Diabetes Mellitus

| What is diabetes mellitus? | What is the impact of diabetes? | What causes diabetes mellitus? | What are the different types of diabetes mellitus? | What are the symptoms of diabetes mellitus? | How is diabetes mellitus diagnosed? | What is the oral glucose tolerance test? | What may the results of the oral glucose tolerance test indicate? | Why is blood sugar checked at home? | What is a hemoglobin A1c (A1c)? | What are the acute complications of diabetes mellitus? | What are the chronic complications of diabetes mellitus? | What can be done to slow diabetes complications? | How is diabetes treated? | Medications for type 2 diabetes mellitus? | Medications that increase the insulin output by the pancreas - sulfonylureas and meglitinides | Medications that decrease the amount of glucose produced by the liver | Medications that increase the sensitivity of cells to insulin | Medications that decrease the absorption of carbohydrates from the intestine | Treatment of diabetes with insulin | Different methods of delivering insulin | The future of pancreas transplantation | Diabetes Mellitus At A Glance | Diabetes Associated Bladder Dysfunction in Older Adult |

Medications that increase the insulin output by the pancreas - sulfonylureas and meglitinides

Sulfonylureas

Historically, increasing the insulin output by the pancreas has been the major area targeted by medications used to treat type 2 diabetes.

These medications belong to a class of drugs called sulfonylureas. Sulfonylureas primarily lower blood glucose levels by increasing the release of insulin from the pancreas.

Older generations of these drugs include chlorpropamide and tolbutamide, while newer drugs include Glyburide (DiaBeta), glipizide (Glucotrol), and glimepiride (Amaryl).

These drugs are effective in rapidly lowering blood sugars, but run the risk of causing hypoglycemia. In addition, they are sulfa compounds, and should be avoided in patients with sulfa allergies.

Meglitinides [repaglinide (Prandin) and nateglinide (Starlix)]

Recently, a new class of drugs that affect insulin release has been approved for use in type 2 diabetes.

This class is known as meglitinides and these drugs also work on the pancreas to promote insulin secretion.

Unlike sulfonylureas that bind to receptors on the insulin producing cells, meglitinides work through a separate potassium based channel on the cell surface.

Repaglinide (Prandin) and nateglinide (Starlix) are short acting agents that are taken 30 minutes before meals. Unlike the sulfonylureas, which last longer in the body, Prandin and Starlix are very short acting, with peak effects within one hour. For this reason, they are given up to 3 times a day just before meals.

Since these drugs also increase circulating insulin levels, they may also cause hypoglycemia, but the literature suggests this is less frequent than the hypoglycemia seen with sulfonylurea agents.

Prandin

In a 3-month study, repaglinide (Prandin) dropped fasting blood glucose values by 61 mg/dL and post meal blood glucose values by 100 mg/dL.

Because Prandin is short acting and given before meals, it is particularly beneficial in lowering blood glucose after meals and does not tend to lower fasting glucose levels to the same degree. Prandin has been used in combination with other medications, such as metformin (Glucophage), with impressive results.

Prandin does interact with other medications. The doctor must be aware of all other medications the patient is taking before prescribing Prandin.

The usual starting dose is 0.5mg before each meal, and can be increased to 4 mg. The maximum daily dose is 16 mg. Prandin is used with caution in people with kidney or liver abnormalities.

Since Prandin increases insulin levels, it has the risk of causing abnormally low blood sugars. Blood sugars that remain severely low, can result in sweating, tremors, confusion, and may lead to coma and seizure. In addition, the use of Prandin has been associated with headaches, muscle and joint aches, along with sinus infections in some individuals.

This drug should not be used in pregnancy or by nursing mothers. The dose may need to be adjusted in older people, since they may metabolize (eliminate) medications at a slower rate.

Starlix

Nateglinide (Starlix) has essentially the same profile of side effects and interactions as Prandin.

The major benefit of Starlix is that the starting dose of 120mg does not need to be adjusted upward, but rather remains constant. These medications are also relatively safe to use in people with impaired kidney function.

Medications that decrease the amount of glucose produced by the liver

A class of drugs called biguanides has been used for many years in Europe and Canada.

Glucophage is unique in its ability to decrease glucose production from the liver. Briefly, because metformin does not increase insulin levels, when used alone, it does not usually cause hypoglycemia. In addition, metformin has an effect whereby it tends to suppress appetite, which may be beneficial in this population.

Metformin may be used by itself or in conjunction with other oral agents, or insulin. It should not be used in patients with kidney impairment, and should be used with caution in those with liver impairment.

The older parent compounds of metformin were associated with a serious condition called lactic acidosis with a dangerous acid build up in the blood resulting from accumulation of the drug and its breakdown products.

