Diabetes / Metabolic Syndrome

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

Sections

A Failure in understanding and treatment approach to Metabolic Syndrome and Diabetes Type 2 - the Need for a More Holistic Approach

In 2012, Dr. Phil Zeitler of the University of Colorado, and Dr. Mitchell Geffner of the Children's Hospital Los Angeles, released the findings of a long-term study on treatment protocol with teenage onset of Diabetes Type 2, or Metabolic Syndrome, published in the New England Journal of Medicine online, April 29, 2012. The study of 699 overweight and obese teenagers followed for 4 years after a diagnosis of diabetes found that standard treatment normalized circulating blood sugars initially, but four years later, a majority of these patients did not have their circulating blood sugars normalized with standard medication protocol.

These patients were divided into 3 groups, one of which received Metformin (glucophage), another which received Metformin plus Avandia (withdrawn from the market in some countries in 2011 due to evidence of significantly increased cardiovascular risk), and the third which tried to control the blood sugars with some counseling on diet and exercise. These study authors stated: "A single pill or single approach is not going to get the job done." In other words, utilization of a holistic treatment approach, and integration of Complementary Medicine (CIM/TCM), is needed, and standard medical counsel regarding diet and lifestyle changes are inadequate. Metformin, the standard therapeutic, is a pharmaceutical biguanadine derived from the herb Galega officianalis, commonly called Goat's rue, or French lilac, which was long used to treat Diabetes Mellitus in Europe. With Complementary and Integrative Medicine, a Galega tincture may be just a small part of the overall treatment protocol, individualized for each patient. In TCM, the treatment protocol may combine acupuncture, a variety of herbal extracts, and nutrient medicines, with different protocols not only for each type of diabetes, but for each patient to some extent. In addition, the TCM physician may also include dietary and lifestyle advice to manage the disorder that is also individualized. Much evidence of the effectiveness of various herbal and nutrient medicines are presented in the section of this article entitled Additional Information, with links to the published research. This research, along with centuries of clinical evidence, should be integrated into a more comprehensive treatment protocol for Metabolic Syndrome and Diabetes, and more and more patients are choosing to take a pro-active approach to their health problems and integrated this Complementary Medicine.

Dr. Zeitler, a pediatric endocrinologist, is a professor at the University of Colorado who has led research sponsored by the U.S. National Institutes of Diabetes, Digestive and Kidney Diseases since 2003, which has focused on the alarming rise in Metabolic Syndrome, obesity, and Diabetes Type 2 in young Americans, and the treatment options to counter this health problem which now accounts for a majority of health spending on the nation's youth. A prior report, published in the Journal of Clinical Endocrinology and Metabolism, (July 8, 2009, 94(7):2215-2220), reported that the understanding of nonautoimmune-mediated type 2 diabetes is complicated by a variability in definition, an inadequate understanding of causes, especially antigens not considered previously to be significant causes of this highly variable disease, or syndrome, and a failure to distinguish properly between type 1 diabetes, or autoimmune driven, and type 2, as well as the failure to address individuals who have a phenotypic overlap between type 1 and type 2 diabetes (phenotype refers to the combination of environmental and genetic traits). Dr. Zeitler has pointed to the possibility of onset of the disease, or syndrome, in the womb, as well as the findings of long-term morbidity and mortality (risk of an early death), accompanying Metabolic Syndrome and Type 2 Diabetes in youth. He notes the significant risks of newer diabetic medications, such as Avandia, in regards to long-term cardiovascular risk, and thus the need to avoid these medications in the treatment of younger patients. All patients, both young and old, would benefit from integration of Complementary Medicine (CIM/TCM), where better metabolic management and improvement in underlying health problems could insure less overall drug dependency, and consequently, less long-term adverse risk of medication side effects. The utilization of CIM/TCM involves a more thoughtful and proactive approach from patients, and hopefully some day, their Medical Doctors. Short courses of acupuncture with a more persistent step-by-step approach with herbal and nutrient medicine, aided by discussion of diet and lifestyle considerations, and individualized to each patient and stage of disease, will achieve the realistic goals in reversing the metabolic dysfunctions, and even the autoimmune destruction of true diabetes.

