Chronic diseases related to nutrition and metabolism are developing rapidly in China, and the number of people with diabetes is increasing rapidly, among which elderly patients (≥60 years old by Chinese standards) are the mainstream population with diabetes. Due to various factors, domestic and international studies lack sufficient evidence on the diagnosis and treatment measures for elderly diabetic patients, and the guidelines of several academic groups on the diagnosis and treatment of elderly diabetes lack specific implementation measures, and there are many misconceptions in the diagnosis and treatment of elderly diabetes, which affect the improvement of the overall level of diabetes prevention and treatment. Liu Hongliang, Department of Geriatrics, The First Affiliated Hospital of Henan College of Traditional Chinese Medicine
Drawing on the relevant guidelines and consensus of the academic organizations of endocrinology and metabolism at home and abroad in recent years, we have compiled the “Expert Consensus on Geriatric Diabetes Diagnosis and Treatment Measures” by collecting the clinical research and practice summaries of the endocrinologists of the Society and summarizing the opinions of the famous experts in this specialty in China, in order to promote the improvement of the level of geriatric diabetes prevention and treatment.
I. Clinical characteristics and problems of geriatric diabetes mellitus
The prevalence of diabetes among the elderly aged 60 years or older was 20.4%, estimated at 35.38 million, accounting for 38.1% of the total number of patients. According to the development trend of aging in China, the prevalence of diabetes is increasing along with the aging population, which indicates that the number of elderly people with diabetes will increase significantly.
A number of domestic studies have shown that the incidence of diabetes still tends to increase with age after the age of 60, and tends to level off after the age of 70, but the overall prevalence is still increasing. Similar to the young and middle-aged population, the prevalence of diabetes in the elderly population has a tendency to be slightly higher in urban than in rural areas, and slightly higher in women than in men.
According to data published by the International Diabetes Federation (IDF) in 2013, 5.1 million people died from diabetes-related diseases worldwide, accounting for 8.39% of all deaths. Studies in China in recent years have reported a significant increase in the rate of death from diabetes, with increases of 1.12 times (Beijing 1991-2000), 4.15 times (Shanghai Xuhui District 1986-2005) and 11.61 times (Wuhan 1975-2006) during 10, 20 and 30 years, respectively, and diabetes can cause premature death, with a per capita death loss of life years of 5.4 to 6.8 person-years, all women than men, with a significant increase in people over 60 years of age.
The main cause of death in Europe and the United States is cardiovascular disease, domestic reports are cardiovascular and cerebrovascular disease, followed by malignant neoplasm, lung infection, kidney failure. 60-70 years old to malignant neoplasm ranked the highest, 80-90 years old cardiovascular disease, lung infection rose to the highest. Hypertension and dyslipidemia are the most important risk factors for cardiovascular death in the elderly, and diabetes combined with hypertension and dyslipidemia will increase the risk of cardiovascular death by 3 times.
Older patients with diabetes can be divided into two types of cases: those who have diabetes before old age and those who have new onset of diabetes after old age. They differ in terms of their condition, clinical features of diabetes, other diseases and pre-existing organ impairment. In the case of similar environmental factors, the later the disease, the better the islet β-cell compensatory capacity. Compared to those with pre-existing disease in old age, those with diabetes in later life are more likely to show significant insulin resistance and compensatory insulin hypersecretion.
Forty to 70% of the elderly population suffer from hypertension and 30% to 50% from dyslipidemia, both of which are higher than the prevalence of diabetes, and abdominal obesity is more common in elderly patients than simple BMI increase. The combination of glucose metabolism disorders, hypertension, centripetal obesity, and hypertriglyceridemia (metabolic syndrome) is as high as 30% to 40% in older adults, while less than 10% do not have any of the above. Geriatric syndromes are a common combination of age-related disorders in the elderly population, including deficits in mental and physical abilities, decreased protection from self and other injuries, increased risk of falls and fractures, cognitive impairment and depression, urinary incontinence, pain, and overuse of medications. These can also have a negative impact on the self-management of older patients with diabetes.
The awareness, diagnosis, and treatment rates of elderly patients with diabetes are low, and postprandial glucose elevation is common in elderly diabetes, especially in newly diagnosed patients, even when combined with fasting glucose and glycated hemoglobin (HbA1c) to screen for miscellaneous 1/3 of patients with postprandial hyperglycemia are missed. This situation is more pronounced in rural areas where medical conditions are relatively poor, involving about 65% of the country’s elderly population. The prevalence of prediabetes in the elderly population is much higher than in the young and middle-aged population, and is a group that should be concerned in the strategy to control the rapid development of diabetes.
As national life expectancy increases, old age will involve 20-30 life years for each individual. According to the available information, it is estimated that abnormal glucose metabolism affects about 100 million elderly people in China in their later years, and the elderly are also a high-risk group for a variety of chronic diseases. If there is a lack of scientific prevention and treatment behaviors, the harm caused by diabetes will not only reduce the survival years, but also make a considerable part of elderly patients’ quality of life greatly reduced due to blindness, disability and intellectual impairment.
The overall level of blood glucose control in China’s diabetic patients is not ideal, in the middle-aged and elderly (age > 45 years old) population of the two national multi-provincial diabetic patients to adjust the crisp school HbAlc <6.5% < span=""> as the standard, the rate of achievement were 20.3% (2009) and 16.8% (2010). The attainment rate of HbA1c control in the cadre population with good health care conditions (63.5%) was higher than that of elderly patients in the Beijing community (46.5%). It can be seen that good health care conditions positively contribute to the glycemic control of elderly patients.
