Khalid Siddiqui

Variation in Macro and Trace Elements in Progression of Type 2 Diabetes

Macro elements are the minerals of which the body needs more amounts and are more important than any other elements. Trace elements constitute a minute part of the living tissues and have various metabolic characteristics and functions. Trace elements participate in tissue and cellular and subcellular functions; these include immune regulation by humoral and cellular mechanisms, nerve conduction, muscle contractions, membrane potential regulations, and mitochondrial activity and enzyme reactions. The status of micronutrients such as iron and vanadium is higher in type 2 diabetes. The calcium, magnesium, sodium, chromium, cobalt, iodine, iron, selenium, manganese, and zinc seem to be low in type 2 diabetes while elements such as potassium and copper have no effect. In this review, we emphasized the status of macro and trace elements in type 2 diabetes and its advantages or disadvantages; this helps to understand the mechanism, progression, and prevention of type 2 diabetes due to the lack and deficiency of different macro and trace elements.

Epidemiology of abnormal glucose metabolism in a country facing its epidemic: SAUDI‐DM study

Saudi Arabia is a community thrilled by sudden social and economical changes, leading to a sharp increase in the prevalence of abnormal glucose metabolism. Age‐specific diabetes and impaired fasting glucose prevalence is the focus of this study with the expected risk factors.

Meta-analysis of diabetic nephropathy associated genetic variants in inflammation and angiogenesis involved in different biochemical pathways

BackgroundDiabetes mellitus is the most common chronic endocrine disorder, affecting an estimated population of 382 million people worldwide. It is associated with microvascular and macrovascular complications, including diabetic nephropathy (DN); primary cause of end-stage renal disease. Different inflammatory and angiogenic molecules in various pathways are important modulators in the pathogenesis and progression of diabetic nephropathy. Differential disease risk in DN may be partly attributable to genetic susceptibility. In this meta-analysis, we aimed to determine which of the previously investigated genetic variants in these pathways are significantly associated with the development of DN and to examine the functional role of these genes.MethodsA systematic search was conducted to collect and analyze all studies published till June 2013; that investigated the association between genetic variants involved in inflammatory cytokines and angiogenesis and diabetic nephropathy. Genetic variants associated with DN were selected and analyzed by using Comprehensive Meta Analysis software. Pathway analysis of the genes with variants showing significant positive association with DN was performed using Genomatix Genome Analyzer (Genomatix, Munich, Germany).ResultsAfter the inclusion and exclusion criteria for this analysis, 34 studies were included in this meta-analysis. 11 genetic variants showed significant positive association with DN in a random-effects meta-analysis. These included genetic variants within or near VEGFA, CCR5, CCL2, IL-1, MMP9, EPO, IL-8, ADIPOQ and IL-10. rs1800871 (T) genetic variant in IL-10 showed protective effect for DN. Most of these eleven genetic variants were involved in GPCR signaling and receptor binding pathways whereas four were involved in chronic kidney failure. rs833061 [OR 2.08 (95% CI 1.63-2.66)] in the VEGFA gene and rs3917887 [OR 2.04 (95% CI 1.64-2.54)] in the CCL2 gene showed the most significant association with the risk of diabetic nephropathy.ConclusionsOur results indicate that 11 genetic variants within or near VEGFA, CCR5, CCL2, IL-1, MMP9, EPO, IL-8, ADIPOQ and IL-10 showed significant positive association with diabetic nephropathy. Gene Ontology or pathway analysis showed that these genes may contribute to the pathophysiology of DN. The functional relevance of the variants and their pathways can lead to increased biological insights and development of new therapeutic targets.

ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: A meta-analysis

In this meta-analysis study, SNPs were investigated for their association with type 2 diabetes (T2D) in both Arab and Caucasian ethnicities. A total of 55 SNPs were analyzed, of which 11 fulfilled the selection criteria, and were used for analysis. It was found that TCF7L2 rs7903146 was significantly associated with a pooled OR of 1.155 (95%C.I.=1.059-1.259), p<0.0001 and I(2)=78.30% among the Arab population, whereas among Caucasians, the pooled OR was 1.45 (95%C.I.=1.386-1.516), p<0.0001 and I(2)=77.20%. KCNJ11 rs5219 was significantly associated in both the populations with a pooled OR of 1.176(1.092-1.268), p<0.0001 and I(2)=32.40% in Caucasians and a pooled OR of 1.28(1.111-1.475), p=0.001 among Arabs. The ACE I/D polymorphism was found to be significantly associated with a pooled OR of 1.992 (95%C.I.=1.774-2.236), p<0.0001 and I(2)=83.20% among the Arab population, whereas among Caucasians, the pooled OR was 1.078 (95%C.I.=0.993-1.17), p=0.073 and I(2)=0%. Similarly, MTHFR C677T polymorphism was also found to be significantly associated among Arabs with a pooled OR of 1.924 (95%C.I.=1.606-2.304), p<0.0001 and I(2)=27.20%, whereas among Caucasians, the pooled OR was 0.986 (95%C.I.=0.868-1.122), p=0.835 and I(2)=0%. Meanwhile PPARG-2 Pro12Ala, CDKN2A/2B rs10811661, IGF2BP2 rs4402960, HHEX rs7923837, CDKAL1 rs7754840, EXT2 rs1113132 and SLC30A8 rs13266634 were found to have no significant association with T2D among Arabs. In conclusion, it seems from this study that both Arabs and Caucasians have different SNPs associated with T2D. Moreover, this study sheds light on the profound necessity for further investigations addressing the question of the genetic components of T2D in Arabs.

A community-based survey for different abnormal glucose metabolism among pregnant women in a random household study (SAUDI-DM)

Objective To assess the prevalence and risk factors of gestational diabetes mellitus (GDM) in a population known to have a high prevalence of abnormal glucose metabolism. Methods A household random population-based cross-sectional study of 13 627 women in the childbearing age, who were subjected to fasting plasma glucose if they were not known to have been diagnosed before with any type of diabetes. GDM cases were diagnosed using the International Association of Diabetes and Pregnancy Study Group (IAPSG) criteria. Results The overall GDM prevalence was 36.6%, categorised into 32.4% new cases and 4.2% known cases. Another 3.6% had preconception type 1 or 2 diabetes. GDM cases were older and had a significantly higher body mass index, in addition to a higher rate of macrocosmic baby and history of GDM. Monthly income, educational level, living in urban areas and smoking were not found to be significantly different between normal and GDM cases. The most important and significant risk factors for GDM were history of GDM, macrosomic baby, obesity and age >30 years. However, hypertension, low high-density lipoprotein, family history of diabetes and increased triglycerides did not show any significant effect on GDM prevalence in this cohort. Conclusions This society is facing a real burden of abnormal glucose metabolism during pregnancy, where almost half of the pregnant women are subjected to maternal and neonatal complications. Early screening of pregnant women, especially those at a high risk for GDM, is mandatory to identify and manage those cases.

Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients

Albuminuria is widely used to indicate early phases of diabetic nephropathy although it is limited by the fact that structural damage might precede albumin excretion. This necessitates identifying better biomarkers that diagnose or predict diabetic nephropathy. This is a cross-sectional hospital based study recruiting type 2 diabetic patients cohort aged 35–75 years with diabetes duration of ≥10 years. Out of total eligible 467 patients, 200 patients were with normal albumin excretion, 184 patients with microalbuminuria and 83 patients with macroalbuminuria. All the patients were tested for the 22 selected biomarkers including serum, plasma and urinary markers. Sensitivity, specificity, and area under the curve (AUC) were calculated as measures of diagnostic accuracy. Out of the tested biomarkers, urinary transferrin, urinary Retinol binding protein (RBP) and serum osteopontin had the best diagnostic value for diabetic nephropathy presence based on the AUC value. The rest of the biomarkers had comparatively less or even no discriminative power. The urinary transferrin and RBP and serum osteopontin, had the best diagnostic value in type 2 diabetic patients at different stages of diabetic nephropathy. Further longitudinal prospective studies are needed to evaluate the predictive power of those markers for detecting diabetic nephropathy before any structural damage occurs.