The United States National Heart, Lung and Blood Institute (NIH) describes Metabolic Syndrome as a group of risk factors that raises the risk for diabetes, stroke and heart disease. This poorly defined health syndrome was just called a pre-diabetic state for decades, and patents were treated with a medication protocol as if they had diabetes, resulting in great deal of unnecessary adverse effects from a polypharmaceutical approach that has proven to be the wrong choice. There are many factors that raise the risk of coronary heart disease, stroke and real diabetes, and dumbing down this subject has not helped patients achieve their goals of regaining metabolic health and reducing incidence of these common diseases. In fact, the most common drug used in treating Metabolic Syndrome, the statin drugs to lower cholesterol lipids, has been shown to increase the progression from Metabolic Syndrome to true diabetes, especially when combined with antidepressant SSRI and antipsychotic medications. Many of the new drugs introduced to treat Diabetes Type 2 have been shown to increase cardiovascular risk, and many new drugs introduced to treat autoimmune disorder, with combinations of immune suppressing biologics and corticosteroids, have now been shown to dramatically increase the risk of developing Diabetes. Metabolic Syndrome is still poorly defined by just a few health conditions, weight gain at the midsection, high triglycerides, low HDL cholesterol (not high cholesterol), and a high fasting blood sugar that may be episodic. The standard recommendation, simple diet and lifestyle protocols of quitting cigarette smoking, eating less saturated fat, adopting a plant-based diet mainly of fresh whole grains and vegetables, and getting at least 150 minutes, or just 1.5 hours, of moderate exercise per week, was found in 2016 to be followed by only 2.7 percent of Americans, according to experts at the Oregon State University College of Public Health and Human Sciences, generated from the National Health and Nutrition Examination Survey from 2003 to 2006. Obviously, Medical Doctors are not doing a very good job in treating their patients with Metabolic Syndrome and Diabetes Type 2, which now is estimated to involve between 15-40 percent of the U.S. population! Patients need help to formulate an actual proactive and comprehensive protocol to reverse this amazing threat to public health, and CIM/TCM offers and array of proven protocols for the many goals in therapy and disease prevention.

What are the implications of these findings for the adult with Metabolic Syndrome, Diabetes Type 2, or a high risk of this syndrome or disease? Many patients are beginning to question the treatment protocols in standard medicine for their Metabolic Syndrome or Diabetes, and gaining insight into the lack of an individualized approach that accounts for the variability of the disease, and the underlying health problems, which are not addressed by the standard one-size-fits-all approach. A study from 2001, published in the New England Journal of Medicine, February 7, 2002 (346:393-403), and conducted by the Diabetes Prevention Program Research Group, found that in a randomized study of 3234 non-diabetic patients with elevated blood sugars, that lifestyle intervention was significantly more effective than Metformin, reducing the future incidence of diabetes by 58 percent compared to placebo. The average follow-up was about 3 years, and the incidence of a diabetic diagnosis in the placebo group (average age of 51 years) was 11 percent. With the introduction of a goal of a 7 percent weight loss, and at least 150 minutes of physical activity per week, the reduction of risk of diabetes was reduced by nearly 60 percent, whereas the prescription of Metformin, with considerable long-term side effects possible, reduced the future incidence by 31 percent, achieving only about half the results of prevention of disease as a simple healthy regimen of improved diet and exercise. Unfortunately, the advice given to patients still emphasizes that we can just take a pill and skip all of that diet and lifestyle stuff, with only lip-service really provided to patients by their M.D.s and less than 3 percent of the U.S. population adopting even the 4 most basic diet and lifestyle changes.

A similar failure has occurred in the treatment of real diabetes, commonly called Diabetes Type 1. A study following 1441 patients with Type 1 Diabetes between 1983 and 1989 that were randomly assigned more intensive control of blood sugars, now termed Intensive Glycemic Control, or standard treatment with two type of insulin, showed in long-term follow-up study that those who achieved a more controlled daily blood sugar experienced a substantial reduction in diabetic complications and risk of ocular surgery to correct diabetic retinopathy (PMID: 25923552). This study is called the DCCT (Diabetes Control and Complications Trial). The definition of Intensive Glycemic Control involves attention to blood sugar levels before, after and between meals and maintaining a blood sugar before meals of 70-130 mg/dL, postprandial blood sugar 2 hours after eating of less than 180 mg/dL, and an A1C ideally at less the 7 percent. This can be achieved with the least degree of long-term complications from insulin medication by both adjusting the insulin intelligently, and achieving less need for high dosages of insulin by integrating a more holistic protocol, or regimen.

Another key treatment strategy for those with Metabolic Syndrome and at risk for diabetes type 2 is the widespread use of cholesterol lowering statin drugs, now one of the most prescribed medications in the United States. A meta-review of clinical trials by Harvard Medical School and the Joslin Diabetes Center, published in 2012 in the New England Journal of Medicine, followed up on the JUPITER trial, a large study to reassess the use of statins in diabetes prevention. This study (cited below in additional information with a link) shows that there is a 25 percent increased risk of developing diabetes for pre-diabetic patients with Metabolic Syndrome that are prescribed statins.

