International Journal of Science and Research (IJSR)

ISSN: 2319-7064
ResearchGate Impact Factor (2018): 0.28 | SJIF (2018): 7.426

Effects of Type 2 Diabetes upon Cardiovascular

Diseases
Nimesha Gunathilaka¹, Bhagya Manjaree¹*

Department of Biomedical Science, International college of Business and Technology, Sri Lanka
nimzd97[at]gmail.com, bhagya[at]icbtcampus.edu.lk

Abstract: Nowadays Type 2 diabetes is becoming a major health problem in the world. It has identified that Type 2Diabetes Mellitus
will lead to serious cardiovascular outcomes, which can cause several damages to the organs of the body and even death. This paper will
emphasize the risk factors, which cause both Type 2 Diabetes Mellitus and Cardiovascular diseases and main microvascular and
Macrovascular outcomes, which can conceivable in type 2 diabetic patients. A research has done in England with the information of
CALIBER program, to investigate the association between T2DM and initial manifestations of CVD. [17] University of occupational and
environmental health in japan has done a cross sectional study about, how does fluctuating of glucose level affect to vascular
endothelial function.[8] Study design and participant ADVANCE was a factorial randomized controlled trial evaluates the effects of
blood pressure-lowering and intensive blood glucose on vascular outcome, which was done by ADVANCE collaborative group. They
have consisted 11149 participants from 215 centers in 20 countries. Swedish national diabetes register has done a research about
additive effects of glycaemia and dyslipidemia on risk of cardiovascular diseases in type 2 diabetes mellitus. This study is consisted 22135
participants according to age (30–75 years), HbA1c ≥5% (≥31 mmol/mol), BMI ≥18 kg/m2 and plasma creatinine <150 μmol/l. A history
of CVD was present in 15%, a history of heart failure in 4% and atrial fibrillation in 3% of participants.[13]. People with type 2 diabetes
have higher risk of cardiovascular morbidity. [19] Risk of myocardial infarction, stroke and even death is strongly associated with type 2
diabetes [3]. Diabetes and ischemic stroke are common that frequently occurring together [9]. Coronary heart disease is one of long-
term complication in people with diabetes. [26] Diabetic retinopathy, diabetic neuropathy and diabetic nephropathy are microvascular
complications that occurred due to diabetes. The risks of these microvascular complications are proportional to duration and magnitude
of hyperglycemia. [18]There are common risk factors for both DM and CVD. High blood pressure, glycated HbA1c, total cholesterol are
described in this article. Ultimately, it can be concluded as, there is a considerable relation between type 2 diabetes and cardiovascular
diseases. However managing the appropriate threshold levels can reduce the risk of any kind of cardiovascular diseases.

Keywords: DM-diabetes mellitus, CVD-cardiovascular disease, UKPDS-United Kingdom prospective diabetes study

