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Diabetes management

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The main goal of diabetes management is to keep blood glucose levels as normal as possible.[1] If diabetes is not well controlled, further challenges to health may occur.[1] People with diabetes can measure blood sugar by various methods, such as with a blood glucose meter or a continuous glucose monitor, which monitors over several days.[2] Glucose can also be measured by analysis of a routine blood sample.[2] Usually, people are recommended to control diet, exercise, and maintain a healthy weight, although some people may need medications to control their blood sugar levels. Other goals of diabetes management are to prevent or treat complications that can result from the disease itself and from its treatment.[3]

Description

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Diabetes is a chronic disease and it is important to have control of the diabetes as it can cause many complications. Diabetes can cause acute problems such as too low (hypoglycemia) or high blood sugar (hyperglycemia). Diabetes affects the blood vessels in the body, such as capillaries and arteries, which are the routes blood take to deliver nutrients and oxygen to the organs in the body.[4] By affecting the blood flow, diabetes increases the risk of other conditions such as strokes and heart disease (heart attacks).[2] Diabetes also affects small blood vessels, such as capillaries, in organs such as the eyes and the kidneys to cause diabetic retinopathy and diabetic nephropathy, respectively.[4]

Therefore, it becomes important to lower the sugar levels in the body in addition to control other risk factors that also contribute to the major complications such as smoking, alcohol use, weight, high blood pressure, and high cholesterol.[1] Often, the recommended treatment is a combination of lifestyle changes such as increasing exercise and healthy eating, along with medications to help control the blood glucose levels in the long term.[2]

Measurement

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There are several methods in which blood sugar is measured including with a glucose meter, continuous glucose monitor and routine bloodwork.

Image 1: Picture of healthcare worker using lancet to get blood sample from patient.

The glucose meter is a common a simple method in which glucose levels can be measured at home or in a clinical setting and is usually done several times per day. The test works by taking a small blood sample of blood using a lancet (a sterile pointed needle) to prick a finger (Image 1). The blood droplet is usually collected at the bottom of a test strip, while the other end is inserted in the glucose meter.[5] The drop of blood is drawn into the meter and can directly measure the glucose in the sample. The units of blood sugar level from a glucose meter, with the result either in mg/dL (milligrams per deciliter in the US) or mmol/L (millimoles per liter in Canada and Eastern Europe) of blood.[6] Control of diabetes may be improved by patients using home glucose meters to regularly measure their glucose levels.[7]

An image of a continuous glucose monitor attached on the skin

Continuous glucose monitors are another method to measure blood glucose levels. A CGM is a device that sits on the surface of the skin and measures the amount of glucose between the cells with a probe. The device does not directly measure the blood sugar but calculates it based on the sample of the measurements it takes from the probe.[6] The device will report the glucose level continuously and usually it has an alarm that will alert patients if the glucose level is too high or low.[6] The device also is able to graph the glucose readings over the time the sensor was in use and is very useful for adjusting treatment.[6]

In addition to the above tests, glucose can be measured on routine labs. One common test ordered by healthcare providers is a Basic Metabolic Panel (BMP) which is a blood test that looks at several different substances in the body, including blood glucose.[8] People are told to fast for 8 hours before drawing the labs so that the provider can see the fasting glucose level.[2] The normal level for fasting blood sugar in non-diabetic patients is 70 to 99 mg/dL (3.9 and 5.5 mmol/L).

Another useful test that has usually done in a laboratory is the measurement of blood HbA1c (hemoglobin A1c) levels. In the blood, there is a molecule called hemoglobin which carries oxygen to the cells. Glucose can attach itself to this molecule and if the blood glucose is consistently high, the value of the A1c will go up. This test, unlike the other tests, is measured as a percentage because the test measure the proportion of all the hemoglobin that has glucose attached.[2][9] This test measures the average amount of diabetic control over a period of about 3 months.[9] In non-diabetic people, the HbA1c level ranges from 4.0 to 5.7%.[9]

Optimal management of diabetes involves people measuring and recording their own blood glucose levels. By keeping a diary of their own blood glucose measurements and noting the effect of food and exercise, patients can modify their lifestyle to better control their diabetes. For people on insulin, involvement is important in achieving effective dosing and timing.

Goals

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They are suggested in clinical practice guidelines released by various national and international diabetes organizations.[10][11]

The targets are:

  • HbA1c of less than 6% or 7.0% if they are achievable without significant hypoglycemia[12][13]
  • Preprandial blood glucose: 3.9 to 7.2 mmol/L (70 to 130 mg/dL)[12]
  • 2-hour postprandial blood glucose: <10 mmol/L (<180 mg/dL)[12]

Goals should be individualized based on:[12]

In older patients, clinical practice guidelines by the American Geriatrics Society recommend, in frail patients who have a life expectancy of less than 5 years, a target a Hb A1c of 8% is appropriate as the risk of very low blood sugar outweighs the long term benefits of a lower A1c.[14]

Lifestyle modification

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Diet

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Main article: Diet in diabetes

