula, basal ganglia, cerebrum, limbic system and brain stem. Using the SPSS 25 statistical software package, general linear regression analysis, Student's t-test, and Mann-Whitney U-test were applied for statistical analyses. RESULTS: Multivariate linear analysis identified that BMI and age are significantly (p < 0.0001) associated with perfusion, and patient group was slightly above threshold (p = 0.0524). We also found that the presence of diabetes was an independent significant predictor of normalized regional brain perfusion only in the insula (p < 0.001). Other independent predictors of normalized regional brain perfusion were: age in the insula (p < 0.001) and in the limbic region (p < 0.01), and BMI in the brain stem (p < 0.01). CONCLUSIONS: Age and BMI proved to be general, and diabetes regional predictor of brain hypoperfusion. BMI appeared to be a novel factor affecting brain perfusion. In one specific region, the insula, we detected a difference between the obese and the diabetic group. These findings may be significant in the understanding of the development of cognitive impairment in metabolic diseases.

Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus.

Megakaryocyte (MK)-derived miRNAs have been detected in platelets. Here, we analysed the expression of platelet and circulating miR-223, miR-26b, miR-126 and miR-140 that might be altered with their target mRNAs in type 2 diabetes mellitus (DM2). MiRNAs were isolated from leukocyte-depleted platelets and plasma samples obtained from 28 obese DM2, 19 non-DM obese and 23 healthy individuals. The effect of hyperglycaemia on miRNAs was also evaluated in MKs using MEG-01 and K562 cells under hyperglycaemic conditions after 8 hours up to four weeks. Quantitation of mature miRNA, pre-miRNAs and target mRNA levels (P2RY12 and SELP) were measured by RT-qPCR. To prove the association of miR-26b and miR-140 with SELP (P-selectin) mRNA level, overexpression or inhibition of these miRNAs in MEG-01 MKs was performed using mimics or anti-miRNAs, respectively. The contribution of calpain substrate Dicer to modulation of miRNAs was studied by calpain inhibition. Platelet activation was evaluated via surface P-selectin by flow cytometry. Mature and pre-forms of investigated miRNAs were significantly reduced in DM2, and platelet P2RY12 and SELP mRNA levels were elevated by two-fold at increased platelet activation compared to controls. Significantly blunted miRNA expressions were observed by hyperglycaemia in MEG-01 and K562-MK cells versus baseline values, while the manipulation of miR-26b and miR-140 expression affected SELP mRNA level. Calpeptin pretreatment restored miRNA levels in hyperglycaemic MKs. Overall, miR-223, miR-26b, miR-126 and miR-140 are expressed at a lower level in platelets and MKs in DM2 causing upregulation of P2RY12 and SELP mRNAs that may contribute to adverse platelet function.

Mannose-Binding Lectin Levels and Carotid Intima-Media Thickness in Type 2 Diabetic Patients.

INTRODUCTION: Mannose-binding lectin (MBL) activates complement system and has been suggested to play a role in vascular complications in diabetics. Carotid intima-media thickness (cIMT) detects subclinical atherosclerosis. We evaluated the association of MBL and IMT in type 2 diabetic (T2DM) patients. METHODS: Serum MBL levels and cIMT were measured in a total of 103 diabetics and in 98 age-matched healthy controls. RESULTS: There was no significant difference in MBL level in T2DM versus controls. As expected, IMT was significantly higher in T2DM patients than in controls (P = 0.001). In T2DM, the lowest cIMT was seen in patients with normal MBL level (500-1000) while cIMT continuously increased with both high MBL and absolute MBL deficiency states. This was especially significant in high MBL versus normal MBL T2DM patients (P = 0.002). According to multiple regression analysis the main predictors of IMT in T2DM are age (P < 0.003), ApoA level (P = 0.023), and the MBL (P = 0.036). CONCLUSIONS: Our results suggest a dual role of MBL as a risk factor for cIMT in T2DM. MBL may also be used as a marker of macrovascular disease, as both low and high levels indicate the susceptibility for atherosclerosis in T2DM.

[Acatalasemia and type 2 diabetes mellitus]. / A veleszületett katalázhiány (acatalasaemia) és a 2-es típusú diabetes mellitus.

The catalase enzyme decomposes the toxic concentrations of hydrogen peroxide into oxygen and water. Hydrogen peroxide is a highly reactive small molecule and its excessive concentration may cause significant damages to proteins, deoxyribonucleic acid, ribonucleic acid and lipids. Acatalasemia refers to inherited deficiency of the catalase enzyme. In this review the authors discuss the possible role of the human catalase enzyme, the metabolism of hydrogen peroxide, and the phenomenon of hydrogen peroxide paradox. In addition, they review data obtained from Hungarian acatalasemic patients indicating an increased frequency of type 2 diabetes mellitus, especially in female patients, and an early onset of type 2 diabetes in these patients. There are 10 catalase gene variants which appear to be responsible for decreased blood catalase activity in acatalasemic patients with type 2 diabetes. It is assumed that low levels of blood catalase may cause an increased concentration of hydrogen peroxide which may contribute to the pathogenesis of type 2 diabetes mellitus.

