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2. The Qatar Genome: A Population-Specific Tool for Precision Medicine in the Middle East

Author

Fakhro, Khalid A., Staudt, Michelle R., Ramstetter, Monica Denise, Robay, Amal, Malek, Joel A., Badii, Ramin, Al-Marri, Ajayeb Al-Nabet, Khalil, Charbel Abi, Al-Shakaki, Alya, Chidiac, Omar, Stadler, Dora, Zirie, Mahmoud, Jayyousi, Amin, Salit, Jacqueline, Mezey, Jason G., Crystal, Ronald G., and Rodriguez-Flores, Juan L.

Subjects
Quantitative Biology - Genomics
Abstract

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific reference genome for the indigenous Arab popula-tion of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million SNP and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual ge-nome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%), and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in the QTRG reference. The benefit for using QTRG varies across ances-tries, a factor that should be taken into consideration when selecting an appropriate reference for analysis., Comment: Includes supplementary figures missing from publisher website

Published
2018
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3. Harnessing Pharmacomultiomics for Precision Medicine in Diabetes: A Comprehensive Review.

Author

Dhieb, Dhoha, Mustafa, Dana, Hassiba, Maryam, Alasmar, May, Elsayed, Mohamed Haitham, Musa, Ameer, Zirie, Mahmoud, and Bastaki, Kholoud

Subjects
TYPE 2 diabetes, INDIVIDUALIZED medicine, DRUG efficacy, PHARMACOGENOMICS, TRANSCRIPTOMES, EPIGENOMICS
Abstract

Type 2 diabetes (T2D) is the fastest-growing non-communicable disease worldwide, accounting for around 90% of all diabetes cases and imposing a significant health burden globally. Due to its phenotypic heterogeneity and composite genetic underpinnings, T2D requires a precision medicine approach personalized to individual molecular profiles, thereby shifting away from the traditional "one-size-fits-all" medical methods. This review advocates for a thorough pharmacomultiomics approach to enhance precision medicine for T2D. It emphasizes personalized treatment strategies that enhance treatment efficacy while minimizing adverse effects by integrating data from genomics, proteomics, metabolomics, transcriptomics, microbiomics, and epigenomics. We summarize key findings on candidate genes impacting diabetic medication responses and explore the potential of pharmacometabolomics in predicting drug efficacy. The role of pharmacoproteomics in prognosis and discovering new therapeutic targets is discussed, along with transcriptomics' contribution to understanding T2D pathophysiology. Additionally, pharmacomicrobiomics is explored to understand gut microbiota interactions with antidiabetic drugs. Emerging evidence on utilizing epigenomic profiles in improving drug efficacy and personalized treatment is also reviewed, illustrating their implications in personalized medicine. In this paper, we discuss the integration of these layers of omics data, examining recently developed paradigms that leverage complex data to deepen our understanding of diabetes. Such integrative approaches advance precision medicine strategies to tackle the disease by better understanding its complex biology. [ABSTRACT FROM AUTHOR]

Published
2025
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4. Insulin Inertia Among People With Type 2 Diabetes Mellitus in Qatar: The INERT‐Q Study

Author

Bashir, Mohammed, primary, Thani, Noora Al, additional, Khalid, Abeer, additional, Khalil, Obada, additional, Alamer, Zaina, additional, Hamad, Mohammed Khair, additional, Karuppasamy, Gowri, additional, Abufaeid, Mohammed, additional, Elbidairi, Mutwakil, additional, Al‐Mohnnadi, Dhabia, additional, Elhadd, Tarik, additional, and Zirie, Mahmoud, additional

Published
2024
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5. Glucose‐lowering medication associated with weight loss may limit the progression of diabetic neuropathy in type 2 diabetes

Author

Ponirakis, Georgios, Al‐Janahi, Ibrahim, Elgassim, Einas, Hussein, Rawan, Petropoulos, Ioannis N., Gad, Hoda, Khan, Adnan, Zaghloul, Hadeel B., Siddique, Mashhood A., Ali, Hamda, Mohamed, Fatima F. S., Ahmed, Lina H. M., Dakroury, Youssra, El Shewehy, Abeer M. M., Saeid, Ruba, Mahjoub, Fadwa, Al‐Thani, Shaikha N., Ahmed, Farheen, Homssi, Moayad, Mahmoud, Salah, Hadid, Nebras H., Obaidan, Aisha Al, Salivon, Iuliia, Mahfoud, Ziyad R., Zirie, Mahmoud A., Al‐Ansari, Yousuf, Atkin, Stephen L., Malik, Rayaz A., Ponirakis, Georgios, Al‐Janahi, Ibrahim, Elgassim, Einas, Hussein, Rawan, Petropoulos, Ioannis N., Gad, Hoda, Khan, Adnan, Zaghloul, Hadeel B., Siddique, Mashhood A., Ali, Hamda, Mohamed, Fatima F. S., Ahmed, Lina H. M., Dakroury, Youssra, El Shewehy, Abeer M. M., Saeid, Ruba, Mahjoub, Fadwa, Al‐Thani, Shaikha N., Ahmed, Farheen, Homssi, Moayad, Mahmoud, Salah, Hadid, Nebras H., Obaidan, Aisha Al, Salivon, Iuliia, Mahfoud, Ziyad R., Zirie, Mahmoud A., Al‐Ansari, Yousuf, Atkin, Stephen L., and Malik, Rayaz A.

