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==Preamble==
==Preamble==
Diabetes (diabetes mellitus) is one of the metabolic diseases with higher blood sugar level, either due to the pancreatic beta cells do not produce enough insulin, or the cells do not respond to the insulin that is produced.<cite>1</cite> Its clinical symptoms include three polies: polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). Diabetes is categorized as three types in the clinic: Type 1 diabetes (T1D, diabetes mellitus 1, DM1) results from pancreatic beta cell destruction and thus fails to produce insulin, and is insulin dependent which relies on insulin injection, it is also named insulin-dependent diabetes mellitus (''IDDM''). Since T1D happens mostly in juveniles it is also called juvenile-onset diabetes. Type 2 diabetes (T2D, diabetes mellitus 2, DM2) results from the reason that the beta cells do not respond to insulin (insulin resistance), and it may co-exist with the situation of partially or fully insulin-dependent, which is also named non-insulin-dependent diabetes mellitus (''NIDDM'') or adult-onset diabetes. In some type 2 diabetes, concomitant insulin therapy may be necessary (''IDDM2''). The third type is gestational diabetes occurs while pregnancy.  
Diabetes (diabetes mellitus) is one of the metabolic diseases with higher blood sugar level, either due to the pancreatic beta cells do not produce enough insulin, or the cells do not respond to the insulin that is produced.<cite>1</cite> Its clinical symptoms include three polies: polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger).  
 
Diabetes is categorized as three types in the clinic: Type 1 diabetes (T1D, diabetes mellitus 1, DM1) results from pancreatic beta cell destruction and thus fails to produce insulin, and is insulin dependent which relies on insulin injection, it is also named insulin-dependent diabetes mellitus (''IDDM''). Since T1D happens mostly in juveniles it is also called juvenile-onset diabetes. Type 2 diabetes (T2D, diabetes mellitus 2, DM2) results from the reason that the beta cells do not respond to insulin (insulin resistance), and it may co-exist with the situation of partially or fully insulin-dependent, which is also named non-insulin-dependent diabetes mellitus (''NIDDM'') or adult-onset diabetes. In some type 2 diabetes, concomitant insulin therapy may be necessary (''IDDM2''). The third type is gestational diabetes occurs while pregnancy.  
 
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
! colspan="3"|Comparison of type 1 and 2 diabetes<cite>4</cite>
|-
!Feature
!Type 1 diabetes
!Type 2 diabetes
|-
|'''Onset'''
|Sudden
|Gradual
|-
|'''Age at onset'''
|Mostly in children
|Mostly in adults
|-
|'''Body habitus'''
|Thin or normal<cite>5</cite>
|Often obese
|-
|'''Ketoacidosis'''
|Common
|Rare
|-
|'''Autoantibodies'''
|Usually present
|Absent
|-
|'''Endogenous insulin'''
|Low or absent
|Normal, decreased or increased
|-
|'''Concordance in identical twins'''
|50%
|90%
|-
|'''Prevalence'''
|~10%
|~90%
|}


There is no cure for diabetes currently except that most of the gestational diabetes disappears when the pregnancy is ended, but it is treatable. The current therapies are insulin, other non-curing medications, and pancreatic replacement therapies like pancreatic islet transplantations which have been applied to severe T1D cases successfully since 1980s’.<cite>2</cite>Since both T1D and T2D are chronic diseases and the progresses of modern medicine, acute complications like hypoglycemia and ketoacidosis are under well controlled, and thus chronic and long-term complications like chronic renal failure, and diabetic retinopathy, especially cardiovascular diseases (''CVD''), are drawing attentions.  
There is no cure for diabetes currently except that most of the gestational diabetes disappears when the pregnancy is ended, but it is treatable. The current therapies are insulin, other non-curing medications, and pancreatic replacement therapies like pancreatic islet transplantations which have been applied to severe T1D cases successfully since 1980s’.<cite>2</cite>Since both T1D and T2D are chronic diseases and the progresses of modern medicine, acute complications like hypoglycemia and ketoacidosis are under well controlled, and thus chronic and long-term complications like chronic renal failure, and diabetic retinopathy, especially cardiovascular diseases (''CVD''), are drawing attentions.  
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===Introduction===  
===Introduction===  
As per the World Health Organization (''WHO''), an estimated 347 million people world-wide have  diabetes in 2012.<cite>77</cite> The number of deaths attributed to diabetes was previously estimated at just over 800,000. However, it has long been known that the number of deaths related to diabetes is considerably underestimated. With regarding the causes of death of diabetes, one important factor contributing the increased morbidity and mortality in diabetic individuals is the development of cardiovascular disease, one of the chronic complications of diabetes. Several studies have demonstrated that diabetic patients have a risk of death that is two to three times higher than that among people without diabetes.<cite>4</cite>   
As per the World Health Organization (''WHO''), an estimated 347 million people world-wide have  diabetes in 2012.<cite>77</cite> The number of deaths attributed to diabetes was previously estimated at just over 800,000. However, it has long been known that the number of deaths related to diabetes is considerably underestimated. With regarding the causes of death of diabetes, one important factor contributing the increased morbidity and mortality in diabetic individuals is the development of cardiovascular disease, one of the chronic complications of diabetes. Several studies have demonstrated that diabetic patients have a risk of death that is two to three times higher than that among people without diabetes.<cite>4</cite>   
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" width="600px"
|-
! colspan="2"|The following is a comprehensive list of other causes of diabetes:<cite>16</cite>
|-
|
*'''Genetic defects of ß-cell function'''
**Maturity onset diabetes of the young
**Mitochondrial DNA mutations
*'''Genetic defects in insulin processing or insulin action'''
**Defects in proinsulin conversion
**Insulin gene mutations
**Insulin receptor mutations
*'''Exocrine pancreatic defects'''
**Chronic pancreatitis
**Pancreatectomy
**Pancreatic neoplasia
**Cystic fibrosis
**Hemochromatosis
**Fibrocalculous pancreatopathy
|
*'''Endocrinopathies'''
**Growth hormone excess (acromegaly)
**Cushing syndrome
**Hyperthyroidism
**Pheochromocytoma
**Glucagonoma
*'''Infections'''
**Cytomegalovirus infection
**Coxsackie B4 virus
*'''Drugs'''
**Glucocorticoids
**Thyroid hormone
**ß-adrenergic agonists
**Statins<cite>17</cite>
|}