There are many diets that are effective at managing diabetes and it is important that patients understand that there is no one diet that all patients should use.[15] Some diets that have commonly been used successfully in diabetes management and help with weight loss include Mediterranean, vegetarian, low carb or carb-controlled.[15] It is recommended that patients choose a diet that the patient can adhere to in the long run as a diet that is very ideal is impractical if the patient has trouble following it.[15]

A regular diet that has reduced variability in carbohydrates is an important factor in producing normal blood sugars. Patients with diabetes should eat preferably a balanced and healthy diet. Meals should consist of half a plate of non-starchy vegetables, 1/4 plate of lean protein, and 1/4 plate of starch/grain.[15] Patients should avoid excess simple carbs or added fat (such as butter, salad dressing) and instead eat complex carbohydrates such as whole grains.[1] In the long term, it is helpful to eat a consistent diet and amount of carbohydrate to make blood sugar management easier.[16] It is important for patients to eat 3 meals a day as well in order to reduce the chances of hypoglycemia, especially with patients that take insulin.[1]

There is a lack of evidence of the usefulness of low-carbohydrate dieting for people with type 1 diabetes.[17] Although for certain individuals it may be feasible to follow a low-carbohydrate regime combined with carefully managed insulin dosing, this is hard to maintain and there are concerns about potential adverse health effects caused by the diet.[17] In general people with type 1 diabetes are advised to follow an individualized eating plan rather than a pre-decided one.[17]

Exercise

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Along with diet, exercise is also important for the management of diabetes.[18] Not only does exercising regularly help manage blood sugar levels and weight, it helps reduce the risk of heart attack and stroke, reduces cholesterol levels, reduces risk of diabetes related complications, increases the effect of insulin, provides a boost in energy levels, helps reduce stress, and contributes to positive self-esteem.[19] By exercising, the body becomes more sensitive to insulin, allowing for better absorption of glucose by the muscle cells, for up to 24 hours after exercise.[20] Therefore, an ongoing exercise program is required to maintain the health benefits associated with exercising.[21]

In patients with type 2 diabetes, the combination of aerobic (cardio) exercise and strength training, as recommended by the American Diabetes Association (ADA) guidelines, is the most effective when it comes to controlling glucose and cholesterol.[22] Aerobic exercise has been shown to largely improve HbA1c, and contributes to weight loss and the enhanced regulation of cholesterol and lipoproteins.[21] This may be any form of continuous exercise that elevates breathing and heart rate such as walking, swimming, or dancing.[23] During the last 20 years, resistance training has gained considerable recognition as an optimal form of exercise for patients with type two diabetes.[21] By building muscle strength, strength training was linked to a 10% to 15% increase in strength, Bone Mineral Density, insulin sensitivity, muscle mass and decrease in blood pressure.[21]

Several studies have made it clear that exercise helps with blood sugar control and has shown to lower HbA1c levels by approximately 0.6% in patients with type 2 diabetes. The ADA recommends 150 minutes of moderate to vigorous aerobic exercise a week spread over 3 to 7 days with no more than 2 day break between days. Moreover, patients should also pair the aerobic exercise with 2 to 3 nonconsecutive sessions of strength training.

In type 1 diabetes, there also have been studies that show that, in children and adolescent, there is an association between exercise and lower HB A1c.[24] Furthermore, studies have shown that the longer the length of the exercise program, there is a further reduction in the HB A1c and patients have less insulin requirements.[24] Although the population of these studies are limited to patients under the age of 18, exercise is beneficial in managing diabetes, whether its type 1 or 2.[2] There are many benefits of exercise such as a decreased risk of cardiovascular diseases, including blood pressure, lipid profiles, body composition and insulin sensitivity.[25]

Medications

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Main article: Anti-diabetic drug

There are several medications classes that are commonly used to control blood sugar levels in patients with diabetes. Most of the medications used are either oral or injected.[1] In patients with type 1 diabetes, insulin is require because the body no longer produces insulin.[2] In patients with type 2 diabetes, management is largely more variable as lifestyle changes can have a significant impact. However, medications may be added to further help control blood glucose levels if the lifestyle changes are not effectively controlling the condition. Unlike type 1 diabetic patients, patients with type 2 diabetes can still produce insulin, so usually these patients take oral medications first before requiring insulin for diabetic control.[2]

Patient education[26] and compliance with treatment is very important in managing the disease. Improper use of medications and insulin can be very dangerous causing hypo- or hyper-glycemic episodes.

Insulin

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Main article: Insulin therapy
Insulin pen used to administer insulin

Insulin is the hormone that is made by the body that controls the cell intake of glucose. Normally, the pancreas produces insulin in response to high glucose levels in the body to bring the blood glucose levels down. For type 1 diabetics, there will always be a need for insulin injections throughout their life, as the pancreatic beta cells of a type 1 diabetic are not capable of producing sufficient insulin.[27] Insulin can not be taken orally because insulin is a hormone and is destroyed by the digestive track. Insulin can be injected by several methods, including a hypodermic needle, jet injector, or insulin pump. There is also inhaled insulin that can be used in adults with diabetes.[28]

There are several types of insulin that are commonly used in medical practice, with varying times of onset and duration of action.[27]

- Rapid acting (i.e. insulin lispro) with onset in 15 minutes and duration of about 4 hrs.