Further acatalasemia mutations in human patients from Hungary with diabetes and microcytic anemia.

In blood, the hydrogen peroxide concentration is regulated by catalase. Decreased activity of catalase may lead to increased hydrogen peroxide concentration, which may contribute to the manifestation of age-related disease. The aim of this study is to examine association of decreased blood catalase activity and catalase exon mutations in patients (n=617) with diabetes (n=380), microcytic anemia (n=58), beta-thalassemia (n=43) and presbycusis (n=136) and in controls (n=295). Overall, 51 patients (8.3%) had less than half of normal blood catalase activity. Their genomic DNA was used for mutation screening of all exons and exon/intron boundaries with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and PCR-heteroduplex analyses, and mutations were verified with nucleotide sequencing. Seven patients (type 2 diabetes (n=3), gestational diabetes (n=1), microcytic anemia (n=2)) had four novel catalase exon mutations namely, c.106_107insC, p.G36Afs*5(n=3, Hungarian type G1), c.379C>T, p.R127Y (n=2, Hungarian type H1), c.390T>C, p.R129L, (n=1, Hungarian type H2) and c.431A>T, p.N143V (n=1, Hungarian type H3). In patients with decreased blood catalase, the incidence of acatalasemia mutations was significantly high (P<0.0002) in microcytic anemia, type 2 and gestational diabetes. The four novel mutations were probably responsible for low blood catalase activity in 7/51 patients. In the remainder of the cases, other polymorphisms and epigenetic/regulatory factors may be involved.

Temperature sensitivity of some nerve conduction parameters in diabetic polyneuropathy.

BACKGROUND: We tested whether in diabetic polyneuropathy the temperature dependence of the median nerve conduction parameters reflects the severity of neuropathy. METHODS: We validated an electrophysiological score against clinical signs of polyneuropathy. Electroneurography was performed at temperatures from 20-40 degrees C in diabetic patients with mild, moderate and severe neuropathy and controls. RESULTS: The electrophysiological score reflected the clinical severity of polyneuropathy. At room temperature there were significant differences among groups in almost all parameters. In thermal sensitivity studies were significant differences in distal and proximal motor and sensory areas and in sensory conduction velocities. These four parameters normalized to 1 degree C change in temperature also significantly differed among the four groups and were largest in controls and smallest in severe polyneuropathy. CONCLUSIONS: The use of an integral parameter--areas are essentially amplitudes integrated over time--increases the probability of detecting decreased thermal sensitivity of peripheral nerves in diabetes.

Bone metabolism and the 10-year probability of hip fracture and a major osteoporotic fracture using the country-specific FRAX algorithm in men over 50 years of age with type 2 diabetes mellitus: a case-control study.

The aim of the study was to evaluate the 10-year probability of hip fracture and a major osteoporotic fracture using the FRAX algorithm, vitamin D status, bone mineral density (BMD), and biochemical markers of bone turnover in men over 50 years of age with type 2 diabetes mellitus (T2DM). We estimated FRAX-predicted 10-year fracture probability, levels of 25-hydroxyvitamin D (25-OH-D), markers of bone turnover, and bone mineral density at the L1-L4 (lumbar spine (LS)) and femur neck (FN) in 68 men with T2DM and compared these with an age-matched group (n = 68). The mean (range) age of the T2DM group was 61.4 (51-78) years. The prevalence of hypovitaminosis D (25-OH-D <75 nmol/L) was 59 %. The mean (range) FRAX hip fracture and FRAX major osteoporotic fracture was 0.7 (0-2.8) and 3.2 (0-8.5) %, respectively. BMD at the FN (0.974 vs. 0.915 g/cm(2), p = 0.008) and LS (1.221 vs. 1.068 g/cm(2), p < 0.001) was significantly higher in the T2DM cohort as compared to the healthy age-matched males. 25-OH-vitamin D (67.7 vs.79.8 nmol/L, p < 0.001), crosslaps (0.19 vs. 0.24 µg/L, p = 0.004), and osteocalcin (13.3 vs. 15.7 µg/L, p = 0.004) were significantly lower in the T2DM group. There was no difference in FRAX-related fracture probability between the two groups. Acknowledging the limitations of our study size, we suggest that the increased BMD in T2DM and the noninclusion of T2DM as a secondary risk factor in the FRAX algorithm may be probable explanations for the discordance between literature-observed and FRAX-related fracture probabilities.

