Diabetes Treatment

Insulin resistance means that although the body can produce insulin, the body's cells do not respond properly to the insulin that is made.

Diabetes mellitus is a metabolic disease characterized by high blood sugar (glucose) levels that result from defects in insulin secretion or the body’s ability to use insulin.

Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas. Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas. This release of insulin promotes the uptake of glucose into body cells. In patients with diabetes, the absence of insufficient production or lack of response to insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime.

In type 1 diabetes, the pancreas cannot produce insulin. Type 1 diabetes was formerly known as juvenile diabetes or insulin-dependent diabetes. Type 2 diabetes is more a result of insulin resistance (cells not being able to use insulin effectively or at all. It was formerly known as adult-onset diabetes or non-insulin-dependent diabetes.

Prediabetes is the term used to describe elevated blood sugar (glucose) that has not yet reached the level for a type 2 diabetes diagnosis. It can be treated by lifestyle changes such as consuming a healthy diet, weight loss, and regular exercise.

Endocrinologists are specialists in endocrine disorders such as diabetes and as such, manage many patients with diabetes. Primary care specialists, including internists and family practice specialists, may also treat patients with diabetes.

The major goal in treating type 1 and type 2 diabetes is to control blood sugar (glucose) levels within the normal range, with minimal excursions to low or high levels.

Type 1 diabetes is treated with the following:

• Insulin
• Exercise
• Type 1 diabetes diet

Type 2 diabetes is treated with the following:

• First with weight reduction, a type 2 diabetes diet, and exercise
• Diabetes medications (oral or injected) are prescribed when these measures fail to control the elevated blood sugars of type 2 diabetes.
• If other medications become ineffective treatment with insulin may be initiated.

Note that these medications used to treat type 2 diabetes are typically not used in pregnant or breastfeeding women. At present, the only recommended way of controlling diabetes in women who are pregnant or breastfeeding is by diet, exercise, and insulin therapy. You should speak with your health-care professional if you are taking these medications, are considering becoming pregnant, or if you have become pregnant while taking these medications.

Medications for type 2 diabetes are designed to do the following:

• Increase insulin output by the pancreas
• Decrease the amount of glucose released from the liver
• Increase the sensitivity (response) of cells to insulin
• Decrease the absorption of carbohydrates from the intestine
• Slow emptying of the stomach, thereby delaying nutrient digestion and absorption in the small intestine

A preferred drug can provide more than one benefit (for example, lower blood sugar and control cholesterol). Varying combinations of medications can control diabetes. Not every patient with type 2 diabetes will benefit from every drug, and not every drug is suitable for each patient.

The medications for type 2 diabetes fall into specific classes based on the way they work to achieve control of blood sugar. These drug classes include:

Metformin is a biguanide drug that increases the sensitivity of the body’s cells to insulin. It also decreases the amount of glucose produced by the liver. In 1994, the FDA approved the use of the biguanide called metformin (Glucophage) for the treatment of type 2 diabetes. Today, this is still typically the first drug prescribed for type 2 diabetes.

In addition, metformin tends to suppress appetite, which may benefit people who are overweight.
Metformin often does not reduce blood glucose enough on its own and may be given with other medications such as other oral drugs or insulin.

Possible side effects of metformin include nausea and diarrhea. These usually resolve over time.

Medications that increase insulin output by the pancreas belong to the class of drugs called sulfonylureas. Older generations of these drugs including chlorpropamide (Diabinese) and tolbutamide were abandoned due to association with higher risk of cardiovascular events.

The newer sulfonylurea drugs include glyburide (DiaBeta), glipizide (Glucotrol), and glimepiride (Amaryl).

These drugs rapidly lower blood sugar, but can cause abnormally low blood sugar (called hypoglycemia). In addition, sulfonylureas contain sulfa and should be avoided by those who are allergic to sulfa. Weight gain is a possible side effect of the sulfonylurea drugs.

