Dhekra AlNaqeb

Diabetic Nephropathy and Its Risk Factors in a Society with a Type 2 Diabetes Epidemic: A Saudi National Diabetes Registry-Based Study

Aims The prevalence of diabetic nephropathy and its risk factors have not been studied in a society known to have diabetes epidemic like Saudi Arabia. Using a large data base registry will provide a better understanding and accurate assessment of this chronic complication and its related risk factors. Methodology A total of 54,670 patients with type 2 diabetes aged ≥25 years were selected from the Saudi National Diabetes Registry (SNDR) and analyzed for the presence of diabetic nephropathy. The American Diabetes Association (ADA) criterion was used to identify cases with microalbuminuria, macroalbuminuria and end stage renal disease (ESRD) for prevalence estimation and risk factor assessment. Results The overall prevalence of diabetic nephropathy was 10.8%, divided into 1.2% microalbuminuria, 8.1%macroalbuninuria and 1.5% ESRD. Age and diabetes duration as important risk factors have a strong impact on the prevalence of diabetic nephropathy, ranging from 3.7% in patients aged 25–44 years and a duration of >5 years, to 21.8% in patients ≥65 years with a diabetes duration of ≥15 years. Diabetes duration, retinopathy, neuropathy, hypertension, age >45 years, hyperlipidemia, male gender, smoking, and chronologically, poor glycemic control has a significantly high risk for diabetic nephropathy. Conclusion The prevalence of diabetic nephropathy is underestimated as a result of a shortage of screening programs. Risk factors related to diabetic nephropathy in this society are similar to other societies. There is thus an urgent need for screening and prevention programs for diabetic nephropathy among the Saudi population.

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.

Risk Factors for Thyroid Dysfunction among Type 2 Diabetic Patients in a Highly Diabetes Mellitus Prevalent Society

Diabetes and thyroid dysfunction found to exist simultaneously. In this regard, the present study looked into the prevalence of different forms of thyroid dysfunction and their risk factors among Type 2 diabetic Saudi patients. Methodology. A cross-sectional retrospective randomized hospital-based study of 411 Type 2 diabetic Saudi patients of >25 years of age was conducted to test the prevalence of different types of thyroid dysfunction and their risk factors. Results. The prevalence of different types of thyroid dysfunction is 28.5%, of which 25.3% had hypothyroidism, where 15.3%, 9.5%, and 0.5% are clinical, subclinical, and overt hypothyroidism, respectively. The prevalence of hyperthyroidism is 3.2%, of which subclinical cases accounted for 2.7% and overt hyperthyroidism accounted for 0.5%. Risk factors for thyroid dysfunction among Saudi Type 2 diabetic patients are family history of thyroid disease, female gender, and duration of diabetes of >10 years, while the risk was not significant in patients with history of goiter and patients aged >60 years. Smoking and parity show a nonsignificant reduced risk. Conclusion. Thyroid dysfunction is highly prevalent among Saudi Type 2 diabetic patients, and the most significant risk factors are family history of thyroid disease, female gender, and >10 years duration of diabetes.

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.

All-cause mortality and its risk factors among type 1 and type 2 diabetes mellitus in a country facing diabetes epidemic

AIM Diabetes mellitus is associated with an increased risk of premature death mainly secondary to macrovascular and microvascular complications. Mortality data from the Eastern Mediterranean region known for its high diabetes prevalence are lacking. We aimed to assess all-cause mortality and its predictors using large cohort from the Saudi National Diabetes Registry (SNDR). METHODS The study population comprised of 40,827 individuals with type 1 and type 2 diabetes mellitus aged ⩾25years registered in SNDR between January 2007 and December 2013. All patients were followed until death, according to the date of death or reaching 100years of age or end of the study. Death was verified from the national civil affairs database. The general population during the study period was used as a reference for standardized mortality ratio (SMR) calculation. RESULTS With a total of 152,038 person-years of follow up, 2582 patients were deceased giving all-cause mortality rate of 16.98 per 1000 person-years and SMR (95% CI) of 1.93 (1.86-2.00). Mortality rates were higher among men and increased with age, while SMR attenuated with increasing age. The independent predictors for all-cause mortality were longer diabetes duration, presence of macrovascular complications, nephropathy, retinopathy, hypertension, male gender and older age, while morbid obesity and the presence of hyperlipidemia were associated with reduced risk. CONCLUSIONS The unexpectedly low mortality rate in this population would be associated with higher number of deaths as a result of the high prevalence of diabetes and its complications. Reducing the prevalence of diabetes and its complications would reduce the risk of mortality.

A null mutation in TNIK defines a novel locus for intellectual disability.

Intellectual disability (ID) is one of the most common disabilities and, although many genes have been implicated in its etiology, the genetic heterogeneity of ID continues to expand. The purpose of the study was to describe a novel autosomal recessive non-syndromic ID locus. Autozygome and linkage analysis, and exome sequencing followed by RNA and protein analysis of the candidate disease gene were performed. We describe two multiplex consanguineous families with non-syndromic ID phenotype, which maps to a critical linkage locus on 3q26. Exome sequencing of the index in each family revealed the same homozygous truncating mutation in TNIK that results in complete loss of the protein. TNIK is a kinase with a well-established role in dendrite development and synaptic transmission. The phenotype we observe in human patients who lack TNIK is consistent with the previously published Tnik−/− phenotype in the murine model. Our data strongly implicate TNIK deficiency in the causation of ID in humans.

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.

The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach.

Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases.

Assessment of knowledge, attitude and practice towards consanguineous marriages among a cohort of multiethnic health care providers in saudi arabia

This study aimed to assess knowledge, attitude and practice related to consanguinity among multiethnic health care providers in the Kingdom of Saudi Arabia. Using a cross-sectional study design, a validated, self-administered close-ended questionnaire was randomly distributed to health care providers in different health institutions in the country between 1st August 2012 and 31st July 2013. A total of 1235 health care providers completed the study questionnaire. Of the 892 married participants (72.23% of total), 11.43% were married to a first cousin, and were predominantly Arabs, younger than 40 years and male. Only 17.80% of the patients seen by the health care providers requested consanguinity related counselling. A knowledge barrier was expressed by 27.49% of the participants, and 85.67% indicated their willingness to have more training in basic genetic counselling. A language barrier was expressed as a limiting factor to counselling for consanguinity among non-Arabs. The health care providers had a major dearth of knowledge that was reflected in their attitude and practice towards consanguinity counselling. This finding indicates the need for more undergraduate and postgraduate medical and nursing education and training in the counselling of consanguineous couples. It is recommended that consanguinity counselling is included in the current premarital screening and counselling programmes in the Kingdom.