At present, the status quo of treatment for diabetic patients in China is not optimistic, most diabetic patients do not seek timely diagnosis, the clinical treatment status of diabetes is far from the requirements of diabetes treatment guidelines, and the situation of blood glucose not meeting the standard is very serious. Insulin application is one of the main reasons, therefore, in order to improve the status quo of diabetes treatment and improve the rate of glycemic control, I combine many years of practical experience in the application of insulin for the treatment of diabetes, the following points of experience.
1.Insulin analogues
1.1 Porcine and bovine insulin have 1 and 2 amino acids respectively different from human insulin, and human insulin prepared by genetic recombination is a milestone in the treatment of diabetes mellitus. The recent modification of the amino acid sequence of human insulin to produce 3 insulin analogues is a new milestone. It includes two fast-acting (Lispro, trade names NovoRel and Aspart) and one long-acting (Glargine, also known as glargine insulin or Lexapro) insulin analogues.
2. Choice of insulin type and injection time
2.1 Choice of insulin type Human insulin analogues (Aspart and Lispro, Glargine) are still heterologous peptides that may sensitize and produce antibodies. Human insulin should be used in the following groups: women who are pregnant or intend to become pregnant, allergic individuals, those who are immune to animal-derived insulin, those who have just started insulin therapy, those who wish to intermittently use insulin, and those who have been using human insulin analogues for a long time with reduced efficacy. In addition, for new patients, if the original insulin species is not known, human insulin is always used.
2.2 Duration and efficacy of insulin injection
2.2.1 The fast-acting insulin analogs Aspart and Ljspro should be injected within l5min before or immediately after three meals, and the injection time is random and popular. The peak effect time is just right to control the hyperglycemia after this meal, and there is no risk of hypoglycemia before the next meal.
2.2.2 Short-acting regular insulin should be injected 3Omin before three meals. If you eat 2-3min after injection, or inject only after eating, the danger is that it is difficult to control hyperglycemia after each meal and there is an increased risk of hypoglycemia before the next meal.
2.2.3 Glargine and NPH are recommended to be injected at bedtime (instead of before dinner), the effect is to control “dawn phenomenon” hyperglycemia and nocturnal hyperglycemia caused by glucose toxicity during the day, Glargine can also replace basal insulin secretion between three meals. The risk of nocturnal hypoglycemia is lower with Glargine than with NPH, and because of the low pH of the insulin Glargine diluent, it should only be injected alone and not mixed with any other insulin.
2.2.4 After the normal dose of NPH is injected before breakfast its peak effect strength is difficult to control post-lunch hyperglycemia (so oral hypoglycemia should be added before lunch), and once the dose is increased to be able to control post-lunch hyperglycemia, pre-dinner hypoglycemia is likely to occur (so lunch should be divided and snacked between lunch and dinner).
2.2.5 Compared with pre-dinner injection, NPH bedtime injection is more effective in controlling nocturnal hyperglycemia and has a lower probability of nocturnal hypoglycemia.
2.2.6 Premixed insulin is injected before breakfast. If 70 medium-acting/30 rapid-short-acting formulation is chosen, it should first aim at the 70% medium-acting dose to be able to control post-lunch hyperglycemia. The remaining fast- and short-acting insulin in the premix is often insufficient to control post-breakfast hyperglycemia and requires the addition of oral medication before breakfast. If a 50 intermediate/50 rapid short-acting formulation is used before breakfast, one should first be aware of the possibility of hypoglycemia caused by an overdose of 50% short-acting. The remaining intermediate-acting insulin in the premix is often insufficient to control post-lunch hyperglycemia and requires the addition of oral medication before lunch.
2.2.7 Premixed insulin is injected before dinner. If a 70-medium/30-rapid short-acting formulation is used, it should be aimed at controlling the “dawn phenomenon” hyperglycemia with a dose of 70% medium-acting. The remaining rapid-acting insulin in the premix is often insufficient to control post-dinner hyperglycemia and requires the addition of oral medication before dinner. If a 50-medium/50 rapid-acting short-acting formulation is used before dinner, the aim should be to control the “dawn phenomenon” hyperglycemia with 50% medium-acting and to avoid the nighttime hypoglycemia caused by 50% short-acting insulin. If the dose is difficult to adjust, oral hypoglycemic agents must be added.
2.2.8 Glargine or NPH before bedtime (but not before dinner) is the “golden key” to control “dawn phenomenon” hyperglycemia and nocturnal hyperglycemia caused by glucose toxicity during the day. It is better than any pre-mixed insulin before dinner. Anyone who applies insulin, sulfonylurea or glinide before dinner, or NPH/Glargine before bedtime, should eat a small amount of carbohydrates before bedtime (dinner portion) to prevent nighttime hypoglycemia.
