Chapter 8
Avoiding Diabetes and Related Conditions
In This Chapter
Linking vitamin D and diabetes
Preventing and treating diabetes with enough vitamin D
Finding a role in metabolic syndrome and polycystic ovary syndrome
Diabetes, especially the form called type 2 diabetes, is spreading throughout the United States and the world at an epidemic pace. By 2010, 26 million Americans were affected. By 2007, 17.4 million American were affected. The percent of the population with diabetes rose from 2.5 to 8.6. Most of this increase can be attributed to increasing rates of obesity and a sedentary lifestyle, but deficiency of vitamin D may be playing a role, too.
In this chapter, I explain what diabetes is and how vitamin D may contribute to its prevention and treatment. I also take a look at how vitamin D relates to conditions that are related to diabetes: metabolic syndrome and polycystic ovarian syndrome.
The Basics of Diabetes
Diabetes is a condition in which the body fails to regulate blood sugar (glucose) levels. It comes in two major forms: type 1 and type 2 diabetes mellitus. In type 1 diabetes, the body is unable to make insulin. In type 2 diabetes, the body doesn’t respond to insulin as well as normal and tries to make more to compensate. Insulin is a hormone that regulates the blood sugar levels and helps the body use sugar and other carbohydrates for energy.
The two forms of diabetes are actually very different diseases, based on the way they occur, their likelihood of being passed down in a family, their treatments, and the severity of their complications. They’re so different that some people, especially people with type 1 diabetes, have advocated assigning a different name to the disease, so far to no avail.
In the following sections, I tell you what the two types of diabetes have in common and then explain each type in more detail. For a much more in-depth discussion, see my books Diabetes For Dummies and Type 1 Diabetes For Dummies (Wiley).
Identifying the symptoms of diabetes
Type 1 and type 2 diabetes share several common signs and symptoms when the blood sugar is far out of control:
Fatigue
Frequent urination
Increase in hunger
Increase in thirst
Unless these symptoms are severe, nothing special calls attention to them — you might attribute frequent thirst to living in a warm climate, for example. Both kinds of diabetes thus are often missed until they reach a fairly severe level. For most people diabetes is silent until the blood sugar levels are very high, but in the meantime those high levels are causing damage to the heart, eyes, kidneys, and other organs.
Making a diagnosis
A diabetes diagnosis is based on the level of the sugar glucose in your blood. Many types of sugar exist in the body, but the main one your body uses for energy is glucose. The diagnosis involves the following measures:
A casual blood glucose of 200 milligrams per deciliter (mg/dl) (11.1 mmol/L) or more at any time of day or night. This type of reading is taken from blood collected at any time of the day with no regard for when you last had a meal. It’s used along with symptoms such as fatigue, frequent urination and thirst, slow healing of skin, urinary infections, and vaginal itching in women. Normal casual blood glucose levels are between 70 and 139 mg/dl (3.9 to 7.7 mmol/L).
A fasting blood glucose of 126 mg/dl (7 mmol/L) or more. This type of reading is taken from blood collected only when a person has not eaten for at least eight hours. A normal fasting blood glucose is less than 100 mg/dl (5.6 mmol/L).
A blood glucose of 200 mg/dl (11.1 mmol/L) or greater two hours after consuming 75 grams of glucose.
A hemoglobin A1c value of 6.5 percent or greater. Hemoglobin A1c is a portion of the oxygen-carrying protein hemoglobin which has been altered by having glucose bound to it. The A1c level is determined from a blood test. Because red blood cells (which contain hemoglobin) survive in the circulation for about three months, glucose can constantly become bound to hemoglobin. As a result, the A1c level correlates to the average blood glucose level for the last 60 to 90 days.
A diagnosis of diabetes requires at least two abnormal levels on two different occasions. Don’t accept a lifelong diagnosis of diabetes on the basis of a single test.
Type 1 Diabetes: When the Body Attacks Itself
Type 1 diabetes used to occur only in children and was called juvenile diabetes or insulin-dependent diabetes. During the past 20 years, adults also have been diagnosed with type 1 diabetes, so it now has a more generic name.
Type 1 diabetes is an autoimmune disease that results from destruction of the insulin-producing beta cells of the pancreas. Insulin is the key hormone that controls the blood glucose (sugar) levels. Without insulin, glucose doesn’t enter the cells that make up your muscles and blood glucose levels rise, especially after you eat a meal. Researchers believe that a genetic tendency is required to develop type 1 diabetes, but that this tendency is triggered by something else, like a virus. Regardless of how type 1 diabetes starts, the end result is that antibodies are produced that attack the insulin-producing beta cells of the pancreas. The autoimmune reaction that develops gradually destroys the beta cells until no more insulin can be produced.
In the following sections, I describe type 1 diabetes in some detail. Then I outline how vitamin D may play a role in preventing and treating the disease.
Describing type 1 diabetes
Type 1 diabetes usually begins abruptly, although the disease may have been simmering for years. Researchers have seen autoantibodies against pancreatic beta cells in the blood long before the onset of clinical disease. Some of the major features of type 1 diabetes include the following:
Usual onset in children (the reason it used to be called juvenile diabetes)
Underweight condition of the patient
Presence of glutamic acid decarboxylase (GAD) autoantibodies in the blood, consistent with the autoimmune condition
Sudden onset of increased thirst, increased urination, increased hunger, and weight loss
Episodes of ketoacidosis, a condition where the blood glucose levels are very high and the body tears down protein and fat to make glucose, which makes the blood become very acidic; this is a life-threatening condition
Absolute need for insulin to sustain life
Need to balance insulin, food, and exercise to avoid both high and low blood glucose
Development of the following complications if blood glucose isn’t kept at a reasonable level over ten or more years:
• Kidney failure
• Blindness
• Nerve disease, including pain and loss of sensation
• Heart attacks and strokes
Treatment and prognosis
Treatment of type 1 diabetes requires insulin, which is usually administered through a pen injection device, or an insulin pump, or the old mainstay of a needle-and-syringe. The insulin treatment must be balanced by the amount and type of food eaten and exercise. Insulin and exercise lower the blood glucose; food raises it. A person with type 1 diabetes has to measure his blood glucose at least four times daily, usually before meals, and then he decides on an insulin dose based on the current blood glucose and the grams of carbohydrate to be eaten. Measurements after meals are also needed to fine-tune the control of blood glucose.
One of the treatment goals is to keep the level of hemoglobin A1c as close to normal as can be safely accomplished. The American Diabetes Association and Canadian Diabetes Association have set a goal of less than 7 percent for hemoglobin A1c. This is the level at which long-term complications are almost the same as what we see in non-diabetics (with the exception of heart attacks and strokes).
The American Association of Clinical Endocrinologists set its goal at less than 6.5 percent. The problem with this lower goal is that it increases the risk of hypoglycemia or low blood glucose. In an attempt to achieve the goal, the blood glucose occasionally falls to a dangerously low level; in extreme cases, this can render a patient unconscious. When this happens someone has to give an injection of glucose or glucagon, a medication that raises blood glucose within the body by stimulating the breakdown of protein and fat into glucose.
The prognosis for type 1 diabetes is much better today than it was 60 years ago. Today a patient has the ability to measure his or her blood glucose easily and can then respond with the appropriate amount of insulin, calories, or exercise. Insulin pumps are available that can slowly provide insulin under the skin at a rate similar to what a normal pancreas would supply. Scientists currently are working on an insulin pump that can be combined with a continuous blood glucose-measuring device to produce an artificial pancreas. Work is now progressing on a form of insulin that can be ingested rather than injected.
Another major direction for treatment development is the transplantation of a pancreas or islet cells, the cells that make insulin. Patients can become independent of insulin when this is successful, but it requires taking potent drugs to suppress immunity to avoid rejecting the tissue from another person. Islet cells derived from a patient’s own tissue are being used but these islet cell transplants are experimental and do not last as long as pancreas transplants.