1. Introduction Type 2 Diabetes is a bulk of chronic diseases. One of the

main complication arising from hyperglycemia is either
Diabetes mellitus is defined as a heterogeneous metabolic injury to vasculature classify as microvascular or injury to
disorder characterized by common feature of chronic the large body vessels also known as macro vascular.[18]
hyperglycemia and glycosuria (presence of glucose in
urine), with disturbance of carbohydrate, fat, and protein Neuropathy is microvascular which, developing in
metabolism. Type 2 diabetes is known as maturity onset patients with diabetes. Neuropathy is known to be
diabetes or non-insulin dependent diabetes mellitus. heterogeneous by their symptoms, patterns of neurologic
Mainly it affects older individuals and obese adolescent involvement, course, risk covariates and pathologic
children. Type 2 diabetes can be occurred due to genetic alterations.[7]. Peripheral neuropathy is one of the most
predisposition and environmental and behavioral risk common microvascular complications in type 2 diabetes.
factors.[10]
Neuropathic ulcer is the most common type of
Type 2 diabetes is the most prevalent form of diabetes. It neuropathy. Neuropathy may be asymptomatic or
is appeared later in life. It is a combination of insulin symptomatic; when symptoms are present, it might be
resistance (impairment in insulin-mediated glucose negative or positive. Negative symptoms are loss of
disposal) and defective secretion of insulin by beta cells. sensation, loss of strength. Positive symptoms include
Moreover, all the cells will undergo atrophy gradually pricking or pain.[4]
when we are aging, therefore, production and secretion of
insulin decline in advancing age.[5] Diabetic nephropathy develops in approximately 40% of
all patients with type 2 DM. hypertension, which cause
About 60% of patients are affected with both CVD and CVD and main risk factor for diabetes, is a risk factor for
DM. There is the risk of development of acute myocardial diabetic nephropathy as well. Microalbuminuria is also a
infarction in patients with type 2 DM is 6–10 times higher risk factor.[6]
than in a general population. Combination of CVD and Diabetic retinopathy is the most common microvascular
DM increase significant rate of mortality. Usually 50% of complication. It depends on the severity, duration of
people in the world who are at age 40-59 have type 2 diabetes and due to hypertension. These criteria were
diabetes. Those people have significant serious found by UKPDS. Before the diagnosis of diabetes,
complications, such as hypertension, angina, myocardial retinopathy symptoms might be occurred.[18]
infarction and stroke, which depend on their age. MI is the
most adverse outcome in elderly people (above 60), unless Vascular endothelial dysfunction, which is influenced by
DM did not control properly.[2] fluctuation of blood glucose, occurs in early stage of

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ISSN: 2319-7064
ResearchGate Impact Factor (2018): 0.28 | SJIF (2018): 7.426
atherosclerosis, then it will prognosis to atherosclerosis 3. Results
and it will lead to diffuse and multi vascular damages in
coronary arteries. [8]Reykjavik study has reported the Lowering the blood pressure to a treatment goal of below
relative risk was 2 (HR) in both sexes for total mortality 130/80 mmHg in high-risk patients, including people with
and coronary heart disease mortality. Myocardial diabetes, cerebrovascular and coronary arterial disease, or
infarction or strokes were the first complications that they kidney disease. There is a conclusion that reduction of
have. 10mmHg of blood pressure had a greater effect on
reducing the risk of heart disease. It has estimated there
Type 2-diabetes can lead to cardiovascular disease, if it is will be 12% of reduction in the risk of any end related to
not under control. Particularly type 2 diabetes may have diabetes and 15% reduction in risk of death related to
the following condition that contributes to their risk of diabetes. Myocardial infarction is the most common side
developing cardiovascular disease. They are high blood effect in diabetes than microvascular complications such
pressure, high glucose level and cholesterol level. [3] as retinopathy, nephropathy, and neuropathy. Moreover,
10mmHg reduction of systolic blood pressure will be
2. Materials and Methods affected to the diminution of Macrovascular and
microvascular diseases at 11% and 13% respectively.
A research, which is done by England in 2015, by taking According to retrospective cohort study, this was done
information such as linked primary care, hospital with UK general practice database, 1990-2005. Systolic
admission, disease registry and death certificate records blood pressure below 110mm Hg and diastolic blood
from CALIBER program. It links data for people in pressure below 75mmHg were associate with significantly
England recorded in four electronic health data sources. increased risk of death in patients with DM and CVD. In
Selected participant were 30 years or older between patients with diabetes without established cardiovascular
January 1, 1998 to march 25, 2010 and excluded with a disease, systolic blood pressure below 120mmHg and
history of CVD, and record of pregnancy within 6 months diastolic blood pressure below 75mmHg were associated
of entry. with a significant increased risk of mortality.[22]