The meta-analysis shows also that a 13 percent risk of statin-induced diabetes is seen in a review of tens of thousands of patients. While statin drugs, or the natural statin found in red yeast rice extract, may improve the lipid profile and reduce risk of cardiovascular disease in the long term, the risk of these drugs in upsetting the lipid and sugar metabolism, or otherwise stressing the metabolic system, with lowering of CoQ10 and Vitamin D3 hormone cholecalciferol, for example, and actually inducing either insulin resistance or deficient production of insulin, has resulted in a reassessment of the widespread dependency on these drugs to treat metabolic disorders and diabetes. The natural statin in Red Yeast Rice, on the other hand, has shown no adverse effects, and the various other chemicals in this common Chinese food additive and herb (bioflavonoids, GABA, coumarins, lignans) provide an array of benefits as well. These research findings for current drug protocols are coming too late, and are still poorly defined, for many patients, though, who have been on statin drugs as part of their treatment protocol for pre-diabetic states and metabolic syndrome for years.

Today, many pro-active patients are beginning to pay attention to these findings, and exploring how best to prevent and treat this health problem that is overwhelming our healthcare system, and causing extreme stress on government healthcare expenditures. Most patients are finding out that the best protocol is one that incorporates an individualized approach to weight loss, and addresses the whole picture of health. The addition of Complementary Medicine, especially acupuncture, herbal and nutrient medicine, and the advice of the Complementary Medicine physician who has extensively studied diet, nutritional medicine, and lifestyle regimens in relation to disease, is now becoming quite popular. This holistic therapy makes the task for the pro-active patient much easier, and is supported now by much sound research. In addition, many patients that finally step up their exercise routines are finding that muscles and joints in poor health may develop problems related to exercise-induced injury. The Licensed Acupuncturist who is trained in the physiotherapies of Traditional Chinese Medicine, or Tui na, is able to directly address these aches and pains and keep the patient on their protocol. Each health concern in Metabolic Syndrome can be addressed with CIM/TCM therapy, sustained high blood pressure, fluctuating high blood sugar and poor postprandial metabolism of glucose, high triglycerides and fatty liver, the lack of high density lipoproteins (HDL), abdominal obesity, and the signs of slowly advancing cardiovascular disease, shortness of breath and fatigue. Insulin resistance, chronic inflammatory dysregulation, signs of lipid imbalance such as fatty nodules or patchy skin (xanthoma), and signs of insulin resistance and the response of high circulating blood sugars such as peripheral neuropathy and retinopathy, can all be addressed in holistic health care. Will taking a few medications that block metabolism, such as the formation of glucose and cholesterol, or enzymes that regulate insulin response, or that achieve the dumping of glucose in the urine, or the inhibition of androgens and angiotensin, really solve all of these underlying health problems that need to be addressed? No. Utilizing sensible Complementary and Integrative Medicine (CIM/TCM) is perhaps more complicated, but the rewards actually include a healthy life.

Making sure that you understand the medication protocols in diabetes and work with your medical doctor to make the right treatment decisions

In Type I NIDDM your doctor may give you one type of medication, monitor your blood levels, and perhaps change medications and/or dosages if proper regulation of glucose and triglycerides are not maintained. It is important to monitor your blood glucose levels before and after meals, and discuss intelligently with your doctor the need to adjust dosage or change medication. This is important both initially, as carbohydrate metabolism is being regulated, and later as you improve your diet/exercise patterns and are able to regulate the metabolism without aid of medications that have side effects. Insulin levels are best adjusted by use of an implanted pump. By increasing your health and conscious control of blood sugars and lipids, the body will need less insulin and perhaps other pharmaceutical drugs, and the long term side effects will be decreased. Use of dietary regimens and herbs are not contraindicated or harmful if used sensibly, and large studies have shown that they play a beneficial, safe and complementary role in your treatment when monitored by a professional herbalist and knowledgeable Complementary Care physician.

Two types of medications have been typically used to control Type II NIDDM. Since most cases of Metabolic Syndrome may not have yet become a hyperglycemic state, the patient should be sure that they are not being treated prematurely with these drugs. These typical medications in type 2 diabetes are sulfonylurea agents, that stimulate insulin production and enhance insulin binding, and metformin/glucophage, that acts on the liver to decrease sugar production and also enhances insulin binding. Recently, a new class of drugs is popularly prescribed, called glitazones, that seek to correct problems with insulin sensitivity, called Actos and Avandia. Unfortunately, these drugs have numerous side effects, including weight gain, water retention, anemia and hormone inhibition, and with findings of significant cardiovascular risks by the esteemed Cleveland Clinic cardiologist Dr. Steven Nissen, Avandia was banned in Europe and restricted in the United States. Glitazones, especially Avandia, have also been implicated in a complex plot by the drug makers to hide the significant cardiovascular risks seen in patient studies (see links to the New York Times articles on this subject below in additional information). In September of 2010, an FDA advisory panel recommended that Avandia should either be withdrawn from the market or have sales severely restricted due to health risks. Sulfonylureas have fewer side effects and act rapidly, and are thus now the usual first choice in prescription. The patient population has become wary of these new diabetic drugs, though, after the deception and public harm surrounding the glitazones has become well known. This group of new drugs, or sulfonylureas, includes:

  • Tolbutamide/Orinase: short (6–12 hour) duration of action
  • Chlorpropamide/Diabinase: longest acting (60 hours) with a greater danger of hypoglycemic state
  • Tolazamide, Glyburide, and Glipizide: medium duration of action (12–24 hours) and fewer adverse reactions

Actos, or pioglitazone, became the largest selling glitazone after the drug Avandia received such much negative publicity concerning cardiovascular risks, and was banned in parts of Europe. In June of 2011, though, the maker of Actos withdrew this drug from the market in France and Germany as well after pressure from food and drug regulators intensified. In the U.S., the FDA issued black box warnings concerning the risks of congestive heart failure and is considering warnings related to the risk of bladder cancer associated with long-term use. The FDA analyzed data from the first 5 years of a 10 year study and found that Actos was associated with a 40 percent increase in risk of bladder cancer. Pioglitazone is due to receive generic status in 2012, and many different names may then be applied with questions of the requirements of generic manufacturers to include the warnings that the original manufacturer was required to provide. Newer glitazones have had difficulty with approval from the FDA as well. Dr. Harlan Krumholz, a Yale School of Medicine professor who directs its Center for Outcomes Research and Evaluation stated: "It's not clear if this (bladder cancer) risk is real (until more long-term data is collected)...The consensus already is that (Actos) should only be considered...after patients have exhausted all other products (due to links to heart risks, weight gain and possibly bone loss and fractures)."

Metformin/glucophage will have more severe gastrointestinal side effects, such as nausea, bloating, diarrhea and flatulence, and thus should be given first in a small dose, and as blood chemistry is checked, advanced to a larger dose if the patient tolerates. Metformin is beneficial in reducing cholesterol/fatty acids, and is effective if the triglyceride levels are too high. Triglyceride levels, though, may be reduced with less risky herbs and nutrient medicines, and improvement in liver function with the use of acupuncture and Complementary Medicine. Studies do show that a large percentage of patients have insufficient blood sugar control after 5 years of usage of any of these drugs, pointing to the need for adopting an effective dietary, lifestyle and herbal regimen to increase your chances of long term success. Depending completely on drug therapy has been shown to be problematic. To reduce the adverse effects of Metformin, it is often prescribed in smaller dosage in a pill combined with Glipizide, a sulfonylurea, but the U.S. FDA reported that the drug trials for this combination resulted in over 10 percent of patients reporting hypoglycemia at the 5 mg dosage. The 10 mg dosage is not approved by the FDA, and reports of pancreatitis were noted. Metformin is also combined with Saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) as Kombiglyze XR, and common side effects include anxiety, nervousness, depression, urinary difficulties, dizziness, ear congestion, nasal congestion, fast heartbeat episodes, and unusual tiredness, as well as a black box warning that lactic acidosis may occur with use due to metformin accumulation, resulting in malaise, somnolence, abdominal distress, respiratory distress and muscle pain. Liver impairment is associated with poor metabolism of metformin and a higher risk of lactic acidosis. Blood labs to diagnose lactic acidosis include a lactate or lactic acid test, which may be achieved with veinous blood stick or arterial blood, and arterial blood tests may reveal low pCO2, plasma bicarbonate, and anion gap elevation. Mild lactic acidosis is rarely explored.

Another diabetic drug has been added to the regimen to increase effectiveness, called Sitagliptin, most commonly in the form of Januvia. This dipeptidyl-4 peptidase (DPP-4) inhibitor was created to degrade a protein enzyme that plays a role in modulating the hormone incretin, which helps regulate pancreatic insulin production. Unfortunately, during this same recent time period of research, scientists found that dipeptidylpeptidase-4, which Januvia inhibits, is an important enzyme in the lining of the small intestine, and deficiency of DPP-4 is highly linked to Celiac disease, or the inability to fully breakdown gluten and gliadin protein fragments in the lining of the small intestine. Research has also uncovered the fact that other gut hormones, such as enterolactone, may play a beneficial role in modulating incretin and pancreatic insulin production. Plant lignans may stimulate more of these beneficial gut hormones, and a potent plant lignan, in the patented form of NuLignan is a nutrient medicine that may play an important role in this regard. By 2012, the evidence of increased risk of cancers, especially colon cancer metastasis and pancreatic cancer, was also apparent with use of the DDP-4 inhibitors, such as Januvia, prompting a removal of the drug from approved markets in a number of countries. It was found that important glucagon-like peptides that are broken down normally by DDP-4, stimulated increased cell proliferation and migration when these peptides were not broken down. Inhibition of the dipeptidyl peptidase-4 enzyme in the intestinal lining caused considerable problems for the normal healthy homeostasis of the gut, and may be linked to Irritable Bowel Syndrome and problems with protein digestion, especially with glutens and gliadins. In addition, with proof of risk of pancreatitis and pancreatic cancer revealed by the former editor of the journal of the American Diabetes Association and current head of endocrinology at the University of California Los Angeles (UCLA), Dr. Peter Butler, a 2013 renewal of safety review by the U.S. FDA may result in these drugs being restricted or banned. The February 2013 issue of JAMA (Journal of the American Medical Association) published a study by researchers at Johns Hopkins Medical School that confirmed that patients taking dipeptidyl-4 peptidase inhibitors, commonly called incretin mimetics, Januvia, Byetta, Victoza, Tradjenta, Nesina, or Bydureon, had double the rate of acute pancreatitis, apparently confirming the findings of Dr. Peter Butler.

