Diabetes

Japanese: 糖尿病
Diabetes
What kind of disease is it?

●Main symptoms and course Diabetes is a disease in which the amount of glucose in the blood becomes chronically high (hyperglycemia) due to a lack of insulin, a hormone secreted by β cells in the pancreas, or a decline in its function.
A major characteristic of diabetes is that it has almost no noticeable symptoms. Since symptoms do not appear until blood sugar levels become extremely high, it is not uncommon for the condition to become severe by the time it is noticed. However, if you pay attention to changes in your physical condition, you may notice symptoms such as fatigue, dry mouth, the need to drink a lot of water, increased urination, strong hunger, increased food intake, and weight gain or loss. Most patients are diagnosed with diabetes when hyperglycemia or glucose in the urine is discovered during a health checkup or tests taken for other illnesses.
If the condition is left untreated for a long period of time without being noticed, or if you are aware of it but do not manage your blood sugar properly, your blood vessels will become damaged and fragile, leading to various complications.
First, arteriosclerosis progresses in blood vessels throughout the body. Typical complications include retinopathy, which can lead to decreased vision or blindness, nephropathy, which causes proteinuria and swelling, and neuropathy, which causes numbness and paralysis. Furthermore, the risk of developing myocardial infarction and cerebral infarction increases. In addition, resistance weakens, making the patient more susceptible to infections, which can sometimes lead to life-threatening situations.

●Causes of the disease and how symptoms develop Insulin, which is deeply involved in the onset of diabetes, acts as a bridge to take up glucose in the blood into cells. In other words, when insulin function decreases, the glucose in the blood is not used efficiently and remains in the blood for a long time, resulting in a prolonged state of hyperglycemia.
It is believed that in most patients, the disease develops due to a genetic predisposition combined with environmental factors such as overeating, obesity, lack of exercise, and stress. Diabetes can also be caused by diseases or infections of the pancreas, liver, or endocrine system, or by the effects of medication.

●Characteristics of the disease Diabetes is a common disease affecting approximately 9.5 million Japanese people (according to the Ministry of Health, Labor and Welfare in 2012). Diabetes is divided into two types (type 1 and type 2).
Type 1 diabetes occurs when insulin secretion almost completely stops due to some cause, and is a type that often develops in children and young people (usually under 15 years old). Patients with this type absolutely need insulin injections. Type 2 diabetes occurs when insulin secretion is reduced, or insulin is secreted but cells are unable to respond to it properly, and most cases develop in middle age or older (usually over 40 years old).

● About complications of diabetes Diabetic nephropathy: If diabetes is not properly treated for more than 15 years, many patients will develop proteinuria. After that, kidney function will gradually decline, leading to chronic renal failure and the need for artificial dialysis. Currently, this disease is the most common cause among patients who are newly undergoing artificial dialysis.
Diabetic neuropathy: Continuing high blood sugar damages the peripheral and autonomic nerves. Peripheral neuropathy can cause a loss of sensation in the hands and feet, and injuries may go unnoticed. The body's resistance weakens, and small wounds can become infected and cause gangrene, a condition in which cells decay. In severe cases of gangrene, amputation of the affected area may be necessary. Autonomic nerve abnormalities can also cause problems with urination and defecation, abnormal sweating, and erectile dysfunction.
Diabetic retinopathy: If hyperglycemia continues, blood vessels in the retina of the eye will bleed and the cells in the retina will not function normally, causing a decrease in vision and ultimately blindness.

★Diagnostic criteria for diabetes Hyperglycemia is diagnosed as diabetic in the following cases:
●When fasting blood glucose level is 126 mg/dL or higher ●When random blood glucose level is 200 mg/dL or higher ●When blood glucose level 2 hours after loading in 75-g oral glucose tolerance test (75-g OGTT) is 200 mg/dL or higher (any of the above)
When HbA1c (hemoglobin A1c) is 6.5% or higher If two or more tests taken on different days show a diabetic type, the patient will be diagnosed with diabetes. Also, if blood glucose and HbA1c show diabetic type results in a single test, the patient will be diagnosed with diabetes. However, a diagnosis cannot be made with repeated HbA1c tests alone. If there are typical symptoms of diabetes (thirst, excessive drinking, excessive urination) or definite diabetic retinopathy, and blood glucose levels are confirmed to be diabetic even once, the patient will be diagnosed with diabetes.
If the fasting blood glucose level is less than 110 milligrams/deciliter and the 2-hour blood glucose level after a 75-g OGTT is less than 140 milligrams/deciliter, the patient is considered to have normal blood glucose levels; if the level is neither of the above, the patient is considered to have borderline blood glucose levels.
<Procedure for 75g oral glucose tolerance test (75g OGTT)>
1. Fast from 9pm the night before and come to the hospital on an empty stomach until the morning
2. Take a blood sample on an empty stomach and measure your blood sugar level
3. Drink water with 75 grams of glucose dissolved in it (glucose loading)
4. After glucose loading, blood samples are taken 30 minutes, 1 hour, and 2 hours later to measure blood glucose levels.
5. Determine whether the patient is diabetic, normal, or borderline.