Their cohort consisted of 1921260 individuals without Prevention of hypertension in diabetic patient is higher
CVD at baseline according to sex and type 2 DM status. than general population. Especially 40% patients with
In this study, they were aimed association between T2DM type 2 diabetes are hypertensive who is around age 40.
and 12 initial manifestations of CVD.[17] When age comes to 75 the percentage getting increase up
to 60%. Therefore, treatment for hypertension is more
Reactive hyperemia incidence and index of vascular useful and common. Lower BP will reduce the incidence
endothelial function were measured using peripheral of stroke and myocardial infarction and microvascular
arterial tonometry on University of occupational and complications as well. If we will able to control the blood
environmental health in Japan was done a cross sectional pressure tightly, we will obtain 34% of reduction in
study about type 2 DM patients who admitted to it in April myocardial infarction, sudden death, stroke and peripheral
to November for glycemic control. Criteria were age vascular disease. Microvascular disease such as
(>20), blood glucose level at admission of <300mg/dl, no nephropathy, neuropathy and retinopathy can be reduced
diabetic ketosis or non-ketotic hyperosmolar coma and in 37% by controlling tight blood pressure.
absence of cardiac arrhythmia. Infectious diseases and
coronary syndrome also were excluded. They were Joint national committee on prevention, detection,
measured over 24 hours by continuous glucose monitoring evaluation and treatment of high BP has recommended,
on admission day 2 in 57 patients with type 2 DM. the target treatment goal of systolic BP is 130mmHg.[15, 16].
admission day 3.[8] In 2002, American diabetes association also recommended
that 130/80mmHg is the BP treatment goal for diabetic
11,140patients were randomized to intensive or standard patients.[15]
glucose control in the Action in Diabetes and Vascular
disease: Preterax and Diamicron Modified Release Hyperglycemia is strongly associated with risk of
Controlled Evaluation (ADVANCE) trial. Glycemic Macrovascular and microvascular complications. Updated
exposure was assessed as the mean HbA1c measurements mean HbA1c can measure that. Nevertheless, these
during follow-up and proper to the first event. complications are adjusted for age, sex, and ethnic group,
54participants were excluded whole levels of HbA1c at duration of diabetes, lipid concentration, blood pressure
baseline not available. There were 4112 participants from and smoking. Action in Diabetes and Vascular disease:
Asia (China, India, Philippines, and Malaysia) and 6974 Preterax and Diamicron Modified Release Controlled
from Europe, Australia, New Zealand and North America. Evaluation (ADVANCE) study has analysis 11086
[11]Swedish national diabetes register has done a research participants to identify HbA1c level and how does HbA1c
about additive effects of glycaemia and dyslipidemia on level affect to CVD and if we were able to reduce 1% of
risk of cardiovascular disease. This study consisted 22,135 HbA1c how will it affect to the CVD. In patients with
participants. Age 30–75 years, HbA1c ≥5% (≥31 type 2 diabetes, their HbA1c levels were associated with
mmol/mol), BMI ≥18 kg/m2 and plasma creatinine <150 lower risks of Macrovascular Events and death down to
μmol/l. A history of CVD was present in 15%, a history of threshold of 7% and microvascular events down to
heart failure in 4% and atrial fibrillation in 3% of threshold of 6.5%.
participants.[13]
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ISSN: 2319-7064
ResearchGate Impact Factor (2018): 0.28 | SJIF (2018): 7.426
Glycemic exposure to Glycemic levels over time were HbA1c was 7.5%. After the staging, they have estimated
assessed as mean HbA1c of measurement taken at three risk threshold levels of HbA1c for three major
baseline 6 months, 12 months for each individual. That outcomes. They are 6.57 (5.19-7.26) for macro vascular
average HbA1c is measured by weighting each disease, 6.54 (6.16-6.75) for death, 6.14 (4.33-6.51) for
measurement for the individual by the time intervals microvascular disease. Therefore, ultimately it can be
between measurements during follow up and prior to the concluded as the threshold levels in the range of 6.5%-7%
first event. 11086 patients were included in observational for macro vascular disease and death, and 6%-6.5% for
analysis after the exclusion of 54 participants for a whom microvascular diseases.
levels of HbA1c at baseline were not available. The mean