In the treatment of geriatric diabetes, strengthening diabetes education and management is an important conceptual project. The UK Prospective Diabetes Study (UKPDS) and the follow-up study of the Diabetes Control and Complications Trial (DCCT) have given us insight into the “metabolic memory” of enhanced glycemic control, and several studies have shown that good glycemic control given early in the course of diabetes is the cornerstone of later patient benefit.
The effect of intervention of multiple risk factors on microvascular disease, cardiovascular disease, and mortality in type 2 diabetes in Denmark (Steno-2 study) and the effect of long-term optimal glycemic control on diabetic macrovascular disease in type 2 diabetes in Japan (Kumamoto study) have shown that comprehensive treatment of diabetes can lead to good outcomes. Thus, “early prevention and treatment, good glycemic control, and comprehensive control of multiple metabolic abnormalities” is the ideal treatment principle for diabetic patients.
However, one of the reasons why most patients fail to follow this principle in reality is the lack of diabetes screening. (16) The indistinct chain is a major factor in the management of diabetes, and 2/5 are elderly, a population considered at risk by most guidelines for relaxed management. The other 1/5 have severe complications or combined organ function abnormalities or suffer from other pathologies or malignant diseases that are not suitable for strict glycemic control. The remaining patients will also suffer from different reasons for not achieving good treatment goals. As a result, the national adjustment of the criminal quietly insect〉目刂拼拼锉曷适贾詹荒芴嵘
The elderly in China have some advantageous conditions for disease prevention and treatment, the majority of them are no longer under work pressure, and the compliance of treatment is higher than that of young and middle-aged patients after mastering the knowledge of disease prevention. In recent years, the basic medical insurance coverage rate of urban and rural New Agricultural Cooperative has reached 95%, and the majority of elderly diabetic patients can be guaranteed basic medication. The key is to improve the self-management ability of patients and promote the change of management philosophy in different levels of healthcare institutions, in order to strive for safe and beneficial control of damage caused by several metabolic abnormalities and overall improvement of the quality of life of elderly diabetics.
II. Optimization of treatment strategies for geriatric diabetes mellitus
(I) Strategy of comprehensive assessment
The development of individualized treatment plans for geriatric diabetes should be based on a comprehensive assessment of the patient’s condition. There is a need to improve the understanding of the patient. It can be analyzed from 5 aspects.
1. To understand the level of glycemic control of patients: including the overall level (HbA1c is the best evidence), the actual glycemic fluctuation (magnitude and influencing factors), the characteristics of glycemic changes (fasting or postprandial glycemic elevation, short-term or long-term hyperglycemia); factors affecting glycemic control, including diet and exercise, the application of existing hypoglycemic drugs (dose, method), the risk of hypoglycemia, etc. . Ask and urge patients to self-measure blood glucose, firstly recommend monitoring blood glucose before breakfast and dinner (the most basic observation point), and measure blood glucose before three meals and two hours after three meals plus before bedtime as needed (all-day blood glucose observation), to be informed of the type of blood glucose changes of patients, so as to lay a good foundation for adjusting glucose-lowering treatment.
2.Understand the patient’s own glucose regulation ability: For newly diagnosed elderly diabetic patients, the patient’s plasma insulin and/or C-peptide concentration can be measured simultaneously with blood glucose testing when available, and the patient’s pancreatic β-cell secretion level can be understood in combination with the disease duration and blood glucose changes, which helps to select the appropriate glucose-lowering drugs.
3.Evaluate whether the patient is combined with hypertension, dyslipidemia, hyperuricemia and obesity: simultaneously measure the liver enzymes and kidney function indicators in blood, and conditionally measure blood protein, electrolytes, homocysteine level, which helps to assess the patient’s cardiovascular disease risk and determine the diet recipe, and develop a comprehensive treatment plan for the patient.
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Diabetes specialist physicians or specialist nurses should fully understand the above 5 aspects to make a perfect assessment of the patient, and also make program selection according to the actual conditions. Articles 1 and 2 are the basis for rational selection of hypoglycemic drugs and avoidance of drug abuse; articles 3 and 4 are the basis for comprehensive treatment, comprehensive control of cardiovascular risk and protection of organ function, and article 5 helps to assess the patient’s self-management ability and to develop a tailor-made treatment plan for the patient with comprehensive consideration. Primary care units can conduct assessments based on actual conditions and do as much as possible to have a comprehensive understanding of the patient before implementing personalized treatment and management.
(B) “Four early” principle
1, early prevention: the change of concept is very important. The prevention of chronic diseases requires adherence to the concept of “treating the disease before it occurs”, active learning and education on diabetes prevention and treatment, promoting healthy lifestyles, and increasing exercise. In particular, people at high risk of diabetes (people with family history, abdominal obesity, hypertension, hypertriglyceridemia, hyperinsulinemia) should be listed as key targets for prevention and treatment, and primary prevention of diabetes (prevention of disease onset) should be done.
2. Early diagnosis: The occurrence of type 2 diabetes has a long pre-diabetes process, including the compensatory period of high insulin – normoglycemia, pre-diabetes with mild abnormal blood glucose [impaired fasting blood glucose mainly with elevated fasting blood glucose (FPG) and reduced glucose tolerance mainly with elevated glucose 2 hours after glycemic load (2hPG), or both], until the early stage of diabetes (mild to moderate elevation of blood glucose). In cases where the genetic status quo cannot be altered, regular physical examinations and diabetes screening are encouraged in high-risk patients; the beta-cell function of the Brucella Combined fasting glucose (FPG), random or 2hPG and HbA1c (detection methods need to be recognized by international standards), or the use of oral glucose (75g) tolerance test (OGTT) for diabetes screening brother is a popular stumbling block for berkelia T Chen Fan excise quiet insects ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎÌ_ÌÎå
3, early treatment: including early start of therapeutic lifestyle intervention (TLC), timely start of hypoglycemic drug therapy and timely start of insulin therapy. Checking (11) FPG>5.6mmol/L, 2hPG or random blood glucose>7.8mmol/L or HbA1c>6.0% is the warning point to start prevention and treatment of diabetes through TLC. If after 3 months of TLC, HbA1c is still >6.5% need to consider starting non-insulinotropic oral hypoglycemic drug intervention. The Daqing study in China, the Finnish Diabetes Prevention Study (DPS) and the Diabetes Prevention Study (DPP) in the United States showed that TLC alone can reduce the incidence of diabetes by 50%-58%, and the Acarbose and Metformin pharmacological intervention studies reduced the incidence of diabetes by 88% and 77%, respectively, with better efficacy than TLC alone. elderly patients with diabetes on the basis of diet and exercise therapy HbA1c>7.0% need to consider single or combined oral hypoglycemic drug therapy to control HbA1c to 7.0% or less according to the patient’s insulin level, obesity degree and blood glucose fluctuation. If HbA1c is still >7.0% after combined treatment with 2 or more oral hypoglycemic drugs, insulin therapy can be started, and basal insulin therapy is generally preferred. However, patients with poor dietary control, obesity and not low level of their own insulin secretion should not apply insulin prematurely, but need strict lifestyle management and weight reduction first.
4. Early achievement: The personalized control goals for elderly patients with diabetes include blood glucose and other metabolism-related indicators that are not blood glucose. Studies have shown that elderly diabetic patients with multiple cardiovascular risk factors may not receive cardiovascular benefit from glycemic control alone, while they may benefit from comprehensive prevention and treatment of multiple cardiovascular risk factors.
(iii) Development of individualized control goals
The purpose of setting personalized control goals is to maximize the benefits and minimize the risks of patient survival in treatment, and the implementation process should take into account the judgment from the doctor’s perspective and the coordination of the patient’s own tolerance.
1. Glucose-related indicators: Among the many studies that chose HbA1c control criteria, only UKPDS and DCCT have data from studies longer than 10 years, and choosing HbA1c <7.0%< span=""> as an intensive control goal has long-term beneficial results. The study of critical conditions such as coronary heart disease and diabetes mellitus was observed for 10 years before definitive data on the cardiovascular harms of diabetes mellitus were obtained, suggesting a temporal effect of damage caused by chronic hyperglycemia in general. the conclusion of the study that damage from hyperglycemia already exists at HbA1c ≥ 6.5% and can be used as a diagnostic criterion did, and the diagnostic specificity of HbA1c ≥ 6.5% was high and the same in the middle-aged and elderly population. It suggests that blood glucose at this level for more than 10 years is more harmful and needs to be controlled.
In view of the latest “American Academy of Diabetes (ADA)/European Association for the Study of Diabetes (EASD) Position Statement”, it is recommended that when setting individualized HbA1c control criteria, the patient’s life expectancy, the risk of hypoglycemic therapy (β-cell function, hypoglycemia, weight gain), the degree of therapeutic benefit (existing comorbidities, degree of organ dysfunction), and the risk of hypoglycemia should be considered. The assessment of the patient’s ability to tolerate treatment (self-management level, medical conditions) should be made.
Based on the results of the existing studies, the HbA1c control standard for elderly diabetic patients with a life expectancy longer than 10 years, low risk of hypoglycemia, expected treatment benefit, and good medical support was <7.0%< span="">, with corresponding FPG <7.0 mmol/L and 2hPG <10.0 mmol/L, and reduced blood glucose fluctuations and long-term maintenance of these blood glucose levels. level. HbA1c control to near-normal levels may be considered for patients who are newly diagnosed, relatively young, with expected survival >10 years, without complications and concomitant diseases, without risk of hypoglycemia with glucose-lowering therapy, without the need for glucose-lowering drugs or with only single non-insulin agonist glucose-lowering drugs, and with good adherence to therapy.
Although the ADA further enhances HbA1c control in older adults, there is a lack of research evidence on whether older patients with diabetes benefit from optimal glycemic management. The actual situation of elderly patients varies greatly, and different control criteria should be selected based on a comprehensive assessment and following the principle of individualization, which can be referred to the following stratification.
(1) HbA1c<7.5%< span="">: for patients with type 2 and type 1 diabetes with expected survival >10 years, milder comorbidities and concomitant diseases, some risk of hypoglycemia, and on insulinotropic hypoglycemic agents or insulin-based therapy.