- Short acting (i.e. regular insulin) with onset in 30 minutes and duration of about 6 hrs.

- Intermediate acting (i.e NPH insulin) with onset in 2 hours and duration of about 14 hrs.

- Long acting (i.e. detemir) with onset in 1 hr. and duration of about 24 hrs.

- Premixed which are usually combinations of short and long acting insulin.

Insulin is usually taken several times per day in patients who require it to control their diabetes.[27] Often patients usually take long acting insulin once a day and then take insulin before meals. The time of onset of the insulin determines how far in advance patients should take the insulin before they eat.[27]

Insulin therapy requires close monitoring and a great deal of patient education, as improper administration is quite dangerous. Insulin can easily cause hypoglycemia if the patient does not eat after administering insulin or accidently had too much insulin.[27] A previously satisfactory dosing may be too much if less food is consumed causing hypoglycemia.[27] Exercise decreases insulin requirements as exercise increases glucose uptake by body cells whose glucose is controlled by the insulin.[29]

Insulin therapy creates risk because of the inability to continuously know a person's blood glucose level and adjust insulin infusion appropriately. New advances in technology have overcome much of this problem. Small, portable insulin infusion pumps are available from several manufacturers. They allow a continuous infusion of small amounts of insulin to be delivered through the skin around the clock, plus the ability to give bolus doses when a person eats or has elevated blood glucose levels. This is very similar to how the pancreas works, but these pumps lack a continuous "feed-back" mechanism. Thus, the user is still at risk of giving too much or too little insulin unless blood glucose measurements are made.

Complexities

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Daily glucose and insulin cycle

The main complexities stem from the nature of the feedback loop of glucose in the blood stream.

  • The glucose cycle is a system which is affected by two factors: entry of glucose into the bloodstream and also blood levels of insulin to control its transport out of the bloodstream
  • As a system, it is sensitive to diet and exercise
  • It is affected by the need for user anticipation due to the complicating effects of time delays between any activity and the respective impact on the glucose
  • Management is highly intrusive, and compliance is an issue, since it relies upon user lifestyle change and often upon regular sampling and measuring of blood glucose levels, multiple times a day in many cases
  • It changes as people grow and develop
  • It is highly individual

As diabetes is a prime risk factor for cardiovascular disease, controlling other risk factors which may give rise to secondary conditions, as well as the diabetes itself, is one of the facets of diabetes management. Checking cholesterol, LDL, HDL and triglyceride levels may indicate hyperlipoproteinemia, which may warrant treatment with hypolipidemic drugs. Checking the blood pressure and keeping it within strict limits (using diet and antihypertensive treatment) protects against the retinal, renal and cardiovascular complications of diabetes. Regular follow-up by a podiatrist or other foot health specialists is encouraged to prevent the development of diabetic foot. Annual eye exams are suggested to monitor for progression of diabetic retinopathy.[citation needed]

Blood sugar level

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Hypo and hyperglycemia

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Levels which are significantly above or below this range are problematic and can in some cases be dangerous. A level of <3.8 mmol/L (<70 mg/dL) is usually described as a hypoglycemic attack (low blood sugar). Most diabetics know when they are going to "go hypo" and usually are able to eat food or drink something sweet to raise their levels. A patient who is hyperglycemic (high glucose) can also become temporarily hypoglycemic under certain conditions (e.g. not eating regularly, or after strenuous exercise, followed by fatigue). Intensive efforts to achieve blood sugar levels close to normal have been shown to triple the risk of the most severe form of hypoglycemia, in which the patient requires assistance from by-standers in order to treat the episode.[30] In the United States, there were annually 48,500 hospitalizations for diabetic hypoglycemia and 13,100 for diabetic hypoglycemia resulting in coma in the period 1989 to 1991, before intensive blood sugar control was as widely recommended as today.[31] One study found that hospital admissions for diabetic hypoglycemia increased by 50% from 1990–1993 to 1997–2000, as strict blood sugar control efforts became more common.[32] Among intensively controlled type 1 diabetics, 55% of episodes of severe hypoglycemia occur during sleep, and 6% of all deaths in diabetics under the age of 40 are from nocturnal hypoglycemia in the so-called 'dead-in-bed syndrome,' while National Institute of Health statistics show that 2% to 4% of all deaths in diabetics are from hypoglycemia.[33] In children and adolescents following intensive blood sugar control, 21% of hypoglycemic episodes occurred without explanation.[34] In addition to the deaths caused by diabetic hypoglycemia, periods of severe low blood sugar can also cause permanent brain damage.[35] Although diabetic nerve disease is usually associated with hyperglycemia, hypoglycemia as well can initiate or worsen neuropathy in diabetics intensively struggling to reduce their hyperglycemia.[36]

Levels greater than 13–15 mmol/L (230–270 mg/dL) are considered high, and should be monitored closely to ensure that they reduce rather than continue to remain high. The patient is advised to seek urgent medical attention as soon as possible if blood sugar levels continue to rise after 2–3 tests. High blood sugar levels are known as hyperglycemia, which is not as easy to detect as hypoglycemia and usually happens over a period of days rather than hours or minutes. If left untreated, this can result in diabetic coma and death.