Figure 1: Adjusted HR for (a) major coronary events, (b) major cerebrovascular events, (c) cardiovascular death, (d)
peripheral vascular events, (e) new or worsening nephropathy and (f) new or worsening retinopathy by decile of mean HbA1c
levels during follow-up with locally weighted scatter plot smoothing lines

If the HbA1c is above threshold level, it will be 38% microvascular endpoints, 19% in cataract extraction, 43%
higher risk of a macro vascular event, 40% higher risk of in amputation or death from peripheral vascular disease
microvascular event and 38% higher risk of death. and 16% in heart failure.[11]. United Kingdom
Prospective Diabetes Study has clearly shown a direct
UKPDS has proved, there will be a reduction of CVD, by relationship between glycosylated HbA1c levels incidence
decreasing HbA1c level in 1%. Each 1% of HbA1c was of CVD. They have proved intensive glucose control
associated with 37% reduction in risk for microvascular might lead to reduction of all CVD.[23]
disease and 21% reduction in the risk of any endpoint or Cholesterol level is a major risk factor for having
death related to diabetes. Steep for stroke and heart failure cardiovascular and cerebrovascular disease in diabetes
is less than other CVD. In addition, the lowest category of mellitus. There will be defects in synthesis and clearance
updated mean HbA1c will be a reason for myocardial of plasma lipoproteins, which is known as dyslipidemia.
infarction the microvascular disease. Presence of low level of high-density lipoprotein,
cholesterol, hypertriglyceridemia and postprandial lipemia
They have estimated the reduction percentage of each are most frequent characteristics in type 2 diabetes. These
CVD according to reduction of 1% of HbA1c. There will factors accelerate the macro vascular disease.[9]This LDL
be a 14% reduction in fatal and nonfatal myocardial play an important role in Atherogenisis. Cardiovascular
infarction, 12% on fatal and nonfatal stork, 37% in event rates were significantly greater in those with
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 International Journal of Science and Research (IJSR)
ISSN: 2319-7064
ResearchGate Impact Factor (2018): 0.28 | SJIF (2018): 7.426
dyslipidemia, they are LDL-C > 2.6mmol/l, HDL-C ≤ smoking status, systolic blood pressure, cumulative
0.88mmol/l and TG ≥ 2.3mmol/l. these threshold levels Microalbuminuria, plasma creatine, type of hyperglycemic
have given By Fenofibrate Intervention and Event treatment, use of antihypertensive drugs and lipid
Lowering In Diabetes (FIELD) study and in the Action to lowering drugs (43%). They have done a cox regression
Control Cardiovascular Risk in Diabetes (ACCORD). analysis, to estimate 5 years event rates (1-survival rate)
for the outcomes, and they have considered both
Swedish national diabetes register has done this research TCL/HDL and HbA1c. HR was higher with TC/HDL as
by 22135 participants, female and male with type 2 predictor than with HbA1c as a predictor. HR with
diabetes mellitus (age 30-75, 15% with previous CVD, updated mean TC/HDL and HbA1c values were 1.31 and
HbA1c ≥ 55, BMI ≥ 18kh/m², plasma creatine<150μmol/l, 1.13 for fatal/non-fatal CHD, 1.25 and 1.15 for fatal/non-
history of heart failure 4%, atrial fibrillation 3%) followed fatal stroke, 1.29 and 1.13 for fatal/non-fatal CVD, 1.28
for 5years. Total mortality are the outcome that they and 1.18 for fatal CVD. HR for total mortality were 1.18
considered. and 1.07.The risk increase for fatal/non-fatal CHD was
NDR study has examined patients according to baseline 31% per 1 SD increase of TC/HDL and 13% per 1 SD
clinical characteristics such as age, sex, duration of increase of HbA1c, with values of 25% and 15% for
diabetes, HbA1c level, total cholesterol, HDL cholesterol, fatal/non-fatal stroke, and 29% and 13% for fatal/non-fatal
TC/HDL, LDL cholesterol, triglycerol, weight, height, CVD

Figure 2: HRs were adjusted for age, diabetes duration, sex, systolic blood pressure, BMI, smoking, albuminuria >20 μg/min,
antihypertensive drugs, lipid lowering drugs, type of hypoglycemic treatment, atrial fibrillation, history of CVD and history of
heart fail.