In response to the risks and lack of benefits for these DDP-4 inhibitors, the U.S. FDA approved another type of drug to treat Diabetes Type 2 or Metabolic Syndrome, to be used only when other medications failed to control the metabolism. This type of drug, the glucagon-like peptide-1 (GLP-1) receptor agonist, such as Victoza, actually increases the ability of a short-lived protein hormone called an incretin, GLP-1, that is normally regulated by the DDP-4 protein hormone. The sequence of effects, inhibition of the hormone DDP-4 that is secreted by the intestinal membrane to modulate the effects of another hormone secreted locally to the intestine, GLP-1, which is inhibited by other diabetic drugs, creates a further set of problems. Obviously, inhibiting the protein hormone that regulates GLP-1 may present some problems, which are then corrected by prescribing the GLP-1 agonist. This cycle of allopathic drug controls take the patient further away from a restoration of normal metabolic controls, and these hormones affect more than the regulation of insulin and glucagon, with GLP-1 regulating the emptying of the stomach contents and rate of absorption of nutrients through the intestinal membrane. For this reason, there is evidence that the drug may result in weight loss, but the cause of this weight loss appears to be poor digestion and absorption of nutrients, not a healthy restoration of the metabolism and weight regulation. The likelihood that gastrointestinal dysfunction would slowly increase with these drugs is high. Restorative medicine, to actually restore the healthy of the gastrointestinal system, should be integrated with approach, to achieve a healthy states of both digestion and elimination, and the metabolism. Unfortunately, these types of drugs may make restoration of the functional health of the small intestine membrane, the stomach and coordination between the stomach and small intestine, and the large intestine function and health, more difficult to achieve. The U.S. FDA issued black box warnings with the GLP-1 receptor agonists for increased risk of thyroid C-cell cancer and pancreatitis, and the most common side effects are gastrointestinal disturbances.

In 2011, in response to the problems with current medication protocols for Metabolic Syndrome or Diabetes Type 2, another type of drug therapy was introduced, Dapagliflozin, which works by blocking a chemical that inhibits blood glucose excretion via the kidneys, thereby increasing the excretion of blood glucose. A federal advisory committee of the FDA voted 9 to 6 for non-approval of this drug, though, based on safety concerns. While increasing excretion of glucose may seem like a direct therapy for high levels of circulating glucose, this strategy does not resolve the underlying health problems causing the high blood glucose, and does increase risks of various health problems, including urinary tract infections, bladder and breast cancers, and kidney disease. Other safety concerns, regarding hypoglycemia and other effects of the drug on various metabolic cellular mechanisms, were also a concern. The committee advised against early FDA approval until larger studies are completed to determine the extent of long-term adverse effects and health risks. While this drug may prove useful in the future for many patients with uncontrolled high blood sugars, patients need to understand that, once again, the underlying health problems of insulin resistance and fatty growth around visceral organs is not addressed with these various drug strategies, and the smart patient wants to both control their disease manifestations and correct the unhealthy homeostatic mechanisms that created them.

This wide array of drugs prescribed to treat diabetes and Metabolic Syndrome has posed challenges to the patients who wish to understand risks and benefits, and help make the right choices in treatment protocol. With all pharmaceutical drugs, the problems of side effects over time, not the immediate side effects, is usually of greatest concern to the patient. Often, a small percentage of patients experience immediate adverse effects, but a much greater percentage experience long-term adverse effects and health risks. Complementary Medicine is able to address the concerns of side effects and decrease the negative consequences of long-term pharmaceutical management. By improving the underlying causes of diabetes and metabolic syndromes the patient may be able to either reduce the number of drugs, dosage, or even regain health enough to stop the need for medication before the long-term consequences occur. In addition, integration of evidence-based herbal and nutrient medicine into the treatment protocol may increase the success with diabetic control and metabolic normalization, which has proven to be problematic for many patients with current and past pharmaceutical regimens.

