Editor's note: For patients, especially those with chronic diseases such as diabetes, they often need long-term medication. Therefore, therapeutic drugs must not only ensure stable efficacy, but also withstand the long-term persistence of patients. In the "Dazao New Forces" 2021 Degu Insulin Quality Compliance Case Competition, Dr. Zhang Qi, Physician of the Department of Endocrinology, Affiliated Hospital of Weifang Medical College, shared the experience of how a patient with type 2 diabetes (T2DM) with poor blood glucose control achieved stable blood glucose standards through medication treatment adjustment.
Qi Zhang, Physician
The Affiliated Hospital of Weifang Medical College
Case profile
The patient, a 45-year-old woman, was admitted to the hospital mainly for "finding high blood sugar for 10 years and poor glycemic control in February".
Present medical history
10 years ago, the patient's physical examination found that the blood sugar was elevated, the fasting blood glucose (FPG) > 10 mmol/L, the local hospital diagnosed "diabetes", and the "metformin and glimepiride" were given to lower the sugar (specific unknown), and the blood glucose control was up to standard. 5 years ago, the patient's blood glucose gradually increased, FPG 9 ~ 10 mmol / L, there were acid reflux, heartburn and other gastrointestinal reactions, adjusted the hypoglycemic regimen as "insulin glargine U100 12 u qd + acarbose 100 mg tid", insulin glargine U100 gradually increased to 20 u / d. In the past 2 months, the patients had 8 to 9 mmol/L FPG, 14 to 16 mmol/L blood glucose (PPG) 2 h after meals, and had symptoms of pre-meal or night panic and sweating, with an average of 1 to 2 times a month, measuring random blood glucose 3.7 mmol/L, complaining of fear of hypoglycemia reactions, and gaining 1 kg of weight in the past 2 months.
Past history
20 years after caesarean section, denial of history of hypertension and coronary heart disease.
History of marriage and childbearing
Plain menstrual regularity. She had 1 daughter with a birth weight of 3.2 kg and denied abnormal blood glucose during pregnancy.
Family history
His mother was deceased, suffered from "diabetes" and died of "myocardial infarction".
physical examination
Height 163 cm, weight 67.5 kg, BMI 25.4 kg/m2, waist circumference 84 cm, blood pressure 123/77 mm Hg. There are no abnormalities in the head and neck, and no obvious positive signs are seen on heart, lung, or physical examination. A longitudinal surgical scar of about 8 cm long can be seen in the middle of the lower abdomen and heals well. Muscle strength and tone of the limbs are normal, the skin temperature of both lower limbs is normal, there is no edema, and the dorsal artery pulsation of both feet is normal. Lower extremity depth sensory, negative double Babinski sign, negative meningeal irritation sign.
Adjunctive testing
On June 2, 2020, the examination center saw: blood glucose: FPG 9.2 mmol/L↑, HbA1c8.7%↑; lipids: TG 4.29 mmol/L↑, LDL-C 4.2 mmol/L↑, HDL-C 1.32 mmol/L, TC 6.28 mmol/L↑. Liver function, kidney function, and nail function are normal. Ultrasound of the abdomen: fatty liver (mild). Cardiac ultrasound and cervical vascular ultrasound did not see significant abnormalities.
On June 9, 2020, the endocrinology outpatient examination was as follows: FPG 9.0 mmol/L↑, PPG 13.2 mmol/L↑, fasting C-peptide 0.85 ng/ml (reference value 0.8 to 4.2 ng/ml), indicating insufficient endogenous insulin secretion and impaired islet function; urinary albumin creatinine ratio (ACR) 10.2 mg/g; and negative diabetes antibody test. No significant abnormalities were seen on fundus examination.
Initial diagnosis
1, T2DM;2, hyperlipidemia
Diagnosis and treatment ideas and experiences
The patient is a middle-aged woman with a diabetic history of up to 10 years, preprandial blood glucose and PPG are not up to standard, and PPG relative to preprandial blood glucose increase is not too high, mainly FPG and preprandial blood glucose is not up to standard, resulting in poor overall blood glucose control, HbA1c8.7%, there is endogenous insulin secretion is insufficient, so insulin therapy is needed; at the same time, with elevated blood lipids, overweight, no history of smoking, hypertension, no target organ damage, so the blood glucose control goal is relatively strict; patients have repeatedly experienced panic, Hypoglycemic reactions such as sweating, weight gain of 1 kg in the past 2 months.
Adjust the hypoglycemic regimen for the patient according to the characteristics of the disease. Because the patient could not tolerate the gastrointestinal reaction caused by the drug, the acarbose 100 mg tid was replaced by dapagliflozin 10 mg qd, and the dose of insulin glargine U100 was increased from 20 u qd to 24 u qd, taking into account that the patient's preprandial blood glucose was not up to standard. After adjusting the plan for a period of time, although the preprandial blood glucose and PPG have decreased, they still do not meet the standard (Figure 1). The patient was not satisfied with the treatment effect and came to the outpatient clinic again after 1 week to adjust the plan. Analyze the reasons for its blood glucose failure, is the irrational diet structure? Not exercising enough? Stressed at work, poor rest and sleep? Or is there a problem with the choice of hypoglycemic drugs or the dosage is not in place?
