Insulin Sensitizers
Diabetes is a disease of either decreased insulin secretion or decreased insulin effect (i.e., insulin resistance), and often both. Improving the sensitivity of peripheral insulin receptors is the goal of the "glitazones," pioglitazone (Actos) and rosiglitazone (Avandia).
Metformin (Glucophage) is also in this category. It actually works in multiple ways to lower blood glucose. Metformin increases insulin sensitivity, reduces hepatic glucose production, and reduces gastrointestinal absorption of glucose.
Several natural medicines also seem to improve insulin sensitivity.
Cassia cinnamon (Cinnamomum aromaticum) started receiving a lot of attention when in 2004 a preliminary clinical study suggested that it could lower fasting blood glucose by 18% to 30%. Constituents contained in cinnamon seem to increase insulin receptor sensitivity.
But since then the picture has become unclear. In 2006, another clinical study came out showing that cassia cinnamon does NOT decrease blood glucose in postmenopausal women.
This is not likely to be the last word on cinnamon for diabetes. Other studies are in the works and we should know more in the near future.
Researchers are using 1-6 grams (1 teaspoon = 4.75 grams) of cinnamon daily, often sprinkled on oatmeal or pudding, or in a capsule.
Keep in mind that there are lots of different types of cinnamon. So far, beneficial effects have only been shown for a specific type, Cassia cinnamon...also known as Chinese cinnamon. Cinnamomum verum is the most common type used in the Western world. But cassia cinnamon is not hard to find in Western food stores. For example, McCormick's Ground Cinnamon contains cassia cinnamon.
Chromium has been used for years for patients with diabetes. Chromium deficiency is associated with some of the features of diabetes...impaired glucose tolerance, hyperglycemia, glycosuria, a decrease in the number of insulin receptors, poor insulin binding, and neuropathies.
Chromium is sometimes referred to as "glucose tolerance factor" or GTF. But this is not entirely correct. GTF is actually a complex of molecules found in the body. It includes chromium bound to single molecules of glycine, cysteine, glutamic acid, and two molecules of nicotinic acid. Chromium by itself is NOT the same as GTF. But chromium is thought to be the active component of the complex. Nonetheless, you'll see chromium supplements on store shelves called Chromium GTF or other similar names.
Not surprisingly, diabetes patients with chromium deficiency have better glucose control if they correct the deficiency by taking chromium supplements. The big question is whether chromium helps patients WITHOUT a deficiency.
At this point, the answer is not clear. Some clinical research shows that patients who take chromium picolinate have decreased blood glucose levels, insulin levels, and HbA1c.1But much of this research is from small scale, poor quality trials.
The American Diabetes Association only recommends chromium for patients with documented chromium deficiency. The problem is that documenting chromium deficiency is difficult, and probably not practical for most patients.
There is not enough evidence to recommend chromium supplements across the board for all diabetes patients. But if type 2 diabetes patients want to try it, a trial run might be worthwhile. Advise these patients to take 100 mcg twice daily up to 500 mcg twice daily. Lower doses seem to be just as effective as higher doses, but higher doses might result in a more rapid improvement.
Vanadium is another trace element used for diabetes. It is thought to enhance the action of insulin by activating insulin receptors. Vanadium is also thought to stimulate hepatic glycogen synthesis and inhibit gluconeogenesis, lipolysis, and intestinal glucose transport. It also seems to increase glucose intake, utilization, and conversion to glycogen within skeletal muscle.3012,3013
Preliminary clinical research shows that type 2 diabetes patients who take vanadium in the form of vanadyl sulfate have improved insulin sensitivity and reduced blood glucose.3055,3056,3057 But studies have been very small...enrolling a total of less than 40 people. There is also concern that the high doses needed, about 31 mg of elemental vanadium, might not be safe long-term. Taking vanadium in doses over 1.8 mg/day for long periods of time might increase the risk of renal damage. Until more is known about long-term safety, advise diabetes patients against using vanadium.
Ginseng is traditionally thought of as a "tonic" for improving energy and vigor. But there has been growing interest in using both Panax ginseng and American ginseng (Panax quinquefolius) for diabetes.
One clinical trial shows that taking Panax ginseng 200 mg daily lowers blood glucose and HbA1c.
More research has been done on American ginseng. Clinical trials show that taking American ginseng 3 grams up to 2 hours before a meal reduces postprandial blood glucose. Panax ginseng and American ginseng both contain ginsenosides, which are thought to decrease insulin resistance and improve insulin sensitivity. Some products with low levels of ginsenoside content don't seem to be beneficial for lowering blood glucose.
These ginseng products look promising for diabetes, but more evidence is needed about the long-term effectiveness and safety.
Prickly pear cactus (Opuntia ficus-indica), also known as opuntia, is a cactus found in Mexico and elsewhere. It's prominent in Mexican folk medicine as a treatment for diabetes and is commonly used in Mexican populations and in the Southwestern states of the US. The cooked broad leaves of the cactus are called "nopals." In fact, prickly pear cactus is sometimes called "nopal."
Several small, single-dose studies show that eating the broiled stems of one specific prickly pear cactus species, Opuntia streptacantha, can reduce blood glucose levels by 17% to 46% But other species don't seem to have this effect.
Some researchers speculate that prickly pear cactus works due to an insulin sensitizing effect. But it might also help by slowing carbohydrate absorption in the gut.7028
More evidence is needed to determine if routine, prolonged consumption of prickly pear cactus is beneficial. For now, don't recommend it.
Hypoglycemic Agents
Hypoglycemic agents are often first choice drugs for patients with type 2 diabetes. These include the sulfonylureas...chlorpropamide (Diabinese), glipizide (Glucotrol), glyburide (Diabeta, Micronase), glimepiride (Amaryl), tolazamide (Tolinase), and tolbutamide (Orinase). Sulfonylureas work by stimulating beta-cells in the pancreas to produce more insulin.
The hypoglycemic agents also include nateglinide (Starlix) and repaglinide (Prandin). These drugs also increase beta-cell production of insulin. But they do it slightly differently than the sulfonylureas.
These agents are just for type 2 diabetes. The hypoglycemic agents don't work for patients with type 1 diabetes, or patients with type 2 diabetes if they've lost the ability to produce insulin.
Some natural medicines have hypoglycemic effects by stimulating insulin production similar to conventional drugs. Other natural medicines have a hypoglycemic effect due to constituents that have a direct insulin-like action.
Banaba (Lagerstroemia speciosa) is the name for a species of crepe myrtle...those beautiful pink, purple, or lavender flowering shrubs. Extracts of the banaba leaves are very popular in the Philippines and Southeast Asia. It is now being used by LOTS of diabetes patients in North America. We can tell because we receive many questions about it.
Banaba contains two important constituents and has two important effects in people with diabetes. Banaba extracts containing corosolic acid and ellagitannins seem to have an insulin-like effect and also activate insulin receptors. Preliminary clinical research shows that type 2 diabetes patients who take a specific banaba extract (Glucosol) for 2 weeks have lower blood glucose levels.
Banaba looks promising. But the evidence is too preliminary...and there isn't much known about safety. Don't recommend it until we know more.
Bitter melon (Momordica charantia) looks like a light green, pointed cucumber. It is another popular Southeast Asian natural product used for diabetes. Bitter melon, like banaba, also seems to have an insulin-like effect. Bitter melon contains a polypeptide known as "p-insulin," "plant-insulin," or "polypeptide-P." It has similar pharmacokinetics to bovine insulin...onset between 30 and 60 minutes and peak effect at about 4 hours.
Lots of different formulations of bitter melon have been tried in people with type 2 diabetes...bitter melon juice, powder, extracts, and even fried bitter melon. Some diabetes patients seem to have improved glucose control and decreased HbA1c after using these bitter melon formulations.But so far, there are no high quality, reliable studies.
Like banaba, don't recommend bitter melon until there is more evidence about its safety and effectiveness.
Fenugreek (Trigonella foenum-graecum) seeds are used as a spice...they taste and smell similar to maple syrup. Preliminary research shows that type 2 diabetes patients who mix 15 grams of ground, powdered fenugreek seeds with a meal have lower postprandial glucose levels compared to controls. This might be due to a bulk laxative effect...slowing carbohydrate absorption from the GI tract. But fenugreek also seems to enhance insulin release due to its 4-isoleucine and other constituents.
There isn't enough evidence to know how effective eating fenugreek is long-term...or if taking dietary supplement capsules containing fenugreek has any benefit. Explain to patients that there just isn't enough reliable information to rely on fenugreek for diabetes.
Tell patients to avoid fenugreek if they are allergic to other plants in the Fabaceae family such as soybeans, peanuts, or green peas. These patients might also be allergic to fenugreek.
Gymnema (Gymnema sylvestre) is an Indian plant referred to as "gurmar" in Hindi, which means "sugar destroying." Gymnema has been tested as a hypoglycemic agent in combination with insulin in a number of preliminary studies. The results are encouraging. Preliminary research shows that taking 200 mg/day of a specific gymnema extract called GS4 seems to cut the required insulin dose in half...and lower HbA1c in both type 1 and type 2 diabetes. When GS4 400 mg is taken with conventional hypoglycemic drugs, such as glyburide or tolbutamide, some people can reduce the dose or even discontinue their conventional hypoglycemic drug.
The gymnema extract GS4 seems to work by increasing endogenous insulin production. Serum C-peptide increases in some people who take GS4 and insulin. C-peptide is a chain of amino acids that is cleaved from the proinsulin molecule released by the pancreas to form insulin. Therefore, C-peptide is used as a marker for the release of endogenous insulin.
The specific gymnema extract GS4 looks promising...and there is some evidence that it can be safely used for up to 20 months. But gymnema is still lacking substantial reliable evidence to back it up. Don't recommend it until there is more evidence.
Despite the lack of strong evidence for these products, many patients are already taking them. Keep in mind that these natural medicines might INCREASE the risk of hypoglycemia...because they increase insulin production, increase insulin release, or contain constituents that work like insulin. Tell diabetes patients to use these products cautiously, especially if they already take insulin or other hypoglycemic drugs.
Carbohydrate Absorption Inhibitors
The conventional drugs acarbose (Precose) and miglitol (Glyset) work by decreasing or slowing absorption of carbohydrates in the gut. This results in lower blood glucose levels.
Lots of natural medicines also have this effect, but they work through a different mechanism. Most of these fall into the category of fiber.
There are two basic types of fiber...soluble and insoluble. Soluble fibers do what the name implies...they dissolve in water. Insoluble fiber doesn't.
Soluble fibers are usually gummy and gel-like. Insoluble fiber is typically course and rough (think "roughage").
Soluble fiber products increase the viscosity of the intestinal contents, slow gastric emptying time, and act as a barrier to diffusion. When these fibrous products are consumed in conjunction with a meal, they can slow the absorption of glucose and reduce postprandial blood glucose levels. The husks of blond psyllium (Plantago ovata) seed (Metamucil, Fiberall, Konsyl, others) are a soluble fiber. Several small-scale clinical trials show that consuming blond psyllium lowers postprandial blood glucose concentrations by 14% to 20%. Best results seem to occur when psyllium is taken with a meal. Psyllium has the added benefit of reducing total and low-density lipoprotein (LDL) cholesterol in diabetes patients.
Guar gum (Cyamopsis tetragonoloba) is a soluble fiber from the guar plant. Small clinical trials show that it reduces fasting and postprandial blood glucose levels in patients with both type 1 and type 2 diabetes.
