Systematic Review on Homocysteine as an Early Indicator of Macrovascular Complications in Type 1 Diabetes Mellitus
Nada Mohammed Abu Seada;
Abstract
L
ong-standing type 1 diabetes mellitus (T1DM) patients are susceptible to microvascular complications, including nephropathy, retinopathy and neuropathy and to macrovascular complications (CAD and PVD). Mortality in T1DM has increased four- to seven fold over the matched non-diabetic population, and nephropathy and CAD are the main causes of death. Therefore, successful management of CVD associated with diabetes represents a major challenge to the clinicians. An effective way of tackling this problem is to detect the associated risk factors and to target treatment toward their improvement.
Hyperhomocysteinemia has been shown to be a strong risk factor for CVD and for mortality in diabetic patients than in subjects without diabetes.
Determination of the role of hyperhomocysteinemia in macrovascular and microvascular diabetes complications could be of importance in their prevention through dietary and pharmacological modifications of homocysteine levels.
In view of these data, we conducted this systematic review for assessment of Hcy as an indicator for MVC in T1DM, by searching Pubmed and Cochrane library databases.
Methododolgy in this systematic review was done according to the guidelines of the QUORUM statement previously mentioned in Table (22).
First we defined the components (PICOS) of the question required to be answered by the review: patients with T1DM having HHcy compared with others with T1DM also but without HHcy, and measuring the number of cases in both groups developing MVC.
Searching both databases and handsearching of reference lists of relevant studies revealed 703 potentially relevant papers. Only human studies were included, there was no language limitation and any type of observational studies was included.
The included studies should have data that allow the cross tabulation of the number of T1DM patients with HHcy with and without MVC, and T1DM patients without HHcy with and without MVC (ABCD), in order to calculate standard deviation, mean, OR and C.I.
The search was done by one reviewer twice and any confusion was solved by taking the supervisors’ opinion.
639 papers were excluded by reviewing the title and/or the abstract, while the full text of 64 papers was retrieved. Of the latter: 29 studies did not meet the inclusion criteria, 26 studies had non-extractable data, 2 papers could not retrieve their full text, 3 papers were duplicated and only 4 studies were included in the review (Munshi et al., 1996, Hofmann et al., 1997, Chico et al., 1998, Agullo´-Ortun˜o et al., 2002). Search strategy resulte were displayed in a trial flow diagram.
Manual searching of the reference lists of all relevant studies did not reveal any new studies that could be included.
We also contacted the authors of those papers with non-extractable data asking for the missing data by sending mails to the corresponding author twice, but unfortunately we got no response.
The characteristics of the 4 included studies were listed and data were extracted, tabulated and the O.R, effect size, 95% C.I and weight of each study were calculated.
After conducting the meta-analysis, the IV pooled ES was 1.219 which means that MVC was found to increase in T1DM patients with HHcy by about 22% than those with normal tHcy levels.
All results were displayed in forest plot diagram.
Tests for evaluating heterogeneity (Cochrane's Q test and I-squared statistic) were done and showed no heterogeneity between the included studies.
We checked for publication bias by drawing a funnel plot which showed asymmetry indicating publication bias which was ensured by the results of the contour enhanced funnel plot
The included studies also showed that the relation between HHcy and MVC might be to a great extent independent of the renal condition and other MVC risk factors.
The total number of patients included in the four studies collectively was 217 patients, which is very small to make a true judge or decision that could be generalized. Also authors focus more on studying the relationship between HHcy and MVC in T2DM, and between HHcy and microvascular complications in T1DM, showing the true need for more studies on this topic with larger number of patients and sufficient extractable data.
Finally, hyperhomocysteinemia appears to be a risk factor for cardiovascular events in patients with diabetes. Specific treatment of hyperhomocysteinemia appears attractive and may be an inexpensive therapy for reducing risk and improving prognosis of patients with established MVC, although further clinical trials in patients with diabetes are waranted.
ong-standing type 1 diabetes mellitus (T1DM) patients are susceptible to microvascular complications, including nephropathy, retinopathy and neuropathy and to macrovascular complications (CAD and PVD). Mortality in T1DM has increased four- to seven fold over the matched non-diabetic population, and nephropathy and CAD are the main causes of death. Therefore, successful management of CVD associated with diabetes represents a major challenge to the clinicians. An effective way of tackling this problem is to detect the associated risk factors and to target treatment toward their improvement.