Abstract

Aim: Obesity is a major risk factor for diabetic peripheral neuropathy (DPN) in type 2 diabetes (T2D). This study investigated the effect of glucose lowering medication associated with weight change on DPN. Methods: Participants with T2D were grouped based on whether their glucose lowering medications were associated with weight gain (WG) or weight loss (WL). They underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function and corneal confocal microscopy (CCM) at baseline and follow‐up between 4 and 7 years. Results: Of 76 participants, 69.7% were on glucose lowering medication associated with WG, and 30.3% were on glucose lowering medication associated with WL. At baseline, participants in the WG group had a significantly longer duration of diabetes (p < .01), higher douleur neuropathique en 4 (DN4) score (p < .0001) and VPT (p = .01) compared with those in the WL group. Over a 56‐month period, participants in the WG group showed no significant change in body weight (p = .11), HbA1c (p = .18), triglycerides (p = .42), DN4 (p = .11), VPT (p = .15) or Sudoscan (p = .43), but showed a decline in corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) (p < .0001). Participants in the WL group showed a reduction in weight (p = .01) and triglycerides (p < .05), no change in DN4 (p = .30), VPT (p = .31) or Sudoscan (p = .17) and a decline in the corneal nerve branch density (p < .01). Conclusions: Participants treated with glucose lowering medication associated with weight gain had worse neuropathy and greater loss of corneal nerves during follow‐up, compared to patients treated with medication associated with weight loss.

Published
2024

9. Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial

Author

Taheri, Shahrad, Chagoury, Odette, Zaghloul, Hadeel, Elhadad, Sara, Ahmed, Salma Hayder, Omar, Omar, Payra, Sherryl, Ahmed, Salma, El Khatib, Neda, Amona, Rasha Abou, El Nahas, Katie, Bolton, Matthew, Chaar, Henem, Suleiman, Noor, Jayyousi, Amin, Zirie, Mahmoud, Janahi, Ibrahim, Elhag, Wahiba, Alnaama, Abdulla, Zainel, Abduljaleel, Hassan, Dahlia, Cable, Tim, Charlson, Mary, Wells, Martin, Al-Hamaq, Abdulla, Al-Abdulla, Samya, and Abou-Samra, Abdul Badi

Published
2018
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11. Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus

Author

Cheema, Amrita K, Kaur, Prabhjit, Fadel, Amina, Younes, Noura, Zirie, Mahmoud, and Rizk, Nasser M

Subjects
regulators, Disorders, Pathway analysis, Bioinformatics, type 2 diabetes mellitus, biomarkers, bioinformatics, pathway analysis, Type 2 diabetes mellitus, Regulators, disorders, Targets and Therapy [Diabetes, Metabolic Syndrome and Obesity], Biomarkers, health care economics and organizations, Original Research
Abstract

Amrita K Cheema,1 Prabhjit Kaur,1 Amina Fadel,2 Noura Younes,3 Mahmoud Zirie,4 Nasser M Rizk2,5 1Department of Oncology, Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, DC, USA; 2Biomedical Sciences Department, College of Health Sciences and Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; 3Clinical Chemistry Lab, Hamad Medical Corporation, Doha, Qatar; 4Endocrine Department, Hammad Medical Corporation, Doha, Qatar; 5Physiology Department, Mansoura Faculty of Medicine, Mansoura, EgyptCorrespondence: Nasser M RizkBiomedical Sciences Department, College of Health Sciences, Biomedical Research Center, QU Health, Qatar University, Doha, QatarEmail nassrizk@qu.edu.qaObjective: The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers.Methods: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database.Results: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest, such as STAT3 and HIF alpha, as well as many kinases such as JAK kinases, which affects the gene expression of the dataset in T2DM. Interleukin 6 (IL6) is the top regulator of the DRGs, followed by leptin (LEP). Monitoring the dysregulation of the coupled expression of the following biomarkers (TNF, IL6, LEP, AGT, APOE, F2, SPP1, and INS) highlights that they could be used as potential prognostic biomarkers.Conclusion: The integration of data obtained by advanced metabolomic and proteomic technologies has made it probable to advantage in understanding the role of these biomarkers in the identification of significant biological processes, pathways, and regulators that are associated with T2DM and its comorbidities.Keywords: type 2 diabetes mellitus, pathway analysis, regulators, biomarkers, disorders, bioinformatics