EBM checks on common treatments and care

[Treatment and care] Because disease management is important, provide education about diabetes. [Rating] ☆☆☆☆
[Evaluation points] Diabetes is essentially a chronic disease, and clinical studies have shown that the patient's own management of the disease greatly influences its course. Doctors, nurses, nutritionists, pharmacists, psychotherapists, etc. work together as a team to educate patients and their families on how to take the initiative in managing their diet and exercise, strictly measuring their own blood glucose levels and taking appropriate drug treatments, and responding to changes in the environment and infectious diseases. There are also clinical studies that show that blood sugar control improves when patients have sufficient knowledge. (1)(2)

[Treatment and care] Based on diet and exercise therapy [Rating] ☆☆☆☆☆
[Evaluation Points] There are highly reliable clinical studies that show that dietary therapy centered on restricting energy and salt intake reduces weight, lowers blood pressure, improves insulin secretion and response, and improves blood sugar control. Therefore, dietary therapy is performed on all diabetic patients. First, the total energy intake is determined based on 30 kilocalories per kilogram of body weight, based on standard body weight. This standard can be increased or decreased depending on the intensity of daily activity (work volume, gender, age, etc.). Next, the balance of the intake ratio of the three major nutrients should be in the range of 50 to 60 percent carbohydrates, 1 to 1.2 grams of protein per kilogram of standard body weight, and the remainder lipids. Highly reliable clinical studies have shown that such an appropriate dietary therapy improves blood sugar levels.
There are highly reliable clinical studies that show that exercise therapy is useful for keeping blood sugar levels within an appropriate range and for preventing the onset of arteriosclerosis, a disease that often accompanies diabetes. Therefore, patients who are in a condition where they can safely carry out general exercise should exercise, but middle-aged or older patients who have had diabetes for a long time are recommended to undergo a check-up to evaluate the risk of serious heart disease caused by exercise before starting exercise therapy. (3)-(5)

[Treatment and care] For type 1 diabetes, patients should self-inject insulin and perform more strict blood glucose control by self-monitoring of blood glucose. [Rating] ☆☆☆☆☆
[Evaluation points] In type 1 diabetes, insulin secretion almost stops, so treatment with frequent insulin injections (3-4 times a day) or continuous subcutaneous insulin infusion (CSII) is necessary. There are highly reliable clinical studies that show that injecting insulin 3-4 times a day while monitoring your own blood glucose levels keeps blood glucose levels within an appropriate range better than injecting insulin 1-2 times a day, and reduces the risk of diabetic microangiopathy (retinal, renal, and neuropathy) worsening. (6)(7) It is also effective in preventing the worsening of macroangiopathy (ischemic heart disease and cerebrovascular disease). (8)(9)

[Treatment and care] For type 2 diabetes, oral hypoglycemic drugs are used. [Rating] ☆☆☆☆☆
[Evaluation points] There is highly reliable clinical research that suggests that oral hypoglycemic drugs should be used in type 2 diabetes when blood glucose levels cannot be kept within a sufficiently appropriate range even with dietary and exercise therapy. Oral hypoglycemic drugs are broadly divided into three types based on their action: 1) drugs that suppress glucose absorption or promote excretion, 2) drugs that improve insulin resistance, and 3) drugs that promote insulin secretion. The effectiveness of all types in improving blood glucose control has been confirmed in highly reliable clinical research. The combined use of drugs with different actions is also recommended in similar clinical studies.
As a new type of oral medication, various formulations of DPP-4 inhibitors have been approved since 2009, followed by SGLT2 inhibitors in 2014. DPP-4 inhibitors promote postprandial insulin secretion depending on blood glucose levels, and have the characteristic that the risk of hypoglycemia when used alone is very low, and are becoming one of the first-choice drugs for type 2 diabetes. SGLT2 inhibitors lower blood glucose levels by excreting glucose in urine directly from the body along with the urine. Side effects such as hypoglycemia and urinary tract infections have also been observed, so caution is required when using them. (10)-(24)

[Treatment and care] Insulin therapy is also used for type 2 diabetes [Rating] ☆☆☆☆☆
[Evaluation points] In type 2 diabetes, when proper blood glucose levels cannot be maintained despite dietary therapy, exercise therapy, and oral administration of appropriate oral hypoglycemic drugs, or when hyperglycemia itself has reduced insulin secretion or worsened insulin resistance (glucose toxicity), highly reliable clinical research has shown that self-injection of insulin can improve the course of the disease. Such patients are judged to be in a state of relative insulin deficiency due to reduced insulin secretion from the pancreas or increased insulin resistance throughout the body. It is considered effective to completely switch from oral hypoglycemic drugs to insulin therapy, or to use them in combination. According to highly reliable clinical research, when using insulin therapy alone, it is necessary to decide when to self-inject insulin with different types of insulin with different durations of action depending on the daily blood glucose level fluctuations and daily life style, and when used in combination with oral hypoglycemic drugs, blood glucose levels can be controlled with a smaller amount of insulin. (25)-(36)

[Treatment and care] GLP-1 receptor agonists are sometimes used in type 2 diabetes [Rating] ☆☆☆☆☆
[Evaluation Points] GLP-1 receptor agonists are injectable preparations that promote postprandial insulin secretion depending on blood glucose levels. They are used either alone or in combination with other oral hypoglycemic agents. (37)