A blood glucose test strip for an older style (i.e., optical color sensing) monitoring system

Prolonged and elevated levels of glucose in the blood, which is left unchecked and untreated, will, over time, result in serious diabetic complications in those susceptible and sometimes even death. There is currently no way of testing for susceptibility to complications. Diabetics are therefore recommended to check their blood sugar levels either daily or every few days. There is also diabetes management software available from blood testing manufacturers which can display results and trends over time. Type 1 diabetics normally check more often, due to insulin therapy.

A history of blood sugar level results is especially useful for the diabetic to present to their doctor or physician in the monitoring and control of the disease. Failure to maintain a strict regimen of testing can accelerate symptoms of the condition, and it is therefore imperative that any diabetic patient strictly monitor their glucose levels regularly.

Glycemic control

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Glycemic control is a medical term referring to the typical levels of blood sugar (glucose) in a person with diabetes mellitus. Much evidence suggests that many of the long-term complications of diabetes, especially the microvascular complications, result from many years of hyperglycemia (elevated levels of glucose in the blood). Good glycemic control, in the sense of a "target" for treatment, has become an important goal of diabetes care, although recent research suggests that the complications of diabetes may be caused by genetic factors[37][38] or, in type 1 diabetics, by the continuing effects of the autoimmune disease which first caused the pancreas to lose its insulin-producing ability.[39]

Because blood sugar levels fluctuate throughout the day and glucose records are imperfect indicators of these changes, the percentage of hemoglobin which is glycated is used as a proxy measure of long-term glycemic control in research trials and clinical care of people with diabetes. This test, the hemoglobin A1c or glycated hemoglobin reflects average glucose levels over the preceding 2–3 months. In nondiabetic persons with normal glucose metabolism the glycated hemoglobin is usually 4–6% by the most common methods (normal ranges may vary by method).

"Perfect glycemic control" would mean that glucose levels were always normal (70–130 mg/dL, or 3.9–7.2 mmol/L) and indistinguishable from a person without diabetes. In reality, because of the imperfections of treatment measures, even "good glycemic control" describes blood glucose levels that average somewhat higher than normal much of the time. In addition, one survey of type 2 diabetics found that they rated the harm to their quality of life from intensive interventions to control their blood sugar to be just as severe as the harm resulting from intermediate levels of diabetic complications.[40]

In the 1990s the American Diabetes Association conducted a publicity campaign to persuade patients and physicians to strive for average glucose and hemoglobin A1c values below 200 mg/dL (11 mmol/L) and 8%. Currently, many patients and physicians attempt to do better than that.

As of 2015 the guidelines called for an HbA1c of around 7% or a fasting glucose of less than 7.2 mmol/L (130 mg/dL); however these goals may be changed after professional clinical consultation, taking into account particular risks of hypoglycemia and life expectancy.[41][42] Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms and long-term benefits, many people – for example people with a life expectancy of less than nine years – who will not benefit are over-treated and do not experience clinically meaningful benefits.[43]

Poor glycemic control refers to persistently elevated blood glucose and glycated hemoglobin levels, which may range from 200 to 500 mg/dL (11–28 mmol/L) and 9–15% or higher over months and years before severe complications occur. Meta-analysis of large studies done on the effects of tight vs. conventional, or more relaxed, glycemic control in type 2 diabetics have failed to demonstrate a difference in all-cause cardiovascular death, non-fatal stroke, or limb amputation, but decreased the risk of nonfatal heart attack by 15%. Additionally, tight glucose control decreased the risk of progression of retinopathy and nephropathy, and decreased the incidence peripheral neuropathy, but increased the risk of hypoglycemia 2.4 times.[44]

Monitoring

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A modern portable blood glucose meter (OneTouch Ultra), displaying a reading of 5.4 mmol/L (98 mg/dL).

Personal (home) glucose monitoring

Glucose monitoring is both expensive (largely due to the cost of the consumable test strips) and requires significant commitment on the part of the patient. Lifestyle adjustments are generally made by the patients themselves following training by a clinician.

Regular blood testing, especially in type 1 diabetics, is helpful to keep adequate control of glucose levels and to reduce the chance of long term side effects of the disease. There are many (at least 20+) different types of blood monitoring devices available on the market today; not every meter suits all patients and it is a specific matter of choice for the patient, in consultation with a physician or other experienced professional, to find a meter that they personally find comfortable to use. The principle of the devices is virtually the same: a small blood sample is collected and measured.

Self-testing is clearly important in type I diabetes where the use of insulin therapy risks episodes of hypoglycemia and home-testing allows for adjustment of dosage on each administration.[45] Its benefit in type 2 diabetes has been more controversial, but recent studies[46] have resulted in guidance[47] that self-monitoring does not improve blood glucose or quality of life.

Regular 6 monthly laboratory testing of HbA1c (glycated hemoglobin) provides some assurance of long-term effective control and allows the adjustment of the patient's routine medication dosages in such cases. Type 2 patients with poor long term control despite home blood glucose monitoring, either have not had this integrated into their overall management, or are long overdue for tighter control by a switch from oral medication to injected insulin.[48]

Digital tools

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Electronic health records

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Sharing their electronic health records with people who have type 2 diabetes helps them to reduce their blood sugar levels. It is a way of helping people understand their own health condition and involving them actively in its management.[49][50]

m-health monitoring applications

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The widespread use of smartphones has turned mobile applications (apps) into a popular means of the usage of all forms of software.[51] As a consequence, the use of mobile apps in managing people's health and supporting their chronic conditions is receiving popularity, especially among healthcare systems, which are showing a great tendency toward using these apps to integrate patient-generated data into electronic health records, and to modify and improve treatment plans accordingly.[52] The number of health-related apps accessible in the App Store and Google Play is approximately 100,000, and among these apps, the ones related to diabetes are the highest in number. Conducting regular self-management tasks such as medication and insulin intake, blood sugar checkup, diet observance, and physical exercise are really demanding.[53] This is why the use of diabetes-related apps for the purposes of recording diet and medication intake or blood glucose level is promising to improve the health condition for the patients. However, despite the high number of apps, the rate of their usage among the patients is not high. One of the reasons for this could be due to the design problems that affect their usability.[54] In addition, a 2016 study of 65 diabetes apps for Android revealed that sensitive data, such as insulin and blood glucose levels, "was routinely collected and shared with third parties".[55][56]

Foot checking

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Monitoring a person's feet can help in predicting the likelihood of developing diabetic foot ulcers. A common method for this is using a special thermometer to look for spots on the foot that have higher temperature which indicate the possibility of an ulcer developing.[57] At the same time there is no strong scientific evidence supporting the effectiveness of at-home foot temperature monitoring.[58]

The current guideline in the United Kingdom recommends collecting 8-10 pieces of information for predicting the development of foot ulcers.[59] A simpler method proposed by researchers provides a more detailed risk score based on three pieces of information (insensitivity, foot pulse, previous history of ulcers or amputation). This method is not meant to replace people regularly checking their own feet but complement it.[57][60]

Driving

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Paramedics in Southern California attend a diabetic man who lost effective control of his vehicle due to low blood sugar (hypoglycemia) and drove it over the curb and into the water main and backflow valve in front of this industrial building. He was not injured, but required emergency intravenous glucose.

Studies conducted in the United States[61] and Europe[62] showed that drivers with type 1 diabetes had twice as many collisions as their non-diabetic spouses, demonstrating the increased risk of driving collisions in the type 1 diabetes population. Diabetes can compromise driving safety in several ways. First, long-term complications of diabetes can interfere with the safe operation of a vehicle. For example, diabetic retinopathy (loss of peripheral vision or visual acuity), or peripheral neuropathy (loss of feeling in the feet) can impair a driver's ability to read street signs, control the speed of the vehicle, apply appropriate pressure to the brakes, etc.

Second, hypoglycemia can affect a person's thinking process, coordination, and state of consciousness.[63][64] This disruption in brain functioning is called neuroglycopenia. Studies have demonstrated that the effects of neuroglycopenia impair driving ability.[63][65] A study involving people with type 1 diabetes found that individuals reporting two or more hypoglycemia-related driving mishaps differ physiologically and behaviorally from their counterparts who report no such mishaps.[66] For example, during hypoglycemia, drivers who had two or more mishaps reported fewer warning symptoms, their driving was more impaired, and their body released less epinephrine (a hormone that helps raise BG). Additionally, individuals with a history of hypoglycemia-related driving mishaps appear to use sugar at a faster rate[67] and are relatively slower at processing information.[68] These findings indicate that although anyone with type 1 diabetes may be at some risk of experiencing disruptive hypoglycemia while driving, there is a subgroup of type 1 drivers who are more vulnerable to such events.

Given the above research findings, it is recommended that drivers with type 1 diabetes with a history of driving mishaps should never drive when their BG is less than 70 mg/dL (3.9 mmol/L). Instead, these drivers are advised to treat hypoglycemia and delay driving until their BG is above 90 mg/dL (5 mmol/L).[66] Such drivers should also learn as much as possible about what causes their hypoglycemia, and use this information to avoid future hypoglycemia while driving.

Studies funded by the National Institutes of Health (NIH) have demonstrated that face-to-face training programs designed to help individuals with type 1 diabetes better anticipate, detect, and prevent extreme BG can reduce the occurrence of future hypoglycemia-related driving mishaps.[69][70][71] An internet-version of this training has also been shown to have significant beneficial results.[72] Additional NIH funded research to develop internet interventions specifically to help improve driving safety in drivers with type 1 diabetes is currently underway.[73]

Exenatide

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The U.S. Food and Drug Administration (FDA) has approved a treatment called Exenatide, based on the saliva of a Gila monster, to control blood sugar in patients with type 2 diabetes.

