10 questions to clarify the management strategy of "type 2 diabetes combined with cardiovascular disease" World Diabetes Day

World Diabetes Day' WDD was jointly launched by the World Health Organization and the International Diabetes Federation in 1991 to raise global awareness
and awareness of diabetes 。 At the end of 2006, the United Nations passed a resolution: from 2007, the "World Diabetes Day" was officially renamed "United Nations Diabetes Day", and the expert and academic behaviors were elevated to the actions of governments of various countries, prompting governments and all sectors of society to strengthen the control of diabetes and reduce the harm of diabetes, and the theme of World Diabetes Day in 2022 is - Diabetes: education to protect tomorrow
.

Cardiovascular disease is an important cause of death in patients with type 2 diabetes, and this paper summarizes the following 10 questions in combination with the "Industry Standard for the Diagnosis and Treatment of Type 2 Diabetes Combined with Cardiovascular Disease" recently issued by the China Endocrine and Metabolic Disease Specialist Alliance, and clarifies the management strategy
of "type 2 diabetes combined with cardiovascular disease".

Diagnostic criteria for type 2 diabetes: 7.
0, 11.
1, 6.
5%

Typical diabetic symptoms plus random venous blood glucose ≥11.
1 mmol/L, or fasting blood glucose ≥ 7.
0 mmol/L, or oral glucose tolerance test (OGTT) 2-hour blood glucose ≥ 11.
1 mmol/L can diagnose diabetes
.
If there are no typical symptoms of diabetes, it is necessary to re-examine and confirm
on another day.

In healthcare facilities that use standardized testing methods and have strict quality control, HbA1c ≥6.
5% can be used as supplementary diagnostic criteria
for diabetes.

Second, blood sugar goals: individualized, most people recommend < 7.
0%

Blood glucose management goals: For most adults with diabetes, the recommended HbA1c control target < 7.
0%.
<b10> For patients with type 2 diabetes with a long duration of diabetes, a history of ASCVD, or a very high risk of ASCVD, the recommended HbA1c control target is <8.
0%.

Elderly diabetic patients with diabetes, high risk of hypoglycemia, chronic kidney disease or other serious diseases need to conduct a comprehensive assessment of their health status and determine individualized glycemic control goals and treatment strategies
.

Third, the choice of hypoglycemic drugs: metformin is the first line, facing a high risk of cardiovascular disease, should be combined with SGLT2i/GLP-1RA

1.
Hypoglycemic drugs with metformin as the first-line treatment
.
Not recommended in patients with acute and decompensated heart failure
.

2.
Whether the HbA1c level is up to standard, combined with ASCVD or ASCVD high risk, and heart failure, it is recommended to use GLP-1RA or SGLT2i drugs with evidence of cardiovascular disease and chronic kidney disease benefits on the basis of standard treatment such as metformin
.
SGLT2i
is preferred for patients with heart failure.

3.
If HbA1c does not meet the standard, a different class of drugs can be added to the above treatment, such as insulin secretagogues, α-glycosidase inhibitors, DPP-4i, thiazolidinedione (TZD) drugs, or basal insulin injection drugs
.

4.
If HbA1c still does not meet the standard, consider multiple injections of insulin, including basal insulin combined with mealtime insulin, or the use of premixed insulin
.

Try to choose drugs that are not likely to cause hypoglycemia, such as metformin, α-glycosidase inhibitors, DPP-4i, SGLT2i, and GLP-1RA.

Fig.
1 Pathway of simple treatment for hyperglycemic patients with type 2 diabetes

Fourth, blood pressure management goals: It is recommended that most people aim for "<130/80mmHg"

For patients with general diabetes and hypertension, the recommended blood pressure target < 130/80 mmHg<b10>.

5.
Antihypertensive program: individualized according to "blood pressure level"

➤ Blood pressure >120/80mmHg: lifestyle interventions should be started immediately to prevent the development of hypertension;

➤ Blood pressure ≥140/90mmHg: antihypertensive drug therapy can be considered;

➤ Blood pressure ≥160/100 mmHg (or target 20/10 mmHg >): antihypertensive therapy should be started immediately, and a combination regimen
should be applied.

Sixth, the choice of antihypertensive drugs: it is not recommended to combine ACE inhibitors and ARBs

The five commonly used antihypertensive drugs are ACEI, ARB, calcium channel blockers, diuretics and selective β receptor blockers, all of which can be used in diabetic patients and angiotensin receptor neprilyprilysin inhibitors (ARNIs)
with newly indicated indications for hypertension.

