~Diabetes, Part 6 - Testosterone and Type II Diabetes

~Diabetes, Part 6 - Testosterone and Type II Diabetes
DOES TESTOSTERONE PLAY A ROLE IN TYPE II DIABETES?

Testosterone, a hormone produced by both men and women, is not new to endocrinologists as a treatment for diabetes. European clinicians have used testosterone to treat severe cases of diabetes since the 1960s and 1970s. Supplementing to normal testosterone levels of a healthy 25- to 30-year-old man raises HDL cholesterol and reduces blood pressure, triglycerides, and abdominal obesity. However, of equal importance, testosterone appears to lower blood glucose and insulin levels, along with HbA1c (a reflection of blood glucose levels over the last 2-3 months).

Edward M. Lichten, M.D., voiced excitement concerning testosterone's ability to stabilize blood sugar levels, citing near miraculous results, evidenced by the following case studies:
  • A 43-year-old male experienced a drop in blood sugar levels from 450 mg/dL to 160 mg/dL in 6 weeks. Insulin requirements were adjusted from 100 units a day to 50 units. Treatment consisted of testosterone pellets implanted in subcutaneous tissue.
  • A 53-year-old male realized a drop in HbA1c from 9.9 to 5.5 in 4 months using injectable testosterone 2 times a month; subject was previously treated with Glucophage and Glynase.
Dr. Lichten declared that testosterone might be fixing a defect that develops in a diabetic's body. If, however, diabetes has progressed to an advanced stage in which multiple complications have arisen, testosterone is not the complete answer. Dr. Lichten cautions that the time for intervention is before severe complications develop.

On numerous occasions, Dr. Lichten has been able to eliminate antidiabetic drugs and, in some cases, the need for insulin injections among his patients. This is explainable, in part, because normal levels of free testosterone decrease the need for insulin. Dr. Lichten says that blood glucose control is the primary concern in diabetic management, but the pathophysiology of insulin appears the determinant in diabetic survival.

Dr. Lichten states that his research has established a definite relationship between the amount of free testosterone in the bloodstream and sensitivity to insulin. Healthy men show higher levels of free testosterone and lower sex hormone-binding globulin (SHBG) levels. A nondiabetic male teenager may have a free testosterone of 2 in relationship to SHBG; an 80-year-old man with diabetes and on dialysis may have a free testosterone level of 0.1-0.2.

Men with disease and aging also have an increase in testosterone blockers such as estrogen and SHBG that neutralize or bind testosterone. SHBG amplifies estrogen by preferentially tying up testosterone; in fact, estrogen turns off the brain's signals to supply testosterone.

Dr. Lichten uses pellets (having a 6- to 12-week life) implanted in subcutaneous tissue or injections administered every other week to reestablish testosterone levels. Testosterone can also be administered topically, applying creams, gels, and patches, but the injection route used by Dr. Lichten provides a higher dose. A complete blood count, PSA (prostate specific antigen), DRE (digital rectal examination), and an SMA 12 (to track liver function and lipid values) are among a battery of tests routinely ordered. For information concerning safely increasing testosterone levels in men, refer to the Male Hormone Modulation protocol.

In women, a relative hyperandrogenicity is statistically associated with insulin resistance and centralization of body fat, which are predictors for the development of noninsulin-dependent diabetes mellitus. Newborn female rats undergoing androgenization (high doses of testosterone) experienced similar developmental patterns, that is, insulin resistance and changes in adipose tissue distribution (Nilsson et al. 1998).

Researchers reporting in the journal Diabetes agreed that administering testosterone to a group of oophorectomized female rats, those having one or both ovaries removed, resulted in a decrease in whole-body insulin-mediated glucose uptake (Rincon et al. 1996). In an unrelated study, researchers from Kaiser Permanente (Oakland, CA) announced that estrogen replacement therapy might prove beneficial in maintaining glycemic control in older women with Type II diabetes. Mean HbA1c levels were significantly lower in women using hormone replacement therapy compared to women not receiving the treatment (Ferrara et al. 2001).