Other regimens

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Artificial intelligence can be used in a case-based reasoning system to aid in diabetes management providing automated support to diabetes patients and their professional care providers.[74][75]

Dental care

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High blood glucose in diabetic people is a risk factor for developing gum and tooth problems, especially in post-puberty and aging individuals. Diabetic patients have greater chances of developing oral health problems such as tooth decay, salivary gland dysfunction, fungal infections, inflammatory skin disease, periodontal disease or taste impairment and thrush of the mouth.[76] The oral problems in persons with diabetes can be prevented with a good control of the blood sugar levels, regular check-ups and a very good oral hygiene. By maintaining a good oral status, diabetic persons prevent losing their teeth as a result of various periodontal conditions.

Diabetic persons must increase their awareness about oral infections as they have a double impact on health. Firstly, people with diabetes are more likely to develop periodontal disease, which causes increased blood sugar levels, often leading to diabetes complications. Severe periodontal disease can increase blood sugar, contributing to increased periods of time when the body functions with a high blood sugar. This puts diabetics at increased risk for diabetic complications.[77]

The first symptoms of gum and tooth infection in diabetic persons are decreased salivary flow and burning mouth or tongue. Also, patients may experience signs like dry mouth, which increases the incidence of decay. Poorly controlled diabetes usually leads to gum recession, since plaque creates more harmful proteins in the gums.

Tooth decay and cavities are some of the first oral problems that individuals with diabetes are at risk for. Increased blood sugar levels translate into greater sugars and acids that attack the teeth and lead to gum diseases. Gingivitis can also occur as a result of increased blood sugar levels along with an inappropriate oral hygiene. Periodontitis is an oral disease caused by untreated gingivitis and which destroys the soft tissue and bone that support the teeth. This disease may cause the gums to pull away from the teeth which may eventually loosen and fall out. Diabetic people tend to experience more severe periodontitis because diabetes lowers the ability to resist infection[78] and also slows healing. At the same time, an oral infection such as periodontitis can make diabetes more difficult to control because it causes the blood sugar levels to rise.[79]

To prevent further diabetic complications as well as serious oral problems, diabetic persons must keep their blood sugar levels under control and have a proper oral hygiene. A study in the Journal of Periodontology found that poorly controlled type 2 diabetic patients are more likely to develop periodontal disease than well-controlled diabetics are.[77] At the same time, diabetic patients are recommended to have regular checkups with a dental care provider at least once in three to four months. Diabetics who receive good dental care and have good insulin control typically have a better chance at avoiding gum disease to help prevent tooth loss.[80]

Dental care is therefore even more important for diabetic patients than for healthy individuals. Maintaining the teeth and gum healthy is done by taking some preventing measures such as regular appointments at a dentist and a very good oral hygiene. Also, oral health problems can be avoided by closely monitoring the blood sugar levels. Patients who keep better under control their blood sugar levels and diabetes are less likely to develop oral health problems when compared to diabetic patients who control their disease moderately or poorly.

Poor oral hygiene is a great factor to take under consideration when it comes to oral problems and even more in people with diabetes. Diabetic people are advised to brush their teeth at least twice a day, and if possible, after all meals and snacks. However, brushing in the morning and at night is mandatory as well as flossing and using an anti-bacterial mouthwash. Individuals with diabetes are recommended to use toothpaste that contains fluoride as this has proved to be the most efficient in fighting oral infections and tooth decay. Flossing must be done at least once a day, as well because it is helpful in preventing oral problems by removing the plaque between the teeth, which is not removed when brushing.

Diabetic patients must get professional dental cleanings every six months. In cases when dental surgery is needed, it is necessary to take some special precautions such as adjusting diabetes medication or taking antibiotics to prevent infection. Looking for early signs of gum disease (redness, swelling, bleeding gums) and informing the dentist about them is also helpful in preventing further complications. Quitting smoking is recommended to avoid serious diabetes complications and oral diseases.

Diabetic persons are advised to make morning appointments to the dental care provider as during this time of the day the blood sugar levels tend to be better kept under control. Not least, individuals with diabetes must make sure both their physician and dental care provider are informed and aware of their condition, medical history and periodontal status.