While metformin is safer in this regard, it is recommended that the drug be discontinued for 24 hours before any dye-related procedure (such as IVP kidney study) or surgery is performed. The dyes may impair kidney function and cause a build up of the drug in the blood. Metformin can be restarted after these procedures once the patient has urinated normally.

Medications that increase the sensitivity of cells to insulin

At present in the United States, the class of drugs known as thiazolidinediones lowers blood glucose by improving target cell response to insulin (increasing the sensitivity of the cells to insulin).

Troglitazone (Rezulin) was the first of this type of compound introduced in the United States.

Because of severe toxic liver effects, troglitazone has been taken off the market.

Sister compounds are now available with a better safety profile. These drugs include pioglitazone (Actos) and rosiglitazone (Avandia).

Pioglitazone (Actos) and rosiglitazone (Avandia) are new thiazolidinediones that have been approved for use in the United States. While they are sister compounds to Rezulin, extensive studies have failed to show any liver problems associated with these particular drugs.

Patients should be aware, however, that these drugs are still relatively new, and its long-term safety profile is not yet known.

Both Avandia and Actos act by increasing the sensitivity (responsiveness) of cells to insulin. It improves sensitivity to insulin in muscle and fat tissue. These drugs have been effective in lowering blood sugars in patients with type 2 diabetes, Actos and Avandia act within 1 hour of administration and are dosed daily.

It is important to note that it takes up to 6 weeks to see a drop in blood glucose levels on these agents and up to 12 weeks to see a maximum benefit.

Actos and Avandia have been approved as first line therapy in diabetes, and for use in combination. Both medications may be used in patients taking other oral agents as well as those using insulin

While reported liver problems on these agents are mild (and reversible with discontinuation of the drug) if present, most physicians choose to follow recommendations and do blood tests on patients to follow their liver test every 2 months or so during the first year of therapy.

After that point, the frequency of monitoring may be decreased. If at any point the liver tests increase to 3 times the normal limit, the drug should be stopped.

The most significant contraindications to these medications include any type of liver disease, and heart failure. These medications may cause a significant increase in fluid retention. While the reports are 3-8 pounds, clinical experience shows up to 12-15 pounds of weight gain can occur.

Usually the majority of this is fluid, but an absolute body weight gain can also occur. This is likely dose dependent, and increases with higher dosages of medication, and occurs more pronounced in patients who are also on insulin therapy.

In general, the resulting ankle swelling and puffiness can be controlled with the addition of a diuretic such as lasix, or by reducing the dose. On occasion, patients may be symptomatic enough to warrant the withdrawal of the medication.

As an aside, Actos and Avandia have an added benefit of changing cholesterol patterns in diabetes.

HDL (or good cholesterol) increases on these medications, and triglycerides often decrease, while there is some controversy regarding what happens to bad cholesterol (LDL) levels.

In this population that is already at an increased risk for heart disease, a benefit in cholesterol profile is a beneficial outcome. As more and more data becomes available there is mounting evidence that this class of drugs may provide direct benefits on the heart and large blood vessels, and may actually be valuable in preventing the progression of diabetes in high-risk individuals.

Medications that decrease the absorption of carbohydrates from the intestine

Before being absorbed into the bloodstream, carbohydrates must be broken down into smaller sugar particles, such as glucose, by enzymes in the small intestine.

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.

Precose

The name of the alpha glucosidase inhibitor available in the United States is Precose.

As a single agent, Precose is not as effective as the other medications listed. Since Precose works on the intestine, its effects are additive to diabetic medications that work at other sites, such as sulfonylureas.

Clinical studies have shown statistically better blood glucose control in patients treated with Precose and a sulfonylurea versus the sulfonylurea alone. Precose is currently used alone or in combination with a sulfonylurea.

Precose is taken three times a day at the beginning of meals. The dosage varies from 25 mg to 100 mg with each meal. The maximum recommended dose is 100 mg three times a day.

At doses greater than this, reversible liver abnormalities may be seen. Because of its mechanism of action, Precose has significant gastrointestinal side effects.

Abdominal pain, diarrhea, and gas are common and are seen in up to 75% of patients taking Precose. For this reason, Precose is administered using a low initial dose that is increased over weeks depending on the patient's tolerance.

Most of the gastrointestinal symptoms tend to subside over the course of a few weeks, although some patients report persistent problems.

Combination Medications:

Glucovance, Avandamet, and Metaglip are 3 relatively new combination pills that are on the market to treat diabetes.

Glucovance combines glyburide with metformin in varying doses.

Avandamet is a combination of varying doses of Avandia and metformin.

And Metaglip is a combination pill containing glipizide and metformin in varying strengths.

The benefit to these agents is fewer pills to take, hopefully leading to better compliance.

Treatment of diabetes with insulin <.....more>

The above opinionated views and information serves to educated and informed consumer .  The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. .It should not replaced professional advise and consultation.A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions