1. Case overview
Sun Moumou, male, 54 years old, a middle-level cadre of a governmental organ, visited the community health service station because of “increased blood glucose and blood lipids for 10 days”, without “thirst, excessive drinking, polyuria, polyphagia and emaciation, no palpitation, chest tightness, no numbness or pain in the limbs”. The patient usually likes to eat sweets and high-fat food such as animal offal, and has little activity and no exercise every day. Physical examination: height 171 cm, weight 83 kg, body mass index (BMI) 28.4 kg/O, waist circumference 97 cm, blood pressure 125/75 mmHg, no abnormal cardiopulmonary auscultation, no edema in both lower limbs, no diminished dorsalis pedis artery pulsation bilaterally. Laboratory examination: fasting glucose 7.10 mmol/L, triglyceride (TG) 3.91 mmol/L, total cholesterol (TC) 6.89 mmol/L, HDL-C (HDL-C) 1.10 mmol/L, LDL-C (LDL-C) 4.27 mmol/L, normal liver and kidney function. He had no history of hypertension, coronary artery disease, intermittent claudication, denied history of drug allergy, and had a history of smoking and alcohol consumption. His father and brother had diabetes mellitus.
2. Initial diagnosis and management by the general practitioner
I. Medical history characteristics
(1) The patient had several risk factors for diabetes, including age >45 years, obese body type, family history of diabetes, waist circumference ≥90 cm, dyslipidemia, and sedentary lifestyle. However, blood pressure was normal.
(2) The patient’s lifestyle was unhealthy, with a preference for high-sugar and high-fat foods, alcohol and tobacco consumption, and low daily activity and physical inactivity.
(3) The patient had elevated blood glucose and lipids in the past physical examination, but because they were mildly elevated, the patient did not pay attention to them.
(4) The current laboratory tests revealed hyperglycemia, hyper-TGemia, hyper-TCemia and hyper-LDL-Cemia, so the diagnosis of diabetes mellitus with dyslipidemia was initially considered.
II. Preliminary treatment
To clarify the diagnosis of diabetes mellitus and hyperlipidemia, the general practitioner ordered the patient to receive venous blood sampling early the next morning after fasting for 8 hours, and measured fasting blood glucose, 2-hour postprandial blood glucose and lipid levels, the results were fasting blood glucose 7.4 mmol/L, 2-hour postprandial blood glucose 14.8 mmol/L, TG 3.67 mmol/L, TC 6.92 mmol/L, HDL-C 1.07 Based on the examination results, the community general practitioner initially diagnosed the patient as having diabetes mellitus with mixed hyperlipidemia. Later, the general practitioner performed other tests to further clarify the patient’s condition. The results were as follows: glycated hemoglobin 6.8%, urinary albumin/creatinine ratio 15 mg/g, and normal urinary routine. Since the patient was newly diagnosed with diabetes mellitus, he had to be referred to a general hospital to clarify the diagnostic classification and understand the chronic complications of diabetes mellitus, so the general practitioner referred the patient.
3. Endocrine specialist’s consultation and treatment
After the patient was referred to the endocrine specialist at the general hospital, she was tested for fasting insulin, fasting C-peptide, 2-hour postprandial insulin and 2-hour postprandial C-peptide, and also tested for islet autoimmune markers including glutamic acid decarboxylase antibody, anti-islet cell antibody and protein tyrosine phosphatase-like protein antibody. type 2 diabetes. In addition, the specialist screened the patient for chronic complications of diabetes including diabetic microangiopathy and macroangiopathy. The screening for diabetic microangiopathy included urine microalbumin, fundus photography and electromyography; the screening for diabetic macroangiopathy included carotid vascular ultrasound, lower limb arterial ultrasound and electrocardiogram. Liver and kidney function and lipid levels were also reviewed. After the comprehensive examination, the specialist diagnosed the patient with type 2 diabetes mellitus with macroangiopathy and mixed hyperlipidemia, and gave the patient lifestyle interventions including diet control, exercise therapy, correction of poor lifestyle including smoking cessation and reduction of alcohol consumption, and medication. Pharmacological treatment included glycemic control with metformin 500 mg Tid, along with atorvastatin 20 mg Qd for lipid control and stable control of atherosclerotic plaque, and aspirin 100 mg QN for prevention of cardiovascular and cerebrovascular events. After 9 days of hospitalization, the patient’s blood glucose was well controlled, so he was transferred back to the community for further treatment.
4. The general practitioner developed a long-term management plan
(1) Characteristics of diabetes mellitus combined with hyperlipidemia
The incidence of dyslipidemia in type 2 diabetic patients is significantly higher than that in non-diabetic patients. According to the survey, the rate of type 2 diabetic patients with dyslipidemia in China is 78.51%, but the awareness rate of patients is only 55.5%, and the overall treatment rate of dyslipidemia is only 44.8%. The dyslipidemia in type 2 diabetes is related to a variety of factors, such as hyperinsulinemia, abdominal obesity and other metabolic disorders, and the dyslipidemia in type 2 diabetes is mostly mixed hyperlipidemia. The characteristic lipid profile includes: elevated fasting and postprandial TG levels, decreased HDL-C levels, normal or mildly elevated TC levels and LDL-C, and more importantly, a change in the nature of LDL-C in patients, with more conversion to small and dense LDL-C, which has a stronger role in atherosclerotic lesions.
(2) Diagnosis of hyperlipidemia in combination with diabetes mellitus
According to the guidelines for the prevention and treatment of dyslipidemia in Chinese adults (2007), the appropriate range of serum TC in Chinese is <5.18 mmol/L (200mg/dl), 5.18-6.19 mmol/L (200-239mg/dl) is borderline elevated, and ≥6.22 mmol/L (240mg/dl) is elevated; the appropriate range of serum LDL-C is <3.37 mmol/L (130mg/dl), 3.37-4.12 mmol/L (130-159mg/dl) as borderline elevation, ≥4.14 mmol/L (240mg/dl) as elevation; serum HDL-C in the appropriate range of ≥1.04 mmol/L (40mg/dl), ≥1.55 mmol/L ( 60 mg/dl) as elevated and <1.04 mmol/L (40 mg/dl) as decreased; the appropriate range of TG was <1.70 mmol/L (150 mg/dl), 1.70-2.25 mmol/L (150-199 mg/dl) as borderline elevated, and ≥2.26 mmol/L (200 mg/dl) as elevated.
According to the above diagnostic criteria, this patient had hyper-TGemia, hyper-TCemia and hyper-LDL-Cemia, and therefore was diagnosed with mixed hyperlipidemia.
(3) Strategies and targets of lipid-regulating therapy in patients with type 2 diabetes mellitus
Whether patients with type 2 diabetes mellitus with dyslipidemia need lipid-regulating therapy and the choice of drug therapy should be based on a comprehensive assessment of the risk of cardiovascular events, so the assessment of cardiovascular risk before drug therapy for patients with diabetes mellitus with hyperlipidemia is crucial. High-risk groups include: (1) those without cardiovascular disease but aged 40 years with more than 1 risk factor for cardiovascular disease (hypertension, smoking, obesity, microalbuminuria, family history of early-onset ischemic cardiovascular disease, age >45 years in men, age >55 years in women, postmenopausal women, etc.). (2) No cardiovascular disease, age <40 years, but LDL-C ≥2. 6 mmol/ L (100 mg/ dl) or a combination of multiple risk factors. Patients with diabetes mellitus combined with cardiovascular disease, diabetes mellitus combined with carotid plaque or stenosis, and diabetes mellitus combined with peripheral arterial disease were considered to be at very high risk, regardless of their baseline LDL-C levels.
According to the clinical characteristics of this patient, not only the combination of several cardiovascular disease risk factors including male age >45 years, smoking, obesity, etc., but also the combination of diabetic macrovascular disease, so it is a very high-risk group.
Interventions for dyslipidemia in type 2 diabetic patients should be based on therapeutic lifestyle changes and should be carried out throughout the treatment of type 2 diabetes. Therapeutic lifestyle changes include dietary modification (reducing the intake of saturated fatty acids and TC and controlling the intake of carbohydrates), increasing exercise, reducing body weight, quitting smoking, limiting alcohol and limiting salt.
In lipid-modifying therapy, LDL-C reduction should be the primary goal, and LDL-C control goals are: for patients at high risk of cardiovascular disease, statins are preferred, with LDL-C target values < 2. 6 mmol/ L (100 mg/ dl); for very high-risk patients, statin lipid-modifying drugs are immediately selected, with LDL-C target values < 2. 07 mmol/ L (80 mg/ dl). If these goals are not achieved after treatment with the maximum tolerated dose of statins, a 30-40% reduction in LDL-C from baseline is recommended as a target value, and other lipid-modifying agents such as TC absorption inhibitors can also be used in combination.
The treatment goal for hyper-TGemia is TG<1. 7 mmol/ L (150 mg/ dl), emphasizing strict glycemic control first, and TG can be normalized in some patients after glycemic control; for TG in the range of 1. 70-2. 25 mmol/ L, therapeutic lifestyle interventions should be started first; for TG in the range of 2. 26-4. 5 mmol/ L, therapeutic lifestyle interventions should be started at the same time. If TG is >4. 5 mmol/ L, first consider rapid reduction of TG levels with fibrates.
The therapeutic goals for hypoHDL-Cemia are: in case of hyperLDL-Cemia, the primary goal remains to lower LDL-C; for HDL-C: >1. 04 mmol/L (40 mg/dl) in men and >1. 4 mmol/L (50 mg/dl) in women. This can be achieved by therapeutic lifestyle interventions or by the use of fibrates.
