ORCID Profile
0000-0001-9037-1937
Current Organisations
University Hospitals Birmingham NHS Foundation Trust
,
University of Birmingham
,
Heart of England NHS Foundation Trust
,
World Obesity Federation
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Publisher: American Society for Clinical Investigation
Date: 03-06-2013
DOI: 10.1172/JCI64162
Publisher: Springer Science and Business Media LLC
Date: 07-2009
Publisher: American Diabetes Association
Date: 14-08-2012
DOI: 10.2337/DC11-2076
Abstract: Impairment of skin quality may contribute to diabetic foot ulceration (DFU). Our goal was to determine whether high-risk patients exhibited specific skin structural and metabolic deficits that could predispose to foot complications. A total of 46 patients comprising 9 diabetic control subjects, 16 with diabetic peripheral neuropathy (DPN) alone, and 21 with recurrent DFUs (including 9 with Charcot neuroarthropathy [CNA]) were recruited and compared with 14 nondiabetic control (NDC) subjects. DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Skin punch biopsies (3 mm) were performed on upper and lower leg skin for measurements of intraepidermal nerve fiber density (IENFD), structural analysis, type 1 procollagen abundance, tissue degrading matrix metalloproteinases (MMPs), and poly(ADP-ribose) (PAR) immunoreactivity. MNSI scores were comparable across DPN groups. IENFD was decreased by diabetes and DPN but did not differ between neuropathic groups. Skin structural deficit scores were elevated in all neuropathic subjects, particularly in the DFU group. Type 1 procollagen abundance was reduced in DFU subjects 387 ± 256 units (mean ± 1 SD) compared with NDC subjects (715 ± 100, P & 0.001). MMP-1 and MMP-2 were activated by diabetes. PAR immunoreactivity was increased in DFU (particularly in the CNA group P & 0.01) compared with other DPN subjects. Increased PAR, reduced type 1 procollagen abundance, and impaired skin structure are associated with foot complications in diabetes. The potential of therapies that improve skin quality to reduce DFU needs to be investigated.
Publisher: Wiley
Date: 27-05-2010
Publisher: Oxford University Press (OUP)
Date: 02-05-2018
DOI: 10.1093/SLEEP/ZSY085
Abstract: In this systematic review and meta-analysis, we aimed to examine the relationship between obstructive sleep apnea (OSA) and metabolic abnormalities in women with polycystic ovary syndrome (PCOS). Electronic databases (Medline, Embase, Cinahl, PsycInfo, Scopus, Web of Science, Opengrey, and CENTRAL), conference abstracts, and reference lists of relevant articles were searched. No restriction was applied for language or publication status. Six studies involving 252 participants were included. Women with PCOS and OSA had significantly higher body mass index (mean difference [MD]: 6.01 kg/m2, 95% confidence intervals [CI]: 4.69-7.33), waist circumference (MD: 10.93 cm, 95% CI: 8.03-13.83), insulin resistance, systolic and diastolic blood pressure, and worse lipids' profile and impaired glucose regulation compared with women with PCOS without OSA. Most studies did not adjust for weight in their between-groups analysis. Total and free testosterone levels were not significantly different between the two groups. The majority of studies were found to be at high risk of selection bias, did not account for important confounders, were conducted in one country (United States), and used different methodologies to assess testosterone levels (preventing a meta-analysis for this specific outcome). OSA is associated with obesity and worse metabolic profiles in women with PCOS. However, whether the effects of OSA are independent of obesity remain unclear. As OSA is a treatable condition, research focused on the independent effects of OSA on key clinical outcomes in women with PCOS, including fertility, psychological health, type 2 diabetes, and cardiovascular risk, is lacking and needed. PROSPERO registration number: CRD42016048587.