UK prospective diabetes study has mentioned ethnic group, smoking condition, lipid concentration.
dyslipidemia is one of the major risk factors for CHD. When systolic blood pressure reaches 170mmHg, it can
Total cholesterol and LDL-cholesterol have been cause myocardial infarction, stroke or any other
consistently associated with CHD.[13] microvascular complications.[1, 22]

4. Discussion Higher blood pressure is become most serious heart

condition in type 2 diabetic patient because it is most
High blood pressure is most common risk factor that common reason for heart disease as well. Therefore, it has
diabetic patients have. Therefore, pumping system get been recommended to control the blood pressure to
affected if someone has diabetes. Normal blood pressure diabetic patients. Tight control of blood pressure aiming at
of human body is 120/80mmHg. Diabetes will mainly a blood pressure of 150/85mmHg (with the angiotensin
affect to the systolic blood pressure. Systolic blood atenolol as main treatment) or with less tight control
pressure is the highest pressure described as blood pushes aiming at a blood pressure of 180/85mmHg.According to
through ventricles of heart to arteries. The type 2 diabetes, UK prospective diabetes studies has proved significant
which can cause Macrovascular and microvascular reductions in risk of diabetes related diseases by
disease, mostly affects systolic blood pressure. Systolic controlling blood pressure.[10, 12]
blood pressure will be affected to development of
Macrovascular and microvascular disease. Even The main reason for diabetes is high level of glucose in
cardiovascular diseases are strongly associated with the blood. Due to the dysfunction of β cells of pancreas,
systolic blood pressure. Mortality related diabetes and all excess glucose will remain in the blood rather than storing
type of mortality were both strongly associated with blood in the liver or skeletal muscle. High glucose can reduce
pressure. Normally type 2 diabetic patients are having the levels of the powerful vasodilation nitric oxide in
≥140/90mmHg blood pressure. It can be increased up to blood vessel, then that increases the risk of high blood
170mmHg (systolic blood pressure) according to age, sex, pressure and gradually narrows down the vessels.