(2) HbA1c<8.0%< span="">: For elderly diabetic patients with expected survival >5 years, moderate complications and concomitant diseases, at risk of hypoglycemia, treated with insulinotropic hypoglycemic agents or mainly with multiple insulin injections.
(3) HbA1c<8.5%< span="">: In case of life expectancy< 5< span=""> years, complete loss of self-management ability, etc., the control standard of HbA1c can be relaxed to <8.5%< span="">, and it is still necessary to avoid the occurrence of acute complications of diabetes and refractory infections caused by severe hyperglycemia (>16.7 mmol/L). Elimination of glycosuria (blood glucose level <11.1 mmol/L) is an important goal in the treatment of elderly diabetic patients, which facilitates the improvement of hyperglycemic osmotic diuresis (causing reduced blood volume, nocturnal urination, etc.) and negative nutritional balance (urinary sugar excretion).
2. Other metabolism-related indicators of non-glucose (see later section).
Measures of glucose-lowering treatment for geriatric diabetes
Glucose-lowering treatment requires mastering the characteristics of various types of blood glucose changes in patients, and providing them with highly targeted, suitable and easy-to-operate glucose-lowering drug treatment plans in order to achieve ideal blood glucose control effects.
(I) Pay attention to basic treatment
The basic treatment of diabetes includes both education and management, diet and exercise. Lack of knowledge of diabetes control is the main reason for poor blood glucose control. Emphasis on education and management of elderly patients is an important measure to improve the treatment of diabetes.
Nutritional management is an important part of diabetes treatment for patients of any age. The effectiveness of diet and exercise interventions has been clearly established for the prevention of diabetes in the elderly. However, for elderly patients, some special issues remain to be noted.
As the human body enters old age, metabolic levels gradually decline with age, while motor function also gradually decreases, resulting in a decrease in lean body mass year by year. Some elderly patients have a long-term energy intake overload phenomenon, manifested as excessive visceral fat storage and muscle stock decay obesity; some other elderly patients have a combination of loss of appetite, abnormal taste or smell, swallowing difficulties, oral or dental problems and various dysfunctions that may affect the process of digesting food, leading to the occurrence of underweight and/or oligomenorrhea. Poor dietary habits (homogeneous diet and poor eating patterns) are important influences that contribute to high blood glucose fluctuations, and inappropriate restrictive diets can pose additional risks for older diabetics.
The dietary management of elderly diabetic patients should ensure the required calorie supply, reasonable dietary structure (appropriate restriction of sweet foods, more energy-dense foods rich in dietary fiber and low glycemic index) and meal pattern (less frequent meals, slow eating, and main meals later) to maintain good nutritional status and improve the quality of life.
In the diet structure of elderly diabetic patients, carbohydrate energy supply should account for 50%-60%, and protein intake should be 1.0-1.3 g-kg-1-d-1 without renal disease restriction, and high-quality protein such as eggs, dairy products, animal meat and soy protein is recommended. The specific configuration needs to be individualized to suit the needs of the elderly with large differences.
Exercise management for elderly patients needs to be more individualized. The normally fit, the old and frail, the physically handicapped, and the mentally handicapped choose whole-body or limb exercise modalities that can be performed and easily adhered to, respectively. Exercise safety assessments need to be conducted before exercise. Combine light and moderate exercise exertion to arrange time, and advocate the combination of moderate indoor activity after meals and physical exercise 3-4 times a week, which is conducive to alleviating postprandial hyperglycemia and maintaining or enhancing physical fitness. Combining with planned resistance exercises, such as lifting weights and leg lifts for retention, can help delay muscle loss in elderly patients. Obese people can burn fat stores by appropriately increasing the amount of aerobic exercise.
(B) Rational application of hypoglycemic drugs
1, the selection principles of hypoglycemic drugs: from the process of pathological changes, the development of type 2 diabetes includes four representative stages: early normoglycemic-insulin compensatory hypersecretion stage, prediabetes (mildly elevated blood glucose), diabetic insulin secretion deficiency stage, and diabetic insulin secretion deficiency. Differences are needed in the strategy of choosing glucose-lowering drugs. Diabetes can be prevented if TLC intervention can be started in the normoglycemic-insulin hypersecretion compensatory stage to eliminate the causes of insulin resistance.
The pathological characteristics of prediabetes are characterized by insulin resistance + relative hypersecretion. Protecting pancreatic β-cells, reducing insulin resistance, and supplementing with non-insulinotropic agents and enteroglucagon drugs if necessary, can delay the onset of diabetes mellitus. When diabetes develops to the stage of insulin deficiency, multiple mechanisms to lower blood glucose by combining insulin secretagogues and, if necessary, basal insulin are required. When diabetes develops to the stage of insulin deficiency, it is necessary to meet the body’s demand for insulin, and insulin therapy is the main treatment (multiple treatment modes can be used), supplemented with oral hypoglycemic drugs. The pathway of glucose-lowering drugs selection for elderly type 2 diabetes in general is shown in Figure 1.
Note:DPP-4: dipeptidyl peptidase 4; GLP-2: glucagon-like peptide-1
Figure 1 Geriatric type 2 diabetes hypoglycemic drug treatment pathway
Multiple insulin injections (intensive therapy): In case of newly diagnosed diabetes mellitus with hyperglycemia (HbA1c>9.0%), co-infection or acute complications, surgery or stress, application of antagonistic insulin drugs (e.g. glucocorticoids) and other special circumstances, due to the presence of obvious insulin resistance, high glucose toxicity, high lipotoxicity and other factors aggravating pancreatic β-cell damage, active use of Short-term multiple times a day insulin intensive treatment mode to release β-cell toxicity and correct hyperglycemia as early as possible. Re-evaluate and adjust the treatment mode after the disease is stabilized. It is generally not recommended to adopt the difficult to operate multiple insulin therapy mode in the conventional glucose-lowering treatment for elderly patients.
The mechanisms of action of all current glucose-lowering drugs are relatively limited, and when blood glucose cannot be achieved with single drug therapy, drugs with complementary mechanisms in combination have greater advantages. Except for insulin pumps, which can adjust insulin dosage as needed, other insulin preparations are often difficult to take into account the needs of patients with changes in blood glucose at three meals, and combining oral hypoglycemic drugs to make up for the lack is a very practical and effective treatment mode.
The ratio of combined macrovascular and microvascular lesions in patients with pre-diabetes is much higher than that of those with diabetes after old age, and the function of pancreatic β-cells in these patients is mostly very poor. Especially to prevent the occurrence of severe hypoglycemia.
The symptoms of hypoglycemia in the elderly are mostly atypical, and more often seen are non-specific neurological and psychiatric symptoms, especially vertigo, disorientation, falls or sudden behavioral changes. For the elderly with cognitive dysfunction, failure to recognize hypoglycemia in time can sometimes have serious consequences, and its harm is much higher than that of mild to moderate hyperglycemia. The possibility of hypoglycemia should be thought of in the presence of falls and sudden behavioral abnormalities in the elderly. Elderly patients and/or family members treated with insulin promoters or insulin need to be informed of the prevention and control measures of hypoglycemia at the first time. Elderly patients who have experienced the occurrence of severe hypoglycemia, if the cause of occurrence cannot be completely blocked, the goal of blood glucose control needs to be relaxed in a big step, with the goal of no hypoglycemia and no severe hyperglycemia.
2.Note on the application of various types of hypoglycemic drugs:
【Non-insulin promoter】.
Metformin: existing domestic and international diabetes guidelines recommend metformin as the first choice or first-line drug for controlling hyperglycemia in patients with type 2 diabetes. Its less risk of hypoglycemia is beneficial for the elderly, but the gastrointestinal reactions and weight loss associated with the drug may be detrimental for l weak elderly patients.
Metformin itself is not nephrotoxic as it is excreted from the kidneys in prototype form. Metformin should be reduced if the estimated glomerular filtration rate (eGFR) is between 45 and 60 ml/min, and metformin should not be used if the eGFR is <45 ml/min. Metformin is contraindicated in patients with hepatic insufficiency, heart failure, hypoxia or undergoing major surgery to avoid the development of lactic acidosis. Metformin should be temporarily discontinued when iodinated contrast agents are used for imaging examinations.
a-Glycosidase inhibitors: a-Glycosidase inhibitors include acarbose, voglibose and miglitol. They mainly lower postprandial glucose and have a lower risk of hypoglycemia, and are more suitable for elderly diabetic patients whose main source of energy is carbohydrate. Currently, acarbose is the only glucose-lowering drug in China that has an indication for prediabetes in its specification.
Gastrointestinal reactions after taking the drug may affect the use of these drugs, and the use of small doses to start and gradually increase the dosage can effectively reduce adverse reactions. Hypoglycemia does not usually occur with this class of drugs taken alone. If hypoglycemia occurs in patients with combined a-glucosidase inhibitors, treatment requires the use of glucose preparations, and consumption of sucrose or starchy foods is poorly effective in correcting hypoglycemia. More than 95% of this class of drugs are excreted after intestinal hydrolysis without increasing the metabolic burden of liver and kidney.
Glitazones: including rosiglitazone and pioglitazone, which have clear effects on increasing insulin sensitivity and have clinical efficacy in delaying the progression of diabetes and stabilizing blood sugar for a longer period of time. However, there is a risk of weight gain, edema, aggravation of heart failure, fracture, and some negative effects of their application in the elderly. It is generally not recommended for use in elderly diabetic patients except for those who are in early age or have special needs.
Enterostatin analogs]
Dipeptidyl peptidase 4 (DPP-4) inhibitor: Improves glucose metabolism by prolonging the action of the body’s own glucagon-like peptide-1 (GLP-1). It mainly lowers postprandial glucose with little risk of hypoglycemia, is relatively well tolerated and safe, does not increase body weight, and has more benefit for elderly patients.
GLP-1 receptor agonists: GLP-1 receptor agonists mainly lower postprandial glucose, with low risk of hypoglycemia. This drug can be considered for those with poor glycemic control, obesity or bulimia treated by other hypoglycemic drugs. However, these drugs may lead to gastrointestinal adverse effects such as nausea and weight loss, and are not suitable for relatively lean elderly patients. The drug needs to be reduced in the case of renal insufficiency. It should be used with caution in patients with a history of pancreatitis. There is a lack of experience with the use in the elderly.