Published
2020

13. Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes

Author

Ponirakis, Georgios, primary, Al‐Janahi, Ibrahim, additional, Elgassim, Einas, additional, Gad, Hoda, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, Ali, Hamda, additional, Siddique, Mashhood A, additional, Gul, Wajiha, additional, Ferdousi, Maryam, additional, Kalteniece, Alise, additional, Mohamed, Fatima FS, additional, Ahmed, Lina HM, additional, Dakroury, Youssra, additional, El Shewehy, Abeer MM, additional, Al‐Mohamedi, Abdulrahman, additional, AlMarri, Fatema, additional, Homssi, Moayad, additional, Qazi, Murtaza, additional, Hadid, Nebras H, additional, Al‐Khayat, Fatima, additional, Mahfoud, Ziyad R, additional, Azmi, Shazli, additional, Alam, Uazman, additional, Zirie, Mahmoud A, additional, Al‐Ansari, Yousuf, additional, Jayyousi, Amin, additional, Rigby, Alan S, additional, Kilpatrick, Eric S, additional, Atkin, Stephen L, additional, and Malik, Rayaz A, additional

Published
2022
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14. Prevalence and risk factors for diabetic peripheral neuropathy, neuropathic pain and foot ulceration in the Arabian Gulf region

Author

Ponirakis, Georgios, primary, Elhadd, Tarik, additional, Al Ozairi, Ebaa, additional, Brema, Imad, additional, Chinnaiyan, Subitha, additional, Taghadom, Etab, additional, Al Kandari, Jumana, additional, Al Wotayan, Rehab, additional, Al Ozairi, Abdulla, additional, Aljohani, Naji, additional, AlMistehi, Wael, additional, Al Qahtani, Nora, additional, Khan, Shawana, additional, Dabbous, Zeinab, additional, Siddique, Mashhood A, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, Almuhannadi, Hamad, additional, Ashawesh, Khaled AE, additional, Dukhan, Khaled M, additional, Mahfoud, Ziyad R, additional, Zirie, Mahmoud A, additional, Jayyousi, Amin, additional, and Malik, Rayaz A, additional

Published
2022
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15. Quality of diabetes care in patients with schizophrenia: a case-control study in Qatar

Author

Karim, Mustafa Abdul, Al-Baz, Nadeen, Ouanes, Sami, Khalil, Ali, Assar, Ahmed H., Alsiddiqi, Abdulkarim, Dabbous, Zeinab, Zirie, Mahmoud, Woodruff, Peter, Malik, Rayaz A., and Haddad, Peter M.

Subjects
Glycated Hemoglobin, Diabetes mellitus, Diabetes Mellitus, Type 2, lcsh:RC435-571, lcsh:Psychiatry, Case-Control Studies, Schizophrenia, Humans, Clinical sciences, Qatar, Retrospective Studies, Research Article, Diabetes care
Abstract

Background Patients with schizophrenia are at least twice as likely to develop diabetes mellitus compared to the general population. This is of significance in Qatar given the high prevalence of obesity and diabetes. Furthermore, the lifespan of people with schizophrenia is shortened by approximately 15 years, partly due to long-term microvascular and macrovascular complications. High quality diabetes care can significantly reduce morbidity and mortality. We assessed the level of diabetes care delivered to patients in Qatar with schizophrenia and diabetes compared to those with diabetes alone. Methods We performed a retrospective chart review of patients with diabetes mellitus with (n = 73) and without (n = 73) schizophrenia. Demographic information and electronic medical records were reviewed to determine adherence to American Diabetes Association standards of diabetes care in the last 6 and 12 months. Optimal diabetes care was defined as having completed glycated hemoglobin (HbA1c), lipid profile and retinal examination within 12 months. Results Optimal diabetes care was significantly lower in patients with schizophrenia and diabetes compared to diabetes alone [26.0% (n = 19/73) vs 52.1% (n = 38/73), p = 0.002]. Patients with diabetes and schizophrenia were also significantly less likely to have had body mass index recorded within 6 months (p = 0.008) and HbA1c (p = 0.006), lipid profile (p = 0.015), estimated glomerular filtration rate (eGFR) (p = 0.001) and order for retinal examination (p = 0.004) over 12 months. After adjusting for multiple comparisons, only assessment of eGFR (p = 0.01) and order for retinal examination (p = 0.04) remained significant. Conclusion Patients in Qatar with schizophrenia and diabetes, receive sub-optimal diabetes care compared to those with diabetes alone.Other Information Published in: BMC Psychiatry License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1186/s12888-021-03121-5

Published
2020

16. Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary health care in Qatar

Author

Ponirakis, Georgios, Elhadd, Tarik, Chinnaiyan, Subitha, Hamza, Abdul H, Sheik, Sanaulla, Kalathingal, Mohamed A, Anodiyil, Mohamed S, Dabbous, Zeinab, Siddique, MashhoodA, Almuhannadi, Hamad, Petropoulos, Ioannis, Khan, Adnan, Ashawesh, Khaled AE, Dukhan, Khaled M, Mahfoud, Ziyad R, Zirie, Mahmoud A, Jayyousi, Amin, Murgatroyd, Christopher, Slevin, Mark, Malik, Rayaz A, Ponirakis, Georgios, Elhadd, Tarik, Chinnaiyan, Subitha, Hamza, Abdul H, Sheik, Sanaulla, Kalathingal, Mohamed A, Anodiyil, Mohamed S, Dabbous, Zeinab, Siddique, MashhoodA, Almuhannadi, Hamad, Petropoulos, Ioannis, Khan, Adnan, Ashawesh, Khaled AE, Dukhan, Khaled M, Mahfoud, Ziyad R, Zirie, Mahmoud A, Jayyousi, Amin, Murgatroyd, Christopher, Slevin, Mark, and Malik, Rayaz A