Checking commonly used drugs with EBM

Oral hypoglycemic drug [Drug use] Insulin secretion promoter [Drug name] Amaryl (glimepiride) (16)
[Rating] ☆☆☆☆☆
[Drug name] Starsis (nateglinide) (17)
[Rating] ☆☆☆☆☆

[Medicinal use] Glucose absorption retardant [Drug name] Glucobay (acarbose) (10)-(12)(15)
[Rating] ☆☆☆☆☆
[Drug name] Baysin (voglibose) (18)
[Rating] ☆☆☆☆☆

[Medicinal use] Insulin resistance improving drug [Drug name] Actos (pioglitazone hydrochloride) (13)
[Rating] ☆☆☆☆☆
[Drug name] Metgluco (metformin hydrochloride) (14)
[Rating] ☆☆☆☆☆
[Evaluation points] There is highly reliable clinical research that shows that oral hypoglycemic drugs should be used in type 2 diabetes when blood sugar levels cannot be kept within an adequate range despite diet and exercise therapy.

[Medicinal use] DPP-4 inhibitor [Drug name] Januvia (sitagliptin phosphate hydrate) (19)
[Rating] ☆☆☆☆☆
[Drug name] Nesina (alogliptin benzoate) (20)
[Rating] ☆☆☆☆☆
[Drug name] Equa (vildagliptin) (21) (22)
[Rating] ☆☆☆☆☆
[Evaluation points] As a new type of oral medication, various DPP-4 inhibitor preparations have been approved one after another since 2009. DPP-4 inhibitors have the effect of promoting postprandial insulin secretion depending on blood glucose levels, and are characterized by an extremely low risk of hypoglycemia when used alone.

[Medicinal use] SGLT2 inhibitor [Drug name] Forxiga (dapagliflozin propylene glycol hydrate) (23)
[Rating] ☆☆☆☆☆
[Drug name] Canaglu (Canagliflozin hydrate) (24)
[Rating] ☆☆☆☆☆
[Evaluation points] SGLT2 inhibitors have the effect of lowering blood sugar levels by excreting glucose in urine from the body along with the urine.

Insulin [drug name] Ultra-rapid acting insulin (25)-(27)
[Rating] ☆☆☆☆☆
[Drug name] Rapid-acting insulin (25)-(27)
[Rating] ☆☆☆☆☆
[Drug name] Semi-rapid acting insulin (25)-(27)
[Rating] ☆☆☆☆☆
[Drug name] Intermediate-acting insulin (25)-(27)
[Rating] ☆☆☆☆☆
[Drug name] delayed-acting insulin (25)-(27)
[Rating] ☆☆☆☆☆
[Drug name] Long-acting insulin (28)-(32)
[Rating] ☆☆☆☆☆
[Drug name] Biphasic insulin preparation (25)-(27)
[Rating] ☆☆☆☆☆
[Evaluation points] In patients with type 2 diabetes who are unable to maintain blood glucose levels within an appropriate range despite diet therapy, exercise therapy, and appropriate oral hypoglycemic drug therapy, there are highly reliable clinical studies which show that self-injecting insulin can improve the course of the disease.

GLP-1 receptor agonist [drug name] Victoza (liraglutide) (37)
[Rating] ☆☆☆☆☆
[Drug name] Byetta (exenatide) (37)
[Rating] ☆☆☆☆☆
[Evaluation points] GLP-1 receptor agonists are injectable drugs that promote postprandial insulin secretion depending on blood glucose levels. They are used either alone or in combination with other oral hypoglycemic agents.


Overall, it is currently the most reliable treatment method .<br /> If you can keep your blood sugar level at a healthy level, you can live a normal lifespan. Diabetes has a large number of patients and can cause various complications, so many clinical studies have been conducted around the world. As a result, it is known that if you can control your blood sugar level to roughly the same level as healthy people by making good use of diet therapy, exercise therapy, and various drug therapies, you can avoid most complications and live an average life expectancy.
Therefore, in order to keep blood glucose levels before and after meals within the normal range, it is necessary to combine appropriate energy and salt restriction with regular exercise (such as at least 30 minutes of brisk walking per day), oral hypoglycemic drugs, self-injection of insulin, and other treatments that suit each individual's lifestyle.

Appropriate dietary therapy is the basis First, total energy intake is determined based on 30 kcal per kilogram of body weight, with standard weight as a guide. This standard can be increased or decreased depending on the intensity of daily activity (amount of work, gender, age, etc.). Next, the intake ratio of the three major nutrients should be in the range of 50-60 percent carbohydrates, 1-1.2 grams of protein per kilogram of standard weight, and the remainder lipids. Many hospitals provide dietary advice and diabetes classes by doctors, nurses, and nutritionists to help patients incorporate it into their daily habits.

Exercise prevents arteriosclerosis Moderate exercise is effective in keeping blood sugar levels within a good range and preventing complications. For people who are able to safely engage in general exercise, we set a target amount of exercise that suits them and encourage them to exercise. However, for people middle-aged or older who have had diabetes for a long time, there is a possibility that narrowing of the coronary arteries has already occurred even if they have no symptoms, so we check in advance before deciding whether or not to engage in exercise therapy.