Note: Indian researchers investigated the effects of long-term administration of testosterone enanthate, a derivative of primary endogenous androgen testosterone. Researchers evaluated testosterone enanthate's effects on glucose metabolism including glucose tolerance and fasting serum insulin levels in adult rhesus monkeys. Significant changes in glucose tolerance were not seen in animals treated with testosterone therapy; however, serum insulin levels decreased significantly from months 27-32 of treatment (Tyagi et al. 1999).

DOES SMOKING CONTRIBUTE TO DIABETES?

Cigarette smokers have increased insulin resistance and hyperinsulinemia, higher triglyceride levels, and lower HDL cholesterol compared to nonsmokers. Researchers from Stanford University assembled 40 healthy volunteers (20 nonsmokers and 20 individuals who had smoked at least one pack of cigarettes for 6 years) (Facchini et al. 1992). The smokers showed more insulin resistance, higher levels of circulating insulin, and slightly higher blood glucose levels compared to nonsmokers. Triglyceride-rich VLDL increased by more than 40% and HDL cholesterol levels fell by about 23% among the smokers. According to information released from the 15th World No Tobacco Day, the negatives associated with chronic smoking (20 cigarettes a day) are long lasting; the ill effects endure beyond the actual smoking experience.

There is overwhelming evidence linking active smoking to periodontal disease, a newer risk factor for diabetes, according to Sara G. Grossi, D.D.S. (University at Buffalo senior research scientist and chief researcher in the study). Dr. Grossi announced that even exposure to passive tobacco smoke increases the risk of periodontal disease up to 70%. Gum detachment and the incidence of bleeding gums increased 1.5- to 2.5-fold. The researchers concluded that smoking and exposure to passive smoke should be considered a risk factor for periodontal disease; gum disease, in turn, increases the risk of developing diabetes and makes blood glucose control more difficult in confirmed diabetics (Baker 1999b).

DRUG AND NUTRIENT INFLUENCE ON DIABETES

Some beta-blockers, diuretics, antipsychotic, and sulfonylurea drugs appear to increase insulin resistance and the risk of developing (or worsening) diabetes mellitus (Lithell et al. 1996; Lukaczer 1999; Hagg et al. 2001). Unfortunately, the majority of drugs used to treat hyperglycemia stimulates the pancreas to produce more and more insulin. While this temporarily lowers blood glucose levels, it ultimately further degrades the cells' receptivity and hastens pancreatic exhaustion.

Most calcium channel blockers (used to reduce blood pressure) are seen as neutral in regard to increasing or decreasing insulin sensitivity. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, appears to actually improve insulin sensitivity while lowering blood pressure. The New England Journal of Medicine reported that another angiotensin II receptor blocker (Avapro or the generic Irbesartan) is effective in protecting against diabetic nephropathy. This protection is independent of the reduction in blood pressure that Irbesartan typically causes (Lewis 2001).

The ACE inhibitor ramipril (brand name Altace) may prove to be of particular advantage to diabetic patients. Over the 4.5 years of the HOPE project (a study to determine the effectiveness of ACE inhibitors in preventing cardiac disease), the number of patients who developed new diabetes in the ramipril group was one-third that of the placebo group. If it can be substantiated that the incidence of diabetes is reduced during ramipril usage, it would indicate that the renin-angiotensin system is also involved in the pathogenesis of diabetes (Yusuf et al. 2000). With drug options, hypertensive individuals who are at a high risk for diabetes mellitus should be steadfast about requesting a drug with a dual purpose: the ability to lower blood pressure and simultaneously increase insulin sensitivity.