Insulin stimulants
Sulfonylurea: It is a glucose-lowering drug with more clinical experience and relatively lower price in the insulin stimulant class. The hypoglycemic risk of these drugs is relatively large for elderly patients, and the hypoglycemic risk of glibenclamide is the largest and should not be used for elderly patients. For elderly diabetic patients with normal liver and kidney function, consider choosing a once-daily sulfonylurea or a short- to medium-acting sulfonylurea according to the characteristics of the glycemic profile. Packaged dosage forms of extended-release (gliclazide) and controlled-release (glipizide), which are taken once daily and have a flat body drug concentration and less occurrence of hypoglycemia, are recommended for elderly patients. Patients with mild to moderate renal insufficiency may consider glipizide as an option.
Glineprone: It is a non-sulfonylurea short-acting insulin promoter, which mainly reduces postprandial blood glucose and needs to be taken before meals, with fast onset of action and short half-life. Under the premise of the same hypoglycemic efficacy, the risk of hypoglycemia of glinides is lower than that of sulfonylureas. Repaglinide (excreted from bile) is less affected by renal function than nateglinide.
[Insulin agents].
There are many varieties of insulin preparations available, including animal-derived, genetically synthesized human insulin or insulin analogues. According to the onset of action after subcutaneous injection, they are divided into rapid-acting, short-acting, intermediate-acting, long-acting and super-long-acting, as well as short- (rapid-) and intermediate-acting premixed preparations with different ratios according to demand. It can be selected according to the specific blood sugar changes of elderly patients.
Due to the special characteristics of the elderly population, the risk of hypoglycemia should be carefully considered before using insulin for glucose-lowering therapy. The results of a study conducted in healthy older adults in good health (mean age 66 years) showed a low incidence of hypoglycemia, either by insulin pump or by multiple subcutaneous injections a day to maintain HbA1c at 7% for up to 12 months.
In a series of clinical trials, the addition of long-acting insulin in older patients with type 2 diabetes (all 69 years of age) was equally effective in achieving HbA1c targets and did not increase the incidence of hypoglycemia compared with younger patients (mean age 53 years). Data from studies in older adults aged over 75 years or with multiple comorbidities are scarce. Compared to human insulin, insulin analogs have a relatively lower risk of hypoglycemia, but are also more expensive. The use of insulin can lead to weight gain, especially if the daily dosage is 40 U or more, and may be combined with oral hypoglycemic agents (metformin, glucosidase inhibitors).
Problems with vision or manual dexterity may be a barrier to insulin therapy in some older adults. Although insulin pens are easier to use, they are more expensive compared to vials and syringes. Patients treated with insulin usually need more blood glucose monitoring, which also increases part of the treatment burden.
3. Efficacy assessment and dose adjustment after drug application: After selecting the treatment mode for patients, efficacy observation and subsequent treatment adjustment is an important part of the process. Arranging further follow-up and observation plans, focusing on patient effectiveness education, improving communication with patients and/or family members, and timely adjustment of treatment according to changes in the condition are effective measures to improve the overall glycemic control rate to meet the standard.
Blood glucose fluctuation in glucose-lowering therapy is an inevitable phenomenon, and excessive blood glucose fluctuation is a risk factor for aggravating vascular damage and occurrence of hypoglycemia. Patients are cautioned to pay attention to adjusting the three-point balance between glucose-lowering drugs and the amount of food and exercise in daily life, which is conducive to promoting effective and smooth glucose-lowering.
(iii) Other hypoglycemic treatments
Stem cell therapy and gastrointestinal surgery are the rapidly developing hypoglycemic treatments in the field of diabetes treatment in recent years, and there are no indications for their application in elderly diabetic patients.
IV. Comprehensive treatment of elderly diabetes mellitus combined with multiple metabolic abnormalities
Elderly diabetic patients are often combined with other metabolic abnormalities. On the basis of comprehensive assessment of treatment risks, appropriate control targets for blood pressure, blood lipids, blood uric acid and weight should be selected according to the characteristics of elderly diabetes. Elderly diabetic patients often have multiple coexisting diseases and need to take multiple therapeutic drugs. Treatment requires attention and understanding of drug interactions and effects, as well as monitoring of corresponding indicators and timely adjustment of treatment.
1.Control of hypertension: According to the current recommendations of several domestic and foreign cardiovascular professional guidelines, the target of blood pressure control for elderly patients with diabetes combined with hypertension is <140/80mmHg (1mmHg=0.133kPa) (B). Different blood pressure control goals can be set according to the patient's diabetes duration, general health status, presence of cardiovascular and cerebrovascular pathology and urine protein level. Diabetic patients should be actively treated with antihypertensive therapy, and the principle of "the sooner the better" should be applied, and drug therapy can be started when blood pressure is at 130~140/80~90mmHg level and lifestyle interventions are ineffective for more than 3 months. Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor antagonist (ARB) antihypertensive drugs are the first choice and basic medication for elderly diabetic patients, followed by long-acting calcium antagonist (CCB) and/or selective beta-blocker, and diuretics should be used with caution, especially in combination with hyperuricemia. Advocate combination therapy for complementary benefits.