Be proactive in your treatment Behavioral change in diet and exercise, which is an important point in diabetes treatment, is not as easy as taking medicine, and in many cases requires changing your way of thinking and living. The effectiveness of many diabetes treatments has been confirmed by highly reliable research, so it is most important to listen to a thorough explanation, be convinced from the bottom of your heart, and voluntarily approach treatment while enjoying changing your lifestyle.

(1)The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986.
(2)Minet L, Moller S, Vach W, Wagner L, et al. Mediating the effect of self-care management intervention in type 2 diabetes: a meta-analysis of 47 randomized controlled trials. Patient Educ Conns. 2010;80:29-41.
(3) Japan Diabetes Society. Guide to Diabetes Dietary Guidance and Therapy Using the Food Exchange Table. Bunkodo. 1998.
(4)Boule NG, Haddad E, Kenny GP, et al. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001; 286: 1218-1227.
(5)Mittleman MA, Maclure M, Tofler GH, et al. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med. 1993; 329: 1677-1683.
(6)The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993; 329: 977-986.
(7)The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia. 1998; 41: 416-423.
(8)Lawson ML, Gerstein HC, Tsui E, et al. Effect of intensive diabetes therapy on early macrovascular disease in young individuals with type 1 diabetes : a systematic review and meta-analysis. Diabetes Care 22(Suppl 2).1999 : B35-B39.
(9)Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005; 353: 2643-2653.
(10)Hotta N, Kakuta H, Sano T, et al. Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study. Diabet Med. 1993;10:134-138.
(11)Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study. Diabetes Care. 1994;17:561-566.
(12)Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. Am J Med. 1997;103:483-490.
(13)Aronoff S, Rosenblatt S, Braithwaite S, et al. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care. 2000;23:1605-1611.
(14)Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865.
(15)Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (UK Prospective Diabetes Study 44). Diabetes Care. 1999;22:960-964.
(16)Rosenstock J, Samols E, Muchmore DB, et al. Glimepiride, a new once-daily sulfonylurea. A double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group. Diabetes Care. 1996;19:1194-1199.
(17)Gribble FM, Manley SE, Levy JC. Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166). Diabetes Care. 2001; 24: 1221-1225.
(18)Vichayanrat A, Ploybutr S, Tunlakit M, et al. Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients. Diabetes Res Clin Pract. 2002;55:99-103.
(19)Scheen AJ, Chapentier G, Ostqren CJ, et al. Efficacy and safety of saxagliptin in combination with metformin compared with sitagliptin in combination with metformin in adult patients with type 2 diabetes mellitus. Diabetes Metab Res Rev. 2010; 26: 540-549.
(20)DeFronzo RA, Fleck PR, Wilson CA, Mekki Q; Alogliptin Study 010 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes and inadequate glycemic control: a randomized, double-blind, placebo-controlled study. Diabetes Care. 2008; 31: 2315-2317.
(21)Pratley RE, Jauffret-Kamel S, Galbreath E, et al. Twelve-week monotherapy with the DPP-4 inhibitor vildagliptin improves glycemic control in subjects with type 2 diabetes. Horm Metab Res. 2006; 38: 423-428.
(22)Dejager S, Razac S, Foley JE, et al. Vildagliptin in drug-naïve patients with type 2 diabetes: a 24-week, double-blind, randomized, placebo-controlled, multiple-dose study. Horm Metab Res. 2007; 39: 218-223.
(23)Strojek K, Yoon KH, Hruba V, Elze M, et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2011; 13: 928-938.
(24)Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013; 36: 2508-2015.
(25)Genuth S. Management of the adult onset diabetic with sulfonylurea drug failure. Endocrinol Metab Clin North Am. 1992;21:351-370.
(26)Dagogo-Jack S, Santiago JV. Pathophysiology of type 2 diabetes and modes of action of therapeutic interventions. Arch Intern Med. 1997;157:1802-1817.
(27) Meltzer S, Leiter L, Daneman D, et al. 1998 clinical practice guidelines for the management of diabetes in Canada. Canadian Diabetes Association. CMAJ. 1998;159(Suppl 8):S1-S29.
(28)Ratner RE, Hirsch IB, Neifing JL, et al. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. US Study Group of Insulin Glargine in Type 1 Diabetes. Diabetes Care. 2000; 23: 639-643.
(29)Rosetti P, Pampanelli S, Fanelli C, et al. Intensive replacement of basal insulin in patients with type 1 diabetes given rapid-acting insulin analog at mealtime: a 3-month comparison between administration of NPH insulin four times daily and glargine insulin at dinner or bedtime. Diabetes Care. 2003; 26: 1490-1496.
(30)Yki-Järvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. HOE 901/3002 Study Group. Diabetes Care.2000; 23: 1130-1136.
(31)Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003; 26: 3080-3086.
(32)Hermansen K, Davies M, Derezinski T, et al. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006; 29: 1269-1274.
(33)Shank ML, Del Prato S, DeFronzo RA. Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM. Diabetes. 1995;44:165-172.
(34)Riddle MC. Combined therapy with a sulfonylurea plus evening insulin: safe, reliable, and becoming routine. Horm Metab Res. 1996;28:430-433.
(35)Buse J. Combining insulin and oral agents. Am J Med. 2000;108(Suppl 6a):23S-32S.
(36)Johnson JL, Wolf SL, Kabadi UM. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials. Arch Intern Med. 1996;156:259-264.
(37) Shyangdan DS, Royle P, Clar C, et.al. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2011;5:CD006423. doi: 10.1002/14651858.CD006423.pub2.

