1. Diabetes, Heart Disease, and Stroke, how are they related?
2. Diabetes causing cardiovascular disease: State the Epidemiology, biological mechanisms, treatment recommendations, and future research of why this happens in a patient with diabetes
3. How do Diabetes mellitus leads to stroke? State its prevention?
4. Type 2 Diabetes Mellitus and Cardiovascular Disease: State its Genetic and Epigenetic Links
5. Sheds light on how to manage diabetes and also prevent heart attack and stroke by giving us the guideline on lifestyle management to reduce their risk
1- People with diabetes tend to develop heart disease at a younger age than people without diabetes. In adults with diabetes, the most common causes of death are heart disease and stroke. Adults with diabetes are nearly twice as likely to die from heart disease or stroke as people without diabetes.
Diabetes is a well-established risk factor for stroke. It can cause pathologic changes in blood vessels at various locations and can lead to stroke if cerebral vessels are directly affected. Additionally, mortality is higher and poststroke outcomes are poorer in patients with stroke with uncontrolled glucose levels.
This excessive chronic insulin signaling exacerbated heart failure caused by high blood pressure. Importantly, although treating type 1 diabetic mice, which produce no insulin, with insulin stabilized their levels of glucose in the blood, it increased heart failure.
2- The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions.
The incidence of diabetes mellitus (DM) is increasing substantially worldwide. Over the past three decades, the global burden of DM has swelled from 30 million in 1985 to 382 million in 2014, with current trends indicating that these rates will only continue to rise. The latest estimates by the international diabetes federation project that 592 million (1 in 10 persons) worldwide will have DM by 2035[2]. While the rates of both type 1 DM (T1DM) and T2DM are growing, T2DM has a disproportionately greater contribution to the rising prevalence of DM globally compared to T1DM. One consequence of the growing rates of DM is a considerable economic burden both for the patient and the healthcare system. In the United States, the total cost of DM averages $2108/patient per year, which is nearly twice that of non-diabetic patients. The economic burden associated with DM is substantial both in terms of the direct costs of medical care as well as indirect costs of diminished productivity tied to diabetes related morbidity and mortality. The direct costs of DM are primarily attributed to both macrovascular and microvascular complications such as coronary artery disease, myocardial infarction, hypertension, peripheral vascular disease, retinopathy, end-stage renal disease and neuropathy.
A close link exists between DM and cardiovascular disease (CVD). CVD is the most prevalent cause of mortality and morbidity in diabetic populations. CVD death rates in the United States are 1.7 times higher among adults (> 18 years) with DM than those without diagnosed DM, largely due to an increased risk of stroke and myocardial infarction (MI). This increased risk of CVD mortality in diabetic patients is found in both men and women. The relative risk for CVD morbidity and mortality in adults with diabetes ranges from 1 to 3 in men and from 2 to 5 in women compared to those those without DM.
Proper control and treatment of DM is critical as both the prevalence and economic burden of the disease continue to mount. As CVD is the most prevalent cause of mortality and morbidity in patients with DM, a primary goal of diabetes treatment should be to improve the cardiovascular (CV) risk of diabetic patients. However, one challenge associated with treating DM and reducing CV events is the complex and multifaceted nature of the relationship linking DM to CVD. CV risk factors including obesity, hypertension and dyslipidemia are common in patients with DM, particularly those with T2DM. In addition, studies have reported that several factors including increased oxidative stress, increased coagulability, endothelial dysfunction and autonomic neuropathy are often present in patients with DM and may directly contribute to the development of CVD. Collectively, the high rates of CV risk factors and direct biological effects of diabetes on the CV system place diabetic patients at increased risk of developing CVD, and contribute to the increased prevalence of MI, revascularization, stroke and CHF. Due to the complexity and numerous mechanisms linking DM to CVD, it is crucial to focus treatment to what will have the greatest clinical impact on improving CV outcomes. This paper examines the mechanisms linking DM to CVD as well as current treatment recommendations and future research in diabetes management.