Recent concerns over new Diabetic drugs: a risk versus benefit concern

In 2007, a well respected cardiologist at the Cleveland Clinic, Dr. Steven E Nissen, conducted a landmark study that suggested that the current best-selling diabetes drug, Avandia, raised the risk of heart attack considerably. This led to a congressional inquiry and subsequent safety warnings, with an appropriate drop in sales that was dramatic. Dr. Nissen was pressured to keep his findings out of publication in 2007, and anticipating the common maneuvering and misuse of scientific study, he secretly taped a meeting with the manufacturers of Avandia, GlaxoSmithKline, when they called him in for a meeting before his study was to be published in the New England Journal of Medicine. This story is presented in the New York Times, February 23, 2010, entitled 'A Face-Off on the Safety of a Drug for Diabetes'. In the meeting, GlaxoSmithKline referred to a yet unpublished, supposedly independent, study, that they purported had data that was contradictory to Dr. Nissen's study, and suggested that he hold off on publication, and accept an offer to perform collaborative research on this subject with their monetary help. GlaxoSmithKline was not supposed to have access to these independent studies until they were published in peer-review journals. Congressional investigations found that the company had been faxed copies of the unpublished studies by a worker at the medical journals who also was paid as a consultant for GlaxoSmithKline. Congressional investigation also revealed that GlaxoSmithKline's own scientists had concluded that Dr. Nissen's study was correct in evaluating an 11 percent increased risk for myocardial ischemia, or heart attack, with chronic use of Avandia, yet the company publicly claimed that Dr. Nissen's study was incorrect and poorly structured. The New York Times quotes the head of research at GlaxoSmithKline, Dr. Moncef Slaoui: "F.D.A., Nissen and G.S.K. all come to comparable conclusions regarding the increased risk for ischemic events, ranging from 30% to 43%." This increased risk may reflect risk of ischemia in both the heart and brain.

In 2013, the giant pharmaceutical Roche abandoned development of a newer glitazone PPAR agonist diabetes drug, aleglitazar, during late-stage human clinical trials due to "safety signals and lack of efficacy". The company cited the increased risk of bone fractures, kidney disease and heart failure in this newer type of glitazone, reportedly like Avandia but without the cardiovascular risks. Roche stated that this newer version of the drug type did not reduce risk of stroke and heart attack as expected. This drug works by activating PPAR alpha and gamma receptors, whereas Avandia and Actos mainly affects only the PPAR gamma receptors. Prior PPAR agonists have also failed the risk versus benefit assessments in human clinical trials, such as AstraZeneca's Galida, Merck's MK-767, and Takeda's TAK-559, due to cancer, kidney and liver problems and risks that outweighed the modest benefits. As a whole, the pharmaceutical industry has found that these newer diabetes drugs present more risks than benefits for most patients, yet this has not affected physician prescriptions dramatically.

Why is Avandia, a glitazone, a risk for cardiovascular disease? This new class of Diabetic drugs addresses insulin resistance and inflammatory dysfunction in fat cells by binding to receptors called PPAR (peroxisome proliferator-activated receptors). By antagonizing these receptor functions, the drugs reduce insulin resistance and inflammatory mechanisms. Unfortunately, these PPAR receptors are now known to be expressed in many types of cells, especially in the heart muscle, liver, blood vessel endothelium, etc. Over time, decreasing the effect of PPAR may have negative consequences in the body, and this is why ischemic problems, as well as liver dysfunction and increase bone fractures have been noted. The ischemic problems affect more than the heart muscle, with increased risk of macular degeneration in the eyes, and increased muscle and joint pathology possible. Just as non-steroidal anti-inflammatory medications were eventually noted to cause inflammatory dysfunction and increase risks of cardiovascular pathology etc. over time, these types of drugs, like Avandia, have both potential beneficial and harmful effects that need to be more carefully considered by each patient and doctor. One important consideration should be the potential use of Complementary Medicine to achieve these goals of reducing insulin resistance, either by correcting the causes underlying the problem, or by enhancing the insulin metabolism to allow the drugs to work more efficiently. A second consideration in Integrative Medicine is the reduction of side effects and risks of these drugs with the use of Complementary Medicine.

