Charbel Abi Khalil

Dairy Consumption and the Incidence of Hyperglycemia and the Metabolic Syndrome Results from a French prospective study, Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR)

OBJECTIVE In the French Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, cross-sectional analyses have shown that a higher consumption of dairy products and calcium are associated with a lower prevalence of the metabolic syndrome (MetS). We assess the influence of dairy products on 9-year incident MetS and on impaired fasting glycemia and/or type 2 diabetes (IFG/T2D). RESEARCH DESIGN AND METHODS Men and women who completed a food frequency questionnaire at baseline and after 3 years were studied (n = 3,435). Logistic regression models were used to study associations between the average year 0 and year 3 consumption of milk and dairy products, cheese, dietary calcium density, and incident MetS and IFG/T2D after adjusting for 1) sex, age, alcohol, smoking, physical activity, fat intake and 2) additionally for BMI. Associations between dairy products and continuous variables were studied by repeated-measures ANCOVA, using the same covariates. RESULTS Dairy products other than cheese, and dietary calcium density, were inversely associated with incident MetS and IFG/T2D; cheese was negatively associated with incident MetS. All three parameters were associated with lower diastolic blood pressure, and with a lower BMI gain. Higher cheese intake and calcium density were associated with a lower increase in waist circumference and lower triglyceride levels. Calcium density was also associated with a lower systolic blood pressure and a lower 9-year increase in plasma triglyceride levels. CONCLUSIONS A higher consumption of dairy products and calcium was associated with a lower 9-year incidence of MetS and IFG/T2D in a large cohort drawn from the general population.

Prognostic Value of the Insertion/Deletion polymorphism of Angiotensin I Converting Enzyme gene in type 2 diabetic subjects: results from the DIABHYCAR, DIAB2NEPHROGENE & SURDIAGENE studies

OBJECTIVE—We tested whether determination of the ACE insertion/deletion polymorphism is useful for renal and cardiovascular prognoses of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS—The French participants (3,126 of 4,912) in the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial were studied for their prognosis over 4 years according to their ACE insertion/deletion polymorphism. We used two cohorts of French type 2 diabetic patients for replication: a 3-year follow-up study (n = 917; Survie, Diabete de type 2 et Genetique [SURDIAGENE] study) and a case-control study on diabetic nephropathy (n = 1,277; Diabete de type 2, Nephropathie et Genetique [DIAB2NEPHROGENE] study). We investigated the effect of the insertion/deletion polymorphism on the primary outcome in the DIABHYCAR trial (defined as the first of the following events to occur: cardiovascular death, nonfatal myocardial infarction, stroke, heart failure leading to hospital admission, or end-stage renal failure) and its components. RESULTS—In DIABHYCAR, the primary outcome and most of its components were not affected by the ACE insertion/deletion genotype. Only renal outcome was favored by the I allele (P = 0.03). The risk of myocardial infarction was not affected by ACE genotype, but the probability of fatal outcome increased with the number of D alleles (P < 0.03). In SURDIAGENE, the association between the ACE I allele and renal outcome was not replicated. In DIAB2NEPHROGENE, no association was found with nephropathy. CONCLUSIONS—We were not able to demonstrate the manifest usefulness of the ACE insertion/deletion polymorphism for the prognosis of type 2 diabetic subjects.

The emerging role of epigenetics in cardiovascular disease.

There is a worldwide epidemic of cardiovascular diseases causing not only a public health issue but also accounting for trillions of dollars of healthcare expenditure. Studies pertaining to epidemiology, pathophysiology, molecular biology, gene identification and genetic linkage maps have been able to lay a strong foundation for both the diagnosis and treatment of cardiovascular medicine. Although the concept of ‘epigenetics’ is not recent, the term in current usage is extended from the initial concept of ‘controlling developmental gene expression and signaling pathways in undifferentiated zygotes’ to include heritable changes to gene expression that are not from differences in the genetic code. The impact of epigenetics in cardiovascular disease is now emerging as an important regulatory key player at different levels from pathophysiology to therapeutics. This review focuses on the emerging role of epigenetics in major cardiovascular medicine specialties such as coronary artery disease, heart failure, cardiac hypertrophy and diabetes.There is a worldwide epidemic of cardiovascular diseases causing not only a public health issue but also accounting for trillions of dollars of healthcare expenditure. Studies pertaining to epidemiology, pathophysiology, molecular biology, gene identification and genetic linkage maps have been able to lay a strong foundation for both the diagnosis and treatment of cardiovascular medicine. Although the concept of ‘epigenetics’ is not recent, the term in current usage is extended from the initial concept of ‘controlling developmental gene expression and signaling pathways in undifferentiated zygotes’ to include heritable changes to gene expression that are not from differences in the genetic code. The impact of epigenetics in cardiovascular disease is now emerging as an important regulatory key player at different levels from pathophysiology to therapeutics. This review focuses on the emerging role of epigenetics in major cardiovascular medicine specialties such as coronary artery disease, heart failure, cardiac hypertrophy and diabetes.

