24 Review Article Volume 25, Number 1, 2010 JOM Dietary Modulation of Insulin and Glucose in Prediabetes Author: Jack Challem Post O!ce Box 30246, Tucson AZ 85751 USA www.jackchallem.com Abstract Prediabetes is usually intertwined with overweight, and both conditions presage type 2 diabetes, coronary artery disease, and many other common diseases. Early signs of prediabetes include abdominal adiposity, mood swings, sugar and carbohydrate cravings, and feeling tired or mentally fuzzy after eating. Standard measures of glucose intolerance, such as fasting glucose, may reveal a “false normal” when a person is actually prediabetic. Combined with tests for glucose, fasting insulin becomes a powerful predictor of type 2 diabetes and sequelae 10 to 15 years before glucose becomes elevated. Such an early warning provides a window to implement dietary changes to restore nor- mal glucose tolerance. Adopting a Paleolithic-style diet that emphasizes fresh, low-fat animal pro- teins and high-fiber vegetables can usually reverse prediabetes. Furthermore, dietary supplements can enhance insulin sensitivity and/or glucose control. !ese supplements include alpha-lipoic acid, chromium, biotin, silymarin, vitamin D3 combined with calcium, and vitamin K. Prediabetes is an opportunity to improve health, and it is wise to seize this opportunity. Not doing so will eventually lead to type 2 diabetes, which is far more difficult to reverse and almost always requires some form of pharmaceutical intervention. Introduction year, one million Americans graduate from Prediabetes, not influenza, is the true prediabetes to type 2 diabetes. Similar trends pandemic. It is intertwined with overweight, are occurring in Canada.1 and both conditions presage type 2 diabetes Depending on the diagnostic test used, mellitus and many other health problems. In prediabetes may be referred to as impaired fact, prediabetes (glucose intolerance) could fasting glucose, impaired glucose tolerance, be considered “ground zero” in many of to- insulin resistance, hyperinsulinemia, meta- day’s chronic health problems. bolic syndrome, syndrome X, and hypoglyce- Overweight and obesity are the most mia. Each of these diagnoses points to a del- common preludes to type 2 diabetes, and eterious metabolic response to carbohydrates, the statistics are nothing less than alarm- particularly refined sugars and starches. ing. In the United States, three-fourths of One might argue that a diagnosis of pre- American adults are currently overweight diabetes medicalizes an illness that does not or obese. Half of those are obese, and one yet exist, much the way some physicians have in every 20 adults is morbidly obese. One- argued in favor of treating prehypertension third of children are also overweight and or moderately elevated cholesterol. Howev- obese. Meanwhile, 24 million Americans er, disease processes are not black and white, have type 2 diabetes, and an estimated 100 with patients being healthy one day and sick million have some form of prediabetes. Each the next. Rather, prediabetes is part of the Challem (5).indd 24 3/16/10 2:30:51 PM Dietary Modulation of Insulin and Glucose in Prediabetes 25 progression from healthy to sick, and early inflammatory diseases, hypercoagulation, treatment (not merely the masking of symp- premenstrual syndrome, early puberty, poly- toms) is far more likely to achieve a complete cystic ovary syndrome, sleep apnea, erectile reversal compared with later treatment. dysfunction, food cravings, anxiety, depres- sion, mood swings, cognitive impairment, The Health Consequences of Predia- and many other health problems.5 betes Recent studies have provided a clearer Which occurs first–prediabetes or over- picture of how prediabetes affects cognitive weight? Or is the question a chicken-or-egg function. Insulin resistance can occur in the conundrum? brain, not just in muscle tissue.6 In addition, Although hyperinsulinemia exists in elevated glucose levels have been shown to one-fourth of thin people,2 a recent clini- slow thinking processes and to increase the cal trial suggests that gaining a very modest number of errors on tests.7 Elevated glucose amount of weight initiates metabolic chang- levels inhibit production of orexins, a family es that lead to prediabetes.3 In the trial, re- of peptides involved in alertness.8 Decreased searchers asked 10 healthy, thin men in their activity of orexins may partly explain post- twenties to increase their food consumption prandial tiredness, another sign suggestive of by 300 to 500 calories daily for four and one- hyperglycemia and prediabetes. half months. !e objective was to track the Some of the other early signs of pre- metabolic consequences of a modest two- diabetes include abdominal adiposity, mood point increase in body mass, approximately swings, and sugar and carbohydrate cravings. 