Source: "EBM: A book that explains correct treatment" Information about the book "EBM: A book that explains correct treatment"

Japanese:
どんな病気でしょうか?

●おもな症状と経過
 糖尿病(とうにょうびょう)は、膵臓(すいぞう)のβ細胞から分泌(ぶんぴつ)されるインスリンというホルモンの分泌量が不足したり、その働きが低下することによって、慢性的に血液中のブドウ糖の量が多くなる(高血糖(こうけっとう))病気です。
 糖尿病はほとんど自覚症状がないのが大きな特徴です。血糖値がよほど高くならないと症状がでないため、気がついたときには重症になっていることも少なくありません。しかし、体調の変化に注意すると、倦怠感(けんたいかん)、口が渇(かわ)く、多量に水を飲みたくなる、尿量が増える、強い空腹感を覚える、食事量が増える、体重が増加あるいは減少するといった症状に気づくこともあります。ほとんどの患者さんは健康診断やほかの病気のために受けた検査で高血糖や尿糖(にょうとう)が発見され、糖尿病の診断がつけられます。
 気づかないで長期間放置したままだったり、気づいていても十分な血糖の管理をしないでいたりすると、血管が障害を受けてもろくなり、さまざまな合併症が引きおこされます。
 まず、全身の血管の動脈硬化が進みます。視力の低下や失明を招くこともある網膜症(もうまくしょう)、たんぱく尿やむくみが現れる腎症(じんしょう)、しびれや感覚が麻痺(まひ)してしまう神経症などが代表的な合併症です。さらには、心筋梗塞(しんきんこうそく)や脳梗塞(のうこうそく)をおこす可能性も高くなります。また、抵抗力が衰えるため感染症にかかりやすくなるなど、ときには生命にかかわる事態を招く場合もあります。

●病気の原因や症状がおこってくるしくみ
 糖尿病の発病と深くかかわっているインスリンは、血液中のブドウ糖を細胞に取り込む橋渡しの役割をしています。つまり、インスリンの働きが低くなると、血液中のブドウ糖が効率よく利用されず、いつまでも血液中に残ることになり、高血糖の状態が続きます。
 ほとんどの患者さんでは、遺伝的な素因に過食、肥満、運動不足、ストレスなどの環境要因が加わって発病すると考えられています。膵臓や肝臓、内分泌などの病気や感染症、薬剤の影響などによって糖尿病が発病することもあります。

●病気の特徴
 日本人のおよそ950万人(2012年、厚生労働省調べ)が糖尿病といわれるほど多くみられる病気です。糖尿病は2つのタイプ(1型と2型)に分けられます。
 1型糖尿病は、なんらかの原因によってインスリンの分泌がほとんど止まってしまうもので、子どもや若年者(多くは15歳以下)で発症することが多いタイプです。このタイプの患者さんはインスリン注射が絶対に必要となります。2型糖尿病は、インスリンの分泌が低下していたり、分泌はされていても細胞がうまくインスリンに反応できなかったりする状態で、中年以降(多くは40歳以上)に発症するのはほとんどこのタイプです。

●糖尿病の合併症について
 糖尿病性腎症:糖尿病をきちんと治療しないで15年以上経過すると、多くの患者さんでたんぱく尿がでるようになります。その後、徐々に腎臓の機能が低下し、慢性腎不全(じんふぜん)に至り人工透析(じんこうとうせき)が必要となります。現在、新たに人工透析を受ける患者さんのなかではこの病気がもっとも多い原因となっています。
 糖尿病性神経障害:高血糖が続くことによって、末梢神経(まっしょうしんけい)や自律神経(じりつしんけい)が傷つけられます。末梢神経障害では、手足の感覚が鈍くなり、けがをしても気がつかないこともあります。体の抵抗力が弱まり、小さな傷が化膿(かのう)して細胞が腐っていく壊疽(えそ)をおこしてしまうこともあります。重症の壊疽では、患部を切断する必要もでてきます。自律神経の異常により、排尿・排便に障害がおこったり、発汗異常、勃起不全などをおこしたりすることもあります。
 糖尿病性網膜症:高血糖状態が続くと、目の網膜の血管から出血し、網膜の細胞が正常に働かなくなります。したがって、視力が低下し、最終的に失明することもあります。