CV RISK FACTORS AND CVD
Obesity
Obesity is common in patients with DM, particularly T2DM, and is associated with an increased risk of CVD. One possible mechanism linking DM and obesity with subsequent CVD is low-grade inflammation. DM and insulin resistance are associated with the overexpression of many cytokines by adipose tissue including tumor necrosis factor-α, interleukin (IL)-1, IL-6, leptin, resistin MCP-1, PAI-1, fibrinogen and angiotensin. The overexpression of these cytokines contributes to increased inflammation and lipid accumulation, which have a deleterious effect on blood vessels and can lead to the development of endothelial dysfunction, MI and cardiomyopathy (CMP). Diabetic patients also have increased amounts of C-reactive protein (CRP), which may contribute to endothelial dysfunction. Many studies have demonstrated that CRP impairs endothelial production of nitric oxide (NO) and prostacyclin, which are vital to vessel compliance. CRP has also been shown to increase the uptake of oxidized low-density lipoprotein (LDL) in coronary vasculature walls, which can contribute to endothelial dysfunction as well as the development of atherosclerotic plaques.Patients with DM also have decreased adiponectin production, which may result in diminished endothelial function. Adiponectin helps limit endothelial dysfunction by increasing NO production and reducing the expression of adhesion molecules. Adiponectin is also protective in the atherosclerotic process by inhibiting LDL oxidation. This increase in atherosclerotic plaque can place diabetic patients at a heightened risk of MI. In particular, increased levels in the inflammatory cytokine IL-1, as seen in patients with DM, can contribute to the destabilization of atheromatous plaques and subsequent MI.Insulin resistance is also associated with an elevation of plasma free fatty acids, leading to increases in muscular triglycerides stores, hepatic glucose production, and increased insulin production in patients with T2DM.Insulin resistance has also been linked to CMP in diabetics via cardiomyocyte hypertrophy and contractile dysfunction.
Hypertension
Hypertension is very common among patients with T1DM and T2DM, with prevalence rates of 30% and 60%, respectively.Hypertension among diabetic patients is closely tied to the development of diabetic nephropathy (DN).With DN, renal cells are stimulated by hyperglycemia, leading to the production of humoral mediators, cytokines, and growth factors. The production of these factors is often responsible for structural alterations seen in the glomeruli of diabetic patients including hyaline arteriolosclerosis (primarily of the efferent arteriole), increased collagen deposition of the extracellular matrix, and increased permeability of the glomerular basement membrane.These structural changes increase filtration pressure and often lead to microalbuminemia with a compensatory activation of the renin-angiotensin system (RAAS). Chronic activation of the RAAS often progresses to hypertension, placing added stress on the glomeruli and causing additional damage to the nephrons of diabetic patients. If left untreated, DN can progress to a nephrotic syndrome, characterized by proteinuria, a hypercoagulable state (due to loss of ATIII) and hyperlipidemia, which may contribute to the increased risk of CVD seen in diabetic patients with renal dysfunction.
Dyslipidemia
Diabetic patients are at increased risk of developing dyslipidemia.One mechanism underlying this connection is increased free fatty-acid release present in insulin-resistant fat cells. High levels of free-fatty acids promote triglyceride production, which in turn stimulates the secretion of apolipoprotein B (ApoB) and very LDL (VLDL) cholesterol. High levels of ApoB and VLDL have both been tied to increased risk of CVD.In addition to high ApoB and VLDL, hyperinsulinemia is associated with low high-density lipoprotein (HDL) cholesterol levels. Hyperglycemia may also negatively impact lipoproteins (particularly LDL and VLDL) through increased glycosylation and oxidation, decreasing vascular compliance and facilitating the development of aggressive atherosclerosis.High circulating FFA’s and triglycerides, increased stimulation of ApoB and VLDL cholesterol, decreased HDL levels and lipoprotein modification have all been appreciated in patients with DM and likely contributes to the high prevalence of CVD in diabetic patients.
