Atherosclerosis and cardiovascular disease WHILE TYPE 2 diabetes is associated with numerous complications, including nerve, kidney, and eye damage, the morbidity and mortality associated with cardiovascular diseases is the most important.21 Simply put, most diabetic patients die of cardiovascular disease. As early as
1949, animal studies demonstrated that insulin treatment causes early atherosclerosis, also called hardening of the arteries, which is a precursor to heart attacks, strokes, and peripheral vascular disease.
Insulin facilitates every single step along the inflammatory pathway that marks the progression of the disease, including initiation, inflammation, foam cell (fat-laden cell) formation, fibrous plaque formation, and advanced lesions.22 Moreover, fibrous plaque contains insulin receptors,23 and insulin stimulates the growth of plaque, which accelerates the atherosclerosis and substantially raises the risk of cardiovascular disease.
Experimentally, these same studies showed that preventing the excessive insulin could reverse the condition.24 If you are not on diabetes medications, the risk of heart disease increases with the degree of hyperglycemia.25 Insulin lowers blood glucose, so it has always been assumed it would protect against disease.
But that is only true if glucotoxicity causes the heart disease, which it does not.
What has not generally been appreciated is that, if you are not on diabetes medications, the degree of hyperglycemia reflects the severity of diabetes.
Trading insulin toxicity for glucotoxicity is not obviously beneficial.
The UK General Practice Database identified more than 84,000 newly diagnosed diabetics between 2000 and 2010.26 Treatment with insulin did not lower heart disease risk; rather, it more than doubled the risk of death.
The same held true for heart attacks, strokes, cancer, and kidney disease.
Insulin could reduce blood glucose but not heart disease or death.27 Patients with an A1C blood glucose level of 6.0 percent, which was considered excellent control, fared just as poorly as those patients with an A1C of 10.5 percent, which is considered uncontrolled diabetes.28 Ultimately, heavy-handed use of insulin could reduce glucotoxicity, but only at the expense of insulin toxicity.
As in type 1 diabetes, high insulin doses were not good; they were bad.
Figure 10.2.
Insulin use and increased risk of mortality in type 2 diabetes29
These results were not new.
Reviews of large population databases, such as the 1996 Quebec Cardiovascular Study, established hyperinsulinemia as a prime risk factor for heart disease.30 In Saskatchewan, Canada, a review of more than twelve thousand newly diagnosed diabetic patients found a “significant and graded association between mortality risk and insulin exposure level.”31 It wasn’t a trivial effect, either.
The high-insulin group had a 279 percent higher risk of death compared to those that did not use insulin.
Treating type 2 diabetes with insulin was not good; it was bad.
Simply put, the higher the insulin dose, the higher the risk of dying.
Moreover, the longer the treatment time with insulin, the greater the risk of cardiovascular disease.32 A 2011 study showed that both low and high blood glucose carried excess risk of death, again reflecting the dual toxicities of glucose and insulin.
Once again, insulin use was associated with a mind-boggling 265 percent increased risk of death.33 A Cardiff University review of almost 10 percent of the U.K. population from 2004 to 2015 found that lower A1C was associated with elevated mortality risk, driven mainly by a 53 percent increased risk with the use of insulin.34 In this study, no other medication increased the risk of death.
A Dutch database associated high daily insulin doses with three times the cardiovascular risk.35 In heart failure patients, insulin use is associated with more than four times the risk of death.36
Excessive insulin is toxic, particularly in a setting of type 2 diabetes, where baseline insulin is already very high. Giving more insulin will lower the blood glucose, but worsen the underlying hyperinsulinemia. Trading insulin toxicity for glucotoxicity is not beneficial.
Cancer DIABETES, AS WELL as obesity and prediabetes, increases the risk of many different types of cancer, including breast, colon, endometrial, kidney, and bladder cancers.37 This suggests that factors other than increased blood glucose play a major role in the development of cancers, further disproving the glucotoxicity paradigm as the major cause of disease.38 Insulin, a hormone well known to promote growth, can drive tumor growth, and women with the highest insulin levels carry a 2.4-fold higher risk of breast cancer.39 Obesity may be a contributing factor, but hyperinsulinemia is associated with an increased risk of cancer, independent of weight.
Lean and overweight women, when matched for insulin level, exhibit the same risk of breast cancer.
The intimate link between insulin and cancer is reinforced by the discovery of a single mutation in the PTEN oncogene that significantly increases the risk of cancer.40 What’s the connection?
This mutation increases the insulin effect.
It lowers the blood glucose and reduces the risk of diabetes, but increases the risk of obesity and cancer.
