Different Pharmacokinetic Response to an Acute Dose of Inorganic Nitrate in Patients with Type 2 Diabetes

2020 ◽  
Vol 20 ◽  
Author(s):  
Zahra Bahadoran ◽  
Parvin Mirmiran ◽  
Mattias Carlström ◽  
Reza Norouzirad ◽  
Sajad Jeddi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Healthy Subjects ◽  
Critical Role ◽  
Healthy Adults ◽  
Repeated Measurements ◽  
Whole Body ◽  
Diabetic Patients ◽  
Acute Dose ◽  
Nr Activity

Aim: We aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3 was also assessed. Methods: Nine healthy adults and nine T2DM patients were recruited to consume a NO3-rich breakfast (~410 mg NO3). Pharmacokinetics of NO3 were examined using repeated measurements of NOx (nitrate+nitrite) concentrations of serum and saliva over 8 hours and NO3 concentrations of spot and 24-h urine samples. Cardiometabolic parameters including serum levels of glucose, insulin, and triglycerides as well as blood pressures were also measured. Results: Compared to patients with T2DM, serum NOx concentration (Δ1= 16.7 vs. 4.4 µmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO3 loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO3 concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 µmol*h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO3-rich meal. Conclusion: T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO3, and diabetic patients with higher NR activity may take more advantages from NO3 supplementation.

scholarly journals Evaluation of Serum High Sensitivity C-reactive Protein (hs-CRP) In Type-2 Diabetic Patient

1970 ◽  
Vol 11 (1) ◽  
pp. 20-23
Author(s):  
AKM Fazlul Haque ◽  
ARM Saifuddin Ekram ◽  
Quazi Tarikul Islam ◽  
Md Sarwar Jahan ◽  
Md Zahirul Haque
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Patient ◽  
Healthy Subjects ◽  
High Sensitivity ◽  
Diabetic Patients ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp ◽  
Type 2 Diabetic

Type-2 diabetes may remain in subclinical form for years before diagnosis. This quiescence of type-2 diabetes is a great concern for health care providers. The earliest change of the type-2 diabetes is the insulin resistance, which is associated with the increased macrovascular risk due to induction of chronic inflammation in the vessels of the body which leads to atherosclerotic change in the vessels. High sensitivity CRP (hs-CRP) is the measure of C-reactive protein with greater accuracy and the lower limit of its assay is .01 mg/L which is more than 100 times as sensitive as the usual CRP measurement (lower limit 5 mg/L). The median level of hs-CRP from blood samples of apparent healthy subjects is 0.8 mg/L. For this, physician uses the hs-CRP parameter as a marker of chronic inflammation in apparently normal healthy individuals, specially for the assessment of atherosclerosis, which is a chronic inflammatory procedure from the very beginning, in type-2 diabetic, obese and hypertensive patients. This vascular atherosclerosis assessment help them to calculate the cardiovascular as well as cerebrovascular risk of those patients. To help the type-2 diabetic patients from the very begining in respect of the prognostic view of the macrovascular risk, estimations of serum hs-CRP in the early stage of these patient may be a enthusiastic one. This descriptive study was carried out by choosing 70 diabetic patient who had no other comorbidity or any complications of diabetes and 35 healthy subjects who were neither diabetic nor had any diseases. Both the groups were non-smoker and non-alcoholic and non-hypertensive, hs-CRP level was measured in both the groups along with the HbA1c%. The mean hs-CRP in diabetic group was 1.13 mg/L and in normal healthy subjects was 0.39 mg/L. This higher level of mean hs-CRP (1.13 mg/L) in diabetic patients is statisticaly significant (P<0.01) compared with that of the normal healthy subjects mean hs-CRP (0.39 mg/L). This mean level of hs-CRP in normal healthy subjects was below the lower level of cardiovascular risk (1 mg/L). Keywords: High sensitivity CRP, C-reactive protein, diabetes DOI:10.3329/jom.v11i1.4263 J Medicine 2010: 11: 20-23

Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

2010 ◽  
Vol 108 (4) ◽  
pp. 830-837 ◽  
Author(s):  
Mette P. Sonne ◽  
Amra C. Alibegovic ◽  
Lise Højbjerre ◽  
Allan Vaag ◽  
Bente Stallknecht ◽  
...  
Keyword(s):  
Physical Activity ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
High Sensitivity ◽  
Whole Body ◽  
Diabetic Patients ◽  
Activity Levels ◽  
Type 2 Diabetic Patients ◽  
Increased Risk

Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group ( n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), LBW group: 6.2 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), and FDR group: 4.3 ± 0.7 to 3.1 ± 0.3 mg·min−1·kg−1( P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 ± 4%, LBW group: 27 ± 4%, and FDR group: 10 ± 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.