★糖尿病の診断基準
 高血糖の判定は、以下のようなときに糖尿病型とすることで下されます。
●空腹時血糖値が126ミリグラム/デシリットル以上のとき
●随時血糖値(ずいじけっとうち)200ミリグラム/デシリットル以上のとき
●75グラム経口ブドウ糖負荷試験(75グラムOGTT)で、負荷後2時間の血糖値が200ミリグラム/デシリットル以上のとき
(以上のいずれか)
●HbA1c(ヘモグロビンエイワンシー)が6.5パーセント以上のとき
 別の日に行った検査で2回以上糖尿病型と判定されれば、糖尿病と診断されます。また、1回の検査でも、血糖値とHbA1cが同時に糖尿病型を示した場合は、糖尿病の診断となります。ただし、HbA1cの反復検査のみで診断することはできません。糖尿病の典型的な症状(口渇感、多飲、多尿)があるか、あるいは確実な糖尿病性網膜症がある場合、血糖値が糖尿病型であることが1回でも確認されれば、糖尿病と診断されます。
 空腹時の血糖値が110ミリグラム/デシリットル未満かつ75グラムOGTT2時間の血糖値が140ミリグラム/デシリットル未満の場合は正常型となり、上記のいずれでもない場合は境界型と判定します。
<75グラム経口ブドウ糖負荷試験(75グラムOGTT)の手順>
1. 前夜9時以後絶食として、朝まで空腹のまま来院
2. 空腹のまま採血し、血糖値を測定する
3. ブドウ糖75グラムを溶かした水を飲む(糖負荷)
4. ブドウ糖負荷後、30分、1時間、2時間後に採血し血糖を測定する
5. 糖尿病型、正常型、境界型のいずれかに判定する



よく行われている治療とケアをEBMでチェック

[治療とケア]病気の管理が重要なので、糖尿病についての教育を行う
[評価]☆☆☆☆
[評価のポイント] 糖尿病は基本的に慢性に経過していく病気で、患者さん自身による病気の管理がその後の経過を大きく左右することが臨床研究によって示されています。食事や運動の管理、自己血糖測定や適切な薬物治療を厳格に実行すること、環境の変化や感染症にかかったときの対応などを患者さんやその家族が主体的に行えるように医師・看護師・栄養士・薬剤師・心理療法士などがチームで教育を行います。患者さんが十分な知識をもつことで血糖コントロールが改善するという臨床研究もあります。(1)(2)

[治療とケア]食事療法と運動療法を基本として行う
[評価]☆☆☆☆☆
[評価のポイント] エネルギー制限や塩分制限を中心とした食事療法は、体重の減量や血圧の低下、インスリンの分泌量や反応する力を改善し、血糖コントロールを改善するという非常に信頼性の高い臨床研究があります。そこで、食事療法はすべての糖尿病の患者さんに行うことになります。まず、総摂取エネルギーを、標準体重を目安に体重1キログラムあたり30キロカロリーを基準として決定します。この基準は生活活動強度(仕事量、性別、年齢など)により増減します。次に、三大栄養素の摂取割合のバランスは、炭水化物を50~60パーセントの範囲とし、たんぱく質を標準体重1キログラムあたり1~1.2グラム、残りを脂質とします。このような適切な食事療法により、血糖値が改善することが、非常に信頼性の高い臨床研究で示されています。
 運動療法は適正な範囲で血糖値を保ち、また、糖尿病にしばしば合併する動脈硬化による病気の発生を予防するのにも有用であるという、非常に信頼性の高い臨床研究があります。したがって、一般的な運動が安全にできる状態の患者さんは運動を行うことになりますが、中年以降の患者さんで、糖尿病にかかっている期間が長い場合は、運動療法を開始する前に、運動による深刻な心臓の病気がおこる危険性を評価するためのチェックを受けるよう推奨されています。(3)~(5)

[治療とケア]1型糖尿病では、インスリン自己注射を行うとともに、自己血糖測定によるいっそう厳格な血糖管理を行う
[評価]☆☆☆☆☆
[評価のポイント] 1型糖尿病ではインスリンの分泌がほとんど止まってしまうため、インスリン頻回注射法(3~4回/日)または持続皮下インスリン注入療法(CSII)による治療が必要となります。インスリンを1日1~2回注射する方法に比べて、自己血糖測定を行いながら1日3~4回注射する方法でより良好に適正な範囲で血糖値が保たれ、糖尿病性細小血管症(網膜、腎、神経障害)が悪化する危険性がより小さくなることを示す非常に信頼性の高い臨床研究もあります。(6)(7) また、大血管症(虚血性心疾患、脳血管疾患)の悪化の抑制にも有効です。(8)(9)

[治療とケア]2型糖尿病では、経口血糖降下薬を用いる
[評価]☆☆☆☆☆
[評価のポイント] 食事療法や運動療法を行っても、なお十分に適正な範囲に血糖値を保つことができない場合に、2型糖尿病では経口血糖降下薬を使用すべきであるという非常に信頼性の高い臨床研究があります。経口血糖降下薬は、その作用によって、大きく①ブドウ糖の吸収を抑制または排泄(はいせつ)を促進する薬剤、②インスリンの抵抗性を改善する薬剤、③インスリンの分泌を促進する薬剤に分けられます。いずれのタイプでも血糖コントロールを改善する効果が非常に信頼性の高い臨床研究で確認されています。作用の異なる薬剤の併用についても同様の臨床研究で推奨されています。
 また、新たな系統の経口薬として、2009年からDPP-4阻害薬の各製剤が順次承認され、2014年からはSGLT2阻害薬が承認されました。DPP-4阻害薬は、血糖値に依存して食後のインスリン分泌を促進する作用をもち、単独では低血糖をきたすリスクが非常に小さいという特徴があり、2型糖尿病における第一選択薬のひとつになりつつあります。SGLT2阻害薬は、尿中のブドウ糖をそのまま尿と共に体外に排泄させて血糖値を下げる作用があります。低血糖や尿路感染などの副作用も認められており、用いる際には注意が必要です。 (10)~(24)

