Integrated datasets of proteomic and metabolomic biomarkers to predict its impacts on comorbidities of type 2 diabetes mellitus

© 2020 Cheema et al. Objective: 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

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

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

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

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

Hypoadiponectinemia in obese and diabetic subjects in the State of Qatar

Background: Obesity is commonly associated with insulin resistance (IR), and is a common cause of type 2 diabetes. Adiponectin is an adipose tissue protein that enhances insulin sensitivity and has anti-atherogenic properties. Objective: This study was done to determine the adiponectin level and its relations to key components of the metabolic syndrome in obese diabetic (OD), obese non-diabetic (OB) and control [non-obese, non-diabetic (NOND)] Qatari subjects. Research design and Methods: We examined 64 (OD), 61 (OB) and 72 (NOND) male and female subjects. After a 12 h overnight fasting, blood samples were withdrawn for determination of plasma glucose, insulin, adiponectin, HbA1C, uric acid, total cholesterol, triglycerides, HDL-C and LDL-C. Results: Plasma levels of adiponectin in OD (10.60 ± 3.64μg /mL) and OB (11.21 ± 3.41μg/mL) were significantly lower than NOND controls (14.73 ± 4.97μg/mL). Significant, inverse correlations were observed between adiponectin levels and BMI (r=-0.241, p<0.05), plasma glucose (r=-0.221, p<0.05), insulin (r=-0.280, p<0.05), C-peptide (r=-0.334, P<0.01), total cholesterol (r=-0.243, p<0.01,), triglycerides (r=-0.438, p<0.01), LDL-C (r=-0. 214, p<0.05) and uric acid (r=-0.286, p<0.05). In addition, correlated positively with HDL-C(r=0.386, p<0.01). In multiple regression analysis, only TG was inversely associated with plasma level of adiponectin in all groups. Conclusion: This study provides the first evidence that adiponectin is reduced in Qatari obese subjects with and without diabetes. The measurement of circulating adiponectin among Qatari obese subjects is suggested to monitor cardiovascular disease (CVD) risks. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of CVD among Qatari obese and diabetic subjects warrants further investigation

Genetics, obesity, and environmental risk factors associated with type 2 diabetes

Aim To determine the association between consanguineous marriages, obesity, and environmental risk factors associated with type 2 diabetes, in the adult Qatari population

Bone density measured by dual energy X-ray absorptiometry in Qatari women

Background: Over the past 10 years, osteoporosis has emerged as a major public health problem. It is characterized by low bone mass with micro architectural deterioration of bone tissue resulting in increase bone fragility and susceptibility to fractures. Bone mineral density measurements are widely used to diagnose osteoporosis and to assess its severity. Commercial dual-energy X-rays absorptiometry (DXA) scanners used to determine bone mineral density (BMD) contains reference data for different populations

Complications of Diabetes Mellitus Among Patients Attending Outpatient Clinics in Qatar

The objective of this study was to explore the prevailing complications of diabetes mellitus and to explore some of the associated factors among Qatari patients previously diagnosed as having diabetes mellitus. A random sample of Qatari diabetic patients attending outpatient clinics (8 am to 12 pm) attached to Hamad General Hospital, between May 2001-2002 were included in the study. The total sample was 225, 74 males, and 151 females. The results revealed that retinopathy was the most prevailing complication (43.6%), followed by nephropathy (40.9%), hypertension (36.9%), neuropathy (28.9%), hyperlipidemia (26.7%), coronary heart disease (18.7%), foot ulcer (4.4%), and thyroid problems (3.6%). A significant association between development of hypertension and high body mass index (BMI) was found. Neuropathy and thyroid problems were significantly higher in females. (56.9%) of the patients were obese (BMI >30 kg/m2), and 28.9% were overweight (BMI 25-29.9). Two thirds of the patients had positive family history of the disease, and females who had diabetic fathers were significantly higher than males.qscienc

Metabolic Syndrome and its components among Qatari population

Metabolic Syndrome (MeS) is a cluster of abnormalities including impaired glucose metabolism, central obesity, dyslipidemia and hypertension. The MeS has not been widely studied among the Arab populations, but the data available suggests that it is an increasingly common problem. Prevalence of MeS and its associated components are not available in Qatar. To estimate the prevalence of MeS and its associated components among the Qatari population and to determine its associated risk factors. A cross-sectional study was carried out among Qatari adults aged 20 years and above. Face to face interviewing using a structured questionnaire followed by laboratory tests were conducted. MeS was defined using the Adult Treatment Panel III (ATP III) criteria as well as the International Diabetes Federation criteria (IDF). The crude prevalence rate of MeS according to ATP III criteria and IDF criteria were 26.4 and 34.0%, respectively. The age-standardised prevalence of the MeS according to ATP III was 27.7% (95% CI 23.3–32.0%), (23.6% among men (95% CI 19.5– 27.7%) and 32.6% among women (95% CI 28.0–37.2%)) and according to IDF criteria, the age standardised prevalence was 35.4% (95% CI 30.7–40.0%), 38.7% (95% CI 34.0–43.5%) for women and 35.8% (95% CI 31.2–40.5%) for men. Age, Body Mass Index and HbA1c were significantly associated with MeS after adjustment for a number relevant variables including; gender, marital status, educational level, exercise, smoking, etc. Prevalence of the MeS in Qatar is considerably higher than anticipated. A well-designed health education programmes to increase the awareness of the public as well as healthcare providers are highly recommended. The programme should focus on the risk factors and the health consequences of MeS