Life Extension Magazine July 2013
As We See It
Blood Levels of Insulin and Hemoglobin A1c in Foundation Members
By William Faloon
Life Extension® has an advantage in identifying modern causes of premature aging and death. That’s because we have direct access to tens of thousands of our members’ blood test results.
Our review of this real-world data enables us to uncover disease risk factors that are overlooked by the mainstream media. We then alert members about simple steps they can take to mitigate these hazards.
Earlier this year, we analyzed fasting insulin and hemoglobin A1c blood levels in over 10,000 members. A startling 66% had higher than desired fasting insulin. Twenty-two percent had hemoglobin A1c levels that placed them in a pre-diabetic state.
Hemoglobin A1c measures the percentage of glycated hemoglobin in one’s blood. Hemoglobin A1c levels should be below 5.6%,1 yet more than one in five people we tested had a reading over 6%.
Gaining early access to this kind of data can spare aging humans the ravages of degenerative illness. Armed with this knowledge, Foundation members can slash their risk of cancer, vascular occlusion, and other complications before frank diabetes is diagnosed.
This article will describe the dangers of elevated fasting insulin and hemoglobin A1c, our recent analysis of member blood tests, and a novel way to protect against glycemic overload.
What Is Insulin Supposed to Do?
Insulin is a hormone that regulates carbohydrate and fat metabolism.2 Insulin enables liver and muscle cells to take up blood sugar (glucose) for energy production or storage.2 Insulin also facilitates the packing of glucose into fat cells as triglycerides.2
A burst of insulin is released in response to food ingestion. Once glucose has been safely shuttled into energy producing cells or stored, insulin levels should drop below 5 µIU/mL.3 Only a tiny amount of residual insulin should be needed to maintain glucose homeostasis.
When fasting insulin is over 5 µIU/mL, this indicates a metabolic problem such as pre-diabetes, which sharply increases risk for degenerative diseases.3 Some medical texts state that insulin should virtually vanish from the blood once glucose levels reach 83 mg/dL.4
In people suffering from metabolic disorders and/or obesity, insulin levels remain stubbornly high. This not only generates damaging reactions throughout the body, but precludes weight loss as glucose is forced into fat cell storage.
Life Extension’s analysis of over 10,000 fasting insulin blood test results showed that 66% were over 5 µIU/mL. Many of these subjects were overweight, which partially explains why such a high percentage had high fasting insulin levels. Insulin control is an important component for successful weight loss.
The Dark Side of Insulin
Those afflicted with type I diabetes do not produce enough insulin. For these individuals, insulin injections become a lifesaving therapy.
Insulin, however, has an insidious dark side. High levels are associated with virtually every aging-related disease, thus making insulin control essential if one is to achieve optimal longevity.
Aging, poor diet, and other factors deprive cells of insulin sensitivity.5-7 Loss of insulin sensitivity contributes to excess insulin release as the body seeks to force serum glucose into cells.
The most immediate and noticeable effect of excess insulin production is unwanted weight gain.8-10 Insulin drives fat into cells, prevents fat from being released from cells, and can result in chronic hunger.11,12 High insulin levels contribute not only to obesity, but also to the disease states associated with being overweight.
Some degenerative disorders associated with too much insulin include heart attack13-16 and cancer.17-19
Insulin saves the lives of type I diabetics who are dependent on it, but becomes a toxic hormone in aging people who secrete too much. Reducing excess serum insulin is a critical component of any scientific program designed to facilitate fat loss and extend life span.
Insulin is produced in the pancreas to stimulate uptake of glucose from blood into the body’s cells. The inability of the body’s cells to utilize insulin is called insulin resistance.
As a result of insulin resistance and other factors, the pancreas produces more insulin than normal so there are higher levels of insulin circulating in the bloodstream. This is called hyperinsulinemia.
In a normal person, one unit of insulin might be needed to help 10 mg of glucose go into a cell group. In hyperinsulinemia, ten units of insulin might be needed to get the same 10 mg of glucose into the cell group.20 Hyperinsulinemia and insulin resistance create myriad problems, including elevated triglycerides,21-24 low HDL,25,26 type II diabetes,27-29 and obesity.14,30-32
Figure 1 on this page shows the pathways to obesity and several degenerative diseases associated with insulin resistance and hyperinsulinemia.