10 pound in weight. With the increased Skipping breakfast (or consuming a high- weight, the men did not secrete more insulin sugar or high-starch breakfast) and eating compared with baseline levels, but they did large, late dinners are also commonly associ- lose their ability to remove insulin from the ated with prediabetes. blood, one of the signs of insulin resistance. Because insulin is lipogenic, the inability The Importance of Measuring Insulin to clear the hormone from the blood likely Levels promotes further weight gain and an exacer- Although health-care practitioners tend to bation of insulin resistance. use glucose (fasting glucose, glucose-tolerance One of the current determinations of test, or hemoglobin A1c;HbA1c) to diagnose prediabetes–having a fasting glucose be- prediabetes and type 2 diabetes, the addition tween 100 to 125 mg/dL–ignores the risks of a fasting insulin test can provide a clearer– associated with relatively small increases in and earlier picture–of prediabetes. Combined the normal range of blood sugar. For exam- with tests for glucose, fasting insulin becomes ple, men with a fasting glucose of 87 mg/dl a powerful predictor of type 2 diabetes. Hy- are far more likely to develop type 2 diabetes, perinsulinemia may exist 10 to 15 years before compared with men who have a fasting glu- glucose levels become elevated and physicians cose of 81 mg/dL.4 In other words, a moder- diagnose type 2 diabetes.9 Such an early warn- ately high-normal glucose is a risk factor for ing provides a window to implement dietary type 2 diabetes. changes to restore normal glucose tolerance. Furthermore, prediabetes is strongly as- !ere are many health consequences of sociated with more than just an increased hyperinsulinemia (as opposed to hyperglyce- risk of type 2 diabetes. !e intertwining of mia per se). In addition to being indicative of prediabetes, type 2 diabetes, overweight, and insulin resistance, hyperinsulinemia can: obesity are also associated with an increased risk of coronary artery disease, cancer, Al- Trigger reactive hypoglycemia zheimer’s disease, serious eye diseases, kid- Promote abdominal obesity ney disorders, sleep problems, gynecomastia Increase activity of 3-hydroxy-3-methylgl- in men, elevated blood lipids, hypertension, utaryl coenzyme A activity Challem (5).indd 25 3/16/10 2:30:51 PM 26 Journal of Orthomolecular Medicine Vol 25, No. 1, 2010 Elevate triglycerides and low high-density (HOMA-IR) calculator. !e HOMA-IR lipoprotein calculator is simple to use and can be down- Increase sodium retention and magnesium loaded without cost from www.dtu.ox.ac.uk/ depletion index.php. Simply input a patient’s fasting Increase arachidonic acid production glucose (in mg/dl or mmol/l) and insulin (in Increase production of interleukin-6 mc/dl or pmol/l) into the HOMA-IR calcu- Contribute to polycystic ovary syndrome lator. !e results of the HOMA-IR calcula- Promote aromatase activity tor correlate closely with those of the eug- Increase the risk of breast and other cancers, lycemic clamp, which is difficult to use in a Increase the risk of gastric reflux clinical (nonresearch) setting. As a generally rule, a HOMA-IR of 3.5 or less is consid- !e measurement of fasting (or post- ered good, and a HOMA-IR of 1.0 if con- prandial) insulin is not a new or novel con- sidered normal for a 35-year-old male. !e cept. !e first research to identify the role lower the number, the more insulin sensitive of hyperinsulinemia in prediabetes (which a patient is; the higher the number, the more was also termed “occult diabetes” and “dia- insulin resistant. betes mellitus in situ”) was published in 1975.10 Like so many studies in nutritional Dietary Causes of Prediabetes medicine, this one has been largely lost to Prediabetes (including overweight) is the dusty pre-internet shelves of medical li- a nutritional disease, and in most cases it braries. In this seminal study, Dr. Joseph R. is best treated nutritionally. !e diagnosis Kraft described patterns of glucose and in- can be frightening for many people, but sulin in 3,650 men and women and noted the negative impact can be balanced with that many subjects had normal glucose levels a positive—that prediabetes is an opportu- but abnormally elevated insulin levels. He nity to improve one’s health. !e nutritional proposed that prediabetes existed in subjects causes have been described in many articles whose fasting insulin levels was 13 mcIU/ml and books, and they include the consump- or higher–a level fairly consistent with the tion of too many calories, too many refined views of many contemporary orthomolecu- sugars and sugarlike carbohydrates (mostly lar physicians. from grains), too many trans fats, and too By measuring fasting insulin, clinicians many “junk” cooking oils, such as soybean can reduce the risk of obtaining a “false nor- and corn oils. Genetics appears to play only a mal” from measuring only fasting glucose, minor role in the risk of prediabetes and type postprandial glucose, or HbA1c. For ex- 2 diabetes, although epigenetics may play a ample, an apparently normal fasting glucose greater role in children and in the multigen- of 87 mg/dl combined with a fasting insu- erational risk of these diseases.