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ISO 13580 | IDF 151: 2005: Yogurt – Determination of total solids content (Reference method)
Type 2 diabetes mellitus T2DM is ixf accompanied by other cardiovascular disease CVD risk factors, such as hypertension, obesity, and dyslipidemia. It is therefore of critical importance to minimize the risk of macrovascular complications by carefully managing modifiable CVD risk factors in patients ief T2DM. Therapeutic strategies should include lifestyle and pharmacological interventions targeting hyperglycemia, hypertension, dyslipidemia, obesity, cigarette smoking, physical inactivity, and prothrombotic factors.
This article discusses the impact of modifying these CVD risk factors in the context of T2DM; the clinical evidence is summarized, and current guidelines are also discussed. The cardiovascular benefits of idff cessation, increasing physical activity, and reducing low-density lipoprotein cholesterol and blood pressure are well established.
For aspirin therapy, any cardiovascular iff must be balanced against the associated bleeding risk, with current evidence supporting this strategy only in certain patients who are at increased CVD risk. Although overweight, obesity, and hyperglycemia are clearly associated with increased cardiovascular risk, the icf of their modification on this idff is less well defined by available clinical trial evidence.
However, for glucose-lowering drugs, further evidence is expected from several ivf cardiovascular outcome trials.
Taken together, the evidence highlights the value of early intervention and targeting multiple risk factors with both lifestyle and pharmacological strategies to give the best chance of reducing macrovascular complications in the long term. A seemingly relentless increase in the incidence of diabetes 1 finds us in the midst of a global diabetes epidemic.
More than million people are currently affected worldwide, and this number isf expected to rise to million by The dynamics of the diabetes epidemic are also changing rapidly. Once a disease of the West and the affluent, type 2 diabetes mellitus T2DM has now spread to every country in the world and is increasingly common among the less 169–2.
Furthermore, rising rates of childhood obesity have resulted in T2DM becoming more common in children and adolescents, particularly in certain ethnic groups. Diabetes is a major risk factor for cardiovascular disease CVDand CVD is the most common cause of death in people with diabetes. Various studies have indicated that, relative to those without diabetes, the presence of diabetes significantly increases the risk two- to fourfold for developing CVD, 4 — 9 and of dying when CVD is present.
Indeed, it has been suggested that CVD risk reduction and prevention of diabetes in the prediabetes population may do more to reduce the CVD burden than aggressive treatment of CVD risk factors once diabetes has fully developed. The management of modifiable CVD risk factors, including hyperglycemia, hypertension, dyslipidemia, obesity, cigarette smoking, and physical inactivity, is therefore critical to minimizing the risk of macrovascular complications of diabetes.
An ixf of the clinical utility of such nontraditional risk factors by the US Preventive Services Task Force concluded that there was insufficient evidence to recommend using them to assess CVD risk in the general population. This article will therefore focus on how the modification of traditional risk factors impacts CVD risk in patients with T2DM, and discuss current guidelines in this regard. Lifestyle management is universally advocated for prevention as well as management of T2DM.
Lifestyle 1692- generally include healthy eating, increased physical 1699-2, and cessation of smoking. Such interventions have several beneficial effects, and can also have an impact on CVD risk. Weight loss is advised for all overweight or obese patients with T2DM. Recommended strategies to reduce weight include regular physical activity and maintaining a healthy eating pattern. Nevertheless, other benefits of weight loss have been clearly demonstrated eg, improvements in quality of life, insulin resistance, and other Dif risk factorsand clinical guidelines therefore continue to recommend weight loss for overweight or obese individuals with T2DM.
Although intensive lifestyle intervention was associated with significant weight loss and improvements in several CVD risk factors, there was no effect on the rate of CV events during long-term follow-up, and the trial was stopped for reasons of futility iidf a median follow-up of almost 10 years. Furthermore, the mean loss of 3. The difference between groups may irf have been reduced by an increased use of potentially cardioprotective drugs in the control group, as well as the provision of educational sessions.
It may also be possible that any effect of lifestyle interventions on CV outcomes requires more than 10 years to become apparent, and would therefore not have been detected.
On the topic of weight loss, it is also important to note that all the major diabetes guidelines refer to bariatric surgery. However, this is based on results from a nonrandomized study in which the control group was contemporaneously matched and 169–2 by several characteristics at baseline.
Physical activity is recommended as part of weight-loss strategies, and the effects of weight ldf on CVD risk were discussed in the previous section. However, physical activity is also thought to influence CVD risk independently of weight loss. The potential mechanisms underlying this link include decreased systemic inflammation, improved early diastolic filling, improved endothelial vasodilator function, and decreased abdominal visceral fat accumulation.