Abstract

AIMS/INTRODUCTION:This study determined the prevalence and risk factors for DPN and pDPN in patients with type 2 diabetes (T2D) in primary health care (PHC) and secondary health care (SHC) in Qatar. MATERIALS AND METHODS:This is a cross-sectional multi-center study. Adults with T2D were randomly enrolled from four PHC centres and two Diabetes Centres in SHC in Qatar. Subjects underwent assessment of clinical and metabolic parameters, DPN and pDPN. RESULTS:1,386 subjects with T2D (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P=0.001) and pDPN (18.1% vs 37.5%, P<0.0001) was significantly lower in PHC compared to SHC, whilst those with DPN at high risk for DFU (31.8% vs 40.0%, P=0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P=0.66) was comparably high but undiagnosed pDPN (24.1% vs 71.5%, P<0.0001) was lower in PHC compared to SHC. The odds of DPN and pDPN increased with age and diabetes duration and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whilst pDPN increased with obesity and reduced physical activity. CONCLUSIONS:The prevalence of DPN and pDPN in T2D is lower in PHC compared to SHC and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, ~80% of patients had not been previously diagnosed with DPN in PHC and SHC. Further, we identify a number of modifiable risk factors for PDN and pDPN.

Published
2021

17. Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Author

Ponirakis, Georgios, primary, Abdul‐Ghani, Muhammad A, additional, Jayyousi, Amin, additional, Zirie, Mahmoud A, additional, Al‐Mohannadi, Salma, additional, Almuhannadi, Hamad, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, Gad, Hoda, additional, Migahid, Osama, additional, Megahed, Ayman, additional, Qazi, Murtaza, additional, AlMarri, Fatema, additional, Al‐Khayat, Fatima, additional, Mahfoud, Ziyad, additional, DeFronzo, Ralph, additional, and Malik, Rayaz A, additional

Published
2021
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18. Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control

Author

Ponirakis, Georgios, primary, Abdul‐Ghani, Muhammad A, additional, Jayyousi, Amin, additional, Zirie, Mahmoud A, additional, Qazi, Murtaza, additional, Almuhannadi, Hamad, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, Gad, Hoda, additional, Migahid, Osama, additional, Megahed, Ayman, additional, Al‐Mohannadi, Salma, additional, AlMarri, Fatema, additional, Al‐Khayat, Fatima, additional, Mahfoud, Ziyad, additional, Al Hamad, Hanadi, additional, Ramadan, Marwan, additional, DeFronzo, Ralph, additional, and Malik, Rayaz A, additional

Published
2021
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21. The Ratio of Thyroglobulin in Wash-Out Fluid From Fine-Needle Aspiration to Serum Thyroglobulin Level in the Evaluation of Metastatic Cervical Lymph Nodes in Patients With Papillary Thyroid Cancer

Author

Ibraheem Hamad, Mohammad Khair Ahmad, primary, Shdid, Reham Abo, additional, Saleh, Ahmed Osman, additional, El Mabrok Abufaied, Mohamad Mahmoud, additional, Jaber, Tania, additional, Farghaly, Hanan, additional, Rohani, Zaina Seros, additional, Zirie, Mahmoud A, additional, and Naem, Emad, additional

Published
2021
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22. Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary healthcare in Qatar

Author

Ponirakis, Georgios, primary, Elhadd, Tarik, additional, Chinnaiyan, Subitha, additional, Hamza, Abdul H, additional, Sheik, Sanaulla, additional, Kalathingal, Mohamed A, additional, Anodiyil, Mohamed S, additional, Dabbous, Zeinab, additional, Siddique, Mashhood A, additional, Almuhannadi, Hamad, additional, Petropoulos, Ioannis N, additional, Khan, Adnan, additional, AE Ashawesh, Khaled, additional, Dukhan, Khaled M, additional, Mahfoud, Ziyad R, additional, Zirie, Mahmoud A, additional, Jayyousi, Amin, additional, Murgatroyd, Christopher, additional, Slevin, Mark, additional, and Malik, Rayaz A, additional

Published
2020
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25. First ever case report of co-occurrence of hobnail variant of papillary thyroid carcinoma and intrathyroid parathyroid adenoma in the same thyroid lobe

Author

Al-Yahri, Omer, Abdelaal, Abdelrahman, El Ansari, Walid, Farghaly, Hanan, Murshed, Khaled, Zirie, Mahmoud A., Al Hassan, Mohamed S., Al-Yahri, Omer, Abdelaal, Abdelrahman, El Ansari, Walid, Farghaly, Hanan, Murshed, Khaled, Zirie, Mahmoud A., and Al Hassan, Mohamed S.