[治療とケア]2型糖尿病においてもインスリン療法を行う
[評価]☆☆☆☆☆
[評価のポイント] 2型糖尿病で食事療法・運動療法・適切な経口血糖降下薬の内服治療を行っても良好に適正な血糖値を保つことができない場合や、高血糖そのものの影響でインスリン分泌能が低下していたりインスリン抵抗性が悪化している場合(糖毒性の状態)、インスリン自己注射を行うことでその後の経過を改善できることを示す非常に信頼性の高い臨床研究があります。こうした患者さんは、膵臓のインスリン分泌が低下しているか、全身のインスリン抵抗性が高まっているために相対的にインスリンが不足している状態にあると判断されます。経口血糖降下薬からインスリン療法に完全に切り替える場合も、併用する場合も有効とされています。非常に信頼性の高い臨床研究によると、インスリン療法単独では、1日の血糖値の動きや日常生活スタイルに応じて作用時間の異なるタイプのインスリン自己注射をいつ行うのかを決定すべきこと、また、経口血糖降下薬と併用すれば、より少ない量のインスリンで血糖値がコントロールできるとされています。(25)~(36)

[治療とケア]2型糖尿病においてGLP-1受容体作動薬が使われることがある
[評価]☆☆☆☆☆
[評価のポイント] GLP-1受容体作動薬は、注射製剤であり、血糖値に依存して食後のインスリン分泌を促進する作用をもっています。単独投与か、あるいはそのほかの経口血糖降下薬と併用して使われます。(37)


よく使われている薬をEBMでチェック

経口血糖降下薬
[薬用途]インスリン分泌促進薬
[薬名]アマリール(グリメピリド)(16)
[評価]☆☆☆☆☆
[薬名]スターシス(ナテグリニド)(17)
[評価]☆☆☆☆☆

[薬用途]グルコース吸収遅延薬
[薬名]グルコバイ(アカルボース)(10)~(12)(15)
[評価]☆☆☆☆☆
[薬名]ベイスン(ボグリボース)(18)
[評価]☆☆☆☆☆

[薬用途]インスリン抵抗性改善薬
[薬名]アクトス(ピオグリタゾン塩酸塩)(13)
[評価]☆☆☆☆☆
[薬名]メトグルコ(メトホルミン塩酸塩)(14)
[評価]☆☆☆☆☆
[評価のポイント] 食事療法や運動療法を行っても、なお十分に適正な範囲に血糖値を保つことができない場合に、2型糖尿病では経口血糖降下薬を使用すべきであるという非常に信頼性の高い臨床研究があります。

[薬用途]DPP-4阻害薬
[薬名]ジャヌビア(シタグリプチンリン酸塩水和物)(19)
[評価]☆☆☆☆☆
[薬名]ネシーナ(アログリプチン安息香酸塩)(20)
[評価]☆☆☆☆☆
[薬名]エクア(ビルダグリプチン)(21)(22)
[評価]☆☆☆☆☆
[評価のポイント] 新たな系統の経口薬として、2009年からDPP-4阻害薬の各製剤が順次承認されました。DPP-4阻害薬は、血糖値に依存して食後のインスリン分泌を促進する作用をもち、単独では低血糖をきたすリスクが非常に小さいという特徴があります。

[薬用途]SGLT2阻害薬
[薬名]フォシーガ(ダパグリフロジンプロピレングリコール水和物)(23)
[評価]☆☆☆☆☆
[薬名]カナグル(カナグリフロジン水和物)(24)
[評価]☆☆☆☆☆
[評価のポイント] SGLT2阻害薬には、尿中のブドウ糖をそのまま尿と共に体外に排泄させて血糖値を下げる作用があります。

インスリン
[薬名]超速効型インスリン(25)~(27)
[評価]☆☆☆☆☆
[薬名]速効型インスリン(25)~(27)
[評価]☆☆☆☆☆
[薬名]準速効型インスリン(25)~(27)
[評価]☆☆☆☆☆
[薬名]中間型インスリン(25)~(27)
[評価]☆☆☆☆☆
[薬名]遅効型インスリン(25)~(27)
[評価]☆☆☆☆☆
[薬名]持効型インスリン(28)~(32)
[評価]☆☆☆☆☆
[薬名]2相性製剤インスリン(25)~(27)
[評価]☆☆☆☆☆
[評価のポイント] 2型糖尿病で食事療法・運動療法・適切な経口血糖降下薬内服治療を行っても良好に適正な範囲で血糖値を保つことができない場合には、インスリン自己注射を行うことで、その後の経過を改善できることを示す非常に信頼性の高い臨床研究があります。