Insulin and Age-Related Disease
An enormous volume of peer-reviewed published studies reveal that excess serum insulin (hyperinsulinemia) is a major health problem. Regrettably, this danger still is not recognized by the medical mainstream.
High serum insulin promotes hypertension by impairing sodium balance.33,34 Too much insulin harms the kidneys.35 The vascular system is severely damaged by prolonged exposure to excess insulin.36,37
By acting as a catalyst in promoting cell growth, excess insulin increases the risk and progression of certain cancers.17,19,38-40 High insulin promotes the formation of beta-amyloid in brain cells and may contribute to the development of Alzheimer’s disease.41 Overproduction of insulin is even a contributory factor to prostate enlargement because of its effects in promoting the overgrowth of prostate cells.42
High serum insulin is associated with the development of abdominal obesity, which exacerbates the many problems induced by insulin resistance and increased belly fat, including atherosclerosis 14,43-45 and impotence.46-50 Obesity is associated with excess insulin and reduced insulin sensitivity, both risk factors for type II diabetes.51
Perhaps the simplest way to evaluate the toxic effects of excess insulin is by examining its effects on human mortality. One study showed that over a 10-year period, the risk of dying was almost twice as great for those with the highest levels of insulin compared to those with the lowest.52 The study authors stated that hyperinsulinemia is associated with increased all-cause and cardiovascular mortality independent of other risk factors.
Why Aging People Gain Weight
A review of the published literature indicates that a significant percentage of degenerative diseases are attributed to excess body fat. Those who are overweight face a significant risk of developing type II diabetes.53-55 The treatments for obesity and type II diabetes are interrelated. By effectively treating either one of these diseases, doctors can mitigate or control the other.
Poor diet, obesity, and aging result in excessive secretion of insulin.5-7 Suppressing the overproduction of insulin is a crucial component of a medically supervised weight-loss program.
A noticeable effect of surplus serum insulin can be constant hunger that results in a vicious cycle in which overeating causes more body fat to accumulate, which in turn causes even greater amounts of unwanted insulin to be secreted from the pancreas.12,56 We now know that hyperinsulinemia predicts diabetes mellitus.51 Even in children, serum insulin levels are far higher in obese than in non-obese children of the same age.57
The effects of consuming high-glycemic foods and the subsequent hyperinsulinemia, hunger, and weight gain that occur were the subject of an article published in the Journal of the American Medical Association titled “The Glycemic Index.”58 The article’s authors summarized their position as follows:
“It is possible that the hunger incident to hyperinsulinemia may be a cause of overeating, and therefore, the obesity that so often precedes diabetes.”58
Dangerous After-Meal Sugar Levels
The excess elevation of blood sugar after eating wreaks havoc in the body via multiple pathological mechanisms. Elevations in postprandial (after-meal) blood sugar, along with the accompanying insulin surge, are major contributors to the development of diabetic and age-related disorders such as heart disease, as well as diseases of the microvasculature (small blood vessels within the eyes, kidneys, and those supplying the nerves).59-67
People who have normal fasting glucose levels but whose average after-meal glucose level exceeds 194 mg/dL are three times more likely to suffer diabetic retino-pathy than those who do not.68
Growing evidence indicates that severe spikes in after-meal blood sugar are a major problem for non-diabetics as well.59,69 The two primary mechanisms by which post-meal hyperglycemia causes such problems are formation of advanced glycation end products (the binding of glucose to body proteins) and increased production of free radicals that lead to arterial wall damage.70,71
To investigate the relationship between glucose metabolism and the severity of heart disease, one study measured how many coronary arteries were blocked in relation to after-meal glucose/insulin blood levels and other atherogenic risk factors. All of the men participating in the study had normal fasting glucose blood readings, but in response to a glucose challenge, demonstrated significantly different rates of glucose-insulin spikes. Men with the highest levels of post-load glucose, insulin, and other measurements of glycemic imbalance had the greatest number of blocked coronary arteries.72
These studies make it abundantly clear that blunting the after-meal increase in blood sugar and insulin is an important goal for those seeking optimal longevity.
Fasting Insulin Blood Levels in Life Extension Members
Since 1996, members of the Life Extension Foundation® have been able request their own blood tests. This has resulted in a significant increase for unique tests that are not routinely ordered by physicians. One of these tests is for fasting insulin. Since it was added to the Male and Female Weight Loss Panels several years ago, the number of fasting insulin tests has surged.