The goals of treatment for mixed hyperlipidemia are to emphasize first strict glycemic control and intensive therapeutic lifestyle interventions. The primary goal is still to lower LDL-C, and statin lipid modifying drugs can be preferred, if LDL-C has been achieved, TG is still ≥ 2. 3 mmol/ L. Switch to fibrates or combine with statins. If TG > 4. 5 mmol/ L betablockers are preferred, if TG < 4. 5 mmol/ L, LDL-C level should be reduced.
According to this patient’s condition, he belongs to a very high-risk group, with TG, TC and LDL-C not meeting the standard, so he was immediately given statin lipid-lowering drug atorvastatin for treatment based on therapeutic lifestyle intervention, with the primary goal of controlling LDL-C to < 2. 07 mmol/ L. After a period of treatment, blood lipids were reviewed and the next treatment plan was adjusted according to the lipid profile.
5. Timing and frequency of lipid testing in patients with type 2 diabetes
After the patient was transferred back to the community hospital, the general practitioner reinforced the patient’s education according to his specific situation and asked him to change his bad lifestyle including quitting smoking, increasing exercise and controlling diet. Patients were also advised to monitor their lipids according to the following principles.
All patients with newly diagnosed type 2 diabetes should have their lipid levels tested at the time of diagnosis. If the patient has normal lipids and no other cardiovascular disease risk, lipid levels should be tested at least once a year during diabetes treatment; if the patient has normal lipid levels but multiple cardiovascular risk factors are present, lipids should be monitored every 3 months after the diagnosis of diabetes; for patients with dyslipidemia in type 2 diabetes, if only For patients with dyslipidemia in type 2 diabetes, if only therapeutic lifestyle interventions are given, it is recommended to review the lipids after 6-8 weeks to decide whether the treatment plan needs to be adjusted; for patients given lipid-regulating drugs, the lipid level should be monitored after 4 weeks of initial treatment, and if the standard is still not reached, the treatment plan should be adjusted and reviewed after 4 weeks; for diabetic patients whose lipid levels are controlled to the standard, it is recommended to monitor the lipids once every 6 months.
6.Several considerations in the treatment of lipid-lowering drugs
(1) Dose and efficacy of lipid-regulating drugs
The lipid-lowering effect of the standard dose of statins is already obvious, so it is not advisable to increase the dose of the drugs excessively for the sake of pursuing a lower LDL-C target value, and it can be combined with other lipid-regulating drugs such as TC absorption inhibitors if necessary.
(2) Safety of combined drug use
Unless the dyslipidemia is particularly serious, it is generally not recommended to combine medications, and attention should be paid to safety when combining medications, because the side effects of combining medications increase significantly. For example, the dose of statins and fibrates in combination should be small, the two drugs should be taken separately, monitored closely, and the elderly should be cautious and stop the drugs in time once abnormalities appear. Comparatively speaking, the combination of statins and TC absorption inhibitor ezetimibe is safer and can be considered clinically.
(3) The need for long-term maintenance therapy
Patients with diabetic dyslipidemia who have achieved the lipid standard through lipid regulation therapy still need long-term maintenance therapy in small doses to maintain the normal lipid target value, so that they can benefit more clinically. It is necessary to avoid discontinuing lipid-regulating drugs after the lipid level is normalized in order to prevent the rebound of lipid level.
(4) Use of niacin lipid-lowering drugs
Since niacin lipid-lowering drugs can lead to abnormal glucose metabolism or deterioration of glucose tolerance, they are generally not recommended for diabetic patients, and if they must be used, blood glucose levels should be monitored regularly.
(5) Monitoring of adverse reactions during drug treatment
The safety of lipid-regulating drugs should be closely monitored, especially in patients of advanced age, low body weight, multi-system diseases, simultaneous use of multiple drugs and perioperative period.
It is recommended to monitor liver function and creatine kinase regularly before treatment and half a month after the start of treatment. If AST and ALT are still more than 3 times the upper limit of normal, it is recommended to suspend the dose and to recheck liver function every week after discontinuation until it returns to normal. If liver function is normal, monitoring is recommended every 3 months.
If there are symptoms of myopathy including muscle pain or weakness, creatine kinase should be tested immediately; if muscle symptoms occur and CK is >5 times the upper limit of normal, discontinue the statin; if CK is >3-5 times the upper limit of normal, monitor the symptoms and CK level weekly and reduce or discontinue the drug if CK gradually increases.
The most common adverse effect of fibrates is gastrointestinal reactions. Therefore, liver and kidney function should be monitored half a month after the start of treatment; individual patients may also experience drug rhabdomyolysis after taking the drug, and blood CK level should be tested immediately if there are the above symptoms. In addition, patients with a history of gallbladder disease or gallstone disorders are prohibited because this drug can increase the secretion of TC into the bile, which can cause gallstones and requires attention.