Effects of rs769217 and rs1001179 polymorphisms of catalase gene on blood catalase, carbohydrate and lipid biomarkers in diabetes mellitus.

Oxidative stress and deficiency of the enzyme catalase, which is the primary scavenger of the oxidant H(2)O(2), may contribute to diabetes. The current study examined two polymorphisms in the catalase gene, -262C>nT in the promoter and 111C>T in exon 9, and their effects on blood catalase activity as well as on concentrations of blood glucose, haemoglobin A1c, triglyceride, cholesterol, HDL, LDL, ApoA-I and ApoB. Subjects were type-1 and type-2 diabetics. We evaluated PCR-single strand conformational polymorphism for 111C>T and PCR-restriction fragment length polymorphism for - 262C>T. TT genotype frequency of 111C>T polymorphism was increased in type-1 diabetes. Type-2 diabetics with the CC or CT genotypes had decreased catalase and increased glucose, hemoglobinA1c and ApoB. Type-2 diabetics who have TT genotype in -262C>T may have elevated risk for diabetes complications; these patients had the lowest mean catalase and HDL, as well as the highest glucose, haemoglobin A1c, cholesterol and ApoB.

[Advances in the prevention, diagnosis and therapy of vascular diseases]. / Újabb ismeretek a különbözo vascularis kórképek megelozésében, diagnosztikájában és terápiájában.

Atherosclerosis is a systemic disease affecting the coronary, carotid, intracerebral, renal and peripherial arteries. The early morphological and functional impairments could be detected in the second or third decades of life and their progression depend on the number and severity of risk factors and individual susceptility. Although the vascular risk factors (smoking, overweight, age, unhealthy diet, lack of physical exercise, hypertension, diabetes mellitus, chronic kidney disease and dyslipidemia) are the same and common in the different vascular diseases, the present clinical routine artificially classifies the diagnosis and therapy of different vascular diseases into different subfields of medicine with the negative impact of possible polypragmasia. Recently, worldwide health surveys (e.g. REACH registry) have proven the usefulness of a holistic approach in the diagnosis and therapy of multiorgan-affected vascular patients. This review summarizes the multidisciplinary advances and future perspective of vascular diseases.

Increased levels of platelet activation markers are positively associated with carotid wall thickness and other atherosclerotic risk factors in obese patients.

The role of platelets in the development of atherosclerosis and obesity-related prothrombotic state is still under investigation. In this cross-sectional cohort study, we measured the levels of different platelet activation markers and evaluated their relationship with carotid intima-media thickness (IMT) along with other atherosclerotic risk factors in obese patients with or without atherosclerotic co-morbidities. We enrolled 154 obese patients, including 98 with either hypertension, type 2 diabetes mellitus or dyslipidaemia, 56 without these co-morbidities and 62 age- and sex-matched healthy controls. Platelet P-selectin expression and the number of platelet-derived microparticles (PMPs) were measured by flow cytometry; soluble P-selectin levels were analysed by ELISA and Thr715Pro P-selectin polymorphism was determined by PCR-RFLP. Carotid IMT was examined by ultrasonography. The levels of platelet activation parameters were significantly elevated in all obese subjects with increased carotid IMT compared to healthy controls. There was no effect of Thr715Pro genotype on soluble P-selectin levels in obese individuals contrary to normal subjects. Significant and positive association was revealed between carotid IMT and platelet P-selectin (p<0.0001), soluble P-selectin (p=0.039) and PMP (p=0.0001) levels. After adjusting for multiple variables, independent association was found between soluble P-selectin and fibrinogen (p=0.007), PMP levels and body mass index (p<0.0001) as well as platelet P-selectin and carotid IMT (p=0.012) plus plasminogen activator inhibitor-1 (p=0.009). In conclusion, P-selectin and PMP levels showed positive associations with abnormal carotid IMT and other risk factors in obesity suggesting a critical role of enhanced platelet reactivity in atherosclerotic wall alteration.

Changes in cerebral blood flow detected by SPECT in type 1 and type 2 diabetic patients.