Medication nonadherence

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Because many patients with diabetes have two or more comorbidities, they often require multiple medications. The prevalence of medication nonadherence is high among patients with chronic conditions, such as diabetes, and nonadherence is associated with public health issues and higher health care costs. One reason for nonadherence is the cost of medications. Being able to detect cost-related nonadherence is important for health care professionals, because this can lead to strategies to assist patients with problems paying for their medications. Some of these strategies are use of generic drugs or therapeutic alternatives, substituting a prescription drug with an over-the-counter medication, and pill-splitting. Interventions to improve adherence can achieve reductions in diabetes morbidity and mortality, as well as significant cost savings to the health care system.[81] Smartphone apps have been found to improve self-management and health outcomes in people with diabetes through functions such as specific reminder alarms,[82] while working with mental health professionals has also been found to help people with diabetes develop the skills to manage their medications and challenges of self-management effectively.[83]

Psychological mechanisms and adherence

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As self-management of diabetes typically involves lifestyle modifications, adherence may pose a significant self-management burden on many individuals.[84] For example, individuals with diabetes may find themselves faced with the need to self-monitor their blood glucose levels, adhere to healthier diets and maintain exercise regimens regularly in order to maintain metabolic control and reduce the risk of developing cardiovascular problems. Barriers to adherence have been associated with key psychological mechanisms: knowledge of self-management, beliefs about the efficacy of treatment and self-efficacy/perceived control.[84] Such mechanisms are inter-related, as one's thoughts (e.g. one's perception of diabetes, or one's appraisal of how helpful self-management is) is likely to relate to one's emotions (e.g. motivation to change), which in turn, affects one's self-efficacy (one's confidence in their ability to engage in a behaviour to achieve a desired outcome).[85]

As diabetes management is affected by an individual's emotional and cognitive state, there has been evidence suggesting the self-management of diabetes is negatively affected by diabetes-related distress and depression.[86] There is growing evidence that there is higher levels of clinical depression in patients with diabetes compared to the non-diabetic population.[87][88] Depression in individuals with diabetes has been found to be associated with poorer self-management of symptoms.[89] This suggests that it may be important to target mood in treatment. In the case of children and young people, especially if they are socially disadvantaged, research suggests that it is important that healthcare providers listen to and discuss their feelings and life situation to help them engage with diabetes services and self-management.[90][91]

To this end, treatment programs such as the Cognitive Behavioural Therapy - Adherence and Depression program (CBT-AD)[83] have been developed to target the psychological mechanisms underpinning adherence. By working on increasing motivation and challenging maladaptive illness perceptions, programs such as CBT-AD aim to enhance self-efficacy and improve diabetes-related distress and one's overall quality of life.[92]

Bariatric surgery

[edit]

While weight loss is clearly beneficial in improving glycemic control in patients with diabetes type 2,[93] maintaining significant weight loss can be a very difficult thing to do. In diabetic people who have a body mass index of 35 or higher, and who have been unable to lose weight otherwise, bariatric surgery offers a viable option to help achieve that goal. In 2018 a Patient-Centered Outcomes Research Institute funded study was published which analyzed the effects of three common types of bariatric surgery on sustained weight loss and long-lasting glycemic control in patients with diabetes type 2.[94] The results of this study demonstrated that, five years after bariatric surgery, there was meaningfully significant weight loss in a large majority of patients. In addition, and more importantly, this study showed that, in type 2 diabetic patients with a body mass index of 35 or higher, bariatric surgery has the potential to lead to complete remission of diabetes in as many as 40% of those people who have the procedure.[95] Like any operation, bariatric surgery is not without risks and complications, and those risks need to weighed against the potential benefits in anyone considering going through with such a procedure.

Research

[edit]
See also: Fluorescent glucose biosensors

Type 1 diabetes

[edit]

Diabetes type 1 is caused by the destruction of enough beta cells to produce symptoms; these cells, which are found in the Islets of Langerhans in the pancreas, produce and secrete insulin, the single hormone responsible for allowing glucose to enter from the blood into cells (in addition to the hormone amylin, another hormone required for glucose homeostasis). Hence, the phrase "curing diabetes type 1" means "causing a maintenance or restoration of the endogenous ability of the body to produce insulin in response to the level of blood glucose" and cooperative operation with counterregulatory hormones.

This section deals only with approaches for curing the underlying condition of diabetes type 1, by enabling the body to endogenously, in vivo, produce insulin in response to the level of blood glucose. It does not cover other approaches, such as, for instance, closed-loop integrated glucometer/insulin pump products, which could potentially increase the quality-of-life for some who have diabetes type 1, and may by some be termed "artificial pancreas".

Encapsulation approach

[edit]
The Bio-artificial pancreas: a cross section of bio-engineered tissue with encapsulated islet cells delivering endocrine hormones in response to glucose

A biological approach to the artificial pancreas is to implant bioengineered tissue containing islet cells, which would secrete the amounts of insulin, amylin and glucagon needed in response to sensed glucose.

When islet cells have been transplanted via the Edmonton protocol, insulin production (and glycemic control) was restored, but at the expense of continued immunosuppression drugs. Encapsulation of the islet cells in a protective coating has been developed to block the immune response to transplanted cells, which relieves the burden of immunosuppression and benefits the longevity of the transplant.[96]

Stem cells

[edit]
See also: Type 1 diabetes § Stem cells, and Type 2 diabetes § Stem cells

Research is being done at several locations in which islet cells are developed from stem cells.