Multiple epidemiologic studies have established diabetes as a major risk factor for the development of all manifestations of cardiovascular disease, including myocardial infarction, stroke, peripheral vascular disease, and heart failure,<cite>5</cite><cite>6</cite><cite>7</cite><cite>8</cite> and recent data suggest that the proportion of cardiovascular disease attributable to diabetes is increasing.<cite>6</cite> It is estimated that cardiovascular disease accounts for 65% of all deaths in persons with diabetes.<cite>9</cite> In a recent meta-analysis of nearly 700,000 people from 102 prospective studies, diabetes conferred an approximate two fold risk for coronary heart disease and stroke, independently from other conventional risk factors.<cite>8</cite> Thus, in order to reduce the health burden of diabetes, it is considered necessary to aggressively prevent and treat cardiovascular disease in these patients.  
Multiple epidemiologic studies have established diabetes as a major risk factor for the development of all manifestations of cardiovascular disease, including myocardial infarction, stroke, peripheral vascular disease, and heart failure,<cite>5</cite><cite>6</cite><cite>7</cite><cite>8</cite> and recent data suggest that the proportion of cardiovascular disease attributable to diabetes is increasing.<cite>6</cite> It is estimated that cardiovascular disease accounts for 65% of all deaths in persons with diabetes.<cite>9</cite> In a recent meta-analysis of nearly 700,000 people from 102 prospective studies, diabetes conferred an approximate two fold risk for coronary heart disease and stroke, independently from other conventional risk factors.<cite>8</cite> Thus, in order to reduce the health burden of diabetes, it is considered necessary to aggressively prevent and treat cardiovascular disease in these patients.  
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The most common cause of death in European diabetic adults is coronary artery disease (''CAD''). Studies have demonstrated that the risk is two to three times higher than that among people without diabetes.<cite>30</cite> The prevalence of coronary artery disease in patients with type 1 or 2 diabetes are widely different.<cite>31</cite><cite>32</cite> In the ''EURODIAB IDDM'' Complication Study which involved 3250 type 1 diabetic patients from 16 countries, the prevalence of cardiovascular disease was 9% in men and 10% in women; and it is increasing with age that it is 6% in the age group of 15–29 years and 25% in the age group of 45–59 years.  In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with cardiovascular disease, while in women, a greater body mass index was associated with increased prevalence of cardiovascular disease. The risk of coronary artery disease in type 1 diabetic patients increases dramatically when they have the onset of diabetic nephropathy.  
The most common cause of death in European diabetic adults is coronary artery disease (''CAD''). Studies have demonstrated that the risk is two to three times higher than that among people without diabetes.<cite>30</cite> The prevalence of coronary artery disease in patients with type 1 or 2 diabetes are widely different.<cite>31</cite><cite>32</cite> In the ''EURODIAB IDDM'' Complication Study which involved 3250 type 1 diabetic patients from 16 countries, the prevalence of cardiovascular disease was 9% in men and 10% in women; and it is increasing with age that it is 6% in the age group of 15–29 years and 25% in the age group of 45–59 years.  In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with cardiovascular disease, while in women, a greater body mass index was associated with increased prevalence of cardiovascular disease. The risk of coronary artery disease in type 1 diabetic patients increases dramatically when they have the onset of diabetic nephropathy.  


[[Image:RCA atherosclerosis.jpg|thumb|right|300px|Coronary Artery Diseases<cite>78</cite>]]
[[Image:RCA atherosclerosis.jpg|thumb|right|300px|Coronary Artery Diseases<cite>78</cite> ]]


Diabetic men and women had comparable mortality rates, whereas coronary mortality among men was significantly higher.<cite>33</cite> Further evidences of the important relations between diabetes and myocardial infarction were obtained from the INTERHEART study in Canada. Diabetes increased the risk of myocardial infarction by more than two times in men and women, and independent of ethnicity. And thus a history of diabetes and myocardial infarction increased cardiovascular disease and mortality markedly. Diabetes or hyperglycemia itself and its complications are very important for the increased risk for coronary artery disease and related mortality.  
Diabetic men and women had comparable mortality rates, whereas coronary mortality among men was significantly higher.<cite>33</cite> Further evidences of the important relations between diabetes and myocardial infarction were obtained from the INTERHEART study in Canada. Diabetes increased the risk of myocardial infarction by more than two times in men and women, and independent of ethnicity. And thus a history of diabetes and myocardial infarction increased cardiovascular disease and mortality markedly. Diabetes or hyperglycemia itself and its complications are very important for the increased risk for coronary artery disease and related mortality.  
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