Like sulfonylureas, meglitinides are a class of drugs that work by promoting insulin secretion from the pancreas. Unlike the sulfonylureas, which last longer in the body, repaglinide (Prandin) and nateglinide (Starlix) are very short-acting, with peak effects within one hour. For this reason, they are given up to three times a day just before meals.

Since these drugs increase circulating insulin levels they may cause hypoglycemia. Weight gain is also a possible side effect.

Thiazolidinedione drugs lower blood glucose by increasing the sensitivity of the cells to insulin (improving target cell response to insulin). Examples include pioglitazone (Actos) and rosiglitazone (Avandia)

These drugs have been linked to serious side effects like an increased risk of heart failure and bone fractures. Weight gain is another possible side effect. These medications are not usually given as a first-line treatment but may be helpful for some people.

Drugs of this class decrease the absorption of carbohydrates from the intestine. Before being absorbed into the bloodstream, enzymes in the small intestine must break down carbohydrates into smaller sugar particles, such as glucose. One of the enzymes involved in breaking down carbohydrates is called alpha-glucosidase. By inhibiting this enzyme, carbohydrates are not broken down as efficiently, and glucose absorption is delayed.

The alpha-glucosidase inhibitors available in the U.S. are acarbose (Precose) and miglitol (Lexicomp). These drugs have gastrointestinal side effects such as abdominal pain, diarrhea, and gas.

These are a relatively new class of drugs used to treat type 2 diabetes. They are oral medications that work by blocking the kidneys' reabsorption of glucose, leading to increased glucose excretion and reduction of blood sugar levels. The US FDA approved the SGLT2 inhibitors canagliflozin (Invokana) in March 2013 and dapagliflozin (Farxiga) in January 2014.

Side effects are similar for these drugs and include vaginal yeast infection and urinary tract infection. Each of these drugs has been used as a single therapy and in combination with other drugs such as metformin, sulfonylurea, pioglitazone, and insulin.

Incretin is a natural hormone that tells the body to release insulin after eating. An enzyme called dipeptidyl peptidase-4 (DPP-4) removes incretin from your body. Stopping (inhibiting) DPP-4 helps the incretin that is in the body to stay there longer. This triggers insulin to be released, which lowers blood sugar.

In 2006, the FDA approved the first drug in this class called sitagliptin (Januvia). Other members of this drug class are saxagliptin (Onglyza), linagliptin (Tradjenta), and alogliptin (Nusina).

Side effects of the DPP-4 inhibitors include symptoms of respiratory and urinary tract infections. They are not associated with weight gain.

GLP-1 (glucagon-like peptide-1) is an incretin, a hormone that signals the body to release insulin after eating. A GLP-1 agonist drug works similarly to DPP-4 inhibitors, by stimulating the action of the incretin GLP-1. GLP-1 agonists are also known as incretin mimetics. Their effects are stronger than those of the DPP-4 inhibitors.

Exenatide (Byetta) was the first drug of the GLP-1 agonist group. It originated from an interesting source, the saliva of the Gila monster. Scientists observed that this small lizard could go a long time without eating. They discovered a substance in its saliva that slowed stomach emptying, thus making the lizard feel fuller for a longer time. This substance resembled the hormone GLP-1.

Other drugs in this class have since been developed. They include liraglutide (Victoza), long-acting exenatide (Bydureon), albiglutide (Tanzeum), and dulaglutide (Trulicity).

These drugs slow stomach emptying and slow the release of glucose from the liver, thereby regulating the delivery of nutrients to the intestine for absorption. They may also work in the brain to regulate hunger and are therefore associated with weight loss.

GLP-1 receptor agonists are often associated with some weight loss. This class of medications is not used alone but rather in combination with other drugs. Possible side effects include nausea and an increased risk of pancreatitis.

