Chronic comorbidities and co-morbidities of diabetes mellitus
I. Diabetes and dyslipidemia
Type 2 diabetes significantly increases the risk of cardiovascular complications, and the National Cholesterol Education Program (NCEP) Adult Treatment Panel III report (ATP III) viewed diabetes as a coronary heart disease equivocal risk, meaning that patients with diabetes have a high absolute risk of coronary heart disease within 10 years, i.e., the percentage of coronary heart disease events occurring within 10 years is ≥20%. The reasons for the high risk of coronary heart disease in diabetic patients are multiple, including hyperglycemia, hypertension, dyslipidemia, smoking, hypercoagulable state and involvement of inflammatory factors. Therefore, in addition to active control of blood glucose and blood pressure in diabetes, attention should be paid to the control of other risk factors for coronary heart disease, including dyslipidemia. Ma Xiaowei, Department of Endocrinology, Peking University First Hospital
(A) Manifestations of dyslipidemia in diabetes mellitus
Type 1 diabetes is often characterized by elevated triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C), as well as elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels without treatment or adequate treatment. With intensive insulin therapy, these lipid and lipoprotein levels can be adjusted to the level of a non-diabetic population of the same age and sex. In addition, LDL-C is susceptible to glycosylation and oxidation in the presence of poor glycemic control. Lipoprotein(a) [Lp(a)] levels are normal or elevated, and elevated Lp(a) levels have been reported in diabetic nephropathy, renal failure, microalbuminuria, or proteinuria.
2. In type 2 diabetes, dyslipidemia is more common, typically manifested by elevated TG and decreased HDL-C, with LDL-C usually not significantly different from the non-diabetic population. Small and dense LDL-C, glycosylated and oxidized LDL-C are increased, and this increase is not necessarily accompanied by an increase in total LDL-C levels. Most studies suggest that in type 2 diabetes, Lp(a) levels do not increase.
3. Dyslipidemia in diabetic patients can also be caused by secondary factors or a combination of secondary factors that should be noted during diagnosis and treatment. Common secondary factors include hypothyroidism, nephrotic syndrome, chronic renal failure, obstructive liver disease, and medications (high-dose thiazide diuretics, beta-blockers, glucocorticoids, etc.). Some patients with severe dyslipidemia may also have a combination of familial inherited lipid metabolism disorders.
(ii) Diabetic lipid control target
LDL-C is an important risk factor for coronary heart disease, and the clinical trial of LDL-C reduction (4S, CARE*) also proved that LDL-C reduction can significantly reduce the incidence of coronary events in diabetic patients, and its effect is greater than or equal to that of non-diabetic population. the control target of LDL-C should be the same as that of people who already have coronary heart disease, i.e. LDL-C <2.5 mmol/L. Since LDL-C accounts for 60% to 70% of TC, with the reduction of LDL-C, TC can also be reduced to the target level.
Low HDL-C levels are inversely correlated with the prevalence of coronary heart disease, and HDL-C is a strong predictor of coronary heart disease in diabetic patients, so HDL-C levels should be >1.1 mmol/L. Several studies and analyses in recent years have shown that high TG is an independent risk factor for coronary heart disease, mainly because certain triglyceride-rich lipoproteins (TGRL) are atherogenic, and in addition In addition, high TG is often combined with other dyslipidemia and metabolic syndrome such as low HDL-C, and TG should be controlled at <1.5 mmol/L.
4S = Scandinavian Simvastatin Survival Trial; CARE = Cholesterol and Relapsing Events Trial
(iii) Treatment of dyslipidemia
The management of dyslipidemia includes diet modification, exercise, weight reduction, glycemic control and use of lipid-lowering drugs.
1. Diet modification and exercise are the basis of lipid regulation therapy. Through diet modification and exercise, weight and TG can be reduced, HDL-C can be increased and LDL-C can be mildly reduced.
This principle is a general requirement for dietary modification, and the actual application should be individualized. Targeted measures should be taken according to the patient’s lipid profile and control goals for blood glucose and body weight. For those with predominantly high LDL-C and TC, LDL-C and TC can be reduced by reducing saturated fatty acid and cholesterol intake, with the caloric portion of the reduction of saturated fatty acids being compensated mainly by increasing carbohydrates or monounsaturated fatty acids. The use of plant sterols (2 g/d) and viscous fiber (10-25 g/d) can help to further reduce LDL-C and TC.
In type 2 diabetic patients with obesity, high TG and low HDL-C with metabolic syndrome as the main manifestation, weight control (control of total calories and increased exercise) and appropriate carbohydrate control (50% of total calories from carbohydrates) are the main options. Excessive carbohydrates () 60% of total calories) are often associated with lower HDL-C and higher TG. Patients are encouraged to get specific dietary guidance through a dietitian, to quit smoking and reduce alcohol consumption, and to change poor lifestyles.
2. For type 1 diabetes without complications, dyslipidemia can be completely corrected through the use of insulin and strict glycemic control. For type 2 diabetes, ideal blood glucose control can reduce TG, HDL-C level is unchanged or mildly elevated, and LDL-C level can be mildly reduced.
3.Commonly used lipid regulating drugs.
(1) Statins: Statins are hydroxymethylglutaryl coenzyme A (HMG-COA) reductase inhibitors, which mainly reduce LDL-C and TC, and have a certain degree of TG reduction, but may require higher doses. Statins are usually taken after dinner or at bedtime and are well tolerated by most people. Their main side effects are elevated liver enzymes and myopathy and are contraindicated in patients with active and chronic liver disease.
(2) Bile acid binding resin: mainly used to reduce LDL-C and TC, the main side effects of the drug include gastrointestinal symptoms and reduced absorption of certain concomitant drugs. The drug is contraindicated in familial abnormal β-lipoproteinemia and is contraindicated in patients with TG > 4.5 mmol/L due to the tendency to elevate TG, and is relatively contraindicated in those with TG > 2.3 mmol/L.
(3) Niacin and niacin derivatives: Niacin can reduce TG, LDL-C and Lp(a), and can also increase HDL-C and convert small LDL to normal size LDL. the main side effects are hepatotoxicity, hyperuricemia and increased blood glucose. It is generally accepted that high-dose niacin (3g/d) should be avoided in patients with type 2 diabetes and that low-dose niacin (<2g/d) may be considered. Niacin is contraindicated in patients with chronic liver disease and severe gout. The niacin derivative acipimox has milder side effects and can be used for type 2 diabetes.
(4) Fibric acid derivatives: i.e. fibrate lipid regulators, mainly for lowering TG and raising HDL-C, and to some extent lowering LDL-C. The main side effects include gastrointestinal symptoms, cholelithiasis, reversible myopathy with elevated creatine kinase, not suitable for patients with severe liver and kidney damage, and should be used with caution or avoided in diabetic patients with renal impairment.
(5) Other lipid-regulating drugs: n-3 fatty acids [linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] can lower TG at larger doses and can be used as an option in the treatment of hyper-TGemia. Current studies have concluded that estrogen replacement therapy is not recommended for treatment aimed at preventing coronary heart disease.
4.The choice of lipid-regulating therapy
(1) Treatment of high LDL-C: The American Diabetes Association (ADA) recommends that if a diabetic patient has combined coronary heart disease or macrovascular disease, when LDL-C ≥ 2.6 mmol/L, drug therapy should be started along with diet, exercise and other lifestyle adjustments; if not accompanied by coronary heart disease or macrovascular disease, when LDL-C ≥ 3.35 mmol/L, diet, exercise and drug therapy; when LDL-C is between 2.6 and 3.35 mmol/L, diet and exercise therapy can be considered first, and drug therapy can be added when the effect is unsatisfactory. Blood glucose control and lipid regulating treatment should be carried out simultaneously. Statins are preferred for drug therapy, followed by bile acid binding resin or fenofibrate (which has better LDL-C lowering effect and is especially suitable for mixed hyperlipidemia). When LDL-C is high and the treatment does not reach the target, consider increasing the dose of statins or combination of drugs, such as statins combined with bile acid binding resin, etc.
(2) Treatment of high TG: Firstly, lifestyle changes, weight reduction, alcohol restriction and strict control of blood sugar are very effective in reducing TG. After blood glucose has been controlled as much as possible, drug therapy can be considered, and drug therapy can be started when TG is 2.3-4.5 mmol/L. Fibrates are preferred, and statins are effective in treating high TG with high LDL-C.
(3) Treatment of mixed hyperlipidemia (high LDL-C and TG): statins can be considered while controlling blood sugar, and higher doses of statins can effectively reduce TG levels. If LDL-C has been achieved, TG ≥ 2.3 mmol/L may be considered for replacement with fibrates or in combination with statins; such combination increases the risk of myopathy and should be used with special caution. In some cases, TG>5.6 mmol/L, the therapeutic goal is first to prevent acute pancreatitis by lowering TG, and only when TG<5.6 mmol/L can attention be focused on lowering LDL-C.
(4) Treatment of hypoHDL-Cemia: Although weight reduction, exercise, smoking cessation and glycemic control are effective in raising HDL-C, pharmacological treatment is required in most cases. Niacin analogs are effective in raising HDL-C, but should be used with caution, in addition to fibrate derivatives.
(iv) Baseline examination, follow-up monitoring and medication adherence
It is recommended that diabetic patients have their blood lipids checked once a year, including TC, TG, HDL-C, LDL-C (calculated by formula or directly measured). According to the lipid examination, if non-lipid-regulating medication such as diet and exercise is started first, the lipid level will be rechecked after 3 months and the treatment will continue after reaching the target, which can be rechecked every 6 to 12 months; if medication is started, the first follow-up is usually 6 to 8 weeks after the medication, which can be changed to every 4 to 6 months or longer (once a year) if the treatment target can be reached. If the target is not achieved after starting treatment, it may be necessary to increase the dose, combine medications or change medications, and still follow up every 6 to 8 weeks until the target is achieved and then reduced to every 4 to 6 months or longer. Follow-up visits include evaluation of lipid-regulating effects and side effects. Follow-up helps patients to adhere to their medication, and patient adherence is an important measure to reduce the risk of coronary heart disease.
II. Diabetes and hypertension
Diabetes mellitus and hypertension are often combined and are extremely dangerous to the cardiovascular system. type 1 diabetes mellitus mostly develops after complications of nephropathy, while type 2 diabetes mellitus is often combined with primary hypertension, which can occur before, at the same time or after the onset of type 2 diabetes mellitus. Active intervention and treatment of people with diabetes mellitus combined with hypertension based on cardiovascular risk assessment is of great importance to prevent macrovascular and microvascular complications of diabetes mellitus, prevent cardiovascular events and improve the quality of survival and prolong the life span of patients.
This section is not suitable for pregnant patients with diabetes mellitus and hypertension.
(I) Cardiovascular system hazards
The combined presence of hypertension and diabetes mellitus has a multiplicative effect on cardiovascular hazards. Hypertension can increase cardiovascular risk in patients with diabetes by nearly twofold, so the net effect of the coexistence of the two on cardiovascular risk is four to eight times greater than in the general population. Similarly, diabetes can increase cardiovascular risk in the hypertensive population by a factor of 2. Thus, when hypertension and diabetes coexist in a population, the chances of atherosclerosis are greatly increased and the probability of developing cardiovascular disease is estimated to be as high as 50%, with coronary heart disease up to 25%, and the risk of cardiovascular death is significantly higher.
According to the guidelines for the prevention and treatment of hypertension developed in 1999, the risk of diabetes combined with hypertension is equivalent to hypertension combined with three risk factors. The risk stratification of hypertension in combination with diabetes is above “high risk”, and diabetes itself is often associated with multiple risk factors, and the occurrence of ocular, renal, cardiovascular and cerebrovascular complications overlap with hypertension. As a result, the risk stratification for the coexistence of the two can often reach “very high risk” levels (Tables 14-3, 14-4).
Hypertension is also a major risk factor for the characteristic microangiopathy of diabetes and may play a greater role than hyperglycemia, with results from the UKPDS prospective study of diabetes showing that lowering blood pressure reduces the risk of microvascular complications by 37%, whereas lowering blood glucose reduces it by only 25%.
Notably, this evidence suggests that hypertension is more associated with the characteristic microangiopathy of diabetes than hyperglycemia, and diabetes is more associated with cardiovascular disease than hypertension.