Pravastatin (Pravachol®), a cholesterol-lowering drug, also appears to cut the risk of diabetes. The West of Scotland Coronary Prevention Study found that of the 5974 men enrolled in the trial and taking pravastatin, 153 subjects developed diabetes. Researchers concluded that pravastatin therapy resulted in a 30% reduction in the hazard of becoming diabetic. By lowering plasma triglyceride levels, pravastatin therapy may favorably influence the development of diabetes, but other explanations such as the anti-inflammatory properties of the drug in combination with its endothelial effects cannot be excluded with these analyses (Freeman 2001).

It has been determined that some diabetics are low in zinc, a deficiency that may decrease insulin's responsiveness (Faure et al. 1992). However, in a small study, administering 220 mg of zinc sulfate (90 mg of actual zinc), 3 times a day for 2 months, increased fasting glucose rose from an average of 177 mg/dL to 207 mg/dL (Raz et al. 1989). Glycosylated hemoglobin levels also increased among a group of Type I diabetics (not the focus of this protocol) receiving 50 mg of zinc a day (Cunningham 1994). Considering these poor statistics, if more than 15 mg of zinc (the RDA) is used a day, close glucose monitoring must accompany supplementation.

Iron is another mineral that may cause problems with blood sugar. Increased iron stores appear to predict the development of Type II diabetes (and diabetic complications) while iron depletion is protective (Fernandez-Real 2002). In a study involving 18 Type II diabetics with relatively high blood sugar, nine (50%) had elevated serum ferritin levels, the stored form of iron. Researchers found that lowering elevated ferritin levels correlated well with diabetes control and improved fasting glucose, triglycerides, and HbA1c in eight of the nine patients (Cutler 1989).

Note: According to isolated reports, restoring normal iron levels reversed diabetic conditions in a small subset of patients (Pharmacist 2000). Request that your iron level be checked if you have a blood glucose problem. (The standard reference range for iron is up to 180 mg/dL; less than 100 mg/dL is considered optimal.) A blood test to measure ferritin is a more accurate way of assessing iron levels than relying upon a standard blood chemistry test. In addition, the gene for hemochromatosis was discovered in the mid-1990s. A relatively new DNA test called HLA-H, or more commonly HFE or Hfe, is available for comprehensive testing.

Certain antidiabetic botanicals function by increasing levels of insulin. This process is contraindicated in individuals with existing high insulin levels. Only if the pancreas fails to supply enough insulin should these herbals be used. The Therapeutic Section of this protocol denotes those herbals that work at the level of the beta cells, the insulin factories.

WHEN SHOULD A DIABETIC PATIENT START INSULIN THERAPY?
  • Glucose Sensor Implants
  • Return to Health
Insulin injections have been relegated to a therapy of last resort in patients with Type II diabetes. This was not always true. In the 1970s, insulin was regularly used to reduce blood glucose levels, sometimes by as much as 30-40 mg/dL. According to a report in JAMA, better glucose control resulted in fewer cardiovascular events occurring among insulin-dependent patients, but (unfortunately) insulin failed to impact the overall death rate (Knatterud et al. 1978).

According to Zachery Bloomgarden, M.D., insulin resulted in a 10-year mean HbA1c level of 7.1% compared with 7.9% in a group not treated with insulin. Hypoglycemia, however, occurred in 37% of patients on insulin, exceeding the 11% who experienced hypoglycemia on chlorpropamide (a first-generation sulfonylurea) and the 18% on glyburide (a second-generation sulfonylurea). Mean weight gain was 6.5 kg over 10 years among insulin users compared to 4.2 kg on chlorpropamide and 5.1 kg on glyburide (1 kg is equal to 2.2 pounds of body weight) (Bloomgarden 2001). Comment: Sulfonylurea drugs stimulate insulin secretion from islet cells; about 30% of patients fail treatment due to beta cell exhaustion.

Refractory hyperglycemia may require insulin therapy to control blood glucose levels, but until the individual has attempted lifestyle modification, insulin appears a poor first choice. Information appearing in the Washington Post (August 9, 2001, page A1) stated that nearly 60% of those who are poised to develop diabetes can avert the disease (and insulin therapy) through lifestyle modification.

Glucose Sensor Implants

Regular, home blood-glucose monitoring is at the core of diabetes control, determining the severity of the peaks and valleys and their duration. Checking blood sugar levels allows the patient to take appropriate actions if glucose is too high. Preventing chronic hyperglycemia warrants a more favorable outcome for the patient.

The patient may participate in a process called covering, that is, administering rapid-acting insulin (e.g., Lispro) to blunt the damage inflicted by long-term exposure to high glucose levels. When covering is not an option, having a glucose read-out allows the physician to adjust the insulin dosage accordingly. A study released by NIH in 1993 showed that tight glucose control could possibly avert 60% of all long-term complications arising from diabetes.

W. Blake Martin (Vanderbilt University) voiced the need for a type of glucose monitoring that employs user-friendly technology. A study conducted at the University of Wisconsin raises hope that glucose sensors may be the answer. Sensors, lasting from 3-5 months, were implanted under the skin of dogs made diabetic for experimentation. Seven days postimplant, the sensors were continuously monitoring, scrutinizing blood glucose levels during periods of glucose infusions and insulin injections. This type of subcutaneous glucose sensor appears to be promising as a continuous and painless long-term method for monitoring blood glucose. Sensors with top-layer materials that stimulate angiogenesis (blood vessel formation) at the sensor/tissue interface may have better measurement ranges and longer life than previously reported sensors (Updike et al. 2000).

Become a Participant in Your Return to Health

Some conditions are better managed with conventional medicine, and others have a better success rate using a natural approach. Type II diabetes appears to have an affinity for the natural, with remarkable gains reported. However, natural methods have little chance of succeeding without patient participation. This means the patient must refuse inappropriate foodstuffs, make time for exercise, and maintain weight within healthy standards. Diabetics should never blame themselves for their illness, but when the condition becomes manageable, the patient can justifiably claim much of the credit.

Results of the Finnish Diabetes Prevention Study (presented at the American Diabetes Association's 60th Annual Scientific Session in June 2000) illustrate the patient principle, i.e., the patient accepting much of the responsibility for the outcome of the disease process. The study showed that lifestyle modification (a structured dietary and exercise program) reduced the incidence of Type II diabetes by 58% in people at high risk for the disease.

The trial participants (522 prediabetic adults, 172 men and 350 women; average age 55 years) were divided into two groups and tracked over a 5-year period (1993-1998). Frequent dietary advice along with an individualized exercise program that included at least three supervised exercise sessions a week was assigned to the intervention group. The remainder of the individuals (acting as a control group) received nutritional tutorage at a yearly meeting and encouragement to upgrade their exercise regime. The weight reduction was about 4.2 kg at 1 year in the intervention group compared to 0.8 kg in the control group. Some backsliding occurred by the end of the second year in the intervention group, resulting in a 3.5-kg overall net weight loss; the control group's weight loss remained constant at 0.8 kg the second year.

At 1 year, the intervention group showed significantly greater reductions in 2-hour glucose, fasting, and insulin levels, as well as blood pressure and serum triglyceride levels. Most of the beneficial changes in cardiovascular risk factors were sustained for 2 years. The researchers concluded that Type II diabetes is preventable in high risk patients by lifestyle modification (Uusitupa et al. 2000; Tuomilehto et al. 2001).

Self-improvement programs, when faithfully approached, are more rewarding than easy. However, behavioral modification has proved successful in helping more people lose weight than any other kind of weight-loss program. Successful attempts at lifestyle modification should include family members and friends. Recall the number of social gatherings planned around carbohydrates. Sugary treats are foods for celebrating, partying, and showing affection. Finding alternatives to sugar is as possible as it is profitable, and the health dividends far more gratifying.

Continued . . .


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