A large body of evidence has established a causal link between cigarette smoking and health risks in the general population. In patients with T2DM, studies also consistently demonstrate that smoking is a risk factor for mortality and coronary heart disease, and to a lesser extent for dif.
A recent study investigating the odf between smoking cessation and weight gain demonstrated CV benefits of smoking cessation in ief without diabetes, despite subsequent weight gain. The same trend was demonstrated for patients with diabetes, although it did not reach statistical significance, possibly because of limited study power.
In the context of elevated blood glucose, the function of the vascular endothelium is altered in ways that promote atherosclerosis reviewed in Bornfeldt and Tabas While epidemiological and pathophysiological studies clearly support the hypothesis that hyperglycemia is associated with an increased risk of CVD, they do not directly address whether interventions to improve hyperglycemia reduce this risk.
In type 1 diabetes mellitus, DCCT Diabetes Control and Complications Trial showed a trend towards a lower risk of CV events with intensive glucose control, but the number of events was small and the result was not statistically significant. The mechanisms underlying this legacy effect are not fully understood. A follow-up of the EDIC cohort 15 years after the study stopped found no significant difference between the intensive- and standard-care groups in terms of cardiac function or remodeling assessed by cardiac magnetic resonance imaging.
Although several meta-analyses have explored this controversial relationship between glucose control and CVD, these studies are not strictly comparable, making it impossible to draw firm conclusions. In summary, improved glucose control in patients with T2DM has not been definitively shown to reduce CVD, although a trend toward benefit has been observed.
Although beneficial effects of glucose control on CVD risk have not been conclusively demonstrated, the benefits of good glucose control on microvascular outcomes are unequivocal, and antihyperglycemic agents therefore remain a cornerstone of T2DM treatment. There are many such agents to choose from and several factors for the physician to consider, including safety. The CV safety of certain antihyperglycemic drugs, particularly rosiglitazone and some sulfonylureas, has been called into question.
The FDA guidance applies to drugs approved sinceand thus many of these trials involve incretin-based therapies dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 agonists and sodium glucose cotransporter SGLT -2 inhibitors, as these are the most recently developed antihyperglycemic drug classes.
There has been cautious optimism that incretin-based therapies may have CV benefits beyond those attributed to reducing hyperglycemia, with evidence of cardioprotective actions in preclinical models of CV dysfunction and beneficial effects on cardiac function in short-term clinical studies of ischemic heart disease.
The pathophysiological relationship between hypertension and diabetes is complex and not well understood. Evidence suggests that insulin resistance plays a significant role in the interplay between diabetes, hypertension, and CVD, but such comorbidities as obesity and dyslipidemia make it difficult to decipher the common pathological mechanisms.
Nevertheless, various studies indicate that the presence of hypertension is a very strong driver of CV outcomes in individuals with diabetes. Intensive lifestyle intervention may be sufficient to lower blood pressure in patients with mild hypertension.
Dyslipidemia is strikingly common in patients with T2DM. The altered lipid profile associated with T2DM is most commonly attributed to insulin resistance,and is generally characterized by a high concentration of plasma triglycerides, low concentration of high-density lipoprotein cholesterol HDL-Cand increased concentration of small dense LDL-C particles.
Currently, very little clinical evidence exists to show that lowering triglycerides leads to a reduction of CVD risk, although in the ACCORD lipid trial, a subgroup of patients who had the highest baseline triglyceride level and lowest HDL-C baseline level appeared to benefit from combination therapy with a statin plus a fibrate.
Prothrombotic and fibrinolytic mechanisms are tightly regulated under normal circumstances, such that there is protection from bleeding without the formation of pathological thrombosis. However, in patients with diabetes, this regulation is disrupted, and there is an increased thrombotic tendency, due to platelet hyperreactivity, decreased fibrinolysis, and increased activation of prothrombotic coagulation factors eg, tissue factor, factor VIII, thrombin, fibrinogen, plasminogen-activator inhibitor 1.
Aspirin inhibits thromboxane A 2 -dependent platelet activation and aggregation by way of its irreversible inhibition of cyclooxygenase 1, and a number of studies have demonstrated that treatment with low-dose aspirin resulted in a significant reduction of serious vascular events in patients with diabetes and CVD. The evidence regarding the use of aspirin for primary prevention of CV events in adults with diabetes is more controversial.