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Contraction of blood vessel get affected (make it more developed new-onset diabetes during follow-up were
contract than normal) due to the hyperglycemia. Glucose analyzed. According to their baseline status of no
will influence arterial myocytes (which made by atrium) diabetes. They excluded people with type 1DM and
and then the cells that compose arterial tissue and blood uncertain type. Their criteria were mean HbA1c (3 years
vessels. Therefore, that phenomenon will leads to get before study and ignoring values occurring after an
heart attacks (myocardial infarction) by blocking coronary endpoint), BMI, HDL Cholesterol, Cholesterol and
arteries. Not only will heart attacks but also there be many systolic blood pressure. Study has presented 12 primary
cardiovascular complications.[24]Usually our red blood CVD such as stable angina, unstable angina, myocardial
cells have combined with glucose, named as glycated infarction, unheralded coronary death, heart failure,
hemoglobin (HbA1C) once they bind. However, there transient ischemic attack, ischemic stroke, subarachnoid
must be reference value of HbA1c. That reference value is hemorrhage, intracerebral hemorrhage, peripheral arterial
2-6% (<6%). HbA1c will indicate how much sugar is in disease, abdominal aortic aneurysm, and a composite
the blood and how does it control over 2-3 months. (RBC outcome classified as arrhythmia or sudden cardiac death,
life span is 3 months)[16] which consisted of cardioversion, ventricular arrhythmia,
implantable cardioverter defibrillator, cardiac arrest, or
Fluctuation in blood glucose level can cause vascular sudden cardiac death. Secondary outcomes were
endothelial dysfunction and play a critical role in onset cardiovascular mortality.
and/or progression of atherosclerosis in type 2 DM. there
were 2-6 times greater risk of having myocardial HbA1c was the measurements, which use to estimate the
infarction in type 2 diabetic people than normal hazard ratio. They grouped patients type 2DM into
population and for stroke it was 2 to 3 times greater. By categories by the HbA1c concentration. These threshold
controlling HbA1c below critical level, we can inhibit the levels were 6.5% (48mmol/mol, threshold for diagnosis of
microvascular complications. [8] diabetes), 7.5% (58mmol/mol, threshold for imitation of
insulin or thiazolidinedione) according to UK guidelines.
In diabetic patients, their LDL concentration is increased
due to very poor glycemic control. Lipogenesis and an These CVD can be different according to age, sex and
exacerbation substrate availability also increased and duration of diabetes. Although absolute risk of coronary
apolipoproteins B-100 degradation decreased as well. heart disease: mortality and morbidity is lower in women
These changes lead lipid profile marked by low-high than men are. Coronary heart disease HR was 2.63for
density lipoprotein cholesterol, high triglyceride, women and 1.85 for men with diabetes. This is because of
increased Apo B synthesis and small dense LDL particles. estrogen hormone, which is present in women and which
This lipid disorder, named as artherogenic dyslipidemia or can increase HDL, decrease LDL, relaxes, smooth and
diabetic dyslipidemia, which is associated with insulin dilates blood vessels so blood flow increases. For other
resistance. This abnormality in lipid count also leads to CVD sex, difference was not affected.
CVD.[19]Cholesterol is very important to health, but
when the cholesterol levels are too high, it can be harmful Peripheral arterial disease was the largest CVD among all
by contributing to blocked or narrowed arteries. the CVD. Though there was a difference between people
Unfortunately, people with diabetes are more prone to with diabetes and without diabetes, women with type 2
having unhealthy high cholesterol levels, which contribute diabetes at age 40 years has 9.7% risk, men at age 40 it
to CVD. Patients with type 2 diabetes are at higher risk of was 11.7% of developing peripheral arterial disease as
CVD. Among CVD, Myocardial infarction and stroke first presentation. At age 80 and without diabetes they
were chosen as primary outcomes of major type two DM. were 3.3% and 4.5%. Moreover, they have observed,
this study needed to investigate and compare the slightly greater risk of non-fatal myocardial infarction
association between type 2 diabetes and future risk of the associated with type 2 DM in women younger than 60
most common initial cardiovascular manifestations in men years than in men younger than 60 years. Although there
and women. was not a significant statistically different between sex.

According to CALIBER study information (They used People with diabetes at age 40 are more prone to have
linked primary care, hospital admission, disease registry, coronary heart disease, transient ischemic attack, ischemic
and death certificate records from the CALIBER stroke and peripheral arterial disease.[17]
program), they have selected particular participants who

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Figure 3: Cumulative incidence curves for the incidence of first presentation of 12 cardiovascular diseases in patients aged
≥40 years, by diabetes status the curves begin at age 40 years rather than 30 years because 40 years is a typical age for a
patient to develop type 2 diabetes

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Figure 4: Hazard ratios for association of type 2 diabetes with 12 cardiovascular diseases by sex and age Hazard ratios by sex
and age group for the association of different initial presentations of cardiovascular disease with type 2 diabetes, adjusted for
age, BMI, deprivation, HDL cholesterol, total cholesterol, systolic blood pressure, smoking status and statin and
antihypertensive drug prescriptions. NA= not applicable.

5. Conclusion https://www.bmj.com/content/354/bmj.i4070/article-
info [Accessed 1 Feb. 2019].
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[3] Almdal, T., Scharling, H., Jensen, J. and Vestergaard,
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