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From the Townsend Letter
April 2014

The Role of Nutritional and Botanical Agents in the Management of Type 2 Diabetes Mellitus
by Mona Morstein, ND
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Diabetes is reaching an epidemic level not only in the US, but also worldwide. There are 26 million patients diagnosed diabetic in the US, and 87 million who are prediabetic; essentially, 1 out of every 3 people in the US are – or are becoming – diabetic. If nothing changes, the Centers for Disease Control (CDC) predicts that by 2050, 50% of Americans will be diabetic. Worldwide, there are 350 million diabetic patients, with a concentration in areas of higher economic status and greater urbanization areas. 90% to 95% of diabetic patients are type 2, and the number diagnosed in the childhood or teenage years is also increasing. Worldwide occurrence of the autoimmune type 1 diabetes is also increasing.
   
The etiological factors for developing type 2 diabetes are multifactorial. They include: excess intake of refined sugar; excess intake of saturated fat; overeating; abdominal weight gain; lack of exercise; environmental toxins (mercury lead, arsenic, bisphenol A, persistent organic pollutants); nutrient deficiencies; genetics; gut dysbiosis; and hormone dysregulation. Insulin resistance is the key metabolic abnormality in type 2 diabetic patients, resulting in increased appetite, elevated glucose levels, higher BMIs, higher insulin secretion, and mixed hyperlipidemia.
   
There are many complications associated with being a prediabetic or diabetic patient, as a result of increased glucose and lack of antioxidants that lead to increased oxidation reactions. Diabetic damage occurs because of increased reactive oxygen species, such as superoxide anion radicals, hydroxyl radicals, peroxynitrite radicals, and lipid peroxidation. Diabetic patients have an increased risk of cardiovascular disease, eye problems (such as retinopathy and cataracts), nephropathy, and neuropathy. Physiologically this is because those body cells do not require insulin, and so cannot screen out excess glucose by becoming insulin resistant, as can fat and liver cells. Therefore, because eye, renal, nerve, and endothelial cells absorb glucose at the level that it is in the serum, a great deal of oxidative damage occurs to the cells and they can suffer devastating complications. Death from diabetes is usually caused by a heart attack or stroke. Diabetic patients have the highest occurrence of adult blindness, and are the highest population developing end-stage renal disease and nontraumatic limb amputations.
   
Standard conventional care of diabetic patients includes medica­tions, beneficial lifestyle changes, and associated medications. There are the oral hypoglycemic medications: metformin, sulfonylureas, DPP-IV inhibitors, SGLT2 sodium-glucose transporter, and the thiazolidinediones. There are also diabetic injections: GLP-1 drugs and the various forms of basal and bolus insulin. Outside of the focus on medication, standard care encourages patients to stop smoking, lose weight, have good stress management, and eat healthfully, although many patients are not given specific directives or counseling in those regards.
   
There are three basic treatment goals for US diabetic patients: A1C <7%; blood pressure ≤ 130/80 mm/hg, and cholesterol <200 and LDL <100. These goals are in accord with the UKPDS (United Kingdom Prospective Diabetes Study) and DCCT (Diabetes Control and Complications Trial), which proved that the lower the A1Cs of a patient, the fewer complications developed. A JAMA study showed that an A1C over 5.5 indicates that the glucose level in the patient is damaging the body. Diabetic patients can often require 3 to 4 separate hypertensive agents to bring their BPs down to a safe level. On top of that, the CDC shows that 68% of Americans are either overweight or obese, and visceral weight is a key factor in insulin resistance. Even so, standard care is failing to control this disease worldwide. A World Health Organization (WHO) bulletin of 2011 stated that unfortunately 90% of American patients do not meet those three treatment goals.
   
Approaches using micronutrients and botanical agents have been shown in numerous clinical studies to afford the best chances of obtaining those treatment goals without risking the sometimes problematic side effects of hypoglycemia from overmedication of glucose-lowering agents.
   
A low-carbohydrate diet is recommended for type 2 patients. The Nutrition and Metabolism Society devotes its entire dietary research to showing that low-carb diets are not just appropriate to type 2 diabetes but also extremely safe and effective at lowering glucose levels, decreasing insulin resistance, enhancing appetite control, and promoting weight loss, as well as normalizing lipid panels. Exercise – including aerobic, resistance, and high-intensity interval training – needs to be offered in ways that motivate patients to perform it regularly. Sleep studies to rule out apnea are vital, and sleep needs to be from 6 to 9 hours to promote appropriate regulation of leptin and ghrelin. Diet diaries, nutrient status measurements, hormonal evaluation, gut dysbiosis, and environmental xenobiotic burdens can all serve as extremely meaningful tests to help discern all possible etiologies for type 2 diabetes development. Last, adding in dietary and botanical supplements has been shown in studies to be very effective in helping the body lower glucose levels, lower lipid levels, decrease blood pressure, and prevent and reverse diabetic complications.
   