Ultra-weak photon emission in healthy subjects and patients with type 2 diabetes: evidence for a non-invasive diagnostic tool

2017 ◽  
Vol 16 (5) ◽  
pp. 736-743 ◽  
Author(s):  
Meina Yang ◽  
Wenyu Ding ◽  
Yanli Liu ◽  
Hua Fan ◽  
Rajendra P. Bajpai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diagnostic Tool ◽  
Healthy Subjects ◽  
Detection System ◽  
Photon Emission ◽  
High Sensitivity ◽  
Whole Body ◽  
Non Invasive ◽  
System P

Ultra-weak, spontaneous photon emission from five body sites in fifty patients with type 2 diabetes and sixty age-matched healthy subjects was measured with a high-sensitivity whole-body biophoton detection system.

scholarly journals Unraveling the Molecular Heterogeneity in type 2 Diabetes: A Potential Subtype Discovery Study Followed by Metabolic Modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Expression Pattern ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Unsupervised Classification ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract Background Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. Methods We have explored the muscle gene expression pattern in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification along with examining the potential of sub-typing based on the gene expression pattern in patients.Results A machine-learning technique applied to identify a pattern of gene expression that could potentially discriminate between normoglycemic and diabetic groups. A gene set comprises 26 genes identified, which was able to discriminate healthy from diabetic individuals with 94% accuracy after 10-fold stratified cross-validation. In addition, three distinct clusters with different dysregulated genes and metabolic pathways identified in diabetic patients. Conclusion This study implies that it seems the disease has triggered through different cellular/molecular mechanisms and it has the potential to be sub-typing. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group and lead to the recommendation of the appropriate precision therapy for each subtype in the future.

scholarly journals Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery study followed by metabolic modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Gene Expression Pattern ◽  
Gene Expression Patterns ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence in the world. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake, thus plays a critical role in T2DM. Here, we attempted to provide a better understanding of abnormalities in this tissue. MethodsThe muscle gene expression patterns in healthy and newly diagnosed T2DM individuals were explored using supervised and unsupervised classification approach. Moreover, the potential of sub-typing T2DM patients based on the gene expression patterns was evaluated.ResultsA machine-learning technique was applied to identify a gene expression pattern that could discriminate between normoglycemic and diabetic groups. A gene set comprises of 26 genes was found that was able to discriminate healthy from diabetic individuals with 94% accuracy. In addition, three distinct clusters of diabetic patients with different dysregulated genes and metabolic pathways were identified. Conclusions This study implies that it seems the disease has triggered through different cellular/molecular mechanisms, and it has the potential to be categorized in different sub-types. Possibly, subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of abnormalities in each group. Thus, this approach will help to recommend the appropriate treatment for each subtype in the future.

scholarly journals Unraveling the molecular heterogeneity in type 2 diabetes: A potential subtype discovery followed by metabolic modeling

2020 ◽  
Author(s):  
Maryam Khoshnejat ◽  
Kaveh Kavousi ◽  
Ali Mohammad Banaei-Moghaddam ◽  
Ali Akbar Moosavi-Movahedi
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Critical Role ◽  
Unsupervised Classification ◽  
Gene Expression Patterns ◽  
Diabetic Patients ◽  
Molecular Heterogeneity

Abstract BackgroundType 2 diabetes mellitus (T2DM) is a complex multifactorial disease with a high prevalence worldwide. Insulin resistance and impaired insulin secretion are the two major abnormalities in the pathogenesis of T2DM. Skeletal muscle is responsible for over 75% of the glucose uptake and plays a critical role in T2DM. Here, we sought to provide a better understanding of the abnormalities in this tissue. MethodsThe muscle gene expression patterns were explored in healthy and newly diagnosed T2DM individuals using supervised and unsupervised classification approaches. Moreover, the potential of subtyping T2DM patients was evaluated based on the gene expression patterns.ResultsA machine-learning technique was applied to identify a set of genes whose expression patterns could discriminate diabetic subjects from healthy ones. A gene set comprising of 26 genes was found that was able to distinguish healthy from diabetic individuals with 94% accuracy. In addition, three distinct clusters of diabetic patients with different dysregulated genes and metabolic pathways were identified. Conclusions This study indicates that T2DM is triggered by different cellular/molecular mechanisms, and it can be categorized into different subtypes. Subtyping of T2DM patients in combination with their real clinical profiles will provide a better understanding of the abnormalities in each group and more effective therapeutic approaches in the future.

Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes

2014 ◽  
Vol 116 (8) ◽  
pp. 998-1005 ◽  
Author(s):  
Bart B. L. Groen ◽  
Henrike M. Hamer ◽  
Tim Snijders ◽  
Janneau van Kranenburg ◽  
Dionne Frijns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Fiber Type ◽  
Capillary Density ◽  
Boundary Region ◽  
Whole Body ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.

scholarly journals Role of nitrosative and oxidative stress in neuropathy in patients with type 2 diabetes mellitus

2012 ◽  
Vol 03 (01) ◽  
pp. 41-44 ◽  
Author(s):  
Marwan S Al-Nimer ◽  
Fakhir S Al-Ani ◽  
Fatima S Ali
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Conduction Velocity ◽  
Healthy Subjects ◽  
Nitrosative Stress ◽  
Diabetic Patients ◽  
Oxidized Lipoproteins