Abstract

Introduction: The hobnail variant of papillary thyroid cancer (PTC) is rare. Intrathyroid parathyroid adenoma (ITPA) is also rare. Co-ocurrence of PTC and ITPA in the same thyroid lobe is extremely rare. Likewise, primary hyperparathyroidism with such non-medullary thyroid carcinoma is rare. The specific molecular profile of hobnail PTC (HPTC) is different from the classic, poorly differentiated and anaplastic variants and may contribute to its aggressive behavior. HPTC's genetic profile remains unclear. Presentation of case: A 61-year-old woman presented to our endocrine clinic with generalized aches, bone pain, polyuria, and right neck swelling of a few months’ duration. Laboratory findings revealed hypercalcemia and hyperparathyroidism. Ultrasound of the neck showed 4.6 cm complex nodule within the right thyroid lobe. Sestamibi scan suggested parathyroid adenoma in the right thyroid lobe. Fine-needle aspiration (FNA) revealed atypical follicular lesion of undetermined significance. She underwent right lobectomy, which normalized the intraoperative intact parathyroid hormone levels. Final pathology with immunohistochemical stains demonstrated HPTC and IPTA (2 cm each). Next-generation sequencing investigated the mutation spectrum of HPTC and detected BRAFV600E mutation. Conclusions: A parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma. Thyroid evaluation is needed for patients with primary hyperparathyroidism to prevent missing concurrent thyroid cancers. Cytomorphologic features to distinguish thyroid from parathyroid cells on FNA cytology must be considered. Immunohistochemical stains are important. BRAFV600E is the most common mutation in HPTC. This is possibly the first reported case of HPTC and ITPA co-occurring within the same thyroid lobe. Studies that define other molecular abnormalities may be useful as therapeutic targets. © 2020 The Author(s)

Published
2020
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26. Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus

Author

K. Cheema,Amrita K., Kaur,Prabhjit, Fadel,Amena, Younes,Noura, Zirie,Mahmoud, Rizk,Nasser M, K. Cheema,Amrita K., Kaur,Prabhjit, Fadel,Amena, Younes,Noura, Zirie,Mahmoud, and Rizk,Nasser M

Abstract

Amrita K Cheema,1 Prabhjit Kaur,1 Amina Fadel,2 Noura Younes,3 Mahmoud Zirie,4 Nasser M Rizk2,5 1Department of Oncology, Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, DC, USA; 2Biomedical Sciences Department, College of Health Sciences and Biomedical Research Center, QU Health, Qatar University, Doha, Qatar; 3Clinical Chemistry Lab, Hamad Medical Corporation, Doha, Qatar; 4Endocrine Department, Hammad Medical Corporation, Doha, Qatar; 5Physiology Department, Mansoura Faculty of Medicine, Mansoura, EgyptCorrespondence: Nasser M RizkBiomedical Sciences Department, College of Health Sciences, Biomedical Research Center, QU Health, Qatar University, Doha, QatarEmail nassrizk@qu.edu.qaObjective: The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers.Methods: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database.Results: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest

Published
2020

27. Carnosine as a Protective Factor in Diabetic Nephropathy: Association With a Leucine Repeat of the Carnosinase Gene CNDP1

Author

Janssen, Bart, Hohenadel, Daniela, Brinkkoetter, Paul, Peters, Verena, Rind, Nina, Fischer, Christine, Rychlik, Ivan, Cerna, Marie, Romzova, Marianna, de Heer, Emile, Baelde, Hans, Bakker, Stephan J.L., Zirie, Mahmoud, Rondeau, Eric, Mathieson, Peter, Saleem, Moin A., Meyer, Jochen, Köppel, Hannes, Sauerhoefer, Sibylle, Bartram, Claus R., Nawroth, Peter, Hammes, Hans-Peter, Yard, Benito A., Zschocke, Johannes, and van der Woude, Fokko J.

Published
2005

29. Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary healthcare in Qatar.

Author

Ponirakis, Georgios, Elhadd, Tarik, Chinnaiyan, Subitha, Hamza, Abdul H, Sheik, Sanaulla, Kalathingal, Mohamed A, Anodiyil, Mohamed S, Dabbous, Zeinab, Siddique, Mashhood A, Almuhannadi, Hamad, Petropoulos, Ioannis N, Khan, Adnan, AE Ashawesh, Khaled, Dukhan, Khaled M, Mahfoud, Ziyad R, Zirie, Mahmoud A, Jayyousi, Amin, Murgatroyd, Christopher, Slevin, Mark, and Malik, Rayaz A

Subjects
DIABETIC neuropathies, TYPE 2 diabetes, GLYCEMIC control, MEDICAL care, PERIPHERAL neuropathy, DIABETIC foot, PREOPERATIVE risk factors
Abstract

Aims/Introduction: This study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN) and painful DPN (pDPN) in patients with type 2 diabetes in primary healthcare (PHC) and secondary healthcare (SHC) in Qatar. Materials and Methods: This was a cross‐sectional multicenter study. Adults with type 2 diabetes were randomly enrolled from four PHC centers and two diabetes centers in SHC in Qatar. Participants underwent assessment of clinical and metabolic parameters, DPN and pDPN. Results: A total of 1,386 individuals with type 2 diabetes (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P = 0.001) and pDPN (18.1% vs 37.5%, P < 0.0001) was significantly lower in PHC compared with SHC, whereas those with DPN at high risk for diabetic foot ulceration (31.8% vs 40.0%, P = 0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P = 0.66) was comparably high, but undiagnosed pDPN (24.1% vs 71.5%, P < 0.0001) was lower in PHC compared with SHC. The odds of DPN and pDPN increased with age and diabetes duration, and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whereas pDPN increased with obesity and reduced physical activity. Conclusions: The prevalence of DPN and pDPN in type 2 diabetes is lower in PHC compared with SHC, and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, approximately 80% of patients had not been previously diagnosed with DPN in PHC and SHC. Furthermore, we identified a number of modifiable risk factors for PDN and pDPN. [ABSTRACT FROM AUTHOR]

Published
2021
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30. Additional file 1: of Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM-I): a randomised controlled trial to examine the impact of an intensive lifestyle intervention consisting of a low-energy diet and physical activity on body weight and metabolism in early type 2 diabetes mellitus: study protocol for a randomized controlled trial

Author

Shahrad Taheri, Chagoury, Odette, Hadeel Zaghloul, Elhadad, Sara, Ahmed, Salma, Omar, Omar, Payra, Sherryl, Khatib, Neda El, Amona, Rasha, Nahas, Katie El, Bolton, Matthew, Henem Chaar, Suleiman, Noor, Jayyousi, Amin, Zirie, Mahmoud, Janahi, Ibrahim, Elhag, Wahiba, Alnaama, Abdulla, Abduljaleel Zainel, Hassan, Dahlia, Cable, Tim, Charlson, Mary, Wells, Martin, Al-Hamaq, Abdulla, Al-Abdulla, Samya, and Abou-Samra, Abdul

Abstract

SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents*. (DOC 124Â kb)

Published
2018
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31. Whole-methylome analysis of circulating monocytes in acute diabetic Charcot foot reveals differentially methylated genes involved in the formation of osteoclasts

Author

Pasquier, Jennifer, primary, Spurgeon, Mark, additional, Bradic, Martina, additional, Thomas, Binitha, additional, Robay, Amal, additional, Chidiac, Omar, additional, Dib, Marie-Joe, additional, Turjoman, Rebal, additional, Liberska, Alexandra, additional, Staudt, Michelle, additional, Fakhro, Khalid A, additional, Menzies, Robert, additional, Jayyousi, Amin, additional, Zirie, Mahmoud, additional, Suwaidi, Jassim Al, additional, Malik, Rayaz A, additional, Talal, Talal, additional, Rafii, Arash, additional, Mezey, Jason, additional, Rodriguez-Flores, Juan, additional, Crystal, Ronald G, additional, and Khalil, Charbel Abi, additional

Published
2019
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32. Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot

Author

Pasquier, Jennifer, primary, Ramachandran, Vimal, additional, Abu-Qaoud, Moh'd Rasheed, additional, Thomas, Binitha, additional, Benurwar, Manasi J, additional, Chidiac, Omar, additional, Hoarau-Véchot, Jessica, additional, Robay, Amal, additional, Fakhro, Khalid, additional, Menzies, Robert A, additional, Jayyousi, Amin, additional, Zirie, Mahmoud, additional, Al Suwaidi, Jassim, additional, Malik, Rayaz A, additional, Talal, Talal K, additional, Najafi-Shoushtari, Seyed Hani, additional, Rafii, Arash, additional, and Abi Khalil, Charbel, additional

Published
2018
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33. Exome sequencing-based identification of novel type 2 diabetes risk allele loci in the Qatari population

Author

O’Beirne, Sarah L., primary, Salit, Jacqueline, additional, Rodriguez-Flores, Juan L., additional, Staudt, Michelle R., additional, Abi Khalil, Charbel, additional, Fakhro, Khalid A., additional, Robay, Amal, additional, Ramstetter, Monica D., additional, Malek, Joel A., additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, Badii, Ramin, additional, Al-Nabet Al-Marri, Ajayeb, additional, Bener, Abdulbari, additional, Mahmoud, Mai, additional, Chiuchiolo, Maria J., additional, Al-Shakaki, Alya, additional, Chidiac, Omar, additional, Stadler, Dora, additional, Mezey, Jason G., additional, and Crystal, Ronald G., additional

Published
2018
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34. Risk Factors for Microvascular Complications of Diabetes in a High-Risk Middle East Population

Author

Cheema, Sohaila, primary, Maisonneuve, Patrick, additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, Alrouh, Hekmat, additional, Abraham, Amit, additional, Al-Samraye, Sura, additional, Mahfoud, Ziyad, additional, Al-Janahi, Ibrahim Mohammed, additional, Ibrahim, Buthaina, additional, Lowenfels, Albert B., additional, and Mamtani, Ravinder, additional