Diabetic cardiomyopathy
DM appears to contribute directly to the development of CMP, rather than solely viacoronary atherosclerosis and hypertension. This diabetic CMP has been described in many noninvasive studies and includes changes that occur in LV structure and cardiac function of diabetics. Specifically, diabetics tend to have greater cardiac mass, particularly LV mass, than those without DM. This may be related to an increased adipocyte release of cytokines such as leptin and resistin which have hypertrophic effects on cardiomyocytes. One study looking at a multi-ethnic population found that the likelihood of having LV mass that exceeds the 75th percentile is greater in patients with T2DM, even after adjusting for covariates.Patients with DM also tend to have a slightly diminished diastolic function compared to nondiabetics.One possible mechanism could be that increased triglyceride synthesis in patients with DM leads to increased myocardial triglyceride content. Increased cardiac triglyceride accumulation is associated with lipotoxicity and altered calcium hemostasis in myocardium, both of which negatively impact diastolic function.This could help explain the finding that 40%-75% of individuals with DM and no signs of overt coronary artery disease (CAD) suffer from diastolic dysfunction.Subtle abnormalities in systolic function have also been observed in patients with DM using tissue Doppler imaging and Doppler strain analysis of peak systolic velocity.This systolic dysfunction may be related to impaired myocardial sympathetic innervation and impaired contractile reserve.In addition, interstitial fibrosis with increased collagen deposition has been observed in patients with DM and may negatively contribute to the diminished cardiac function seen in diabetics.It is likely that many of the mechanisms that contribute to reductions in systolic and diastolic function seen in diabetic patients also place them at an increased risk of heart failure (HF).The prevalence of HF, particularly heart failure and preserved ejection fraction, is higher in diabetic patients (16%-31%) than the general population (4%-6%).While some of the difference may be accounted for by traditional CV risk factors, DM may independently alter cardiac structure and function by promoting hypertrophy and fibrosis.
Cardiovascular autonomic neuropathy
Cardiovascular autonomic neuropathy (CAN) is common among patients with DM and is correlated with an increased 5-year mortality rate from CVD.The clinical manifestations of CAN are resting tachycardia, postural hypotension, exercise intolerance, abnormal coronary vasomotor regulation, increased QT interval, and perioperative instability. Collectively, the clinical manifestations of CAN are related to an increased risk of renal disease, stroke, CVD and sudden death[52]. The development and progression of CAN is likely related to dysregulation of the autonomic nervous system (ANS) with increased sympathetic activity and elevated inflammatory markers. As the ANS is responsible for maintaining the activity of the sinus node, end diastolic volume, end systolic volume and systemic vascular resistance, ANS dysfunction can lead to arterial stiffness, left ventricular hypertrophy and ventricular diastolic dysfunction.Incidence of CAN increases with age and inadequate glycemic control, which places patients with DM at higher risk of developing both CAN and CVD.
Myocardial infarction and DM
Diabetes is a major risk factor for the development of CAD with a higher incidence of MI in patients with DM than those without.In addition, following a MI, diabetic patients have higher rates of morbidity, mortality and re-infarction than non-diabetics, with one-year mortality rates of nearly 50%. Although the exact pathophysiology of CAD progression in patients with DM has not yet been determined, the most recent studies postulate that the underlying atherosclerotic process is similar between those with and without DM. It is thought that the higher incidence of myocardial infarction in patients with DM is attributable to increased coagulability.Many studies have found that diabetics have increased expression of glycoprotein IIB/IIIA receptors and vWF, which are responsible for platelet activation.Patients with DM also have increased plasminogen activator inhibitor type 1 which could decrease fibrinolysis, increase thrombus formation and accelerate plaque formation. Finally, diabetic patients also tend to have decreased circulating anti-coagulants such as protein c and antithrombin III due in a large part to the proteinuria present with DN.Collectively, these factors place patients with DM in a prothrombotic and procoagulant state, which may account for the higher rates of MI seen in diabetic patients.
TREATMENT
As CVD is the most prevalent cause of mortality and morbidity in patients with DM, effective treatment is critical to lower the subsequent risk of CV events, particularly MI, CAD, stroke and CHF in diabetics. Suboptimal glycemic control, obesity, hypertension, dyslipidemia and autonomic dysfunction are common CV risk factors among diabetic patients, placing them at heightened risk of CV complications. Therapy that is targeted to modify these risk factors can improve CV outcomes, but this can be a challenging to achieve. The guidelines pertaining to these risk factors typically vary from the guidelines for non-diabetic patients and the recommendations often change or differ depending on what organization publishes them. In addition, the research on how these different risk factors affect the CV risk profile of diabetics can be unclear, and at times, contradictory. The purpose of this section is to provide the most recent guidelines for the treatment of glycemic control, hypertension, dyslipidemia and autonomic dysfunction in patients with DM, and also describe the research that pertains to each of these topics.
GLYCEMIC CONTROL
As many studies have linked poor glycemic control to worse CV outcomes, current treatment recommendations for patients with DM place a heavy emphasis on closely monitoring and controlling glycemic levels in an effort to improve cardiac outcomes. The exact glycemic level that should be targeted for diabetics, however, is controversial and varies depending on which organization is making the guideline.
The ACCORD trial was conducted concurrently to the ADVANCE trial and focused primarily on whether intensive glycemic control reduced to risk of CV events. This multi-center randomized control trial investigated if very tight glycemic control (less than or equal to an HbA1c of 6%) had lower rates of nonfatal MI, nonfatal stroke and CV death than standard glycemic control (HbA1c of 7%-7.9%) in older adults. The subjects were followed for an average of 3.4 years and the group with the tighter glycemic control did achieve a significantly lower HbA1c than those with standard treatment (7.3% vs 6.5%). The intensive glycemic control group had slightly lower rates of nonfatal MI, but after 3.7 years the trial was stopped early because the intensive treatment group had increased rates of all-cause and CV mortality. The group with tight glycemic control also had increased weight gain, and risk of hypoglycemia as seen in the ADVANCE trial.
One potential interpretation of the studies thus far is that the concurrent CV risk factors present in diabetics may overwhelm any benefit that intensive treatment of hyperglycemia can provide in reducing risk. Thus, diabetic patients who achieve tighter glycemic control earlier during their disease course and prior to the development of other CV risk factors may see the greatest benefit from more intensive therapy in terms of CV outcomes. For this reason, many of the new recommendations look to tailor A1c goals to the individual patient as opposed to a single A1c cutoff for all diabetic patients. The ACC/AHA and VA/DoD, for example, adjust their glycemic goals based on factors such as age, years with the disease and CV risk.While further studies are needed to determine what the best glycemic treatment goal is for these different patient populations, adjusting the target A1c depending on the individual’s current level of CVD risk may provide benefit to diabetic patients.
Obesity
Obesity is a common comorbidity of DM, particularly T2DM, and is linked with higher rates of CV morbidity and mortality. Thus, current treatment recommendations encourage weight loss in overweight and obese patients with DM to improve their CV risk profile and decrease the risk of CVD. The recommendation is for 5% weight loss over 4 years in diabetic patients that are overweight or obese. A “moderate” amount of evidence suggests that 5% weight loss by lifestyle intervention is associated with an increase in HDL-c, a reduction in triglycerides and a decrease in newly prescribed lipid lowering medications in diabetic patients. In addition, there is a “high” level of evidence suggesting that orlistat results in 2-3 kg of weight loss in overweight and obese diabetic patients at 1 and 2 years, and is associated with greater reductions in fasting blood glucose and HbA1c. These recommendations were graded as high, moderate, or low on the basis of scientific methodology, scientific strength, and consistency of results.
As obesity is a major risk factor both for CVD and T2DM, many studies have investigated the efficacy of weight loss in reducing the development and severity of DM. Some studies have focused on body weight reduction in pre-diabetic patients in order to decrease the incidence of subsequent DM. Of note, the diabetes prevention program (DPP) and finnish diabetes prevention studies evaluated the effect of behavior modification on weight loss and consequent risk of developing diabetes in pre-diabetic adults. Both studies yielded similar results in that those randomized to the lifestyle intervention group had significantly greater weight loss and reduced risk of developing diabetes as compared to the control group.Other studies have looked at methods for attaining weight loss and improving the CV risk profile of patients who are already diabetic. A variety of techniques including intensive lifestyle intervention, weight loss medications and bariatric surgery were effective in achieving weight loss and improving the CV risk profile of diabetic patients through improved glycemic control, blood pressure and cholesterol levels.
Although many studies have shown that weight loss can be achieved in diabetic patients, there is mixed evidence as to whether weight loss in these patients actually reduces subsequent CV morbidity and mortality. Thus far, there has been mixed evidence if modest weight loss in patients with DM does improve their CV risk. While the SCOUT trial found that modest weight loss could improve 5-year CV mortality rates among diabetic patients, the Look AHEAD trial did not find that weight loss had any effect on CV mortality, MI, stroke, or angina hospitalization after 9.6 years of follow-up.
The current recommendation for overweight and obese patients with DM is a goal weight loss of 5%. Studies thus far have demonstrated that this goal is attainable both in pre-diabetic and diabetic patients through a variety of techniques including intensive behavioral modification therapy, pharmacological agents and bariatric surgery. In addition, all of these methods of weight loss appear to either decrease the rates of incident DM in pre-diabetic patients, or improve the CV risk profile of diabetic patients.However, it is unclear whether modest weight loss in diabetic patients translates to a decrease in CVD.
It is possible that the CV risk profile is too high in older adults with DM for modest weight loss to make a significant improvement in CV outcomes. It might be more advantageous to focus obesity treatment efforts on pre-diabetics before they develop DM. Programs such as the DPP have demonstrated that weight loss can decrease the rate of incident diabetes, but further research is needed to determine if modest weight loss in pre-diabetic patients results in improved CV morbidity and mortality. It is also possible that while modest weight loss does seem to improve the CV risk profile of patients with DM, even greater weight loss is necessary to see more definitive improvements in the rates of CV events. Further investigation into the effects of weight loss greater than 5% on CVD in diabetic patients may help identify the existence of a dose effect with weight loss and CV health.
Hypertension
Since hypertension is a common comorbidity of patients with DM and a major risk factor for CVD, the current treatment recommendations strongly encourage providers to lower BP in hypertensive diabetics. There are many studies that have investigated the effect of lowering blood pressure in patients with diabetes on CV outcomes. The UKPDS 38 trial examined the effect of tight control of blood pressure control (< 150/85) compared to less tight control (< 180/105) on macrovascular and microvascular complications in patients with T2DM. After 9 years follow-up, mean blood pressure was significantly lower in the tightly controlled BP group (144/82 mmHg) compared to the patients in the less tightly controlled group (154/87 mmHg). In addition, the group with tighter BP control had a 34% reduction in macrovascular disease risk (myocardial infarction, sudden death, stroke, and peripheral vascular disease) and a 37% reduction in risk of microvascular disease (retinopathy requiring photocoagulation, vitreous haemorrhage, and fatal or non-fatal renal failure) compared with the less tightly controlled BP group.
Given the results of these trials, recent treatment recommendations indicate that, pharmacologic treatment should be initiated at a SBP of > 140 mmHg or a DBP of > 90 mmHg for diabetic adults between 18 and 60 years of age. For patients older than 60, the threshold to initiate treatment is a SBP of < 150 mmHg or a DBP of < 90 mmHg. The recommendation on the type of pharmacological therapy that should be used varies in the general nonblack vs black population. For nonblack patients with DM and hypertension, initial treatment should include a thiazide-type diuretic, calcium channel blocker (CCB), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). For black patients with DM and hypertension, the initial treatment should include a thiazide-type diuretic or a CCB. In addition, hypertensive patients with DM and CKD should be treated with an ACE inhibitor or an ARB to improve kidney outcomes.While different antihypertensive agents used to treat hypertension have varying metabolic effects, many studies, including the ALLHAT trail, found no significant difference in the risk of coronary heart disease, nonfatal myocardial infarction, total mortality, or other clinical complications attributable to the initial antihypertensive drug therapy used to treat diabetic patients. This would suggest that metabolic differences between the various antihypertensive agents do not play a major role in the subsequent development of CVD in patients with DM. It should be noted that these recommendations have been controversial and several authors have argued that the guideline is too relaxed in the treatment of certain at-risk groups including African Americans, women and the elderly based on previous studies evaluating blood pressure control and subsequent CVD in these populations.There is likely a therapeutic BP range that provides diabetic patients with a lower CV risk but also protects them from adverse events associated with hypotension. Whether the new guidelines, particularly with the increased systolic BP threshold in adults over 60 years, match this therapeutic BP range is yet to be determined. There is also little evidence as to what the proper treatment range should be for different age groups. In addition, hypertension in different racial subgroups may have different effects on CV health. Further research is needed to investigate the ideal BP range for adults of different age groups as well as different racial groups.