Similarly, medications that raise insulin toxicity are associated with higher rates of cancer.
Insulin use increases the risk of colon cancer by approximately 20 percent per year of therapy.41 The UK General Practice Database revealed that insulin increased the risk of cancer by 42 percent compared with a glucose-lowering drug that did not raise insulin.42 And a review of the newly diagnosed diabetics in the Saskatchewan population disclosed that use of insulin raised the risk of cancer by 90 percent.43 It’s simple to understand why high insulin levels should favor cancer cell growth.
First, insulin is a known hormonal growth factor.
Second, cancer cells are highly metabolically active and need large supplies of glucose to proliferate.
Insulin increases the risk of cancer, and once cancer has been established, high blood glucose enables it to grow faster.
ORAL HYPOGLYCEMICS: NOT THE ANSWER
AS OF 2012, more than 50 percent of the American population has diabetes or prediabetes.1 This stunning statistic means more people in the United States have prediabetes or diabetes than not.
It’s the new normal.
It’s also made selling insulin and insulin-like drugs the money-making opportunity of a lifetime, which may explain why it continues to be prescribed for prediabetics and type 2 diabetics when it doesn’t make sense.
In 2008, a joint statement released by the American College of Endocrinology and the American Association of Clinical Endocrinologists encouraged physicians to consider drug treatment of prediabetic patients despite the fact that no drug had yet been approved by the U.S.
Food and Drug Administration.2 In 2010, the definition of type 2 diabetes was broadened, ostensibly to help with early diagnosis and treatment.
It is perhaps no coincidence that nine of the fourteen outside experts on the panel that made this recommendation worked in various capacities with the giant pharmaceutical companies that made diabetes medications and stood directly in the path of an unending torrent of money.
In the lead-up to this decision, individual members received millions of dollars and the American Diabetes Association itself reaped more than $7 million in 2004 alone from its pharmaceutical “partners.”3
When Dr.
Banting discovered insulin in 1921, he licenced the drug to pharmaceutical companies without a patent because he fervently believed this life-saving miracle should be made available to everybody who needed it.
Yet, insulin, now available in many different formulations , is estimated to have cost the U.S. health care system $6 billion in 2012,4 driven in part by steep price increases.
Between 2010 and 2015, these newer insulins increased in price from 168 to 325 percent.
In 2013, Lantus, a long-acting form of insulin, earned $7.6 billion, making it the world’s bestselling diabetes drug.
Various other insulins took another six of the top ten spots on that list.
Between 2004 and 2013, no less than thirty new diabetes drugs came to market.
Despite several setbacks, by 2015 sales of diabetes drugs had reached $23 billion, which is more than the combined revenue of the National Football League, Major League Baseball, and the National Basketball Association.5
Figure 11.1. Increasing variety of diabetic medications6
The focus of treatment of type 2 diabetes has always been to lower blood glucose because it is associated with better health outcomes. Every 1 percent increase in the hemoglobin A1C is associated with an 18 percent increase in risk of cardiovascular events, 12 to 14 percent increase in the risk of death, and 37 percent increase in risk of eye
disease or kidney disease.7 But correlation is not causation.
Lowering blood glucose with medications, as opposed to diet and lifestyle, is not necessarily beneficial.
Consider two type 2 diabetic patients with an identical A1C of 6.5 percent.
One takes no medications and the other uses 200 units of insulin daily.
These might seem like identical situations, but they’re not.
The first situation reflects mild diabetes while the other reflects severe diabetes.
The use of insulin does not change severe type 2 diabetes into mild type 2 diabetes.
The cardiovascular risks are completely different.
Indeed, insulin may not have any benefits at all.
No evidence exists that these newer insulins are any more effective than the original.
Indeed, health outcomes for type 2 diabetes have only worsened even as these newer insulins have become more widely prescribed.
And exogenous insulin injections are no longer just for type 1 diabetes.
Almost one-third of diabetics in the United States currently use some form of insulin.8 This statistic is slightly horrifying, considering that 90 to 95 percent of diabetes in the United States is type 2, for which the benefits of insulin are highly questionable.
In fact, other medications are available for type 2 diabetes.
Several classes of drugs are or have been available through the years, and are still being prescribed to a bigger and bigger group of patients.
Despite their popularity among doctors, these blood glucose, lowering pills, oral hypoglycemics in medicalspeak, are not long-term solutions to diabetes, either.
I divide these medications into three categories based upon their effect on insulin and thus body weight.
In general, the more they raise insulin levels, the more they cause weight gain and many of the complications associated with diabetes.