Pramlintide (Symlin) was the first in a class of injectable, anti-hyperglycemic medications for use in addition to insulin for type 1 diabetes or type 2 diabetes. Pramlintide is a synthetic analog of human amylin, a naturally occurring hormone made by the pancreas to help control glucose after meals. Similar to insulin, amylin is absent or deficient in a person with diabetes.

Pramlintide used with insulin reduces post-meal blood sugar peaks, reduces glucose fluctuations throughout the day, enhances satiety (the sensation of fullness) leading to potential weight loss, and lowers mealtime insulin requirements.

Pramlintide is administered by injection just before meals (three times each day) for type 1 diabetes as an additional treatment to mealtime insulin therapy for those failing to achieve desired glucose control despite optimal insulin therapy and type 2 diabetes as an additional treatment to mealtime insulin therapy for those failing to achieve desired glucose control with optimal insulin therapy.

Pramlintide with insulin has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in type 1 diabetes. This severe hypoglycemia occurs within 3 hours of injecting pramlintide. Nausea is another possible side effect.

Glyburide/metformin (Glucovance), rosiglitazone/metformin (Avandamet), glipizide/metformin (Metaglip), pioglitazone/metformin (Actoplusmet), and metformin/sitagliptin (Janumet) are five examples of combination pills on the market to treat type 2 diabetes. There are many, many more combination pills available.

These combination drugs carry the benefit of taking fewer pills, which hopefully improves compliance. While they work well, most health-care professionals initiate individual medications to optimize dosing, before switching to a combination pill once the patient has been stable on individual medications for a while.

Insulin is a hormone that allows the body to efficiently use glucose as fuel.

Insulin remains the mainstay of treatment for patients with type 1 diabetes. Insulin is also an important therapy for type 2 diabetes when blood glucose levels cannot be controlled by diet, weight loss, exercise, and oral medications.

Ideally, insulin should be administered in a manner that mimics the natural pattern of insulin secretion by a healthy pancreas. However, the complex pattern of natural insulin secretion is difficult to duplicate. Still, adequate blood glucose control can be achieved with careful attention to diet, regular exercise, home blood glucose monitoring, and multiple insulin injections throughout the day.

Various formulations of insulin differ in pharmacokinetics, i.e., the amount of time until they begin to work and the duration of their action after injection. These different insulins allow for more tailored regimens to optimize blood sugar control.

The types of insulin currently available are:

• Rapid-acting insulin begins to take effect 5 minutes after administration. Peak effect occurs in about 1 hour, and the effect lasts for 2 to 4 hours. Examples are insulin lispro, insulin aspart, and insulin glulisine.
• Regular insulin takes effect within 30 minutes, peaks at 2 to 3 hours after injection, and lasts 3 to 6 hours in total.
• Intermediate-acting insulin typically begins to lower blood glucose about 2 to 4 hours after injection, peaks 4 to 12 hours later and lasts about 12 to 18 hours.
• Long-acting insulin takes effect within 6 to 10 hours. It usually lasts for 20 to 24 hours. The long-acting insulin analogs include glargine and detemir. The lower glucose levels were fairly evenly over 24 hours (without major peaks or troughs).

Not only is the variety of insulin preparations growing, but so are the methods for administering insulin.

Pre-filled insulin pens

In the twentieth century, insulin was available only in an injectable form that required carrying syringes, needles, vials of insulin, and alcohol swabs. Patients found it difficult to take multiple shots each day; as a result, good blood sugar control was often difficult. Many pharmaceutical companies now offer discreet and convenient methods for delivering insulin.

Many manufacturers offer pen delivery systems. Such systems resemble the ink cartridge in a fountain pen. A small, pen-sized device holds an insulin cartridge (usually containing 300 units). Cartridges are available for the most widely used insulin formulations. The amount of insulin to be injected is dialed in, by turning the bottom of the pen until the required number of units is seen in the dose-viewing window. The tip of the pen consists of a needle that is replaced with each injection. A release mechanism allows the needle to penetrate just under the skin and deliver the required amount of insulin.