In the most recent analysis, data was collected from January 2010 to February 2013, a period spanning more than three years. More than 10,000 tests of fasting insulin were reviewed.
An upper limit for fasting insulin of 5 µIU/mL (micro international unit per milliliter) was established for this analysis.3 Only 34% of these blood tests had a fasting insulin level of 5 µIU/mL or lower. A startling 66% showed fasting insulin over 5 µIU/mL, with some in dangerously high ranges of 10-30 µIU/mL.
There is an important confounding factor in this analysis that skewed the results upwards. Most of the people who ordered their fasting insulin blood test did so as part of the Male or Female Weight Loss Panel. Since insulin levels are higher in overweight and obese individuals, it is logical to assume that many of the 66% whose fasting insulin was over 5 µIU/mL also were overweight or obese. Thinner people tend to have lower fasting insulin levels.
Latest Studies on Dangers of Excess Insulin
From 1999 to 2005, Life Extension spent millions of dollars evaluating published studies on the mechanisms and dangers of excess fasting insulin and conducting our own clinical trials on a compound that suppressed pancreatic release of surplus insulin.
We were never able to synthesize sufficient quantities of our insulin-suppressing compound, but another research team has developed an approach to reduce glucose/insulin levels that may revolutionize the way glycemic control disorders are treated.
Just to make sure we were still on the right track, we went back and looked at the peer-reviewed published literature to confirm the deadly effects of hyperinsulinemia.
Liver Diseases Caused by Hyperinsulinemia
As a greater percentage of the public becomes overweight or obese, an illness called non-alcoholic fatty liver disease is becoming prevalent. It is characterized by infiltration of fat into the liver that impairs normal functions.
In 2013, two studies identified hyperinsulinemia as a major causative factor of non-alcoholic fatty liver disease, with fasting insulin being significantly elevated compared to controls.73,74 Two studies published in 2012 also connected hyperinsulinemia with this liver disease.75,76
A 2013 study looked at patients affected with primary liver cancer and found a high prevalence of liver cancer in type II diabetics. Researchers noticed that liver cancer developed in these patients within the first five years after diagnosis of type II diabetes, which is when insulin levels are extremely high.77
Hyperinsulinemia in College Students
A 2012 study looked at college students and found 8 out of 22 subjects were hyperinsulinemic with fasting insulin levels greater than 19 µIU/mL.78
The study concluded by stating that the high prevalence of hyperinsulinemia in this population merits further investigation and intervention.78
Studies of older people often show these high insulin readings, but this study reveals damaging processes occurring early in life. Remember that any fasting insulin reading above 5 µIU/mL is cause for concern and many of these college students were already almost four times as high!
Kidney Failure Linked to Hyperinsulinemia
In the US, a startling 40% of people over age 65 show some sign of kidney failure.79 Between 1980 and 2009, the prevalence of end stage renal disease increased nearly 600%.80
A 2012 study found a strong correlation between hyperinsulinemia and chronic kidney disease in metabolic syndrome patients. Insulin resistance was shown to be an independent risk factor for kidney disease in this patient group.81
High Insulin Initiates Cancer
People with hyperinsulinemia suffer higher rates of deadly malignancies.
A 2013 study showed over a ten-year period that type II diabetics treated with any kind of insulin-augmenting drug had an up to 80% increased risk of experiencing cancer, an adverse cardiac event, or death from any cause compared to patients who only received the drug metformin, which lowers insulin levels.82 Metformin reduces risk of many cancers,83-91 and some of its mechanisms include reducing hepatic production of glucose92-94 and improving insulin sensitivity,95-100 both of which reduce insulin levels.