Focusing on supplementation, some of the most studied, most efficacious, and most beneficial supplements include:

  1. Zinc: Zinc is needed to produce, secrete and activate insulin receptors on the cell. Studies have shown that adding zinc to diabetic patients can be helpful. Hyperglycemia can cause pathological losses of zinc in the urine. Zinc also has an antioxidant effect on cells in diabetic patients.

  2. Chromium polynicotinate: Chromium has a vital role in binding to the insulin receptor to activate it on body cells, reducing insulin resistance. In many studies, chromium as a supplement has been shown to lower glucose levels, lipids, A1C, and insulin in diabetic patients.

  3. Gymnema sylvestre: Known as gurmar, or "sugar destroyer" in Ayurvedic medicine, Gymnema has been consistent in showing its benefits in patients with diabetes. Studies on the herb have shown that it may be helpful in lowering glucose levels. It was shown to regenerate pancreatic tissues, allowing more insulin to be produced, and help regulate insulin secretion. It also increases the utilization of glucose at the cell, via reducing insulin resistance, and can help decrease appetite and reduce sugar cravings.

  4. Cinnamon: Studies continue on cinnamon and have shown that it lowers stomach-emptying times and postprandial glucose levels; it reduces glucose in type 2 diabetes patients who had poor diabetic control. It has also shown to be helpful in lowering insulin levels, blood pressure, and the hemoglobin A1C. This is a safe herb. Cinnamonum cassia (a.k.a. Cinnamonum burmanii) is the type of cinnamon with the best effect on patients.

  5. Berberine HCL: A leading study on humans showed that berberine HCL equaled the effects of metformin on diabetic patients. In the pilot study, the A1C, fasting and postprandial glucose, plasma triglycerides, cholesterol and LDL, and fasting glucose and HOMAR were reduced, as well as body weight. Berberine is also a liver protectant and activates AMP protein kinase at the cell, which promotes GLUT 4 translocation, allowing more glucose to be absorbed from cells. This is very significant, and berberine is an important component in diabetic supplements due to its efficacy and its safety profile.

  6. R-ALA: Alpha-lipoic acid has numerous benefits to the diabetic patient. It is both a water- and fat-soluble antioxidant and has been shown to protect patients with fatty liver from liver disease progression. It can help insulin resistance and has been shown to protect diabetics from developing complications in their nerves, eyes, and kidneys. It is very safe. The R isomer is the only active isomer in the body and, since it can now be stabilized, should be the form recommended to patients, instead of regular lipoic acid wherein half the isomers are the nonhelpful S isomer.

  7. Taurine: Taurine is an inexpensive amino acid, underused as a diabetic treatment. It has been found to be a potent hypoglycemic agent, and it can also enhance the effect of insulin. One study showed that giving taurine to diabetic patients for a month required a reduction in their insulin dosing, to avoid taurine-induced hypoglycemia. It was also noted that patients had reductions in cholesterol and triglycerides as well. Taurine is found naturally in the eye tissue and heart tissue and is protective against oxidative damage in both.

  8. Benfotiamine: Also known as allithiamine, this fat-soluble form of thiamine has been shown in studies to be very capable at reducing the formation of advanced glycation end products (AGEs), which are well known to lead to the development of diabetic complications. Benfotiamine increases the production of thiamine pyrophosphate, which increases transketolase activity; transketolase blocks glucose-induced damage by preventing AGE formation. Since AGE formation promotes oxidative damage throughout the body, benfotiamine has been shown to treat and improve retinopathy, nephropathy, and neuropathy

  9. Bilberry extract: Bilberry extract is rich in bioflavonoids and anthocyanosides, and has a specific affinity for the eyes. In a rat study, it was shown that ingesting bilberry extract reduced hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase. In several studies, bilberry was analyzed in type 2 diabetes patients with retinopathy, and it was found to induce a clear improvement in their retinopathy, with marked reduction or disappearance of retinal hemorrhages. It may also be beneficial in improving microcirculation and lowering glucose levels. As retinopathy is a leading complication in diabetic patients, and diabetes is the main cause of adult blindness, this study is remarkably important.

  10. Green tea leaf extract: Green tea contains the catechin EGCG, which has been shown in numerous studies to be a safe and effective antioxidant. It has been shown to improve glucose tolerance in patients. In a study in Japan, green tea was shown to reduce the risk for type 2 diabetes onset. Green tea was shown to decrease hepatic glucose production, and oversecretion of glucose from the liver is a continual problem, causing hyperglycemia in type 2 diabetes patients. Green tea has also been shown to be an effective antiangiogenesis factor, which may have a significant effect on preventing retinopathy. It has also shown to promote fat oxidation and thermogenesis.

  11. Curcumin extract: Curcumin seems to have multiple benefits in diabetes. It has been shown to be a marked inhibitor of reactive oxygen species, which interferes with protein kinase C, thus providing a benefit in diabetes protection and the prevention of complications. It was shown to reduce progression in NAFLD (nonalcoholic fatty liver disease) patients, renal lesions, broad oxidative damage, and cytokine expression. Curcumin prevented retinopathy in streptozotocin-induced rats.

  12. Gingko biloba: This plant has been associated with reducing the risk of dementia and cognitive decline, but it has also been shown in human studies to reduce fibrinogen levels and improve retinal capillary blood rate in type 2 diabetes patients with retinopathy. It was shown to protect diabetic kidneys in animal studies. Gingko has also been shown to inhibit or reduce functional and morphological retina impairments. It was shown to reduce platelet aggregation in type 2 diabetes patients, too.

  13. Vanadium: This mineral has been shown to be an insulin mimetic, reducing insulin resistance. In numerous studies of the diabetic rat, vanadium has been shown to reduce elevated glucose and lipids. The best absorbed form of vanadium is bis(maltolato)oxovanadium(IV) – it is 2 to 3 times more potent than vanadyl sulfate and has shown less toxicity.

  14. Resveratrol: This is a bioflavonoid that has been shown in diabetic studies to protect pancreatic cells, reduce inflammatory cytokines, and increase antioxidants. It may also help improve insulin's actions and lower levels of glucose, A1C, and insulin. It was also shown to help decrease body weight, systolic BP, cholesterol, and triglycerides.

Using a comprehensive alternative-medicine treatment protocol, many diabetic patients can avoid using medications and even reverse their diabetic condition so that they have well-controlled A1C levels, and also lower lipids, lose weight, and have better energy and well-regulated serum glucose readings. Diabetes is a condition that does not have to lead to progressive complications and early death from cardiovascular disease. It is preventable, treatable, and reversible when treated by astute physicians addressing all the obstacles to cures and setting up a winning treatment plan with their patients.

References
Diabetic Numbers
Fast facts on diabetes [Web page]. National Diabetes Information Clearninghouse. http://diabetes.niddk.nih.gov/dm/pubs/statistics/#fast.

Future Diabetics
Number of Americans with diabetes projected to double or Triple by 2050. Centers for Disease Control. http://www.cdc.gov/media/pressrel/2010/r101022.html.

Obesity
Obesity and overweight. Centers for Disease Control. http://www.cdc.gov/nchs/fastats/overwt.htm.

A1C < 5.5
Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006;295:1707.

Refined Sugar's Leading to Type 2 Diabetes
Goran MI, Ulijaszek SJ, Ventura EE. High fructose corn syrup and diabetes prevalence: a global perspective. Glob Public Health. 2013;8(1):55–64. doi:10.1080/17441692.2012.736257. Epub 2012 Nov 27. http://www.ncbi.nlm.nih.gov/pubmed/23181629.

Saturated Fat and Diabetes
Haitao Wen, Denis Gris, Yu Lei, et al. Fatty acid–induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat Immunol. 2011. doi:10.1038/ni.2022.

Overeating and Diabetes
Scherer T, Lindtner C, Zielinski E, O'Hare J, Filatova N, Buettner C. Short term voluntary overfeeding disrupts brain insulin control of adipose tissue lipolysis. J Biol Chem. 2012;287(39):33061. doi:10.1074/jbc.M111.307348.

Abdominal Weight Gain and Diabetes
Després JP. Intra-abdominal obesity: an untreated risk factor for Type 2 diabetes and cardiovascular disease. J Endocrinol Invest. 2006;29(3 Suppl):77–82. http://www.ncbi.nlm.nih.gov/pubmed/16751711.

Exercise and Diabetes
Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. Physical activity/exercise and type 2 diabetes. Diabetes Care. October 2004;27(10):2518–2539. doi:10.2337/diacare.27.10.2518. http://care.diabetesjournals.org/content/27/10/2518.full.

Nutrient Deficiencies and Diabetes
Huerta MG et al. Magnesium deficiency is associated with insulin resistance in obese children. Diabetes Care. May 2005;28:1175–1181. doi:10.2337/diacare.28.5.1175.

Kostoglou-Athanassiou I. et al. Vitamin D and glycemic control in diabetes mellitus type 2. Ther Adv in Endocrinol and Metab. 2013;4(4):122–128. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281920.

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