3.Insulin treatment plan
3.1 “Physiological insulin supply” program, i.e. 3-4 injections per day (intensive treatment program) Physiological secretion of basal insulin is 0.5~1.Ou per hour, which can regulate blood sugar throughout the night and between meals, and is sufficient to avoid ketoacidosis. After eating, nutrients stimulate the acute secretion of insulin in the first phase, followed by the high secretion in the second phase that lasts all the postprandial hyperglycemic period. It secretes about 5-8u of insulin after each meal and drops back to basal secretion after the blood glucose drops to the pre-meal level.
3.1.1 Complete “physiological insulin supply” regimen (4 injections per day) It is a regimen that completely simulates the physiological secretion of insulin, including:
(1) Glargine injection at bedtime to simulate physiological basal secretion.
(2) Aspart or Lispro injection at three meals to simulate physiological postprandial secretion. Total 4 injections. It has the advantages of random meal timing, fewer hypoglycemic episodes, improved HbAlc levels, simple application and dose adjustment, and good patient compliance. It is the most effective and easiest regimen for dose adjustment.
3.1.2 Incomplete “physiological insulin supply” regimen (3 injections per day) After 3 daily insulin injections, in some cases, the nocturnal basal insulin secretion capacity cannot be restored after the elimination of daytime glucose toxicity, so one of the 3 injections must be a bedtime injection of Glargine or NPH. After 3 daily insulin injections, daytime glucose toxicity is eliminated in most patients, and its efficacy is equivalent to 4 daily injections, so 3 to 4 daily insulin injections are collectively called “insulin intensive therapy”.
3.1.3 Comparison of complete and incomplete “insulin physiological supply” treatment regimens The following insulin application regimens have similar efficacy when compared on the basis of achieving almost normal HbAlc levels.
(1) Regular insulin before three meals combined with bedtime NPH injection was almost as effective as 24h continuous subcutaneous insulin infusion (CSII:pump).
(2) Multiple daytime pre-meal insulin (MDI) injections combined with nocturnal CSII (pump) therapy are almost as effective as 24h CSII-as effective as 24h CSII.
3.1.4 premixed insulin injection before breakfast and dinner It is 2 injections per day, totaling 4 injections of insulin instead of 4 insulin injections, which actually falls far short of the satisfaction of 4 injections per day. type 1 diabetic patients are not suitable for this program, and type 2 diabetic patients can try to change to morning and evening premixed injections combined with oral hypoglycemic drug therapy after 4 injections per day and controlling their disease.
3.2 Insulin injection regimen 1 to 2 times a day (insulin non-intensive therapy) Suitable for type 2 diabetes, not suitable for type 1 and gestational diabetes. No insulin is injected before lunch to allow patients to go out for work, study and recreation during the day. The inevitable periods of hyperglycemia require the addition of oral hypoglycemic drugs, so it is a combination therapy of insulin and oral drugs. Elderly people applying 1/2 maximum dose of oral hypoglycemic drugs will be able to obtain 2/3 maximum efficacy, with high efficacy ratio and low toxicity ratio. Therefore, it is best to combine 1-2 half-dose oral hypoglycemic drugs while applying insulin, following the indications and contraindications. After controlling hyperglycemia after three meals and thus relieving nocturnal glucose toxicity, the ability and sensitivity of basal insulin secretion at night are often restored, so that the “dawn phenomenon” hyperglycemia can be controlled and there is no need to inject Glargine or NPH before bedtime. However, many people still have the “dawn phenomenon” hyperglycemia, and the bedtime injection of Glargine or NPH is still the “golden key” to control the “dawn phenomenon” hyperglycemia. Specific protocols include:
3.2.1 One injection per day
(1) bedtime basal insulin combined with daytime oral hypoglycemic agents, that is, the well-known BIDO treatment program = bedtime Glargine or NPH + daytime oral hypoglycemic agents. Method:Bedtime snack carbohydrate, then NPH or Glargine subcutaneous injection, starting from 4-6u, gradually upward dose (often 6-14u) until fasting blood glucose reaches 6-8mmol/L. Indications:Repeated fasting blood glucose >8mmol/L, while not low blood glucose at 3am (>6mmol/L). Contraindications:Nocturnal hypoglycemia causing rebound fasting hyperglycemia (Somogyi phenomenon). targets for BIDO treatment include: a. long-treatment patients, diet and exercise therapy combined with one to two oral hypoglycemic drugs during the day after a period of effective treatment, blood glucose turn and can not reach the target. b. newly diagnosed type 2 diabetes patients with elevated fasting and postprandial glucose are more pronounced, suggesting the presence of glucose toxicity.
(2) Small doses of NPH (4-8 U) are injected before breakfast as training for patients to self-inject insulin.
(3) Premixed insulin was injected before breakfast, or before dinner.