In 2008, Dr. Peter C. Butler, chief of endocrinology at the University of California Los Angeles, and former editor of the Journal of the American Diabetes Association, finally agreed to conduct study of the effects of the incretin mimetic Januvia on laboratory animals to see if the drug could prevent Diabetes Type 1, for the pharmaceutical Merck. In a May 31, 2013 New York Times article, entitled A Lone Voice Raising Alarms, Dr. Peter Butler stated that he originally told Merck that he was "not interested in your money, go away." With increasing pressure, he agreed to perform the studies for Merck, but found worrisome changes in the pancreases of the laboratory animals he studied. Other researchers working for Merck stated that they had found no increased risk of pancreatic disease in their studies, despite the first drug approved in this class, Byetta, contained FDA warnings of the increased risk of pancreatitis. In pursuing this study, Dr. Butler stated that such studies were usually designed to not show risk of pancreatic cancer by choosing laboratory animals that were young, and had a much lower risk of cancer. By 2013, there was much published skepticism of the risk of pancreatic cancer from incretin mimetics like Januvia and Byetta, but some experts, such as Dr. Edwin Gale, professor emeritus at the University of Bristol, United Kingdom, stated that in his review of the studies, Dr. Butler "should be an American hero, actually, a rugged individualist who is not going to be browbeaten", showing the current state of affairs in professional research. The concern of Dr. Butler was that the drugs work essentially by increasing the levels of of a hormone called glucagon-like peptide-1, which could accelerate the precancerous conditions in middle-aged patients with poor pancreas health, such as pancreatitis, which the class of drugs already has shown to increase the risk of, if not cause. A growing number of lawsuits around the world allege that these drugs caused pancreatitis, and data gathered by the Institute for Safe Medication Practices revealed that drugs like Byetta and Januvia accounted for 43 percent of all reports of acute and chronic pancreatitis by 2013. Dr. Gale stated that all forms of pancreatitis predispose to cancer of the pancreas. In the February 2013 issue of the Journal of the American Medical Association (JAMA) researchers at Johns Hopkins Medical School revealed that patients taking Januvia, Byetta or Bydureon showed double the rate of pancreatitis than the normal population.

The newest drug tactic for diabetes involves the drug liraglutide (Victoza), approved in 2010. By 2013, we already are seeing FDA warnings about increased risk of pancreatitis and thyroid cancer, as well as adverse health effects over time for more than 5 percent of patients with constipation, diarrhea, nausea and headaches. This drug mimics a hormone called GLP-1, stimulating insulin production in Diabetes Type 2, and was designed as part of an expanded polypharmacy approach. Unfortunately, this still overlooks the fact that with insulin resistance at the fat cell and organ receptors, higher insulin results, and excess insulin creates an array of hormonal imbalances that are devastating over time. Simply stimulating more insulin is not the ultimate answer to this problem, obviously. Restoring liver and pancreatic health and function, helping to regulate inflammatory immune responses, decreasing insulin resistance and the underlying problems driving this disorder, and restoring hormonal balance are more sensible goals. Adding another drug to the mix with Januvia, Byetta or Bydureon that adds risk of pancreatic dysfunction and inflammation is ignoring risk versus benefit for many patients.

These widespread concerns about most of the drugs used to treat diabetes have prompted a renewed interest in Complementary Medicine, and the proven ability of herbal and nutrient medicines to effectively improve the health and function of the pancreas, as well as decrease insulin resistance at the organs, fat and muscle cells. A holistic regimen utilizing a variety of researched herbal and nutrient chemicals, as well as acupuncture, shows remarkable potential, and in fact, much proof of efficacy and safety. As always, risk versus benefit must be considered, and if the risks are high, potent drugs with adverse risks should be used, but if the risk is lower, safer medicines should be tried. Even when using pharmaceutical drugs with serious risks, Complementary Medicine should be integrated to decrease these side effects and risks, and benefit the whole health of the individual. Ignoring the integrative potential of Complementary Medicine puts the patient population at risk, and this is finally being realized.

Treatment Options and Strategies in Complementary and Integrative Medicine: better outcomes with integration of short course of acupuncture and an individualized herbal and nutrient protocol

Abundant research now reveals the failures of treatment design in standard medicine for Metabolic Syndrome and Type 2 diabetes, as well as the failure to effect regrowth of damaged beta cells in the pancreas in type 1 diabetes. Much research in recent years now demonstrates that adding acupuncture and herbal nutrient medicine to the protocol provides a broader set of benefits than medication alone, with virtually no risk of harm. Effective treatment with Complementary Medicine is important with the diabetic patient. The variety of types of diabetes and the extent of damage to the system, both from the disease and from chronic long-term use of insulin and other medications makes each individual case unique in its needs. Research continues to expand the effectiveness of herbal formulas to treat these problems, as well as acupuncture. The treatment protocol should be managed by a professional in such a complicated disease. A variety of herbal formulas and nutrient medicines are available to the physician, and need to be individualized in therapy, and often prescribed in a goal oriented, step-by-step approach.