Maturity onset diabetes of the young (MODY)—History, first case reports and recent advances

The world is seemingly facing a global increase in people suffering from diabetes especially in developing countries. The worldwide occurrence of diabetes for all age groups in year 2000 was estimated to be 2.8% and this number is most certainly expected to rise to 4.4% by 2030. Maturity-onset of diabetes of the young, or MODY, is a form of monogenic diabetes that is caused by mutations occurring in a number of different genes. Mutations in different genes tend to cause a slightly different variant of diabetes. MODY is typically diagnosed during late childhood, adolescence, or early adulthood and is usually observed to develop in adults during their late 50s. One of the main drawbacks in its diagnosis is that many people with MODY are misdiagnosed as having type 1 or type 2 diabetes. However, a molecular and genetic diagnosis can result in a better treatment and could also help in identifying other family members with MODY. This article explores the historical prospect and the genetic background of MODY, a brief summary of the first case reported and the significant factors that differentiate it from type 1 and type 2 diabetes.

The Saudi Abnormal Glucose Metabolism and Diabetes Impact Study (SAUDI-DM).

BACKGROUND AND OBJECTIVES Saudi Arabia underwent opulence-driven socio-cultural and lifestyle changes leading to soaring rates of diabetes mellitus. This study exposes the epidemiology of abnormal glucose metabolism namely: diabetes and impaired fasting glucose (IFG) in 13 administrative regions of Saudi Arabia. DESIGN AND SETTINGS This is a nationwide, household, population-based cross-sectional study that was conducted through primary health care centers during the period 2007–2009. PATIENTS AND METHODS A nationwide, household, population-based cohort of 53 370 participants aged 0–100 years adjusted to be compatible with population census was interviewed and anthropometric measures were collected. Fasting blood sample was used to screen for IFG and diabetes. RESULTS The overall prevalence of abnormal glucose metabolism was 34.5%, which included 22.6% patients with IFG, 11.9% patients with diabetes, and 6.2% patients who unaware of their disease. Diabetes prevalence was 40.2% for subjects aged ≥45 years and 25.4% for those aged ≥30 years that decreased to 11.9% when the full age spectrum was considered. Type 1 diabetes prevalence was 0. 8%, contributing only to 6.6% of the total population of patients with diabetes. The top 5 regions with the highest abnormal glucose metabolism prevalence were Makkah (43.4%), Aljouf (41.7%), Eastern region (37.16%), Madinah (35.4%), and Qassim (33.7%). Urbanization, age, and obesity were behind the wide variations in diabetes and IFG prevalence in the 13 regions. CONCLUSION Abnormal glucose metabolism has reached an epidemic state in Saudi Arabia, where one-third of the population is affected and half of diabetic cases were unaware of their disease. This observation warrants an urgent strategy for launching diabetes primary prevention and screening programs.

European, Middle Eastern, and African Society for Biopreservation and Biobanking (ESBB). 2012 Conference Session on Biobanking in Emerging Countries

The European, Middle Eastern and African Society for Biopreservation and Biobanking (ESBB) held its second annual conference in Granada, Spain, in 2012. The Society was created to focus on issues of biobanking in the countries of its regional focus. This year, ESBB dedicated two sessions to the issues of Biobanking in Emerging Countries, focusing on countries of the Middle East and Africa. The sessions addressed Progressive Approaches and Inspirational Examples together with Challenges and Opportunities in emerging countries. Here we present a review of the presentations included in these sessions and the discussions that these presentations solicited from the ESBB audience.

Genetic variants in inflammatory cytokines and angiogenesis associated with diabetic nephropathy- A meta-analysis

Background Diabetes mellitus (DM) is the most common chronic endocrine disorder, affecting an estimated 371 million people worldwide. It is associated with microvascular and macrovascular complications, including diabetic nephropathy (DN), a primary cause of end-stage renal disease (ESRD). Among the Gulf countries, Saudi Arabia has the highest number of people with diabetes and about 30-40% diabetic patients suffer from DN. Diabetes imposes a large economic burden on healthcare systems. Healthcare expenditures due to diabetes account for 11% of the total medical expenditures in the world in 2011. Mostly, individuals exposed to long durations of diabetes with relatively poor glycemic control develop progressive DN. However, some patients appear to be at increased risk while some will remain relatively protected. Differential disease risk in DN may be partly attributable to genetic susceptibility. A recent review identified genetic variants in the ACE and MTHFR genes to be significantly associated with type 2 diabetes in Arabs [1]. Inflammatory cytokines and angiogenic factors are important modulators in the pathogenesis of DN. We aimed to determine which of the previously investigated genetic variants in these pathways are significantly associated with the development of DN in diabetes and to examine the functional role of these genes.