A drug class known as sulfonylureas stimulates pancreatic insulin secretion and temporarily reduces glucose. After the pancreas fails, these patients often resort to insulin injections to keep glucose under control. By giving type II diabetics insulin-augmenting therapies instead of lifestyle changes, nutrients, and metformin, doctors have unwittingly condemned huge segments of their patient population to higher risks of weight gain, neuropathy, renal failure, atherosclerosis, and cancer.101-109
Not every diabetic patient needs insulin-augmenting drugs. Some people can produce all the surplus insulin they need in their pancreas to keep glucose down. Their chronic hyperinsulinemic condition, however, predisposes them to greater cancer incidences as insulin provides a strong signal for malignant cells to proliferate.17 One study found that individuals with the highest insulin levels had a 62% increased risk of cancer mortality.110
Hyperinsulinemic individuals, including type II diabetics and the obese, suffer far greater rates of cancer. Hyperinsulinemia creates chronic inflammation and the generation of free radicals, both of which damage DNA genes needed to regulate healthy cellular proliferation.16,19,38,111,112
A number of studies published in 2012-2013 describe the mechanisms by which hyperinsulinemia increases cancer risk and suggests that understanding and circumventing these pathways may lead to targeted prevention.113-125
Controlling Hyperinsulinemia Critical for Cancer Patients
Once a person is diagnosed with cancer, it becomes imperative to suppress excess insulin secretion. That’s because in addition to initiating cancer, insulin stimulates the proliferation of malignant cells.126
A 2013 review evaluated the scientific literature on the role of hyperinsulinemia in promoting existing cancers. It summarized by stating that the death rate of pancreatic and other cancers can be reduced by an aggressive approach to reversing obesity and hyperinsulinemia and achieving good glycemic control.113
When we consult with oncologists about comprehensive cancer treatments, a central element is for the patient to make significant lifestyle changes and be prescribed the drug metformin to reduce levels of tumor-promoting insulin.
Role in Alzheimer’s Disease
Alzheimer’s disease is the fastest growing threat to health in the United States, according to a report released in 2013 from a team of researchers at the University of Washington in Seattle.127
We know of multiple underlying causes for Alzheimer’s, including mitochondrial dysfunction, oxidative stress, and chronic inflammation.128-135 A study published in 2012 described how insulin is involved in the metabolism of beta-amyloid and concluded that insulin resistance is involved in the pathogenesis of neurodegenerative diseases including Alzheimer’s.136
Other studies published in 2012-2013 describe the toxic effects of hyperinsulinemia in the development of neurodegenerative diseases that result in senility.137-141
Mainstream Medicine’s Lethal Misconception
We don’t blame doctors who desperately sought out therapies to lower surging glucose levels in their diabetic patients. They often had no choice but to administer insulin-augmenting drugs, which temporarily dropped their patient’s glucose to survivable ranges.
A side effect quickly observed was weight gain in those using insulin-augmentation to control blood glucose. As these patients gained weight, they became more insulin-resistant and had to rely on greater quantities of insulin-augmented drugs. Many of these drug labels started carrying warnings of increased risk of heart attack and early death.
Research initiated by Life Extension in 1999 relating to the toxic role of excess insulin in virtually every age-related disease has since been corroborated by numerous independent studies. Hyperinsulinemia is a killer worse than cholesterol, since high insulin levels not only increase vascular risk,36,37,141 but also cancer,17-19,126,142 liver and kidney disease,143-147 neurodegeneration,148,149 and obesity.8,30-32
The scientific literature is unanimous in recognizing the lethal impact of hyperinsulinemia. An analysis of blood test results from Life Extension members reveals that 66% have higher than desired fasting insulin levels (above 5 µIU/mL). Virtually all of these members should be asking their doctors to prescribe metformin, as this drug reduces glucose and insulin blood levels via multiple mechanisms including curbing excessive glucose production (gluconeogenesis) in liver.93
Twenty-two percent of our members had hemoglobin A1c levels over 6%, which places them in a pre-diabetic state. Clearly more has to be done to gain control of these glycemic measurements of future disease risks.
Breakthrough in Preventing Dietary Starches from Converting to Glucose
The modern American diet contains excessive amounts of starches.
What most people don’t realize is that starches are broken down in the intestines and produce rapid elevation of after-meal glucose and insulin blood levels. Even people with “normal” fasting blood sugar levels are at increased cardiovascular risk if their after-meal glucose/insulin levels rise too high, too fast.150,151
A natural enzyme has been discovered that helps reduce after-meal blood sugar and insulin spikes in a totally unique way.152 This enzyme converts rapidly digestible starch in the intestines into a fiber that is not as readily absorbed as glucose.153,154
Based on the evidence you will read in this month’s issue, widespread use of this enzyme before starch-containing meals could help reduce the epidemic of glucose intolerance and hyperinsulinemia that is plaguing the modern world.
For longer life,