scholarly journals Early Disrupted Neurovascular Coupling and Changed Event Level Hemodynamic Response Function in Type 2 Diabetes: An fMRI Study

2015 ◽  
Vol 35 (10) ◽  
pp. 1671-1680 ◽  
Author(s):  
João V Duarte ◽  
João MS Pereira ◽  
Bruno Quendera ◽  
Miguel Raimundo ◽  
Carolina Moreno ◽  
...  

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ting Wang ◽  
D Mitchell Wilkes ◽  
Muwei Li ◽  
Xi Wu ◽  
John C Gore ◽  
...  

Abstract The hemodynamic response function (HRF) characterizes temporal variations of blood oxygenation level-dependent (BOLD) signals. Although a variety of HRF models have been proposed for gray matter responses to functional demands, few studies have investigated HRF profiles in white matter particularly under resting conditions. In the present work we quantified the nature of the HRFs that are embedded in resting state BOLD signals in white matter, and which modulate the temporal fluctuations of baseline signals. We demonstrate that resting state HRFs in white matter could be derived by referencing to intrinsic avalanches in gray matter activities, and the derived white matter HRFs had reduced peak amplitudes and delayed peak times as compared with those in gray matter. Distributions of the time delays and correlation profiles in white matter depend on gray matter activities as well as white matter tract distributions, indicating that resting state BOLD signals in white matter encode neural activities associated with those of gray matter. This is the first investigation of derivations and characterizations of resting state HRFs in white matter and their relations to gray matter activities. Findings from this work have important implications for analysis of BOLD signals in the brain.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 11-LB
Author(s):  
SIMON R. HELLER ◽  
ELISE HACHMANN-NIELSEN ◽  
KAJSA KVIST

2020 ◽  
Vol 21 (14) ◽  
pp. 1152-1160
Author(s):  
Imadeldin Elfaki ◽  
Rashid Mir ◽  
Faisel Mohammed Abu-Duhier ◽  
Chandan Kumar Jha ◽  
Adel Ibrahim Ahmad Al-Alawy ◽  
...  

Background:: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represents 20% CYP proteins in liver cells and is a crucial member of CYPs superfamily. CYP2C19 metabolizes very important drugs such as antiulcer drug omeprazole, the antiplatelet drug clopidogrel and anticonvulsant mephenytoin. Single nucleotide polymorphisms (SNPs) of CYP genes have been associated with unexpected drug reactions and diseases in different populations. Objective:: We examined the associations of CYP2C9*3 (rs1057910) and CYP2C19*3 (rs4986893) with T2D in Saudi population. Methods:: We used the allele-specific PCR (AS-PCR) and DNA sequencing in 111 cases and 104 controls for rs1057910, and in 119 cases and 110 controls for rs4986893. Results:: It is indicated that the genotype distribution of rs1057910 in cases and controls were not significantly different (P=0.0001). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and controls was significantly different (P=0.049). The AA genotype of rs4986893 may be associated in increased risk to T2D with OR=17.25 (2.06-143.8), RR=6.14(0.96-39.20), P=0.008. Conclusion:: The CYP2C9*3 (rs1057910) may not be associated with T2D, while CYP2C19*3 (rs4986893) is probably associated with T2D. These findings need to be validated in follow-up studies with larger sample sizes and different populations.


2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


2020 ◽  
Vol 16 ◽  
Author(s):  
Patricio Lopez-Jaramillo ◽  
Jose Lopez-Lopez ◽  
Daniel Cohen ◽  
Natalia Alarcon-Ariza ◽  
Margarita Mogollon-Zehr

: Hypertension and type 2 diabetes mellitus are two important risk factors that contribute to cardiovascular diseases worldwide. In Latin America hypertension prevalence varies from 30 to 50%. Moreover, the proportion of awareness, treatment and control of hypertension is very low. The prevalence of type 2 diabetes mellitus varies from 8 to 13% and near to 40% are unaware of their condition. In addition, the prevalence of prediabetes varies from 6 to 14% and this condition has been also associated with increased risk of cardiovascular diseases. The principal factors linked to a higher risk of hypertension in Latin America are increased adiposity, low muscle strength, unhealthy diet, low physical activity and low education. Besides being chronic conditions, leading causes of cardiovascular mortality, both hypertension and type 2 diabetes mellitus represent a substantial cost for the weak health systems of Latin American countries. Therefore, is necessary to implement and reinforce public health programs to improve awareness, treatment and control of hypertension and type 2 diabetes mellitus, in order to reach the mandate of the Unit Nations of decrease the premature mortality for CVD.


2020 ◽  
Author(s):  
Charlotte Summers

BACKGROUND People from Black, Asian and Minority Ethnic (BAME) groups are known to have an increased risk of developing type 2 diabetes and face greater barriers to accessing healthcare resources compared to their “white British” counterparts. The main mediators of lifestyle behavioural change are gender, generation, geography, genes, God/religion, and gaps in knowledge and economic resources. Dietary and cultural practices of these individuals significantly vary according to gender, generation, geographical origin and religion. Recognition of these factors and implementing culturally sensitive interventions for type 2 diabetes prevention and management is essential in increasing knowledge of healthy eating, engagement in physical activity and improving health outcomes in BAME communities. Few health apps are tailored for BAME populations, and BAME communities are considered hard-to-reach. OBJECTIVE Our objective was to establish whether the Low Carb Program is a viable scalable solution that can be used as an effective tailored type 2 diabetes intervention for BAME communities. We hypothesized that by taking into account cultural sensitivities, providing the platform in native languages and personalising the platform in accordance with known barriers to health disparities including gender, generation, dietary preferences and religion, the app would engage BAME communities and improve type 2 diabetes related health outcomes. METHODS The study used a quasi-experimental research design comprised of an open-label, single-arm, pre-post intervention using a sample of convenience. All 705 adults with type 2 diabetes who had activated their referral to the Low Carb Program as a result of an NHS consultation between September 2018 and March 2019 were followed for a period of 12 months; mean age 54.61 (SD 16.69) years; 58.2% (410/705) women; 45.1% (318/705) white, 28.5% (201/705) Indian/Pakistani/Bangladeshi/Other Central Asian, 10.8% (76/705) Arab, 6.2% (44/705) Mixed/Multiple ethnic groups, 6% (43/705) black, 1.8% (13/705) other, (7/705) 1% Chinese/Japanese/Other East Asian. Mean starting glycated haemoglobin A1c (HbA1c) 7.99% (SD 2.05%); mean body weight 88.96kg (SD 23.25kg). RESULTS Of the 705 study participants, 513 (72.76%) had completed the Low Carb Program at 12 months. There were statistically significant reductions in body weight and HbA1c in white, Indian/Pakistani/Bangladeshi/Other Central Asian, Arabic and black participants with the most significant differences in the Indian/Pakistani/Bangladeshi/Other Central Asian population HbA1c -1.18% (SD 1.49%) and weight 8.03kg (SD 10.65kg). 82.9% of all participants (419/705) of all participants lost at least 5% of their body weight. CONCLUSIONS Offering the culturally tailored Low Carb Program that empowers members to make dietary and lifestyle changes to different BAME groups is an effective and engaging tool in the management of type 2 diabetes. Most importantly, BAME populations in particular people from Indian/Pakistani/Bangladeshi and Arabic groups who achieve better health outcomes than their white counterparts.


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