Ruchi Mathur, MD, FRCP(C) is an Attending Physician with the Division of Endocrinology, Diabetes and Metabolism and Associate Director of Clinical Research, Recruitment and Phenotyping with the Center for Androgen Related Disorders, Department of Obstetrics and Gynecology at Cedars-Sinai Medical Center.
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
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. In 1994, the FDA approved the use of the biguanide
metformin
(Glucophage) for the treatment of type 2 diabetes in the U.S. Glucophage is
unique in its ability to decrease glucose production by 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 diabetics who tend to be
overweight. Metformin may be used by itself or together with other oral drugs 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 biguanides that
preceded metformin were associated with a serious condition called
lactic
acidosis, 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 procedure
involving the intravenous injection of dyes (such as for some x-ray studies of
the kidney) 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 is urinating normally.
Medications that increase the sensitivity of cells to insulin
The class of drugs known as thiazolidinediones lowers blood glucose by
improving target cell response to insulin (that is, increasing the sensitivity
of the cells to insulin). Troglitazone (Rezulin) was the first of this class in
the U.S. 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 thiazolidinediones
approved for use in the U.S. While they are sister compounds to Rezulin,
extensive studies have failed to show that they are associated with any liver
problems. Both Avandia and Actos act by increasing the sensitivity
(responsiveness) of cells to insulin. They improve the sensitivity of muscle and
fat cells to insulin. These drugs have been effective in lowering blood sugars
in patients with type 2 diabetes, Actos and Avandia act within one hour of
administration and are taken once daily. It is important to note that it takes
up to six weeks to see a drop in blood glucose levels with these drugs 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 with other drugs. Both drugs
may be used in patients taking other oral drugs as well as those using insulin.
Rosiglitazone (Avandia), however, has been associated with an increased risk of
heart attack and
stroke, and experts have debated the severity of these concerns. On September 23, 2010, the U.S. Food and Drug Administration (FDA) announced that it will significantly restrict the use of the diabetes drug Avandia to patients with
type 2 diabetes who cannot control their diabetes on other medications such as Actos. These new restrictions are in response to data that suggest an elevated risk of cardiovascular events, such as heart attack and stroke, in patients treated with Avandia. Also, GlaxoSmithKline (the manufacturer of Avandia) will be required to establish a Risk Evaluation and Mitigation Strategy (REMS) program in which patients, their doctors, and their pharmacists must participate in order to receive, prescribe, or sell Avandia.
While reported liver problems with these agents are mild (and reversible with
discontinuation of the drug), most physicians choose to follow an earlier
recommendation to do blood tests to detect liver injury every two months or so
during the first year of therapy. Recently this recommendation has been removed.
If at any point the liver tests increase to three times the normal upper limit,
the drug should be stopped.
The most important contraindications to these medications include any type of
liver disease, and
heart failure. Fluid retention can be of particular concern in patients with signs or symptoms of heart failure and in those with ejection fractions of less than 40% which indicates poor function of the heart. While the reports are three to eight 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 to be dose-dependent and, therefore, the increases in weight may be greater with higher doses of drug. Weight gain is more pronounced in patients who are also taking insulin.
In general, the ankle swelling and puffiness due to the accumulation of fluid can be controlled with the addition of a
diuretic such as
spironolactone (Aldactone) —
(furosemide (Lasix) does not work as well) — or by reducing the dose. On occasion, patients may be symptomatic enough from fluid retention to warrant withdrawal of the drug. Some recent studies have suggested an association between pioglitazone and rosiglitazone and untoward cardiac events, for example,
heart attacks, though this association is controversial. Regardless of the controversy, it is well established that pioglitazone and rosiglitazone should be avoided in patients with symptomatic heart failure or heart failure.
Another newer concern is an association of treatment with a small
increase in the frequency of fractures of the distal long bones of the arms and
legs. At present, this does not translate into fractures of the hip and spine,
which would be clinically more worrisome. More data is needed to make a
definitive statement about cause and effect at this time.
As an aside, Actos and Avandia have an added benefit of changing
cholesterol
patterns in diabetes. HDL (or good cholesterol) increases with these
medications, and triglycerides often decrease. While there is some controversy
regarding what happens to bad cholesterol (LDL) levels, there is a suggestion
that Actos may be superior in changing lipid profiles than Avandia. In this
population of diabetics that is already at an increased risk for
heart disease, an
improvement in cholesterol profile is beneficial. As more and more data becomes
available, there is mounting evidence that this class of drugs may provide
direct benefits to the heart and large blood vessels and may actually be
valuable in preventing the progression of diabetes in high-risk individuals by
reducing inflammation and by decreasing clotting factors. As time goes on, I
have no doubt that the uses for this class of medications will expand.
Diabetes mellitus is a chronic condition characterized by high levels of sugar (glucose) in the blood. The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent). Symptoms of diabetes include increased urine output, thirst, hunger, and fatigue. Treatment of diabetes depends on the type.
Hypoglycemia is a syndrome caused by low blood sugar. Symptoms of hypoglycemia include palpitations, trembling, intense hunger, sweating, nervousness, and weakness. Consuming lifesavers, table sugar, soda, and juice are good treatment options for hypoglycemia.
Peripheral neuropathy is a problem with the functioning of the nerves outside of the spinal cord. Symptoms may include numbness, weakness, burning pain (especially at night), and loss of reflexes. Possible causes may include carpel tunnel syndrome, meralgia paresthetica, vitamin or nutritional deficiencies, and illnesses like diabetes, syphilis, AIDS, and kidney failure. Most causes of peripheral neuropathy can be successfully treated or prevented.
Insulin resistance is the diminished ability of cells to respond to the action of insulin in transporting glucose (sugar) from the bloodstream into muscle and other tissues. Causes of insulin can include conditions such as stress, obesity, metabolic syndrome, and steroid use. Some of the risk factors for insulin resistance include fatty liver, heart disease, strokes, peripheral vascular disease, high cholesterol, and smoking. Treatment for insulin resistance are lifestyle changes and if necessary, medication.
Peripheral vascular disease (PVD) refers to diseases of the blood vessels (arteries and veins) located outside the heart and brain. While there are many causes of peripheral vascular disease, doctors commonly use the term peripheral vascular disease to refer to peripheral artery disease (peripheral arterial disease, PAD), a condition that develops when the arteries that supply blood to the internal organs, arms, and legs become completely or partially blocked as a result of atherosclerosis. Peripheral artery disease symptoms include: intermittent claudication, rest pain, numbness in the extremities, and more. Treatment for peripheral artery disease include: lifestyle measures, medication, angioplasty, and surgery.
Hyperglycemia is a serious health problem for diabetics. There are two types of hyperglycemia, 1) fasting, and 2)postprandial or after meal hyperglycemia. Hyperglycemia can also lead to ketoacidosis or hyperglycemic hyperosmolar nonketotic syndrome (HHNS). There are a variety of causes of hyperglycemia in people with diabetes. Symptoms include increased thirst, headaches, blurred vision, frequent urination and more. Treatment can be achieved through lifestyle changes or medications changes. Carefully monitoring blood glucose levels is key to prevention.
Diabetic Neuropathy is a complication of diabetes that causes damage to the nerves; this is related to the blood glucose of the body being too high for a long period of time. The four types of neuropathy include peripheral, autonomic, proximal and focal.
The main features of metabolic syndrome include insulin resistance, hypertension (high blood pressure), cholesterol abnormalities, and an increased risk for clotting. Patients are most often overweight or obese. Lifestyle modification such as the Mediterranean diet, exercise, and quitting smoking are the preferred treatment of metabolic syndrome.
Radiculopathy, a condition in which a nerve or nerves along the spine are compressed causing pain, numbness, weakenss, and tingling along the nerve(s). Some causes of radiculopathy include bone spurs, disc hernation, osteoarthritis, tumors, infection, and neuropathy. Treatment depends on the are of nerve compression. Surgery is generally not required.