3.2.2 2 daily injections The treatment protocol includes
(1) Premixed insulin before breakfast + premixed insulin before dinner.
(2) Premixed insulin before breakfast + Glargine/NPH before bedtime.
(3) Premixed insulin before breakfast + rapid short-acting insulin before dinner.
(4) Breakfast rapid short-acting + dinner rapid short-acting.
(5) Breakfast rapid short-acting + dinner premix.
(6) Breakfast rapid short-acting + bedtime Glargine/NPH.
(7)Pre-breakfast medium-acting + pre-bedtime Glargine/NPH.
4.Insulin dose
4.1 Starting dose When there is no ketoacidosis, stress and disease, it is appropriate to start insulin with a small dose, which can be set at 0.25u/(kg.24h), about 12-2Ou throughout the day as the starting dose. The distribution of three meals of rapid short-acting insulin is: the most before breakfast, the least before lunch, and the middle before dinner. When a larger dose of 70N/30R or 5ON/5OR premix is needed, it is appropriate to inject 2/3 before breakfast and 1/3 before dinner.
4.2 Dose adjustment Self-measurement of blood glucose by the patient at home is extremely important for dose adjustment.
4.2.1 Rapid short-acting insulin Dose adjustment of insulin per meal should rather be smaller to prevent hypoglycemia. That is, type 1 diabetes can increase lu insulin every time it exceeds the target blood glucose of about 2.8 mmol/L, while type 2 diabetes increases lu insulin every time it exceeds about 1.7 mmol/L.
4.2.2 NPH and Glargine If fasting hypoglycemia attacks, the dose of NPH and Glargine before bedtime on the first day should be reduced, while >6mmol/L at 3am, while fasting blood glucose >8mmnl/L, indicates that the dose of NPH and Glargine before bedtime should be increased.
4.2.3 Total dose throughout the day The dose can be adjusted every 1 to 2 d. The total dose should be increased by 10% if the average value of blood glucose is >l2mmol/L for 24h6 times throughout the day; if the average value of blood glucose is <6mmnl/l, the total dose should be reduced by 10%. If the finger blood glucose after 2h of insulin injection is <4mmol/L, the corresponding pre-meal insulin injection should also be reduced by 10%.
4.2.4 Periodic change of dose In the process of controlling the disease, the hypoglycemic strength of hypoglycemic drugs is divided into: incremental period, plateau period, decremental period and new plateau period, and hypoglycemia may occur if the patient does not come to the clinic during the decremental period.
5. Selection of insulin regimen for various types of diabetes mellitus
5.1 Type 1 diabetes mellitus The first choice is insulin injections 3-4 times a day. 5 years after LADA patients receive low-dose insulin therapy, C-peptide is not significantly reduced, and 90% of patients still maintain the original islet function; however, for those who apply sulfonylurea, C-peptide is significantly reduced, and 1/3 of cases need insulin therapy. Therefore, when it is difficult to identify type 1 and type 2 diabetes, it is better to give insulin treatment according to type 1. 2 times a day medium/quick short-acting premixed preparations are injected in the morning and evening, and the efficacy is often unsatisfactory. type 1 diabetes can be combined with metformin, glitazones and acarbose, but sulfonylurea and glinides are contraindicated.
5.2 Type 2 diabetes mellitus
5.2.1 Discard old traditions and advocate the best treatment plan It is advisable to consider early and appropriate application of insulin therapy for type 2 diabetes and discard the traditional method of starting insulin only when several oral hypoglycemic drugs are ineffective. Early initiation of insulin therapy is advisable for those who are thin. The current consensus among experts is that the best treatment plan for type 2 diabetes is the combination of oral hypoglycemic agents and insulin, especially when adding bedtime basal insulin, and continuing to apply one or two oral hypoglycemic agents during the day, referred to as the BIDO program. The theory is that: nocturnal basal insulin improves nocturnal glycemic control enough to reduce daytime glucose toxicity and lipotoxicity, so that the daytime oral hypoglycemic agents give full play to insulin pro-secretory and sensitizing effects. If postprandial blood glucose still does not reach the standard, regular insulin can be added before meals, or even short-term intensive treatment with 3 to 4 injections per day.
5.2.2 Three kinds of treatment programs for type 2 diabetes
(1) 1-2 times a day insulin combined with oral hypoglycemic agents. bIDO therapy has a wide range of indications and a high efficiency-cost ratio, often without hospitalization. 2 daily injections of insulin can be premixed insulin before breakfast combined with bedtime Glargine/NPH.
(2) Intensive insulin therapy 3 to 4 times a day is generally applied only for a short period of time. When the disease allows, consider insulin combined with oral hypoglycemic therapy once or twice a day. type 2 diabetic patients without contraindications, metformin and insulin is the best combination.
(3) The beginning stage of some cases can be oral hypoglycemic drugs alone.