Glycosylated Hemoglobin in Relationship to Cardiovascular Outcomes and Death in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

<div><h3>Background</h3><p>Chronic hyperglycemia in type 2 diabetes increases the risk of microvascular events. However, there is continuing uncertainty about its effect on macrovascular outcomes and death. We conducted a meta-analysis of prospective studies to estimate the association of glycosylated hemoglobin level with the risk of all-cause mortality and cardiovascular outcomes among patients with type 2 diabetes.</p> <h3>Methodology/Principal Findings</h3><p>We systematically searched the MEDLINE database through April 2011 by using Medical Subject Heading search terms and a standardized protocol. We included prospective cohort studies that reported data of glycosylated hemoglobin level on the risk of incident cardiovascular events and all-cause mortality. Relative risk estimates (continuous and categorical variables) were derived or abstracted from each cohort study. Twenty six studies were included in this analysis with a mean follow-up rang of 2.2–16 years. The pooled relative risk associated with a 1% increase in glycosylated hemoglobin level among patients with type 2 diabetes was 1.15 (95% CI, 1.11 to 1.20) for all-cause mortality, 1.17 (95% CI, 1.12 to 1.23) for cardiovascular disease, 1.15 (95% CI, 1.10 to 1.20) for coronary heart disease, 1.11 (95% CI, 1.05 to 1.18) for heart failure, 1.11 (95% CI, 1.06 to 1.17) for stroke, and 1.29 (95% CI, 1.18 to 1.40) for peripheral arterial disease, respectively. In addition, a positive dose-response trend existed between glycosylated hemoglobin level and cardiovascular outcomes.</p> <h3>Conclusions/Significance</h3><p>Chronic hyperglycemia is associated with an increased risk for cardiovascular outcomes and all-cause mortality among patients with type 2 diabetes, likely independently from other conventional risk factors.</p> </div

Design Characteristics of Prospective cohort Studies of Glycosylated Hemoglobin and Cardiovascular Outcomes and All-cause Mortality, 1974–2011<b>.</b>^*

*<p>CHD, coronary heart disease; CVD, cardiovascular disease; HF, heart failure; PAD, peripheral arterial disease; DM, diabetes mellitus; BMI, body mass index; BP, blood pressure.</p

Hazard ratios for cardiovascular outcomes risks according to glycosylated hemoglobin by different categories (shown by the first author and year of publication).^*

*<p>CHD, coronary heart disease; CVD, cardiovascular disease; DM, diabetes mellitus; BMI, body mass index; BP, blood pressure; OR, hazard ratio; CI, confidence interval.</p

Forest plot of relative risks (RRs) and 95% confidence intervals (CIs) for the association between glycosylated hemoglobin and the main study outcomes risks in type 2 diabetes.

<p>CVD: cadiovascular diseases; CHD: conoary heart disease; PAD: peripheral arterial disease.</p

Flow diagram of studies assessed and included.

<p>Flow diagram of studies assessed and included.</p

The Contribution of Genetic Diversity to Subdivide Populations Living in the Silk Road of China

<div><p>There are several indigenous ethnic populations along the silk road in the Northwest of China that display clear differences in culture and social customs, perhaps as a result of geographic isolation and different linguistic traditions. However, extensive trade and other interactions probably facilitated the admixture of different gene pools between these populations over the last two millennia. To further explore the evolutionary relationships of the 13 ethnic populations residing in Northwest China and to reveal the features of population admixture, the 9 most-commonly employed CODIS loci (D3S1358, TH01, D5S818, D13S317, D7S820, CSF1PO, vWA, TPOX, FGA) were selected for genotyping and further analysis. Phylogenetic tree and principal component analysis revealed clear pattern of population differentiation between 4 populations living in Sinkiang Uighur Autonomous Region and other 9 populations dwelled in the upper regions of Silk Road. R matrix regression showed high-level gene flow and population admixture dose exist among these ethic populations in the Northwest region of China. Furthermore, the Mantel test suggests that larger percent of genetic variance (21.58% versus 2.3%) can be explained by geographic isolation than linguistic barriers, which matched with the contribution of geographic factors to other world populations.</p></div

Name of the studied populations, number of chromosomes, geographic coordinates, linguistic background, religion and reference.

a<p>: Han_XA represents the Han population living in Xi'an, while Han_XJ represents the Han population in Sinkiang Uighur Autonomous Region.</p>b<p>: “Lamaism” is a branch of Buddhism that is popular in some regions of China, especially in West China.</p

Mantel tests of three different types of distances.

<p>Note: Dgen stands for genetic distance, Dgeo as geographic distance, and Dlan language distance.</p

Neighbor-joining phylogenetic tree based on D_A distance.

<p>Neighbor-joining phylogenetic tree based on D_A distance.</p

Regression plots of 13 populations.

<p>Regression plots of 13 populations.</p