Fetal Exposure to Maternal Type 1 Diabetes Is Associated With Renal Dysfunction at Adult Age

OBJECTIVE In animal studies, hyperglycemia during fetal development reduces nephron numbers. We tested whether this observation translates into renal dysfunction in humans by studying renal functional reserve in adult offspring exposed in utero to maternal type 1 diabetes. RESEARCH DESIGN AND METHODS We compared 19 nondiabetic offspring of type 1 diabetic mothers with 18 offspring of type 1 diabetic fathers (control subjects). Glomerular filtration rate (51Cr-EDTA clearance), effective renal plasma flow (123I-hippurate clearance), mean arterial pressure, and renal vascular resistances were measured at baseline and during amino acid infusion, which mobilizes renal functional reserve. RESULTS Offspring of type 1 diabetic mothers were similar to control subjects for age (median 27, range 18–41, years), sex, BMI (23.1 ± 3.7 kg/m2), and birth weight (3,288 ± 550 vs. 3,440 ± 489 g). During amino acid infusion, glomerular filtration rate and effective renal plasma flow increased less in offspring of type 1 diabetic mothers than in control subjects: from 103 ± 14 to 111 ± 17 ml/min (8 ± 13%) vs. from 108 ± 17 to 128 ± 23 ml/min (19 ± 7%, P = 0.009) and from 509 ± 58 to 536 ± 80 ml/min (5 ± 9%) vs. from 536 ± 114 to 620 ± 140 ml/min (16 ± 11%, P = 0.0035). Mean arterial pressure and renal vascular resistances declined less than in control subjects: 2 ± 5 vs. −2 ± 3% (P = 0.019) and 3 ± 9 vs. −14 ± 8% (P = 0.001). CONCLUSIONS Reduced functional reserve may reflect a reduced number of nephrons undergoing individual hyperfiltration. If so, offspring of type 1 diabetic mothers may be predisposed to glomerular and vascular diseases.

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

An open question in the history of human migration is the identity of the earliest Eurasian populations that have left contemporary descendants. The Arabian Peninsula was the initial site of the out-of-Africa migrations that occurred between 125,000 and 60,000 yr ago, leading to the hypothesis that the first Eurasian populations were established on the Peninsula and that contemporary indigenous Arabs are direct descendants of these ancient peoples. To assess this hypothesis, we sequenced the entire genomes of 104 unrelated natives of the Arabian Peninsula at high coverage, including 56 of indigenous Arab ancestry. The indigenous Arab genomes defined a cluster distinct from other ancestral groups, and these genomes showed clear hallmarks of an ancient out-of-Africa bottleneck. Similar to other Middle Eastern populations, the indigenous Arabs had higher levels of Neanderthal admixture compared to Africans but had lower levels than Europeans and Asians. These levels of Neanderthal admixture are consistent with an early divergence of Arab ancestors after the out-of-Africa bottleneck but before the major Neanderthal admixture events in Europe and other regions of Eurasia. When compared to worldwide populations sampled in the 1000 Genomes Project, although the indigenous Arabs had a signal of admixture with Europeans, they clustered in a basal, outgroup position to all 1000 Genomes non-Africans when considering pairwise similarity across the entire genome. These results place indigenous Arabs as the most distant relatives of all other contemporary non-Africans and identify these people as direct descendants of the first Eurasian populations established by the out-of-Africa migrations.

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

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 genome for the indigenous Arab population 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 single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual genome. 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 QTRG. The benefit for using QTRG varies across ancestries, a factor that should be taken into consideration when selecting an appropriate reference for analysis.

Epigenetics and Cardiovascular Disease in Diabetes

Type 2 diabetes has become a major health issue worldwide. Chronic hyperglycemia induces a low-grade inflammation that, on top of other mechanisms, leads to endothelial dysfunction. Mounting evidence suggests that DNA methylation, post-translational modifications of histones, and long non-coding RNAs play an important role in the initiation, maintenance, and progression of both macro- and micro-vascular complications of diabetes. Long-term exposure to hyperglycemia induces epigenetic changes that could become irreversible, a phenomenon known as the ‘metabolic memory.’ Whether epigenetic-based therapies could be used to slow or limit the progression of cardiovascular disease remains unclear. While non-coding RNAs are currently investigated as potential biomarkers that predict diabetic cardiovascular disease incidence and progression, their therapeutic role is only hypothetical. In this review, we highlight the latest findings in experimental and clinical studies relevant to epigenetics and cardiovascular disease in diabetes.

Cardiovascular disease research activity in the Middle East: a bibliometric analysis

Objectives: The Middle East has a high prevalence of noncommunicable chronic diseases. The objective of this article was to quantify the research activity in cardiovascular disease (CVD) in the Middle East over the last 10 years. Methods: A Medline search was conducted using medical subject headings and author affiliation to retrieve research articles published from the Middle East between 2003 and 2012 (inclusive). Results: Middle Eastern countries produced only 3% of the total number of CVD research articles in the world. However, the overall trend showed an increase in the number of articles over the years, mainly from Turkey and Iran. Within this region, the ratio of CVD to non-CVD publications was highest in Qatar (0.23). Lebanon ranked first in the number of CVD publications per million persons (PMP) averaging 194.2 publications PMP and Turkey ranked highest in the number of CVD publications per US

Kidney Dysfunction in Adult Offspring Exposed In Utero to Type 1 Diabetes Is Associated with Alterations in Genome-Wide DNA Methylation

1000 gross domestic product (GDP) per capita averaging 954 CVD publications per US

BMI is inversely correlated to the risk of mortality in patients with type 2 diabetes hospitalized for acute heart failure: Findings from the Gulf aCute heArt failuRE (Gulf-CARE) registry

1000 GDP per capita. Conclusions: Although there has been a drive towards greater publication of CVD papers in the last decade, research activity in the Middle East still lags behinds developed countries. Greater productivity is anticipated to emerge to accompany the recent significant investment in research in Gulf countries.