Oat bran (Avena sativa) is high in beta-glucan, which is a soluble fiber. Consuming oat bran as part of the diet can significantly reduce blood glucose levels.
Soy (Glycine max) contains both soluble and insoluble fibers. Some researchers believe soy is beneficial for diabetes because of the fiber contained in soy. But there could be other mechanisms, including a direct effect of soy isoflavones. Postmenopausal women with type 2 diabetes who take soy protein 30 grams/day (providing 132 mg isoflavones) seem to have decreased insulin resistance, lower fasting blood glucose, and lower HbA1c. Other preliminary evidence shows that an extract of a fermented soy product called touchi acts as an alpha-glucosidase inhibitor. It modestly lowers blood glucose, HbA1c, and triglycerides in type 2 diabetes patients.
Glucomannan (Amorphophallus konjac) is an insoluble polysaccharide from the tubers of a plant called konjac. It can also delay glucose absorption.Taken daily at doses between 3.6 grams and 7.2 grams for 90 days, it can reduce mean fasting glucose levels by 29% and lead to decreases in the dose of insulin or oral hypoglycemics needed to control blood sugar. Glucomannan can also reduce serum cholesterol and improve glucose tolerance and lipid profiles in people with diabetes.
New Medications/Misc. Medications
A few new diabetes medications have reached the market in recent years. They work differently than other diabetes drugs. Two of these drugs are the injectables Symlin and Byetta.
Symlin (pramlintide) is a synthetic version of amlyn, which is a hormone secreted by the pancreas to lower glucose levels after eating.
Byetta (exenatide) is an "incretin mimetic." It works similar to incretin hormones, which are secreted by the GI tract after meals. These hormones stimulate insulin secretion, slow stomach emptying, and reduce hunger.
Another newcomer is Januvia (sitagliptin). It does NOT mimic incretin like Byetta, but instead enhances the body's own incretins. It inactivates an enzyme that breaks down incretins, therefore, increasing the effects of endogenous incretins.
At present time there are no natural medicines known to work similarly to these medications.
You might get questions from diabetes patients about using alpha-lipoic acid. It's an endogenous coenzyme. It acts as an antioxidant and is thought to regenerate other antioxidants in the body including vitamin E, vitamin C, and glutathione.
In people with type 2 diabetes, taking alpha-lipoic acid supplements orally seems to improve insulin sensitivity and glucose disposal, short-term. But it does not lower HbA1c.
Alpha-lipoic acid also seems to decrease symptoms of diabetic peripheral neuropathy. It reduces sensations of burning, tingling, and prickling of the feet and legs. But it can take 3-5 weeks before improvement is noticed.
Although promising, more evidence is needed about long-term safety of alpha-lipoic acid before it can be recommended for most diabetes patients.
If patients want to try it, explain that doses of 600-1200 mg/day have been used in studies. Lower doses might not help.
You might also get questions from patients about stevia (Stevia rebaudiana). In folk medicine, the leaf from the stevia plant is used to lower blood sugar. Apparently it acts directly on pancreatic cells, causing them to secrete insulin. Now, an extract from the plant, also known as Stevia, is being studied by the FDA as a sweetener that can be added to soft drinks and other foods. Both uses will get the attention of your patients with diabetes. They may want to buy stevia right now in health food stores where it is available as a dietary supplement; so they don't have to wait for the FDA to clear it as a food additive. But, steer your patients away from this product. Tell them there are unanswered questions about possible toxicity and other health effects with stevia.
Over the years there has been interest in selenium for treating or preventing diabetes. It's theorized that oxidative stress contributes to insulin resistance and diabetes. Therefore, the antioxidant effects of selenium have been thought to be beneficial for diabetes patients. But population research has linked high serum levels of selenium to an INCREASED risk of developing type 2 diabetes. A recent clinical trial confirms these findings, showing that older people who take a selenium supplement 200 mcg/day for an average of 7 years have an increased risk of developing type 2 diabetes. Advise patients not to take selenium to treat or prevent diabetes.
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