For example, two recent randomized controlled trials did not show a significant CV benefit of aspirin in patients with diabetes. These results are consistent with the findings of other meta-analyses, — and together they suggest that aspirin may produce a modest reduction in the risk of CV events in patients with diabetes. However, aspirin use is also associated with a significant increase in the risk of intracranial and extracranial hemorrhage, and the relative trade-off between CV events prevented by aspirin and bleeding events caused by aspirin therefore needs careful consideration.
These investigations will provide important information about the role of aspirin for primary prevention in patients with diabetes, and may help identify which patients are at greatest risk, and therefore which patients stand to derive a net benefit from aspirin therapy. Platelet P2Y 12 -receptor blockers are an alternative class of antiplatelet agents that include clopidogrel, prasugrel, and ticagrelor.
Clopidogrel inhibits adenosine diphosphate-dependent platelet function by irreversible inhibition of the platelet P2Y 12 receptor, and has proven clinical efficacy in reducing CV events in patients with diabetes.
Prasugrel also exerts its antiplatelet effect by irreversible inhibition of the P2Y 12 receptor; however, it leads to platelet inhibition more rapidly and with less variability compared with clopidogrel.
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It is currently indicated for the reduction of thrombotic CV events including stent thrombosis in patients with acute coronary syndrome who are to be managed with percutaneous coronary intervention. TRITON-TIMI TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel — Thrombolysis In Myocardial Infarction 38 demonstrated that prasugrel produced a greater reduction in ischemic events than clopidogrel, but was associated with an increased risk of bleeding in patients with acute coronary syndrome undergoing percutaneous coronary intervention.
Ticagrelor also inhibits P2Y 12 receptors, but differs from clopidogrel and prasugrel by virtue of its direct and reversible mechanism of action. PLATO Platelet Inhibition And Patient Outcomes demonstrated that ticagrelor was more effective than clopidogrel in reducing death from CV causes and ldf mortality in a general postacute coronary syndrome cohort, and decreased ischemic events in diabetes patients without increasing the isf of bleeding. Current guidelines recommend aspirin therapy as a potential primary prevention strategy in those with diabetes who are at increased CVD risk and who are not at increased risk for bleeding.
The ADA guideline also draws attention to the fact that evidence supports the use of either ticagrelor or clopidogrel if no percutaneous coronary intervention was performed, irf the use of clopidogrel, ticagrelor, or prasugrel if percutaneous coronary intervention was performed.
In Steno-2 Intensified Multifactorial Idt in Patients with Type 2 Diabetes and Microalbuminuriapatients with T2DM and persistent microalbuminuria idc randomized to receive either conventional intervention involving multiple risk factors, or intensified, targeted, multifactorial intervention involving a combination of medications and focused behavior modification.
At the end of this study, all patients in both groups were informed in detail about the benefits of intensified multifactorial treatments, and the primary care providers to whom the patients were referred were educated about this approach. Patients were subsequently followed observationally for idt mean of 5. This follow-up analysis demonstrated that the intensified multifactorial approach had sustained beneficial effects with respect to vascular complications: Early intervention has the greatest impact on micro- and macrovascular complications of T2DM.
Glycemic control therapies should be started as soon as diabetes is detected, and early intervention for blood pressure and lipids is vital. Treatment strategies for these patients will evolve as new drugs are continually being developed. However, lifestyle changes are also essential to any management plan, and although many patients may need pharmacological therapy to 16-2 targets, the benefits of a healthy lifestyle should not be underestimated.
For a newly diagnosed patient, the range of risk factors requiring consideration may seem overwhelming. Integrated care teams incorporating diabetes educators can greatly help in this respect, providing the support patients need to make lifestyle changes, as iidf as adhere closely to treatment regimens.
Working iff the patient to target multiple risk factors with both lifestyle and pharmacological strategies needs time and effort, but gives the best chance of reducing the likelihood of microvascular and macrovascular complications idff the long term. Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Ann Kerrigan of Envision Scientific Solutions during the preparation of this review. Boehringer Ingelheim was given the opportunity to check the data used in the manuscript for factual accuracy only.
National Center for Biotechnology InformationU. Diabetes Metab Syndr Obes. Published online Kdf Author information Copyright and License information Disclaimer. The full terms of the License are available at http: Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. This article has been cited by other articles in PMC.
Abstract Type 2 diabetes mellitus T2DM is commonly accompanied by udf cardiovascular disease CVD risk factors, such as hypertension, obesity, and dyslipidemia. Introduction A seemingly relentless increase in the incidence of diabetes 1 finds us in the midst of a global diabetes id.
Lifestyle interventions Lifestyle management is universally advocated for prevention as well as management of T2DM. Weight loss Weight loss is advised for all overweight or obese patients with T2DM.