Dyslipidemia
Dyslipidemia is both common in patients with DM and associated with increased risk of CVD. Health providers are encouraged to identify and aggressively treat patients with dyslipidemia to help diminish their risk of subsequent CV events. The current recommendation for treating dyslipidemia in diabetic patients varies by age and is in line with recognition that treatment with fixed-dose statins, rather to specific LDL target levels, is the validated approach from clinical trials. Accordingly, diabetic patients who are under the age of 40 are recommended to take a high-intensity statin if they have clinical evidence of atherosclerotic CVD or a LDL-c greater than 189 mg/dL. All diabetic patients over the age of 40 are encouraged to begin statin therapy. Patients over 40 with an estimated 10-year ASCVD risk greater than 7.5% are treated with a high-intensity statin, and patients with a 10-year ASCVD risk less than 7.5% are treated with a moderate-intensity statin.
There have been many studies conducted to determine the effect of treating dyslipidemia in diabetic patients as a means to lower CV risk. The CARDS study was the first multicenter randomized controlled trial to evaluate statin therapy prospectively in patients with T2DM. Adult patients with T2DM were randomized to either receive a placebo or 10 mg/d of atorvastatin. The median follow-up time was 3.9 years and the group treated with atorvastatin had an average 26% reduction in total cholesterol and a 40% reduction in LDL-c. In addition, the statin therapy group had a 37% reduction in CV events, a 27% reduction in all-cause mortality and a 48% reduction in stroke as compared to the group treated with the placebo. The CARDS trial was stopped early to due the significant benefit demonstrated with statin therapy.
After the CARDS trial found that statin therapy provided a significant CV benefit to diabetic patients, the TNT trial examined the effect of high-dose statins on CAD mortality, non-fatal MI, and fatal or nonfatal stroke in diabetic patients with T2DM. Adult patients with T2DM were randomized to receive either a high dose (80 mg/d) or low dose (10 mg/d) statin and followed on average for 4.9 years. The high dose stain group achieved a greater reduction in LDL-c (77 mg/dL vs101 mg/dL) and had a greater reduction in combined CAD mortality, non-fatal MI, or fatal or nonfatal stroke (8.7% vs 10.9%) compared to the lower dose group. However, it was noted that the higher dose group did have a higher rate of adverse events (myalgia, persistent elevation in alanine aminotransferase, aspartate aminotransferase, or rhabdomyolysis).
As many studies had demonstrated that statins, particularly high-dose statins, had CV benefit in diabetic patients, the 4D study examined the effect of statins in diabetic patients receiving hemodialysis. In the 4D trial, diabetic patients receiving hemodialysis were randomly assigned either 20 mg of atorvastatin per day or a placebo. The purpose of the study was to determine if a low-dose statin in diabetic patients with end stage renal disease lowered the rates of death from cardiac causes, nonfatal myocardial infarction, and stroke as compared to the placibo gorup.
While the previous studies had focused on reducing cholesterol in diabetic patients using statin therapy, other research groups have investigated the effect of non-statin lipid-lowering therapies on CVD in diabetic patients. For example, the FIELD trial evaluated if lowering cholesterol viafenofibrate therapy could improve CV outcomes in patients with DM. In the FIELD trial, diabetic patients (mean age 62 years; 63% men) were randomized to either receive a fenofibrate (200 mg/d) or a placebo and then assessed for subsequent rates of fatal coronary heart disease (CHD) or nonfatal MIs. While the group randomized to the fenofibrate therapy did reduce their cholesterol compared to the placebo group at 4 mo (total cholesterol, LDL-cholesterol, and triglycerides by 11%, 12%, and 29%, respectively), the differences decreased between the groups as the trial continued due in a large part to patients starting additional cholesterol lowering therapies outside of the study. After a median of 5 years, the group randomized to the fenofibrate group had a combined 11% reduction in fatal CHD or nonfatal MIs, but this difference was non-significant. The fenofibrate group did however have a statistically significant reduction (24%) in nonfatal MI’s compared to the placebo group.
Dyslipidemia is prevalent among diabetic patients and a major risk factor for CVD. Current treatment recommendations encourage providers to lower lipid levels in diabetic patients, primarily through the use of statins, with a dose dependent on the patient’s level of risk. Some trials have also investigated if additional CV benefit can be achieved in patients with DM by combining a statin with other lipid-lowering therapies. For example, the IMPROVE-IT trial found that the combination of ezetimibe (a cholesterol absorption inhibitor) with simvastatin was superior to simvastatin alone in reducing CV events for diabetic patients with acute coronary syndrome.The evidence thus far suggests that statin therapy in patients with DM is advantageous for CV health and that higher doses, as well as combined lipid-lowering therapy, can provide additional CV protection. While some meta-analyses have suggested that statin therapy could be associated with increased incidence of DM, the absolute benefit of the therapy in diabetic patients largely outweighs the risk.
CAN
CAN is a common complication of diabetes and places patients with DM at increased risk of CV related morbidity and mortality. The autonomic dysfunction commonly found in diabetic patients is associated with a high risk of cardiac arrhythmias and sudden death, as well as other serious CV sequelae including silent myocardial ischemia, diabetic cardiomyopathy, stroke, and both intraoperative and perioperative CV instability. Some of the most common clinical manifestations of CAN include heart rate variability (variability in the instantaneous beat-to-beat intervals), resting tachycardia, exercise intolerance, orthostatic hypotension and abnormal blood pressure regulation.
FUTURE DIRECTIONS IN THE TREATMENT OF DM
While there have been many trials that have helped further the understanding of DM as it relates to CVD, further research is required to better identify and quantify CV risk in patients with DM. Determining how glycemic control relates to CVD is one another area where additional research is needed. There is some evidence that improved glycemic control does in fact improve CV outcomes patients with DM.One study even found that HbA1c in non-diabetic patients is an independent predictor of coronary artery disease and its severity which would suggest that glycemic control is critical to managing CV health in all patient populations. While this observational trial suggests an independent association may exist between glycemic levels and CVD, large randomized control trials such as ADVANCE and ACCORD have shown that the effect of tight glycemic control on subsequent CVD is modest and largely attributable to coexistent traditional risk factors.
One possible explanation for the conflicting results surrounding the relationship between glycemic control and CVD is due to poor measurement tools. For example, fasting plasma glucose (FPG) is often used as a measure of glycemia, but studies have found a day-to-day within-person variance of 12%-15% in FPG levels of diabetic patients. While the day-to-day within-person variance for HbA1c is far better (< 2%), there is evidence that HbA1c does not accurately reflect glycemic control due to biological variations and differences in RBC survival among patients.If glycemic control does matter, properly measuring glycemia and correlating it to CV risk is essential in order to set clinically meaningful goals for patients with DM.
The duration and onset of improved glycemic control may also contribute to the progression and severity of CVD. The UKPDS demonstrated that tight glycemic control was associated with reductions in CV outcomes in middle-aged adults (median 54 years) who were recently diagnosed with DM.Conversely, the ADVANCE and ACCORD trials reported that tight glycemic control may not provide any reduction in subsequent CVD and may actually be harmful in patients that were slightly older and with a longer duration of diabetes. This might reveal that treating hyperglycemia aggressively in high-risk patients with longer-standing DM is too late to have a clinically significant impact, and that earlier, aggressive treatment among patients shortly after DM diagnosis may be more beneficial. More studies are needed to better understand the relationship between glycemic control and the development of CVD and determine if the onset and duration of treatment matters in the reduction of CV events in patients with DM.
3- If you have diabetes and your doctor suspects your arteries are hardened, they may suggest diet and lifestyle changes -- along with medicines -- to prevent the blockages that lead to stroke. Other ways to lower your odds of a stroke include: Don't smoke. Control your blood sugar level.
Diabetes is a well-established risk factor for stroke. It can cause pathologic changes in blood vessels at various locations and can lead to stroke if cerebral vessels are directly affected. Additionally, mortality is higher and poststroke outcomes are poorer in patients with stroke with uncontrolled glucose levels.
If you have diabetes, you can ward off the risk of stroke by taking steps to keep your heart and blood vessels healthy.
4- Individuals with type 2 diabetes (T2D) have a twofold increased risk for cardiovascular disease (CVD) (myocardial infarction, stroke, peripheral vascular disease), and CVD is the principal cause of death in T2D patients.
Type 2 diabetes does not have a clear pattern of inheritance, although many affected individuals have at least one close family member, such as a parent or sibling, with the disease. The risk of developing type 2 diabetes increases with the number of affected family members.
Genes associated with type 2 diabetes risk include: TCF7L2, which affects insulin secretion and glucose production. ABCC8, which helps regulate insulin. CAPN10, which is associated with type 2 diabetes risk in Mexican-Americans.
About 10 loci in the human genome have now been found that seem to confer susceptibility to Type 1 diabetes. Among these are 1) a gene at the locus IDDM2 on chromosome 11 and 2) the gene for glucokinase (GCK), an enzyme that is key to glucose metabolism which helps modulate insulin secretion, on chromosome 7.
5- poor diet - a healthy diet can help reduce your risk of developing coronary heart disease and stop you gaining weight, reducing your risk of diabetes and high blood pressure. being overweight - this increases the work the heart has to do, and it leads to high blood pressure and abnormal levels of fat in the blood.
Choose foods low in saturated fat, trans fat, and sodium. As part of a healthy diet, eat plenty of fruits and vegetables, fiber-rich whole grains, fish (preferably oily fish-at least twice per week), nuts, legumes and seeds and try eating some meals without meat. Select lower fat dairy products and poultry (skinless).
Fortunately, there are many things you can do to reduce your chances of getting heart disease:
1. Don't smoke or use tobacco
One of the best things you can do for your heart is to stop smoking or using smokeless tobacco. Even if you're not a smoker, be sure to avoid secondhand smoke.
Chemicals in tobacco can damage your heart and blood vessels. Cigarette smoke reduces the oxygen in your blood, which increases your blood pressure and heart rate because your heart has to work harder to supply enough oxygen to your body and brain.
2. Get moving: Aim for at least 30 to 60 minutes of activity daily
Regular, daily physical activity can lower your risk of heart disease. Physical activity helps you control your weight and reduce your chances of developing other conditions that may put a strain on your heart, such as high blood pressure, high cholesterol and type 2 diabetes.
3. Eat a heart-healthy diet
A healthy diet can help protect your heart, improve your blood pressure and cholesterol, and reduce your risk of type 2 diabetes. A heart-healthy eating plan includes:
4. Maintain a healthy weight
Being overweight — especially around your middle — increases your risk of heart disease. Excess weight can lead to conditions that increase your chances of developing heart disease — including high blood pressure, high cholesterol and type 2 diabetes.
One way to see if your weight is healthy is to calculate your body mass index (BMI), which uses your height and weight to determine whether you have a healthy or unhealthy percentage of body fat. A BMI of 25 or higher is considered overweight and is generally associated with higher cholesterol, higher blood pressure, and an increased risk of heart disease and stroke.
5. Get good quality sleep
A lack of sleep can do more than leave you yawning; it can harm your health. People who don't get enough sleep have a higher risk of obesity, high blood pressure, heart attack, diabetes and depression.
Most adults need at least seven hours of sleep each night. Make sleep a priority in your life. Set a sleep schedule and stick to it by going to bed and waking up at the same times each day. Keep your bedroom dark and quiet, so it's easier to sleep.
6. Manage stress
Some people cope with stress in unhealthy ways — such as overeating, drinking or smoking. Finding alternative ways to manage stress — such as physical activity, relaxation exercises or meditation — can help improve your health.
7. Get regular health screenings
High blood pressure and high cholesterol can damage your heart and blood vessels. But without testing for them, you probably won't know whether you have these conditions. Regular screening can tell you what your numbers are and whether you need to take action.
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