GLP-1受容体作動薬
[薬名]ビクトーザ(リラグルチド)(37)
[評価]☆☆☆☆☆
[薬名]バイエッタ(エキセナチド)(37)
[評価]☆☆☆☆☆
[評価のポイント] GLP-1受容体作動薬は、注射製剤であり、血糖値に依存して食後のインスリン分泌を促進する作用をもっています。単独投与か、あるいはそのほかの経口血糖降下薬と併用して使われます。


総合的に見て現在もっとも確かな治療法
血糖値を健康なレベルに保てば、寿命をまっとうできる
 糖尿病については、患者さんの数が多く、さまざまな合併症を引きおこすことから、世界中で多くの臨床研究が精力的に行われてきました。その結果、食事療法や運動療法、種々の薬物療法をうまく使いこなして、血糖値をほぼ健康(けんこう)な人々と同じレベルにコントロールできさえすれば、ほとんどの合併症をおこすことなく、平均的な余命をまっとうできることがわかっています。
 したがって、食前食後の血糖値が正常範囲に入るよう、適切なエネルギー制限や塩分制限と規則的な運動(最低、1日30分程度の早足歩行など)、経口血糖降下薬やインスリン自己注射などの治療方法を、その人自身のライフスタイルに合わせて組み合わせる必要があります。

適切な食事療法が基本となる
 まず、総摂取エネルギーを、標準体重を目安に体重1キログラムあたり30キロカロリーを基準として決定します。この基準は生活活動強度(仕事量、性別、年齢など)により増減します。次に、三大栄養素の摂取割合について、炭水化物を50~60パーセントの範囲とし、たんぱく質を標準体重1キログラムあたり1~1.2グラム、残りを脂質とします。多くの病院では、医師や看護師、栄養士らによる食事指導や糖尿病教室などが行われ、患者さんが毎日の習慣として取り入れられるように、指導をしています。

運動は動脈硬化を予防する
 良好な範囲で血糖値を保ち、合併症を予防するには適度な運動が有効です。一般的な運動が安全にできる状態の人には、その人に合った運動量の目安を定め、運動を行ってもらいます。ただし、中年以降の人で、糖尿病にかかっている期間が長い場合は、自覚症状がなくても冠動脈(かんどうみゃく)の狭窄(きょうさく)がすでにおこっている可能性もありますので、事前にチェックを行ってから、運動療法をするかしないかを決定します。

積極的に治療に取り組もう
 糖尿病治療で重要なポイントである食事と運動にかかわる行動変容(こうどうへんよう)は、薬を飲むように簡単にできることではなく、考え方や生き方自体を変えなくてはならない場合も少なくありません。糖尿病に関する治療は、その有効性が非常に信頼性の高い研究で確認されているものが多いので、十分説明を聞き、心の底から納得して、ライフスタイルを変えることを楽しみながら、自発的に治療に取り組むことがなによりも重要です。

(1)The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986.
(2)Minet L, Moller S, Vach W, Wagner L, et al. Mediating the effect of self-care management intervention in type 2 diabetes: a meta-analysis of 47 randomised controlled trials. Patient Educ Conns. 2010;80:29-41.
(3)日本糖尿病学会.「食品交換表」を用いる糖尿病食事指導療法指導の手引. 文光堂. 1998.
(4)Boule NG, Haddad E, Kenny GP, et al. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001 ; 286 : 1218-1227.
(5)Mittleman MA, Maclure M, Tofler GH, et al. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med. 1993 ; 329 : 1677-1683.
(6)The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993 ; 329 : 977-986.
(7)The effect of intensive diabetes therapy on measures of autonomic nervous system function in the Diabetes Control and Complications Trial (DCCT). Diabetologia. 1998 ; 41 : 416-423.
(8)Lawson ML, Gerstein HC, Tsui E, et al. Effect of intensive diabetes therapy on early macrovascular disease in young individuals with type 1 diabetes : a systematic review and meta-analysis. Diabetes Care 22(Suppl 2).1999 : B35-B39.
(9)Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 ; 353 : 2643-2653.
(10)Hotta N, Kakuta H, Sano T, et al. Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study. Diabet Med. 1993;10:134-138.
(11)Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study. Diabetes Care. 1994;17:561-566.
(12)Hoffmann J, Spengler M. Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. Am J Med. 1997;103:483-490.
(13)Aronoff S, Rosenblatt S, Braithwaite S, et al. Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes: a 6-month randomized placebo-controlled dose-response study. The Pioglitazone 001 Study Group. Diabetes Care. 2000;23:1605-1611.
(14)Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865.
(15)Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care. 1999;22:960-964.
(16)Rosenstock J, Samols E, Muchmore DB, et al. Glimepiride, a new once-daily sulfonylurea. A double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group. Diabetes Care. 1996;19:1194-1199.
(17)Gribble FM, Manley SE, Levy JC. Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166). Diabetes Care. 2001; 24: 1221-1225.
(18)Vichayanrat A, Ploybutr S, Tunlakit M, et al. Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients. Diabetes Res Clin Pract. 2002;55:99-103.
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