Stem cell research has also been suggested as a potential avenue for a cure since it may permit regrowth of Islet cells which are genetically part of the treated individual, thus perhaps eliminating the need for immuno-suppressants.[48] This new method autologous nonmyeloablative hematopoietic stem cell transplantation was developed by a research team composed by Brazilian and American scientists (Dr. Julio Voltarelli, Dr. Carlos Eduardo Couri, Dr Richard Burt, and colleagues) and it was the first study to use stem cell therapy in human diabetes mellitus This was initially tested in mice and in 2007 there was the first publication of stem cell therapy to treat this form of diabetes.[97] Until 2009, there was 23 patients included and followed for a mean period of 29.8 months (ranging from 7 to 58 months). In the trial, severe immunosuppression with high doses of cyclophosphamide and anti-thymocyte globulin is used with the aim of "turning off" the immunologic system", and then autologous hematopoietic stem cells are reinfused to regenerate a new one. In summary it is a kind of "immunologic reset" that blocks the autoimmune attack against residual pancreatic insulin-producing cells. Until December 2009, 12 patients remained continuously insulin-free for periods ranging from 14 to 52 months and 8 patients became transiently insulin-free for periods ranging from 6 to 47 months. Of these last 8 patients, 2 became insulin-free again after the use of sitagliptin, a DPP-4 inhibitor approved only to treat type 2 diabetic patients and this is also the first study to document the use and complete insulin-independendce in humans with type 1 diabetes with this medication. In parallel with insulin suspension, indirect measures of endogenous insulin secretion revealed that it significantly increased in the whole group of patients, regardless the need of daily exogenous insulin use.[98]

Gene therapy

[edit]
Gene therapy: Designing a viral vector to deliberately infect cells with DNA to carry on the viral production of insulin in response to the blood sugar level.

Technology for gene therapy is advancing rapidly such that there are multiple pathways possible to support endocrine function, with potential to practically cure diabetes.[99]

  • Gene therapy can be used to manufacture insulin directly: an oral medication, consisting of viral vectors containing the insulin sequence, is digested and delivers its genes to the upper intestines. Those intestinal cells will then behave like any viral infected cell, and will reproduce the insulin protein. The virus can be controlled to infect only the cells which respond to the presence of glucose, such that insulin is produced only in the presence of high glucose levels. Due to the limited numbers of vectors delivered, very few intestinal cells would actually be impacted and would die off naturally in a few days. Therefore, by varying the amount of oral medication used, the amount of insulin created by gene therapy can be increased or decreased as needed. As the insulin-producing intestinal cells die off, they are boosted by additional oral medications.[100]
  • Gene therapy might eventually be used to cure the cause of beta cell destruction, thereby curing the new diabetes patient before the beta cell destruction is complete and irreversible.[101]
  • Gene therapy can be used to turn duodenum cells and duodenum adult stem cells into beta cells which produce insulin and amylin naturally. By delivering beta cell DNA to the intestine cells in the duodenum, a few intestine cells will turn into beta cells, and subsequently adult stem cells will develop into beta cells. This makes the supply of beta cells in the duodenum self-replenishing, and the beta cells will produce insulin in proportional response to carbohydrates consumed.[102]

Monoclonal antibodies

[edit]

In November 2022 the FDA approved Teplizumab a monoclonal antibody drug which aims to delay type 1 diabetes by reprogramming the immune system to stop mistakenly attacking pancreatic cells.[103][104]

Type 2 diabetes

[edit]

Type 2 diabetes is usually first treated by increasing physical activity, and eliminating saturated fat and reducing sugar and carbohydrate intake with a goal of losing weight. These can restore insulin sensitivity even when the weight loss is modest, for example around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. Diets that are very low in saturated fats have been claimed to reverse insulin resistance.[105][106]

Cognitive Behavioural Therapy is an effective intervention for improving adherence to medication, depression and glycaemic control, with enduring and clinically meaningful benefits for diabetes self-management and glycaemic control in adults with type 2 diabetes and comorbid depression.[92]

Testosterone replacement therapy may improve glucose tolerance and insulin sensitivity in diabetic hypogonadal men. The mechanisms by which testosterone decreases insulin resistance is under study.[107] Moreover, testosterone may have a protective effect on pancreatic beta cells, which is possibly exerted by androgen-receptor-mediated mechanisms and influence of inflammatory cytokines.[108]

According to a 2002 paper, it has been suggested that a type of gastric bypass surgery may normalize blood glucose levels in 80–100% of severely obese patients with diabetes. The precise causal mechanisms are being intensively researched; its results may not simply be attributable to weight loss, as the improvement in blood sugars seems to precede any change in body mass. This approach may become a treatment for some people with type 2 diabetes, but has not yet been studied in prospective clinical trials.[109] This surgery may have the additional benefit of reducing the death rate from all causes by up to 40% in severely obese people.[110] A small number of normal to moderately obese patients with type 2 diabetes have successfully undergone similar operations.[111][112]

MODY is a rare genetic form of diabetes, often mistaken for Type 1 or Type 2. The medical management is variable and depends on each individual case.[113]

Several immunosuppressive drugs targeting the chronic inflammation in type 2 diabetes have been tested.[114]

See also

[edit]
* Ambulatory care sensitive conditions

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