Orthostatic hypotension symptoms include lightheadedness, weakness, blurred vision, and syncope or passing out. Causes of orthostatic hypotension include dehydration, anemia, medication, blood loss, low blood pressure, heat related illnesses and more. Treatment of orthostatic hypotension depends on the underlying cause.
Fatigue can be described in various ways. Sometimes fatigue is described as feeling a lack of energy and motivation (both mental and physical). The causes of fatigue are generally related to a variety of conditions or diseases for example, anemia, mono, medications, sleep problems, cancer, anxiety, heart disease, drug abuse, and more. Treatment of fatigue is generally directed toward the condition or disease that is causing the fatigue.
Enjoying a satisfying sex life as we age is important to both physical and mental health. As we age, diseases and conditions may pose challenges in our sexual health, and sexual experiences. Learn how to manage your conditions and still have a gratifying sex life as you age.
A diabetic diet, or diabetes diet helps keep blood glucose levels in the target range for patients. Exercise and medication may also help stabilize blood glucose levels. Keeping track of when you take your diabetic medicine, keeping track of food choices, eating the proper amount of fruits, vegetables, carbohydrates, and fats will also help maintain proper blood glucose levels.
Diabetes-related foot problems can affect your health with two problems: diabetic neuropathy, where diabetes affects the nerves, and peripheral vascular disease, where diabetes affects the flow of blood. Common foot problems for people with diabetes include athlete's foot, fungal infection of nails, calluses, corns, blisters, bunions, dry skin, foot ulcers, hammertoes, ingrown toenails, and plantar warts.
Prader-Willi syndrome is a condition characterized by severe floppiness (hypotonia), poor growth, delayed development, and poor feeding problems in early infancy later followed in infancy by excessive eating that may lead to extreme obesity. The genitals in both females and males are underdeveloped and most are infertile. Prader-Willi syndrome is related to chromosome 15.
The risks for developing type 2 diabetes include family history, ethnicity, birth weight, metabolic syndrome, and obesity. Warning signs pointing to an increased risk for developing type 2 diabetes include irregular menstruation, impaired fasting glucose, inflammatory markers, and other risks. Gestational diabetes is also a risk factor for developing type 2 diabetes later in life. Prevention of type 2 diabetes can be achieved through a healthy diet (Mediterranean diet), exercise, weight control, not smoking, and medication.
In the United States diabetes is the most common cause of kidney failure. High blood pressure and high levels of blood glucose increase the risk that a person with diabetes will eventually progress to kidney failure. Kidney disease in people with diabetes develops over the course of many years. albumin and eGFR are two key markers for kidney disease in people with diabetes. Controlling high blood pressure, blood pressure medications, a moderate protein diet, and compliant management of blood glucose can slow the progression of kidney disease. For those patients who's kidneys eventually fail, dialysis or kidney transplantation is the only option.
Diabetes and eye problems are generally caused by high blood sugar levels over an extended period of time. Types of eye problems in a person with diabetes include glaucoma, cataracts, and retinopathy. Examples of symptoms include blurred vision, headaches, eye aches, pain, halos around lights, loss of vision, watering eyes. Treatment for eye problems in people with diabetes depend on the type of eye problem. Prevention of eye problems include reducing blood pressure, cholesterol levels, quitting smoking, and maintaining proper blood glucose levels.
Managing your diabetes is important. The goal of diabetic therapy is to control blood glucose levels and prevent the complications of diabetes. Information about exercise, diet diet, and medication will help you manage your diabetes better. Blood glucose reagent strips, blood glucose meters, urine glucose tests, tests for urinary ketones, continuous glucose sensors, and Hemoglobin A1C testing information is also provided in this article.
Having diabetes can mean early onset and increased severity of bladder symptoms (urinary incontinence and urinary tract infections) and changes in sexual function. Men may have erectile dysfunction; and women may have problems with sexual response and vaginal lubrication. Keep your diabetes under control, and you can lower your risk of sexual and urologic problems.
Taking care of a disease such as diabetes is a life-long process. Learn how to care for yourself or loved one with diabetes in situations such as illness, work, school, travel, or a natural disaster.
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