Publisher: Informa UK Limited
Date: 11-2009
Abstract: Type 2 diabetes is a very common worldwide disorder, with major consequences for patients, society, and health care services. Good glycemic control is an important aspect of diabetes management because it has a significant impact on diabetes-related microvascular and possibly macrovascular complications. Based on our understanding of the pathogenesis of diabetes, multiple pharmacological interventions have been developed in the past 60 years. Although effective, none have had a lasting effect on glycemic control because of the progressive nature of type 2 diabetes requiring combination therapies and insulin treatment. In addition, several pharmacologic interventions have undesirable side effects, including hypoglycemia and weight gain. Drugs targeting the incretin pathway are the latest addition to the available antidiabetes agents. Incretin-based therapy is either delivered orally (dipeptidyl peptidase-4 [DPP-4]) inhibitors or injected subcutaneously (glucagon-like peptide-1 [GLP-1] mimetics and analogues). Dipeptidyl peptidase-4 inhibitors are effective either as a single or combination therapy in lowering glycated hemoglobin, fasting and postprandial glucose levels, with a low incidence of hypoglycemia and no weight gain. There are 3 DPP-4 inhibitors currently available (sitagliptin, saxagliptin, and vildagliptin), with more expected to be available in the future. In this article, we review the scientific background for incretin-based therapy and the available evidence regarding the role and efficacy of DPP-4 inhibitors in the treatment of patients with type 2 diabetes.
Publisher: The Endocrine Society
Date: 09-02-2021
Abstract: Diabetes has emerged as an important risk factor for mortality from COVID-19. Metformin, the most commonly prescribed glucose-lowering agent, has been proposed to influence susceptibility to and outcomes of COVID-19 via multiple mechanisms. We investigated whether, in patients with diabetes, metformin is associated with susceptibility to COVID-19 and its outcomes. We performed a propensity score–matched cohort study with active comparators using a large UK primary care dataset. Adults with type 2 diabetes patients and a current prescription for metformin and other glucose-lowering agents (MF+) were compared to those with a current prescription for glucose-lowering agents that did not include metformin (MF−). Outcomes were confirmed COVID-19, suspected/confirmed COVID-19, and associated mortality. A negative control outcome analysis (back pain) was also performed. There were 29 558 and 10 271 patients in the MF+ and MF− groups, respectively, who met the inclusion criteria. In the propensity score–matched analysis, the adjusted hazard ratios for suspected/confirmed COVID-19, confirmed COVID-19, and COVID-19-related mortality were 0.85 (95% CI 0.67, 1.08), 0.80 (95% CI 0.49, 1.30), and 0.87 (95% CI 0.34, 2.20) respectively. The negative outcome control analysis did not suggest unobserved confounding. Current prescription of metformin was not associated with the risk of COVID-19 or COVID-19-related mortality. It is safe to continue prescribing metformin to improve glycemic control in patients with.
Publisher: Springer Science and Business Media LLC
Date: 22-11-2016
Publisher: Elsevier BV
Date: 08-2011
Publisher: Wiley
Date: 10-2015
DOI: 10.1002/PDI.1978
Publisher: Informa UK Limited
Date: 11-2008
Abstract: Exenatide is the first in a novel class of drugs that mimics naturally occurring glucagon-like peptide 1. In patients with Type 2 diabetes mellitus (T2DM), control of both glycemia and bodyweight are important to minimize the risk of diabetes complications. Exenatide improves glycemic control through glucose-dependent insulin secretion, suppression of glucagon secretion, delaying gastric emptying and suppressing appetite. Exenatide therapy significantly reduced glycated hemoglobin (Hb
Publisher: American Diabetes Association
Date: 15-10-2013
DOI: 10.2337/DC13-0450
Abstract: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease (ESRD). Obstructive sleep apnea (OSA) is common in type 2 diabetes and increases oxidative stress. Hence, OSA could promote the development and progression of DN. This was a cohort study in adults with type 2 diabetes. Patients with known OSA or ESRD were excluded. DN was defined as the presence of albuminuria or an estimated glomerular filtration rate (eGFR) & mL/min/1.73 m2. DN progression was based on eGFR measurements. OSA was defined as apnea hypopnea index (AHI) ≥5 events/h. Serum nitrotyrosine abundance (a marker of nitrosative stress) was measured by ELISA. A total of 224 patients were included. OSA and DN prevalence was 64.3 and 40.2, respectively. DN prevalence was higher in patients with OSA (OSA+) compared with those without OSA (OSA−) (49.3% vs. 23.8%, P & 0.001). After adjustment, OSA (odds ratio 2.64 [95% CI 1.13–6.16], P = 0.02) remained independently associated with DN. After an average follow-up of 2.5 (0.7) years, eGFR decline was greater in OSA+ compared with OSA− patients (median −6.8% [interquartile range −16.1 to 2.2] vs. −1.6% [−7.7 to 5.3%], P = 0.002). After adjusting, both baseline OSA (B = −3.8, P = 0.044) and AHI (B = −4.6, P = 0.02) remained independent predictors of study-end eGFR. Baseline serum nitrotyrosine abundance (B = −0.24, P = 0.015) was an independent predictor of study-end eGFR after adjustment. OSA is independently associated with DN in type 2 diabetes. eGFR declined faster in patients with OSA. Nitrosative stress may provide a pathogenetic link between OSA and DN. Interventional studies assessing the impact of OSA treatment on DN are needed.
Publisher: Springer Science and Business Media LLC
Date: 02-2009
DOI: 10.1007/S12325-009-0010-0
Abstract: The single-tablet combination of vildagliptin and metformin addresses key defects of type 2 diabetes for improved glycemic control. By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, vildagliptin raises the levels of the active incretin hormones, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide. This leads to increased synthesis and release of insulin from the pancreatic beta cells and decreased release of glucagon from the pancreatic alpha cells. The combination tablet also contains metformin, which addresses insulin resistance. The complementary mechanisms of action of the two agents in combination have been shown to provide additive and sustained reductions in hemoglobin A(1c) compared with metformin monotherapy. In active-controlled trials, the vildagliptin-metformin combination has been shown to produce equivalent reductions in hemoglobin A(1c) to pioglitazone-metformin and glimepiride-metformin combinations, without significant risk of hypoglycemia and without causing weight gain. In clinical trials, the overall incidence of any adverse event was similar in patients randomized to vildagliptin plus metformin and placebo plus metformin. Available data support the use of vildagliptin in combination with metformin as a promising second-line treatment for the management of type 2 diabetes and this is reflected in the latest UK National Institute for Health and Clinical Excellence draft guideline for consultation on new agents for blood glucose control in type 2 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 13-03-2014
DOI: 10.1007/S00125-014-3211-2
Abstract: The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR > 3.4 mg/mmol) or an estimated (eGFR) < 60 ml min(-1) 1.73 m(-2). CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability. Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (-9.0 ± 17.8% vs -3.3 ± 10.3%, p = 0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β = -3.5, p = 0.03). Spectral analysis variables were also independent predictors of eGFR decline. CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.JDIACOMP.2016.05.025
Abstract: Obstructive sleep apnea (OSA) is associated with increased nitrosative stress, endothelial dysfunction, and peripheral neuropathy in patients with type 2 diabetes. We hypothesized that OSA is associated with Poly ADP ribose polymerase (PARP) activation, lower intra-epidermal nerve fiber density (IENFD), and diabetic foot ulceration (DFU). A cross-sectional study of adults with type 2 diabetes recruited from a secondary care hospital in the UK. OSA was assessed by multi-channel home-based cardio-respiratory device (Alice PDX, Philips Respironics). DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). IENFD and % PAR stained nuclei were assessed using immunohistochemistry staining on skin biopsies. DFU was assessed based on MNSI. Skin biopsies and DFU data were available from 52 and 234 patients respectively. OSA was associated with lower IENFD (12.75±1.93 vs. 10.55±1.62 vs. 9.42±1.16 fibers/mm of epidermis for no OSA, mild OSA and moderate to severe OSA respectively, p<0.001). Following adjustment, mild (B=-2.19, p=0.002) and moderate to severe OSA (B=-3.45, p<0.001) were independently associated with IENFD. The apnea hypopnea index (AHI) was associated with IENFD following adjustment (B=-2.45, p<0.001). AHI was associated with percentage of PAR stained nuclei following adjustment (B=13.67, p=0.025). DFU prevalence was greater in patients with OSA (7.1% vs. 28.1% vs. 26.2% for patients with no OSA, mild OSA and moderate to severe OSA respectively, p=0.001). Following adjustment, OSA was associated with DFU (OR 3.34, 95% CI 1.19-9.38, p=0.022). OSA is associated with lower IENFD, PARP activation and DFU in patients with type 2 diabetes. Our findings suggest that OSA is associated with small fiber neuropathy. PARP activation is a potential mechanisms linking OSA to DPN and endothelial dysfunction in patients with type 2 diabetes. Whether OSA treatment will have a favorable impact on these parameters and DFU requires interventional studies.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Wiley
Date: 10-2008
DOI: 10.1002/PDI.1284
Publisher: MDPI AG
Date: 24-02-2022
DOI: 10.3390/NU14050967
Abstract: We aimed to assess weight loss and metabolic outcomes by severity of weight-related complications following an intensive non-surgical weight management program (WMP) in an Australian public hospital. A retrospective cohort study of all patients aged ≥18 years with body mass index (BMI) ≥ 40 enrolled in the WMP during March 2018–March 2019 with 12-month follow-up information were stratified using the Edmonton Obesity Staging System (EOSS). Of 178 patients enrolled in the WMP, 112 (62.9%) completed at least 12 months’ treatment. Most patients (96.6%) met EOSS-2 (56.7%) or EOSS-3 (39.9%) criteria for analysis. Both groups lost significant weight from baseline to 12 months EOSS-2: 139.4 ± 31.8 kg vs. 131.8 ± 31.8 kg (p 0.001) and EOSS-3: 141.4 ± 24.2 kg vs. 129.8 ± 24.3 kg (p 0.001). After adjusting for baseline age, sex and employment status, mean weight loss was similar but a greater proportion of EOSS-3 achieved % weight loss compared to EOSS-2, (40% vs. 15.9%, p = 0.024). Changes in metabolic parameters including HbA1c, BP and lipids did not differ between EOSS-2 and 3. Despite increased clinical severity, adult patients with class 3 obesity achieved clinically meaningful weight loss and similar improvements in metabolic parameters compared to patients with less severe complications after 12 months in an intensive non-surgical WMP.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/1273789
Abstract: Objectives. To compare the prevalence of diabetic peripheral neuropathy (DPN) and that of cardiac autonomic neuropathy (CAN) between South Asians and White Caucasians with type 2 diabetes and to explore reasons for observed differences. Methods. A cross-sectional study of casually selected South Asian and White Caucasian adults attending a hospital-based diabetes clinic in the UK. DPN and CAN were assessed using the Michigan Neuropathy Screening Instrument (MNSI) and heart rate variability testing, respectively. Results. Patients ( n = 266 ) were recruited (47.4% South Asians). DPN was more common in White Caucasians compared to South Asians (54.3% versus 38.1%, p = 0.008 ). Foot insensitivity as assessed by 10 g monofilament perception was more common in White Caucasians (43.9% versus 23.8%, p = 0.001 ). After adjustment for confounders, White Caucasians remained twice as likely to have DPN as South Asians, but the impact of ethnicity became nonsignificant after adjusting for adiposity measures or height. No difference in prevalence of standardized CAN test abnormalities was detected between ethnicities. Skin microvascular assessment demonstrated that South Asians had reduced heating flux but preserved acetylcholine response. Conclusions. South Asians with type 2 diabetes have fewer clinical signs of DPN compared to White Caucasians. Differences in adiposity (and its distribution) and height appear to explain these differences.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-04-2017
DOI: 10.5664/JCSM.6548
Publisher: American Thoracic Society
Date: 09-2012
Publisher: Springer Science and Business Media LLC
Date: 14-11-2021
DOI: 10.1186/S12902-021-00887-3
Abstract: Although there is a strong association between obesity and obstructive sleep apnoea (OSA), the effects of OSA and CPAP therapy on weight loss are less well known. The aim of this study in adults with class 3 obesity attending a multidisciplinary weight management program was to assess the relationship between OSA and CPAP usage, and 12-month weight change. A retrospective cohort study of all patients commencing an intensive multidisciplinary publicly funded weight management program in Sydney, Australia, between March 2018 and March 2019. OSA was diagnosed using laboratory overnight sleep studies. Demographic and clinical data, and use of CPAP therapy was collected at baseline and 12 months. CPAP use was confirmed if used ≥4 h on average per night on download. Of the 178 patients who joined the program, 111 (62.4 %) completed 12 months in the program. At baseline, 63.1 % ( n =70) of patients had OSA, of whom 54.3 % ( n =38) were using CPAP. The non-OSA group had more females compared to the OSA with CPAP group and OSA without CPAP group (90.2 % vs. 57.9 % and 62.5 %, respectively p =0.003), but there were no significant baseline differences in BMI (50.4±9.3 vs. 52.1±8.7 and 50.3±9.5 kg/m 2 , respectively p =0.636). There was significant weight loss across all three groups at 12 months. However, there were no statistically significant differences across groups in the percentage of body weight loss (OSA with CPAP: 6.3±5.6 %, OSA without CPAP: 6.8±6.9 %, non-OSA: 7.2±6.5 % p =0.844), or the proportion of patients who achieved ≥5 % body weight loss (OSA with CPAP: 57.9 %, OSA without CPAP: 59.4 %, non-OSA: 65.9 % p =0.743). In patients with T2DM, there was a significant reduction in HbA1c from baseline to 12 months (7.8±1.7 % to 7.3±1.4 %, p =0.03), with no difference between groups ( p =0.997). This multidisciplinary weight management program resulted in significant weight loss at 12 months, regardless of OSA diagnosis or CPAP use in adults with class 3 obesity. Larger studies are needed to further investigate the effects of severity of OSA status and CPAP use in weight management programs. Until completed, this study suggests that the focus should remain on implementing lifestyle changes and weight management regardless of OSA status.
Publisher: Elsevier BV
Date: 02-2010
DOI: 10.1016/J.PHARMTHERA.2009.11.001
Abstract: Type 2 diabetes mellitus (T2DM) is a worldwide public health challenge. Despite the availability of many antidiabetes agents and pharmacotherapies targeting cardiovascular risk factors, the morbidity, mortality and economic consequences of T2DM are still a great burden to patients, society, health care systems and the economy. The need for new therapies for glycaemic control is compounded by the fact that existing treatments have limitations either because of their side effects (particularly weight gain and hypoglycaemia) or contraindications that limit their use. Furthermore, none of the current therapies have a significant impact on disease progression. Incretin-based therapies offer a new therapeutic approach to the management of T2DM, and there are also several even newer therapies in development. There are two groups of incretin-based therapies currently available dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 analogues/mimetics. The former are given orally while the latter subcutaneously. These drugs result in glucose-dependent insulin secretion and glucose-dependent glucagon suppression, with consequent low risk of hypoglycaemia when used as mono- or combination therapy (except when used with sulphonylureas). In addition, they are either weight neutral in the case of DPP-4 inhibitors or cause weight loss in the case of incretin mimetics/analogues. Furthermore, animal studies have shown that these agents prolong beta cell survival which offers the theoretical possibility of slowing the progression to T2DM. In this article we will review the currently available antidiabetes agents with particular emphasis on incretin-based and future therapies. In addition, we will review and discuss the evidence relating to glycaemic control and cardiovascular disease.
Publisher: Springer Science and Business Media LLC
Date: 03-2009
DOI: 10.1007/S12325-009-0014-9
Abstract: Type 2 diabetes mellitus (T2DM) is a global epidemic with increasing impact on in iduals and healthcare providers. Available treatments (such as metformin, sulfonylureas, glitazones, and insulin) have proven unsatisfactory in producing a long-lasting impact on glycemic control. In addition, most of these treatments have undesirable side effects such as weight gain and hypoglycemia. As a result, exploring new treatment targets and new therapies is mandatory in order to treat this condition. The incretin pathway, in particular glucagon-like peptide (GLP-1), plays an important pathological role in the development of T2DM, and treatments targeting the incretin system have recently become available. These can mainly be ided into two broad categories GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase-4 (DPP-4 the enzyme responsible for rapid inactivation of incretins) inhibitors (sitagliptin, vildagliptin). Saxagliptin is a novel DPP-4 inhibitor that has recently completed phase 3 studies. Saxagliptin is a potent and specific inhibitor of DPP-4 (in comparison with other dipeptidyl peptidase enzymes) that is given once daily. Current data suggest that saxagliptin as monotherapy or in combination with metformin, glyburide, or a glitazone results in significant reductions in fasting and postprandial plasma glucose and hemoglobin A(1c) (HbA(1c)). Saxagliptin is well tolerated and does not increase hypoglycemia compared with the placebo, and is probably weight neutral. Saxagliptin will be a new effective drug in the currently available variety of antidiabetic medications for patients with T2DM.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Syrian Arab Republic
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Abd Tahrani.