Both acupuncture stimulation and herbal nutrient medicine is now well supported in evidence-based medicine for the treatment of Metabolic Syndrome, Diabetes Type 2, and even as an adjunct therapy in Diabetes Type 1, to improve pancreatic health and function and treat comorbid effects such as peripheral neuropathy and diabetic retinopathy and cardiovascular disease. In recent years, further research has demonstrated the array of effects that are achieved with acupuncture and herbal nutrient medicine, including both peripheral and central benefits to metabolic homeostasis. Acupuncture stimulation itself has been shown to improve problems with insulin resistance, lipid balance, insulin sensitivity, adrenal function, cholinergic function, pancreatic function, and leptin metabolism. Some of this abundant evidence is cited and linked to scientific studies in Additional Information. While the herbal and nutrient research is extensive, and cannot be completely described on an article such as this, here are a few pieces of information that may help the patient understand how herbal and nutrient medicine may benefit them. A number of herbs are proven to help reduce your blood sugar more quickly after you eat, including Crepe Myrtle, American Ginseng and Cinnamon bark. Better utilization and transformation of sugars or carbohydrates can be helped with a number of herbs which have long been used in Chinese hospitals, and are available in professional formulas. Efficient transformation of sugars in the liver may be helped with acupuncture and herbal formulas that stimulate healthier liver function to improve triglyceride and protein metabolism as well as cholesterol and lipid metabolism. Nutrient medicines, such as L-Carnitine and Alpha-Lipoic Acid, have also been found to be helpful in improving metabolic utilization, and N-acetyl cysteine is proven to help reverse pancreatic beta cell damage from inorganic arsenic and mercury toxicity. A variety of herbs and nutrient medicines are now shown to be effective to normalize lipid metabolism and cholesterol, such as bitter melon extract and red yeast rice extract. Specific herbal chemicals, such as berberine, resveratrol, and quercetin are proving useful in this protocol, as well as essential fatty acids found in krill oil and black currant seed extract. Alone, none of these herbal and nutrient molecules may cure diabetes or Metabolic Syndrome, but in a professionally prescribed protocol, they will achieve a variety of goals and restore normal energy metabolism and homeostasis, especially when used with short course of acupuncture stimulation. These are now evidence-based therapies, and the choice of a knowledgeable Complementary Medicine physician, or Licensed Acupuncturist and herbalist is very important.

Both extensive and simple course of therapy in Complementary Medicine may help and integrate well with standard pharmaceutical therapy. Since inflammation is a key problem in diabetes and insulin metabolism, anti-inflammatory herbs, anti-oxidants, amino acids, and essential fatty acid supplements etc. may make a big difference to treat the cause of diabetes and metabolic syndrome. Hormonal balance is also a key issue in healthy restoration. Since insulin is a steroid hormone and the endocrine system needs balance, use of bio-identical progesterone stimulating creams when appropriate have shown great improvement in diabetes clinically. The pioneer M.D., Dr. John R. Lee, has written extensively on this research. Acupuncture and herbal formulas, as well as supplements and creams, also are helpful to correct associated hormonal problems like adrenal stress and subclincial hypothyroid problems, which may be related, and are ongoing underlying causes of metabolic and inflammatory dysfunction. Although the herbal and nutrient medical approach is more complicated than taking a single pill, the end result may be worth the trouble.

Diabetes primarily causes inflammatory deterioration of the blood vessels and nerve sheaths, leading to peripheral neuropathy, circulatory problems, cardiovascular pathology, visual deterioration and kidney failure. On the other hand, Metabolic Syndrome primarily affects the cardiovascular system by increasing atherosclerotic plaques on arterial walls. This is largely driven by a combination of advanced glycation endproducts (AGEs) and chronic vascular inflammation and immune dysregulation. Metabolic Syndrome and insulin resistance usually causes some degree of obesity, and effects a wide variety of hormonal modulations in the body. These effects of insulin resistance may cause problems with brain function, polycystic ovary syndrome, infertility, and a host of related dysfunctions in the body. Allopathic medicine does not address these varied healthy problems that accompany Diabetes and Metabolic Syndrome. Complementary and Integrative Medicine offers the patient a variety of effective treatments for these disorders as well, treating both the manifestation of the disease as well as the disorder itself, and able to individualize the treatment for each patient.

Since the array of problems in diabetes can be so broad, you need to discuss the particular therapies and options with a knowledgeable practitioner. Therapy from the Complementary and Integrative physician, such as the Licensed Acupuncturist and herbalist, or the Naturopathic Doctor, can be used by patients receiving standard pharmaceutical treatment or in patients who are not yet on these drugs, and may address healthy restoration of the metabolism and GI system, side effects of medications, and/or treatment of comorbid health problems associated with Metabolic Syndrome or any type of diabetes. This type of integrative therapy can be tailored to the individual and utilized in a broad array of treatment variations and frequency of treatments. Short courses of acupuncture with more prolonged use various herbal and nutrient medicines in a step-by-step restorative approach works best. The only side effect of CIM/TCM is better overall health and increased quality of life. As always, the health benefits from this treatment strategy will help you to both treat your diabetes and become a healthier and more productive person.