➤ Single fixed combination (ARB/calcium-channel blocker, ARB, or ACE/diuretic) is preferred in combination regimens;

➤ Support the use of renin-angiotensin-aldosterone system blockers (including ACEI, ARB, ARNI) in patients with evidence of end-organ damage such as proteinuria and left ventricular hypertrophy;

➤ The combination of ACEI and ARB is not recommended
.

7.
Blood lipid control target: It is recommended that the LDL-C target value of ASCVD ultra-high-risk patients is <1.
4mmol/L

Diabetic patients should check blood lipids (including total cholesterol, TG, LDL-C, HDL-C) at least once a year and re-examine after 4~6 weeks of lipid-modifying drugs to understand the efficacy and adverse reactions of patients to lipid-lowering drugs, and repeat every 3~12 months as needed
.
With LDL-C reduction as the goal of treatment, LDL-C is reduced to the target value according to the patient's ASCVD risk level:

➤The target value of LDL-C, the primary intervention target for diabetic patients with ASCVD ultra-high-risk patients, was <1.
4mmol/L;

➤ The LDL-C target for diabetic patients with very high risk of ASCVD is <1.
8mmol/L<b10>.

➤ The LDL-C target for diabetic patients and high-risk patients with ASCVD is <2.
6mmol/L<b10>.

8.
Selection of lipid-regulating drugs: It is recommended to start with moderate-intensity statins

➤Lipid-lowering therapy should be started with medium-strength statins;

➤ If the LDL-C level cannot reach the standard, combined with other lipid-modifying drugs (such as ezetimibe), for very high-risk patients, if statins combined with ezetimibe still do not meet the standard after 4~6 weeks, pre-protein invertase subtilisin Kexin9 inhibitor can be added to obtain a safe and effective lipid-regulating effect and further reduce cardiovascular risk;

➤After statin therapy, if non-LDL-C still cannot reach the target value, fibrates and high-purity fish oil preparations can be added to statins;

➤ For patients with severe hyperTGemia, i.
e.
, fasting TG≥ 5.
7 mmol/L, drugs that mainly reduce TG and VLDL-C (such as fibrates and high-purity fish oil preparations)
should be considered first.

9.
Antiplatelet therapy: the use of aspirin

➤Patients with diabetes mellitus and ASCVD need aspirin (75~150mg/d) as secondary prevention, and the risk of bleeding needs to be fully assessed;

➤Patients with diabetes mellitus and ASCVD at high risk usually need aspirin (75~150mg/d) as primary prevention
.

➤Indications include: age ≥ 50 years with at least one major risk factor (family history of early-onset ASCVD, hypertension, dyslipidemia, smoking, or chronic kidney disease/proteinuria) without high risk
of bleeding.

Risk factors for high bleeding include, but are not limited to, prior gastrointestinal bleeding or peptic ulcer disease, history of bleeding from important organs, low body weight, age > 70 years, thrombocytopenia, coagulopathy, CKD, and concomitant use of drugs that increase the risk of bleeding (eg, nonsteroidal anti-inflammatory drugs, steroids, nonvitamin K antagonists, oral anticoagulants, and warfarin).

10.
Antiplatelet therapy: the use of ticagrelor and clopidogrel

➤Patients with acute coronary syndrome need aspirin in combination with 1 P2Y12 receptor antagonist (ticagrelor or clopidogrel, ticagrelor preferential), that is, dual antiplatelet therapy for at least 1 year
.

➤Patients with chronic coronary syndrome who have a high risk of thrombosis (eg, diabetes mellitus, peripheral vascular disease, history of myocardial infarction) and a low risk of bleeding may consider extending the course of
dual antiplatelet therapy.

➤For patients whose revascularization therapy includes percutaneous coronary intervention or coronary artery bypass grafting, a certain course
of dual antiplatelet therapy is recommended.

➤ Patients with aspirin allergy or intolerance to ASCVD can use clopidogrel alone (75 mg/day) as secondary prophylaxis
.

Reference: China Endocrine Metabolic Disease Specialist Alliance.
Industry standards for the diagnosis and treatment of type 2 diabetes mellitus combined with cardiovascular disease.
Chinese Journal of Endocrinology and Metabolism,2022,38(10): 839-842.