Figure 1. After the initial adjustment of the hypoglycemic regimen, glycemic control is still not up to standard (mmol/L)
The glycemic management decision-making ring in the 2020 ADA Guidelines[1] proposes collaborative, patient-centered care designed to prevent or delay complications and improve quality of life. Further analysis of the patient's characteristics: civilian staff, nine to five, less work pressure; lack of concept of food mixing and quantity control, eating at the unit at noon, less exercise; medium economic base, can afford to spend 300 to 400 yuan / month on hypoglycemic drugs; emotional anxiety, fear of hypoglycemia or blood sugar fluctuations; overweight body type, do not want to continue to gain weight. Therefore, the individual characteristics of the patient and the characteristics of the disease need to be formulated for an individualized treatment plan.
According to the 2020 CDS guidelines[2], first-line treatment of metformin is preferred on the basis of adherence to medical nutritional therapy and exercise therapy. However, the patient cannot tolerate the gastrointestinal response caused by metformin and does not have comorbidities such as ASCVD, heart failure, or chronic kidney disease, so other oral hypoglycemic agents or injectable agents may be considered. The patient's islet function is impaired and endogenous insulin secretion is insufficient, making him unsuitable for insulin secretagogues; in addition, there is still a large distance between the patient's blood glucose level and his target value, so basal insulin in combination with other oral hypoglycemic drugs that do not cause gastrointestinal irritation can be selected. Guidelines [2] also state that if the patient has a need to lose weight, a drug with a weight-loss effect, such as an SGLT2 inhibitor, may be selected. At the same time, some of the ideas of the ADA guideline [1] can be adopted, which recommends that drugs with a low risk of hypoglycemia be given priority when selecting basal insulin, and point out that the risk of hypoglycemia is in order of degu insulin/insulin glargine U300
Individualized glycemic control targets were set for HbA1c for this patient
The clinical need for ideal basal insulin is closer to physiological secretion, that is, stable glucose control at 24 h, low blood glucose variability, low risk of hypoglycemia, and flexible injection. The new generation of long-acting basal insulin analogue Degu insulin has a longer half-life, less blood glucose fluctuations, and is truly stable in sugar control for 24 h a day, closer to physiological insulin secretion [3], meeting the clinical needs of basal insulin treatment. The study found that the daytime variability of the hypoglycemic effect of Degu insulin was only one-fourth of that of insulin glargine, with smaller blood glucose fluctuations and smoother sugar control [4]. The EU-TREAT study found that patients with T2DM who switched from other basal insulin to deglue insulin were significantly improved in both HbA1c and FPG after six months of treatment with other basal insulins[ 5]. This is a great advantage for diabetic patients, especially those who often have hypoglycemia and are afraid of hypoglycemia.
Therefore, the patient's hypoglycemic regimen of insulin glargine U100 was replaced by degu insulin 24 u qd, and the oral drug remained unchanged. After 3 days of treatment, the patient's FPG dropped to 4.2 mmol/L, no hypoglycemia occurred, and PPG decreased, so the dose of Degu insulin was reduced to 20 u qd; after 10 days, the blood glucose continued to decline, and the dose of Degu insulin was gradually reduced to 14 u qd, and the final preprandial blood glucose was maintained at 5.6 to 6.3 mmol/L, and the PPG was 7.3 to 8.9 mmol/L (Figure 2).
Figure 2. Blood glucose is gradually controlled after re-adjustment of the treatment regimen (mmol/L)
After several rounds of drug and dose adjustment, the final hypoglycemic regimen was deglue insulin 14 u qd + dapagliflozin 10 mg qd, and the patient did not have a hypoglycemic reaction again, and the weight dropped to 65 kg, which was 2.5 kg less than at the time of initial diagnosis. The monthly treatment cost is about 400 yuan, the patient can accept and maintain for a long time, and the "1 needle + 1 tablet" program is considered convenient to implement. After 3 months of follow-up, the patient's preprandial blood glucose control was 5.2-5.8 mmol/L, PPG was 7.8-8.9 mmol/L, and HbA1c5.8%, all of which met the standards. Ambulatory blood glucose monitoring showed that the blood glucose was stable throughout the day, no nighttime hypoglycemia occurred, and the TIR > 98% per day (Figure 3), and both doctors and patients were satisfied with the treatment effect.
Figure 3. After adjusting the treatment plan, the blood glucose reached a stable standard throughout the day, and the TIR > 98%
Treatment tips
Glycemic control requires multiple dimensions of "blood glucose variability, hypoglycemia, and HbA1c". In the process of blood glucose management, it is necessary to emphasize the patient-centered collaborative blood glucose management model and improve patient participation. In terms of insulin therapy, Degu insulin blood glucose control is more stable, the risk of hypoglycemia is smaller, the dose is more conservic, more economical, and it is the preferred drug in basal insulin.
bibliography
1. American Diabetes Association. Diabetes Care. 2020; 43(1): S1-S158.
2. Diabetes Branch of Chinese Medical Association. Chinese Journal of Diabetes. 2021; 13(4): 315-409.
3. Heise T, et al. Expert Opin Drug Metab Toxicol. 2015; 11(8): 1193-1201.
4. Heise T, et al. J Diabetes Sci Technol. 2018; 12(2): 356-363.
5. Siegmund T, et al. Diabetes Obes Metab. 2018; 20(3): 689-697.