Insulin pumps

An insulin pump is composed of a reservoir similar to that of an insulin cartridge, a battery-operated pump, and a computer chip that allows the user to control the exact amount of insulin being delivered. The pump is attached to a thin plastic tube (an infusion set) that has a cannula (like a needle but soft) at the end through which insulin passes. This cannula is inserted under the skin, usually on the abdomen. The pump continuously delivers insulin, 24 hours a day. The amount of insulin is programmed and is administered at a constant rate (basal rate). Often, the amount of insulin needed over 24 hours varies, depending on factors like exercise, activity level, and sleep. The insulin pump allows the user to program many different basal rates to allow for variations in lifestyle. The user can also program the pump to deliver additional insulin during meals, covering the excess demands for insulin caused by eating carbohydrates.

The most exciting innovation in pump technology has been the ability to combine the pump in tandem with newer glucose-sensing technology. This is called sensor-augmented insulin pump therapy.

A newer option involves devices that use sensors that communicate directly with the insulin pump. One device is approved by the FDA that is a hybrid system (not fully automated), in which the basal insulin doses are automatically adjusted depending on results from the sensor. Users need to manually request insulin doses before meals.

Proper nutrition is essential for all people with diabetes. Control of blood glucose levels is only one goal of a healthy eating plan. A diabetic diet helps achieve and maintain normal body weight while preventing the common cardiac and vascular complications of diabetes.

There is no prescribed diet plan for diabetes and no single “diabetes diet”. Eating plans are tailored to fit each individual's needs, schedules, and eating habits. Each diabetes diet plan must be balanced with the intake of insulin and other diabetes medications. In general, the principles of a healthy diabetes diet are the same for everyone. Consumption of various foods in a healthy diet includes whole grains, fruits, non-fat dairy products, beans, lean meats, vegetarian substitutes, poultry, or fish.

People with diabetes may benefit from eating small meals throughout the day, instead of eating one or two heavy meals. No foods are forbidden for people with diabetes. Attention to portion control and advanced meal planning can help people with diabetes enjoy the same meals as everyone else.

Glycemic index and glycemic load are further considerations in considering a meal plan for people with diabetes. Foods with low glycemic index and load raise blood sugar more slowly than high glycemic index/load foods. The glycemic index refers to a standardized measurement, while glycemic load takes a typical portion size into account.

Meal timing and amount of insulin administration are considerations when planning a diet for people with type 1 diabetes.

Weight reduction and exercise

Weight reduction and exercise are important treatments for type 2 diabetes. Weight reduction and exercise increase the body's sensitivity to insulin, thus helping to control blood sugar elevations.

There have been some small, limited studies as well as anecdotal reports that certain alternative or “natural” treatments can help control blood glucose levels in people with diabetes or otherwise prevent the condition or its complications. These can include herbs or dietary supplements. Examples include garlic, cinnamon, alpha-lipoic acid, aloe vera, chromium, ginseng, and magnesium.

These substances are not considered to be medications by the US FDA and are therefore not regulated as such. This means that there are no standards in place to ensure that a given product contains the substance or dose as described on the label. There are also no requirements to perform studies showing that the products are safe or effective. Side effects of supplements are typically not well understood, and some supplements can interfere with the action of medications.

The American Diabetes Association publishes treatment guidelines for physicians based on all available scientific evidence. In the 2018 guidelines document, Standard of Medical Care in Diabetes, the ADA states that there is not sufficient evidence to support the use of any of the proposed alternative treatments for diabetes. These guidelines state that:

• There continues to be no clear evidence of benefit from herbal or nonherbal (for example, vitamin or mineral) supplementation for people with diabetes without underlying deficiencies.
• Routine supplementation with antioxidants, such as vitamins E and C and carotene, is not advised due to a lack of evidence of efficacy and concern related to long-term safety.
• There is insufficient evidence to support the routine use of herbals and micronutrients, such as cinnamon and vitamin D, to improve glycemic control in people with diabetes