UNLABELLED: Although macrovascular complications are typical for type 2 diabetes mellitus (T2DM), cerebral microvascular damage develops both in type 1 diabetes mellitus (T1DM) and T2DM. Color Doppler ultrasound is widely used for the examination of large- and medium-sized arteries, whereas SPECT and MRI are capable of identifying disturbances in the circulation of microvessels. Former studies using semiquantitative methods showed reduced reactivity and reserve capacity of cerebral vessels in both T1DM and T2DM patients. Our aim was to investigate whether there was any difference in the effects of the 2 types of diabetes mellitus on the global or regional cerebral blood flow, influenced by microvascular damage. METHODS: In our study, the circulation and reserve capacity of cerebral arteries was examined using (99m)Tc-hexamethylpropylene amine oxime SPECT. A total of 17 individuals with T1DM and 43 individuals with T2DM were involved in the study. RESULTS: Both basal and acetazolamide-challenged brain circulation were significantly lower in T2DM patients than in T1DM patients. We did not find a significant difference in the reserve capacity. However, the circulation of the frontal and occipital lobes changed differently in the 2 groups. The ratio of the circulation of the frontal and occipital lobes was significantly reduced both in basal and in acetazolamide-stimulated states in T2DM patients, independently of age (P < 0.0005 and P < 0.017), showing a greater relative decrease in the circulation of the frontal lobe in T2DM patients. CONCLUSION: There was a significant association between basal brain circulation and age, body mass index, and high-density lipoprotein (HDL), whereas acetazolamide-stimulated circulation showed a significant association with serum triglyceride and HDL.

Investigation of Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in type 2 diabetes mellitus.

Increased levels of soluble P-selectin (sP-selectin) have been shown in a number of different disorders, e.g. diabetes mellitus (DM) and cardiovascular disease (CVD). Several studies have attempted to demonstrate the association of the most intensively examined variant of P-selectin gene polymorphism (Thr715Pro) with sP-selectin levels in healthy subjects and in CVD, but contradictory data have been reported. To clarify the effect of Pro715 allele on the sP-selectin levels in type 2 DM, we analysed this polymorphism in diabetic patients and compared these data with sP-selectin levels. Type 2 DM patients (n = 119), 48 BMImatched non diabetic individuals - consisting mostly of overweight subjects - and 57 healthy volunteers were included in the study. TheThr715Pro polymorphism was analysed by PCR-RFLP, while sP-selectin levels were measured by ELISA. Significantly elevated sP-selectin levels were found in both DM and in overweight subjects compared to healthy controls. We confirmed previous reports that in healthy Pro715 allele carriers lower sPselectin levels could be measured; however, this difference was only significant in case of lean subjects. No significant difference was detected in sP-selectin level among DM and overweight individuals according to this genotype. However, significant difference was observed in sP-selectin levels in older DM patients compared to younger ones, but these levels were not accounted for by the Thr715Pro polymorphism. We suggest that in type 2 DM individuals, the significantly elevated sP-selectin levels are not due to the Thr715Pro P-selectin gene polymorphism.

No correlation between impairment of cerebrovascular reserve capacity and electrophysiologically assessed severity of neuropathy in noninsulin-dependent diabetes mellitus.

INTRODUCTION: Microvascular abnormalities have an important role in the most frequent neurological complications of diabetes mellitus: neuropathy and cerebrovascular disorders. Severity of neuropathy as well as of cerebral microvascular damage can be quantitatively evaluated by instrumental methods like nerve conduction studies and transcranial Doppler. In the present study, we investigated whether a correlation exists between the severity of peripheral neuropathy and the impairment of cerebrovascular reserve capacity (CRC) in 20 patients with Type 2 diabetes mellitus. METHODS: CRC was measured by transcranial Doppler and defined as the maximal percentage increase in blood flow velocity in the middle cerebral artery within 20 min after an intravenous dose of 1000 mg of acetazolamide. Nerve conduction studies of the median, ulnar, peroneal, and sural nerves were performed. Severity of neuropathy was scored based on conduction velocities, amplitudes, and distal latencies. RESULTS: There was no correlation between the neuropathic score and CRC (R= .003, P= .99). Neither CRC nor the neuropathic score correlated significantly with age, duration of diabetes, and serum values of HbA(1c), glucose, insulin, von Willebrand factor, and alpha(2) - macroglobulin. Severity of neuropathy but not CRC correlated with microalbuminuria (R= .47, P= .038 and R= .14, P= .54). Improper treatment reflected by HbA(1c) >10% was associated with significantly more severe albuminuria, higher actual blood glucose level, higher von Willebrand factor activity, and marginally higher neuropathic score (21 vs. 13, P=.096), but was not associated with CRC (44% vs. 42%, P= .81). When duration of diabetes was dichotomized to 15 years and less or over 15 years, CRC was significantly smaller (35% vs. 50%, P= .036) and neuropathy was more severe in the subgroup with longer diabetes duration (19 vs. 11.5 points, P= .07). CONCLUSIONS: Although both CRC and peripheral nerve function are affected more severely in patients with long-lasting Type 2 diabetes mellitus, damage in the cerebrovascular system and in the long peripheral nerves occur independently. As in diabetes mellitus pathological changes in autonomic and large peripheral nerves develop simultaneously, decreased CRC in diabetic patients might be predominantly due to structural changes of resistance arteries or to metabolic than to neurogenic factors.