(ii) Diagnosis and Screening
Blood pressure is measured at the same time as diabetes screening, and blood pressure measurement must be an integral part of the daily diabetes clinic, with measurements in different positions if necessary to detect the effect of autonomic neuropathy on blood pressure.
If systolic blood pressure ≥ 130 mmHg or (and) diastolic blood pressure ≥ 80 mmHg are found at the clinic, repeat measurements should be performed on another day to confirm whether blood pressure is elevated.
For people with hypertension (blood pressure ≥140/90 mmHg), blood glucose or postprandial glucose testing should be performed if available, and for those who also have other risk factors such as obesity, family history of diabetes, and age ≥40 years, blood glucose testing is mandatory.
Blood pressure measurement and blood glucose testing should be performed at a certain frequency to detect the combined presence of the two diseases in a timely manner. All diabetic patients should have their blood pressure measured every 3 months, and for those with elevated blood pressure and receiving antihypertensive therapy, it is appropriate to encourage patients to measure their own blood pressure or increase the frequency of blood pressure testing to at least once a week.
(C) Treatment
1.Treatment purpose
(1) To reduce the occurrence of macrovascular and microvascular complications of diabetes.
(2) To protect target organs vulnerable to hypertension damage.
(3) To reduce the rate of death and disability, improve the quality of life of patients and prolong life expectancy.
2.Control targets and blood pressure detection
(1) The general control target is blood pressure ≤ 130/80 mmHg
(2) In the elderly should be ≤ 140/90 mmHg
(3) If the 24-hour urine albumin ≥ 1g, blood pressure should be ≤ 125/75 mmHg
(4) The trough-to-peak ratio within 24 hours of drug therapy should be ≥ 50%.
(5) Patients with diabetes mellitus should begin intervention when blood pressure is ≥130/80 mmHg.
(6) Blood pressure control should be closely monitored after starting treatment to ensure that control meets the standard.
3.Non-pharmacological treatment
Non-pharmacological treatment refers to the optimization of behavior and lifestyle, and should be the basis of treatment of diabetic hypertension and interventions for early blood pressure elevation. Non-pharmacological interventions are advocated at blood pressure levels of 130 to 139/80 to 89 mmHg for up to 3 months, with pharmacological treatment initiated if ineffective. Nonpharmacologic interventions include.
(1) Smoking cessation. All patients should be strongly recommended to quit smoking in the daily clinic, with reasonable counseling and pharmacologic cessation if necessary.
(2) Weight loss, at least 5 kg for those who are 10% or more overweight
(3) Moderate alcohol consumption, men should consume less than 20-30g of ethanol per day, women less than 10-20g.
(4) Restrict sodium salt, sodium chloride ≤ 6g per day.
(5) Optimize diet structure, eat more fruits and vegetables, and reduce fat intake. There is no clear evidence that other measures such as micronutrient supplementation, adding calcium, magnesium, fiber or fish oil are effective.
(6) Enhance physical activity, such as brisk walking or swimming, for 30 minutes five times a week.
(7) Relieve psychological stress and maintain an optimistic state of mind.
4.Drug treatment principles
(1) advocate small doses of monotherapy, such as ineffective to take a combination of drugs, generally do not advocate super conventional dose increase.
(2) Take into account the target organ protection and the benefits of complications while controlling the target.
(3) Avoid drug side effects, such as adverse effects on target organs and metabolism.
5.Indications and contraindications of antihypertensive drugs
6.The combination of drugs
The combination of drugs can reduce the side effects of single drugs with increased doses, enhance the efficacy by using synergistic effects, offset the side effects between each other, and have a comprehensive protective effect on the target organs, and the combination of drugs is often an inevitable trend in secondary and tertiary prevention. The currently recommended combination regimens include.
(1) angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) with diuretics
(2) Calcium channel blocker (CCB) and beta-blocker.
(3) ACEI vs. CCB.
(4) Diuretics vs. beta-blockers.
(5) Recommend the development and production of suitable compound preparations, such as low-dose ACEI plus low-dose diuretics, there are many such preparations abroad, and the clinical efficacy is certain.