Hyperhomocysteinemia has been shown to be a strong risk factor for CVD and for mortality in diabetic patients than in subjects without diabetes.
Determination of the role of hyperhomocysteinemia in macrovascular and microvascular diabetes complications could be of importance in their prevention through dietary and pharmacological modifications of homocysteine levels.
In view of these data, we conducted this systematic review for assessment of Hcy as an indicator for MVC in T1DM, by searching Pubmed and Cochrane library databases.
Methododolgy in this systematic review was done according to the guidelines of the QUORUM statement previously mentioned in Table (22).
First we defined the components (PICOS) of the question required to be answered by the review: patients with T1DM having HHcy compared with others with T1DM also but without HHcy, and measuring the number of cases in both groups developing MVC.
Searching both databases and handsearching of reference lists of relevant studies revealed 703 potentially relevant papers. Only human studies were included, there was no language limitation and any type of observational studies was included.
The included studies should have data that allow the cross tabulation of the number of T1DM patients with HHcy with and without MVC, and T1DM patients without HHcy with and without MVC (ABCD), in order to calculate standard deviation, mean, OR and C.I.
The search was done by one reviewer twice and any confusion was solved by taking the supervisors’ opinion.
639 papers were excluded by reviewing the title and/or the abstract, while the full text of 64 papers was retrieved. Of the latter: 29 studies did not meet the inclusion criteria, 26 studies had non-extractable data, 2 papers could not retrieve their full text, 3 papers were duplicated and only 4 studies were included in the review (Munshi et al., 1996, Hofmann et al., 1997, Chico et al., 1998, Agullo´-Ortun˜o et al., 2002). Search strategy resulte were displayed in a trial flow diagram.
Manual searching of the reference lists of all relevant studies did not reveal any new studies that could be included.
We also contacted the authors of those papers with non-extractable data asking for the missing data by sending mails to the corresponding author twice, but unfortunately we got no response.
The characteristics of the 4 included studies were listed and data were extracted, tabulated and the O.R, effect size, 95% C.I and weight of each study were calculated.
After conducting the meta-analysis, the IV pooled ES was 1.219 which means that MVC was found to increase in T1DM patients with HHcy by about 22% than those with normal tHcy levels.
All results were displayed in forest plot diagram.
Tests for evaluating heterogeneity (Cochrane's Q test and I-squared statistic) were done and showed no heterogeneity between the included studies.
We checked for publication bias by drawing a funnel plot which showed asymmetry indicating publication bias which was ensured by the results of the contour enhanced funnel plot
The included studies also showed that the relation between HHcy and MVC might be to a great extent independent of the renal condition and other MVC risk factors.
The total number of patients included in the four studies collectively was 217 patients, which is very small to make a true judge or decision that could be generalized. Also authors focus more on studying the relationship between HHcy and MVC in T2DM, and between HHcy and microvascular complications in T1DM, showing the true need for more studies on this topic with larger number of patients and sufficient extractable data.
Finally, hyperhomocysteinemia appears to be a risk factor for cardiovascular events in patients with diabetes. Specific treatment of hyperhomocysteinemia appears attractive and may be an inexpensive therapy for reducing risk and improving prognosis of patients with established MVC, although further clinical trials in patients with diabetes are waranted.
Other data
| Title | Systematic Review on Homocysteine as an Early Indicator of Macrovascular Complications in Type 1 Diabetes Mellitus | Other Titles | استعراض منهجي على مادة الهوموسيستايين كمؤشر مبكر لمضاعفات الأوعية الدموية الكبرى في مرضى السكر من النوع الاول | Authors | Nada Mohammed Abu Seada | Issue Date | 2014 |
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