Published
2018
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35. Circulating microparticles in acute diabetic Charcot foot exhibit a high content of inflammatory cytokines, and support monocyte-to-osteoclast cell induction

Author

Pasquier, Jennifer, primary, Thomas, Binitha, additional, Hoarau-Véchot, Jessica, additional, Odeh, Tala, additional, Robay, Amal, additional, Chidiac, Omar, additional, Dargham, Soha R., additional, Turjoman, Rebal, additional, Halama, Anna, additional, Fakhro, Khalid, additional, Menzies, Robert, additional, Jayyousi, Amin, additional, Zirie, Mahmoud, additional, Al Suwaidi, Jassim, additional, Rafii, Arash, additional, Malik, Rayaz A., additional, Talal, Talal, additional, and Abi Khalil, Charbel, additional

Published
2017
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36. Erratum. Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study. Diabetes Care 2017;40:325–331

Author

Abdul-Ghani, Muhammad, primary, Migahid, Osama, additional, Megahed, Ayman, additional, Adams, John, additional, Triplitt, Curtis, additional, DeFronzo, Ralph A., additional, Zirie, Mahmoud, additional, and Jayyousi, Amin, additional

Published
2017
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39. Correction: Type 2 Diabetes Risk Allele Loci in the Qatari Population

Author

O’Beirne, Sarah L., primary, Salit, Jacqueline, additional, Rodriguez-Flores, Juan L., additional, Staudt, Michelle R., additional, Abi Khalil, Charbel, additional, Fakhro, Khalid A., additional, Robay, Amal, additional, Ramstetter, Monica D., additional, Al-Azwani, Iman K., additional, Malek, Joel A., additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, Badii, Ramin, additional, Al-Nabet Al-Marri, Ajayeb, additional, Chiuchiolo, Maria J., additional, Al-Shakaki, Alya, additional, Chidiac, Omar, additional, Gharbiah, Maey, additional, Bener, Abdulbari, additional, Stadler, Dora, additional, Hackett, Neil R., additional, Mezey, Jason G., additional, and Crystal, Ronald G., additional

Published
2016
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41. Type 2 Diabetes Risk Allele Loci in the Qatari Population

Author

O’Beirne, Sarah L., primary, Salit, Jacqueline, additional, Rodriguez-Flores, Juan L., additional, Staudt, Michelle R., additional, Abi Khalil, Charbel, additional, Fakhro, Khalid A., additional, Robay, Amal, additional, Ramstetter, Monica D., additional, Al-Azwani, Iman K., additional, Malek, Joel A., additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, Badii, Ramin, additional, Al-Nabet Al-Marri, Ajayeb, additional, Chiuchiolo, Maria J., additional, Al-Shakaki, Alya, additional, Chidiac, Omar, additional, Gharbiah, Maey, additional, Bener, Abdulbari, additional, Stadler, Dora, additional, Hackett, Neil R., additional, Mezey, Jason G., additional, and Crystal, Ronald G., additional

Published
2016
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42. The Qatar genome: a population-specific tool for precision medicine in the Middle East

Author

Fakhro, Khalid A, primary, Staudt, Michelle R, additional, Ramstetter, Monica Denise, additional, Robay, Amal, additional, Malek, Joel A, additional, Badii, Ramin, additional, Al-Marri, Ajayeb Al-Nabet, additional, Khalil, Charbel Abi, additional, Al-Shakaki, Alya, additional, Chidiac, Omar, additional, Stadler, Dora, additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, Salit, Jacqueline, additional, Mezey, Jason G, additional, Crystal, Ronald G, additional, and Rodriguez-Flores, Juan L, additional

Published
2016
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43. Prevalence of the ApoE Arg145Cys Dyslipidemia At-risk Polymorphism in African-derived Populations

Author

Abou Ziki, Maen D., Strulovici-Barel, Yael, Hackett, Neil R., Rodriguez-Flores, Juan L., Mezey, Jason G., Salit, Jacqueline, Radisch, Sharon, Hollmann, Charleen, Chouchane, Lotfi, Malek, Joel, Zirie, Mahmoud A., Jayyuosi, Amin, Gotto, Antonio M., and Crystal, Ronald G.

Subjects
Polymorphism, Genetic, Genotype, New York, DNA, Polymerase Chain Reaction, Article, Black or African American, Apolipoproteins E, Risk Factors, Prevalence, Humans, Genetic Predisposition to Disease, Alleles, Dyslipidemias
Abstract