2. Control dyslipidemia: serum LDL-C is an indicator that must be paid attention to in elderly diabetic patients. For those who only have abnormal detection indexes related to macrovascular atherosclerosis, LDL-C also needs to be reduced to <2.6 mmol/L, and LDL-C <1.8 mmol/L for those who have other risk factors for cardiovascular and cerebrovascular lesions. Those who fail to reach this standard should take statins for a long time after excluding the effects of renal disease and hypothyroidism. Those with intolerance to statins (presence of liver enzyme and muscle enzyme abnormalities) need to adjust treatment as appropriate. Combination of cholesterol absorption inhibitors is recommended if statins alone do not bring LDL-C to the target. For those with simple hypertriglyceridemia (normal LDL-C), firstly control the fat intake, if the serum TG≥3.5 mmol/L, add beta lipid-lowering drugs, and for those without hyperuricemia, use niacin preparations.
3. Weight management: The management of body weight in the elderly is moderate (BMI: 20-25 kg/m2), and it is not recommended to measure whether the management is up to standard simply by weight change. It is recommended to take the status at the time of consultation as a reference, moderate control of caloric intake for obese people and increased caloric supply for lean people, both cases require dietary structure adjustment and encourage moderate increase of exercise.
4. Control of hyperuricemia: Hyperuricemia is predominant in the elderly, and gout attacks and gout stones are less common than in young and middle-aged people. The current recommended control goal: blood uric acid (SUA) ≤ 360 μmol/L (for patients with gout attacks, SUA < 300 μmol/L.) SUA intervention treatment cut point: men > 420 μmol/L, women > 360 μmol/L. Those whose lifestyle (low purine diet, more water) fails to meet the control standard should take uric acid-lowering drugs. In the elderly, it is recommended to take drugs that inhibit purine synthesis (allopurinol, febuxostat) to gradually reduce blood uric acid levels to target values. If benzbromarone, a drug that promotes uric acid excretion, is used, attention should be paid to the change of renal function [creatinine clearance (Ccr) <60ml/min, benzbromarone ≤50mg/d] and alkalinization of urine, which can be supplemented with sodium bicarbonate (small amount several times) to maintain urine pH around 6.5 (6.2-6.9).
5, vasoactive drugs: more than half of the elderly diabetic patients combined with atherosclerosis, aspirin is the first choice, for the recognized cardiovascular protective effect of antiplatelet agents, easy to use, 100 (75-150) mg daily, avoid taking on an empty stomach. In case of increased fibrinogen, presence of hypercoagulable state, or intolerance to aspirin, clopidogrel hydrogen sulfate (50-75 mg, 1 time/d) or cilostazol (50-100 mg, 2 times/d, preferred for lower extremity lesions) is available.
Patients with definite large-vessel atherosclerotic plaque formation, especially those with lower-extremity arterial occlusive disease, may be given regular intravenous infusion of prostaglandin E1 preparations (10-40 μg/d for 10-20 d as a course of treatment) with vasodilatation, improvement of microcirculation, and inhibition of platelet coagulation as appropriate, or long-term oral administration of beraprost sodium tablets.
6. Control of other cardiovascular risk factors: including smoking cessation and correction of hyperhomocysteinemia, etc. (A).
V. Prevention and control of diabetes mellitus comorbidities in the elderly and the need to take into account
Elderly diabetic patients will not only have diabetes-related comorbidities, but also have organ damage caused by other cardiovascular risk factors. The principles of treatment are early assessment, comprehensive analysis, individualized treatment, weighing the benefits and risks, and comprehensive control of risk factors.
1. Cardiovascular pathology (coronary artery disease, arrhythmia, heart failure): For elderly patients with diabetes, intervention and treatment of cardiovascular risk factors should be started early, including comprehensive cardiovascular risk factor management measures such as starting management in the prediabetes and hypertension period, lifestyle intervention, and timely initiation of LDL-C lowering therapy. Screening of vascular lesions in patients with diabetes mellitus combined with hypertension and/or high LDL-C blood pressure should be focused on the early detection of lesions and timely management. In elderly diabetic patients with cardiac autonomic neuropathy, atypical symptoms such as weakness, palpitations, edema or asymptomatic myocardial infarction may occur, which may easily be combined with arrhythmia or heart failure and may lead to sudden cardiac death. The diagnosis needs to be determined by electrocardiogram and dynamic monitoring of blood muscle enzymes for timely treatment.
2. Ischemic cerebral infarction: more than 90% of the combined cerebrovascular lesions of diabetes mellitus are ischemic cerebral infarction, and nearly 1/3 of the stroke patients have an etiology related to carotid artery stenosis. Primary prevention of cerebral infarction in elderly diabetic patients includes active control of blood pressure, blood glucose, LDL-C at desirable levels, and smoking cessation. In patients at high cardiovascular risk, carotid ultrasound should be tested regularly and antiplatelet medication should be started if small plaque formation is detected or small ischemic foci are found on cranial CT or MRI. In those who have already had cerebral infarction, emphasis should be placed on prevention of recurrence. LDL-C should be controlled at <2.0 mmol/L, HbA1c <7.0%< span="">, and blood pressure should not be controlled too tightly, <150/85 mmHg is sufficient.
3, lower limb arterial occlusion: peripheral arterial disease (PAD) is a common macrovascular complication of diabetes mellitus, which is more frequent in elderly patients, and lower limb arterial occlusion is the most common. Diabetes combined with hypertension will increase the occurrence of PAD and target organ damage. The use of color Doppler ultrasound technology to screen the lawsuit round the haze “Yeol wish to woof white both frightened cupboard scuttle pelican juggle the ZuZhengO tossing plant scrupulously 6猿鱿窒輪弁粗⒆凑撸俅采习刺弁闯潭确旨叮ū2). If the arterial wall is thickened with scattered plaques, antiplatelet drugs should be added. If the arterial lumen stenosis of the lower extremity is >50% and the dorsalis pedis artery is missing or there is weakness of the lower extremity after exercise, cilostazol (50-100mg, 2 times/d) can be combined with long-term treatment. If the condition requires intermediary treatment.