ABSTRACT Objectives : Evidences of oxidative and/or nitrosative stress in type 2 diabetes mellitus were demonstrated in experimental and human studies. This study is aimed to assess the serum peroxynitrite and oxidized lipoproteins in patients with type 2 diabetes mellitus presented with clinical and laboratory evidences of peripheral neuropathy. Materials and Methods : Eighty four patients with type 2 diabetes mellitus (51 of them had neuropathy) and 31 apparent healthy subjects were studied in the unit of neurophysiology at the University Hospital of Medical College, Al-Nahrin University in Baghdad, Iraq. Neuropathy total symptom score (NTSS), neuropathy impairment score in the lower leg (NIS-LL), and nerve conduction velocity of sensory (ulnar and sural) and motor (ulnar and common peroneal) nerves were used to assess the neuropathy. Fasting venous blood was obtained from each participant for the determination of serum glucose and oxidized lipoproteins. Results: The electrophysiology study revealed significant decrease in conduction velocity of ulnar (sensory and motor components), sural, and common peroneal nerves in diabetic neuropathy compared to diabetics without neuropathy and healthy subjects. Significant high level of serum peroxynitrite was found in diabetic patients with or without neuropathy compared with non-diabetics. The changes in serum-oxidized lipoproteins in patients with diabetics with or without neuropathy were non-significantly differed from healthy subjects. Neither nitrosative stress nor oxidative stress indices correlated with the variables that are related to the neuropathy. Conclusion: It concludes that evidence of nitrosative and to less extent the oxidative stress is associated with neuropathy in type 2 diabetes mellitus and their indices not correlated with variables related to neuropathy.

scholarly journals The vascular smooth muscle cell: a therapeutic target in Type 2 diabetes?

2013 ◽  
Vol 125 (4) ◽  
pp. 167-182 ◽  
Author(s):  
Karen E. Porter ◽  
Kirsten Riches
Keyword(s):  
Type 2 Diabetes ◽  
Smooth Muscle ◽  
Cardiovascular Risk ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Experimental Studies ◽  
Metabolic Memory ◽  
Diabetic Patients ◽  
Metabolic Disturbances

The rising epidemic of T2DM (Type 2 diabetes mellitus) worldwide is of significant concern. The inherently silent nature of the disease in its early stages precludes early detection; hence cardiovascular disease is often established by the time diabetes is diagnosed. This increased cardiovascular risk leads to significant morbidity and mortality in these individuals. Progressive development of complications as a result of previous exposure to metabolic disturbances appears to leave a long-lasting impression on cells of the vasculature that is not easily reversed and is termed ‘metabolic memory’. SMCs (smooth muscle cells) of blood vessel walls, through their inherent ability to switch between a contractile quiescent phenotype and an active secretory state, maintain vascular homoeostasis in health and development. This plasticity also confers SMCs with the essential capacity to adapt and remodel in pathological states. Emerging clinical and experimental studies propose that SMCs in diabetes may be functionally impaired and thus contribute to the increased incidence of macrovascular complications. Although this idea has general support, the underlying molecular mechanisms are currently unknown and hence are the subject of intense research. The aim of the present review is to explore and evaluate the current literature relating to the problem of vascular disease in T2DM and to discuss the critical role of SMCs in vascular remodelling. Possibilities for therapeutic strategies specifically at the level of T2DM SMCs, including recent novel advances in the areas of microRNAs and epigenetics, will be evaluated. Since restoring glucose control in diabetic patients has limited effect in ameliorating their cardiovascular risk, discovering alternative strategies that restrict or reverse disease progression is vital. Current research in this area will be discussed.

scholarly journals The prognostic outcome of ‘type 2 diabetes mellitus and breast cancer’ association pivots on hypoxia-hyperglycemia axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ilhaam Ayaz Durrani ◽  
Attya Bhatti ◽  
Peter John
Keyword(s):  
Breast Cancer ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Critical Role ◽  
Health Concern ◽  
Diabetic Patients ◽  
Prognostic Outcome

AbstractType 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated. Both the diseases are leading causes of death worldwide and a causal relationship between the two if not addressed, may translate into a major global health concern. Previous studies have hypothesized hyperglycemia, hyperinsulinemia, hormonal imbalances and chronic inflammation, as some of the possible grounds for explaining how diabetes may lead to cancer initiation, yet further research still needs to be done to validate these proposed mechanisms. At the crux of this dilemma, hyperglycemia and hypoxia are two intimately related states involving an intricate level of crosstalk and hypoxia inducible factor 1, at the center of this, plays a key role in mediating an aggressive disease state, particularly in solid tumors such as breast cancer. Subsequently, elucidating the role of HIF1 in establishing the diabetes-breast cancer link on hypoxia-hyperglycemia axis may not only provide an insight into the molecular mechanisms underlying the association but also, illuminate on the prognostic outcome of the therapeutic targeting of HIF1 signaling in diabetic patients with breast cancer or vice versa. Hence, this review highlights the critical role of HIF1 signaling in patients with both T2DM and breast cancer, potentiates its significance as a prognostic marker in comorbid patients, and further discusses the potential prognostic outcome of targeting HIF1, subsequently establishing the pressing need for HIF1 molecular profiling-based patient selection leading to more effective therapeutic strategies emerging from personalized medicine.

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