Apolipoprotein E, a protein component of blood lipid particles, plays an important role in lipid transport. Different mutations in the apolipoprotein E gene have been associated with various clinical phenotypes. In an initiated study of Qataris, we observed that 17% of the African-derived genetic subgroup were heterozygotes for a rare Arg145Cys (R145C) variant that functions as a dominant trait with incomplete penetrance associated with type III hyperlipoproteinemia. On the basis of this observation, we hypothesized that the R145C polymorphism might be common in African-derived populations. The prevalence of the R145C variant was assessed worldwide in the "1000 Genomes Project" and in 1,012 whites and 1,226 African-Americans in New York, New York. The 1000 Genomes Project data demonstrated that the R145C polymorphism is rare in non-African-derived populations but present in 5% to 12% of Sub-Saharan African-derived populations. The R145C polymorphism was also rare in New York whites (1 of 1,012, 0.1%); however, strikingly, 53 of the 1,226 New York African-Americans (4.3%) were R145C heterozygotes. The lipid profiles of the Qatari and New York R145C heterozygotes were compared with those of controls. The Qatari R145C subjects had higher triglyceride levels than the Qatari controls (p0.007) and the New York African-American R145C subjects had an average of 52% greater fasting triglyceride levels than the New York African-American controls (p0.002). From these observations, likely millions of people worldwide derived from Sub-Saharan Africans are apolipoprotein E R145C. In conclusion, although larger epidemiologic studies are necessary to determine the long-term consequences of this polymorphism, the available evidence suggests it is a common cause of a mild triglyceride dyslipidemia.

Published
2013

44. Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

Author

Rodriguez-Flores, Juan L., primary, Fakhro, Khalid, additional, Agosto-Perez, Francisco, additional, Ramstetter, Monica D., additional, Arbiza, Leonardo, additional, Vincent, Thomas L., additional, Robay, Amal, additional, Malek, Joel A., additional, Suhre, Karsten, additional, Chouchane, Lotfi, additional, Badii, Ramin, additional, Al-Nabet Al-Marri, Ajayeb, additional, Abi Khalil, Charbel, additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, Salit, Jacqueline, additional, Keinan, Alon, additional, Clark, Andrew G., additional, Crystal, Ronald G., additional, and Mezey, Jason G., additional

Published
2016
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45. Copy number variations in the genome of the Qatari population

Author

Fakhro, Khalid A., primary, Yousri, Noha A., additional, Rodriguez-Flores, Juan L., additional, Robay, Amal, additional, Staudt, Michelle R., additional, Agosto-Perez, Francisco, additional, Salit, Jacqueline, additional, Malek, Joel A., additional, Suhre, Karsten, additional, Jayyousi, Amin, additional, Zirie, Mahmoud, additional, Stadler, Dora, additional, Mezey, Jason G., additional, and Crystal, Ronald G., additional

Published
2015
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46. Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population

Author

Upadhyay, Rohit, primary, Robay, Amal, additional, Fakhro, Khalid, additional, Abi Khadil, Charbel, additional, Zirie, Mahmoud, additional, Jayyousi, Amin, additional, El-Shafei, Maha, additional, Kiss, Szilard, additional, D′Amico, Donald J, additional, Salit, Jacqueline, additional, Staudt, Michelle R, additional, O′Beirne, Sarah L, additional, Chen, Xiaoliang, additional, Tuana, Balwant, additional, Crystal, Ronald G, additional, and Ding, Hong, additional

Published
2015
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49. The utility of an electronic adherence assessment device in type 2 diabetes mellitus: a pilot study of single medication

Author

Kheir,Nadir, Greer,William, Yousif, Al-Geed,Hajer, Al Okkah,Randa, Zirie,Mahmoud A., Sandridge,Amy, Zaidan,Manal, Kheir,Nadir, Greer,William, Yousif, Al-Geed,Hajer, Al Okkah,Randa, Zirie,Mahmoud A., Sandridge,Amy, and Zaidan,Manal

Abstract

Nadir Kheir1, William Greer2, Adil Yousif3, Hajer Al-Geed1, Randa Al Okkah1, Mahmoud Zirie4, Amy Sandridge5, Manal Zaidan61College of Pharmacy, 2Sidra Medical and Research Centre, 3Department of Statistics, College of Arts and Sciences, Qatar University, 4Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 5Private Research Consultant, 6Al Amal Cancer Centre, Hamad Medical Corporation, Doha, QatarObjectives: The primary objective of this pilot study was to determine if the Medication Event Monitoring System (MEMS) is capable of providing meaningful estimates of compliance within the indigenous Qatari population. The secondary objective was to highlight any specific problems which might be associated with the use of MEMS within this population.Method: A sample of adult diabetic Qatari patients attending an outpatient diabetic clinic were administered a Knowledge, Attitude, and Practices (KAP) questionnaire and then dispensed one of their regular medications in a MEMS®-fitted bottle. Data contained in the MEMS® were downloaded after the patients returned for a refill and adherence was estimated using 2 methods: pill count and MEMS® data.Results: A total of 54 patients agreed to participate in this pilot study. Adherence to daily doses was 67.7% and with regimen 13.7%. No correlation was found between adherence assessed by pill count and MEMS®. The association between KAP and adherence was generally poor. A number of other issues and challenges in the use of MEMS® that could affect its utility were noted and will be discussed.Conclusions: Our results revealed problems associated with the use of MEMS® that could affect its usefulness in assessing adherence in this part of the world. Some issues identified in this pilot study included retrieving the MEMS®, registering extra opening of MEMS®, desire to hoard medicine by taking doses at different frequency than recorded in MEMS®. All these

Published
2010

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