4, diabetic foot: the occurrence of diabetic foot disease means the simultaneous existence of systemic atherosclerotic changes, which is a high-risk signal for the occurrence of serious cardiovascular and cerebrovascular pathologies, and requires a comprehensive assessment of the patient and comprehensive treatment. Diabetic patients with long duration of disease are required to pay attention to the prevention of foot skin breakdown and careful disposal of foot fetish and nail fetish. Once foot skin ulceration occurs, the patient should be seen by a podiatry specialist as soon as possible and receive comprehensive multidisciplinary treatment to control infection and injury early and reduce the risk of amputation.
5, diabetic nephropathy and chronic renal failure: diabetic kidney injury in the elderly is often multifactorial pathogenesis. Genetic factors, hypertension, hyperglycemia, obesity, high uric acid and nephrotoxic drugs are the main factors affecting the progression of chronic kidney disease in the elderly, and kidney injury due to diabetes only accounts for 1/3. principles of diabetic nephropathy treatment: strict dietary management (intake of high-quality protein, <0.6g-kg-1-d-1< span="">), and Reduction of renal burden. Therapeutic measures include early application of renin angiotensin system (RAS) inhibitors, strict control of blood glucose, weight reduction in obese patients, control of blood pressure (<130/80 mmHg), control of hyperuricemia and improvement of renal microcirculation. If the disease progresses to nephrotic syndrome or uremia, specialist treatment by a nephrologist is also required.
6. Diabetic retinopathy and blindness: Elderly patients need regular fundus examinations to detect lesions in time and start treatment early for maximum benefit. Anti-inflammatory, anti-angiogenic and microcirculation improvement are the treatments being used, and laser photocoagulation therapy is an effective measure to prevent blindness.
7. Diabetic peripheral neuropathy: More than half of the elderly diabetic patients have combined peripheral neuropathy (DPN). Sensory nerve and autonomic nerve damage are the most common, with a variety of clinical manifestations. The diagnosis of DPN requires a comprehensive analysis because of the interplay between the presence of osteoarthropathy, mental abnormalities and cognitive impairment in elderly patients. α-Lipoic acid, prostaglandin and methylvitamin B12 are effective in improving sensory abnormalities, limb numbness and pain caused by DPN, and non-narcotic analgesics and capsaicin are useful in reducing the symptoms of painful neuropathy. .
8, osteoporosis and arthropathy in the elderly: osteoporosis occurs in postmenopausal women and the elderly, appropriate amount of vitamin D and calcium supplements, timely activation of diphosphonate preparations and other anti-osteoporosis drugs are conventional treatment measures, prevention of falls and fractures is the goal. Regular assessment of fall risk and physical function is necessary for the elderly, and the increased risk of falls due to severe hyperglycemia and hypoglycemia should be avoided.
9. Combined medications need to pay attention to drug interactions: Elderly diabetic patients often have multiple coexisting diseases and need to take multiple therapeutic drugs, and need to pay attention to drug interactions. Drugs that can raise blood sugar include: antihypertensive drug CCB, anti-tuberculosis drug rifampin, quinolones (gatifloxacin, moxifloxacin), amylase and pancreatic enzyme preparations, etc. Drugs that lower blood sugar include: allopurinol, quinolones (gatifloxacin, moxifloxacin), proton pump inhibitors (cimetidine, ranitidine). Drugs that elevate blood uric acid: thiazide diuretics, aspirin, niacin lipid-lowering drugs. Drugs that lower blood uric acid: colesartan.
10. Other problems associated with geriatric diabetes: The risk of cognitive dysfunction is higher than normal in older people with diabetes. Screening of patients of advanced age and longer duration of the disease is required with the help of a simple assessment tool sheet (Faltein Mental Status Checklist). Diabetes is also associated with an increased incidence of depression, and untreated depression may increase the risk of death and dementia, requiring early screening of patients using the Geriatric Depression Scale. Elderly patients with abdominal obesity have an increased incidence of sleep apnea syndrome (OSAS), which can be accompanied by fasting hyperglycemia, hyperinsulinemia and early morning hypertension, and has a high risk of increasing sudden death in the morning, requiring prompt examination and treatment to improve the overall prognosis by improving patient ventilation.
11. Comorbidities due to poorly controlled diabetes in the elderly: This has become an important social and economic burden. Unlike young and middle-aged diabetic patients, elderly diabetic patients have a relatively greater need for social help. Therefore, in addition to the requirement of self-management for elderly patients there is also a need to focus on social support. Sources of social support involve all aspects of the patient’s participation in social activities and life outside the hospital. In addition to family (relatives and friends) support, community and neighborhood support is also very important, especially for patients with significant cognitive impairment and motor limitations. The higher the level of social support received by the elderly, the better the quality of life and the better the outcome of diabetes management. Administrative (policy and public opinion campaigns) and financial support (medical coverage) from the government will improve the overall management of geriatric diabetes and related metabolic disorders for the benefit of society and people’s health.