Examining vitamin D’s role in type 1 diabetes
Geographic location seems to play a part in the development of type I diabetes with risk increasing as you move away from the equator. As I explain in Chapter 2, your location on Earth contributes to the amount of vitamin D your body produces, so this type of observation is suggestive, but not proof, that vitamin D affects the development of type 1 diabetes. When you look deeper into the science, there are a number of very interesting studies that support this idea:
Finland, a country that is at latitude far from the tropics, has the highest incidence of type 1 diabetes in the world. In the late 1960s, it was common to supplement an infant’s diet with 2,000 IU vitamin D. When researchers compared the development of type 1 diabetes in people 30 years later based on whether their mothers recalled giving them vitamin D during the first year after birth, they found an 80 percent reduction in the risk of type 1 diabetes later in life. The problem with this study is that very few people chose not to give their babies vitamin D — we don’t know why they would choose to do that, but these people might not be representative of the rest of the population.
Use of cod liver oil, a good source of vitamin A, vitamin D, and omega 3 fatty acids in the first year of life was associated with a lower risk of developing type 1 diabetes. Unfortunately, in the same study, supplemental vitamin D failed to affect the risk.
There’s a mouse model for type 1 diabetes called the NOD mouse. In these mice, severe vitamin D deficiency increases the development of glucose intolerance and diabetes whereas treatment with calcitriol and drugs made to look like active vitamin D suppress development of pancreatic inflammation, T cell recruitment, and development of diabetes.
Calcitriol makes insulin-secreting beta cells resistant to immune system attack. The active vitamin appears to reduce the production of cytokines, substances that kill beta cells.
Calcitriol can reverse pancreatic beta cell injury and prevent type 1 diabetes that is induced by a drug called streptozotocin in rats.
In people who have recently been diagnosed with type 1 diabetes, treatment with calcitriol didn’t improve their disease symptoms. Together with the mouse model, this suggests that vitamin D might stop the development of the disease but isn’t necessarily good for treatment of the disease.
When given a drug similar to calcitriol, patients with a form of autoimmune diabetes called latent autoimmune diabetes experienced preservation of their beta cells, compared with patients not given vitamin D.
Not every study confirms the relationship of low vitamin D status and more type 1 diabetes. Also, the studies with calcitriol don’t necessarily mean that more supplementary vitamin D will be protective. Researchers still need to find the amount of vitamin D or serum 25-hydroxyvitamin D that protects against type 1 diabetes.
You might be wondering why scientists are so cautious to accept associations between serum 25-hydroxyvitamin D and type 1 diabetes risk. Although people can make an argument that links different studies together, this type of deduction can sometimes lead you to the wrong conclusion. Consider the story of a famous surgeon, Dr. Joseph Bell. He was demonstrating the deductive method of diagnosis to a group of students around the bed of a patient who had paralysis of the cheek muscles. “Don’t you play in a band?” he asked the sick man. The patient nodded. “You see gentlemen, I’m right,” said Dr. Bell triumphantly. “This man has a paralysis of the cheek muscles, the result of too much blowing into wind instruments. We have only to inquire to confirm. What instrument do you play, my man?” “The big drum, doctor,” answered the patient.
Type 2 Diabetes: When Your Body Reacts to Your Lifestyle
Type 2 diabetes is 20 times more common than type 1 diabetes, and the incidence is rising at an alarming rate as the population becomes heavier, and more sedentary. Even in a person who seems destined to develop type 2 diabetes because of family history, it’s possible to hold off or prevent the disease by maintaining a normal weight, eating properly, and doing plenty of physical exercise.
Type 2 diabetes develops in response to three factors. First, as body weight increases, your body becomes insensitive to your own insulin and the pancreas puts out high levels of insulin in order to keep the blood sugar normal. Second, over time the pancreas begins to fail so that it can no longer make the large amounts of insulin levels needed by the insulin resistance. Third, the intestines make less of other hormones (called incretins) that normally boost insulin release, slow stomach emptying, and increase the feeling of fullness (satiety) so that you eat less. So with low levels of incretins, people who are developing type 2 diabetes eat more and gain more weight.
Normally, insulin tells muscle to take up glucose after a meal — if your muscle doesn’t hear the signal, it’s just like you’re not making enough insulin and blood glucose levels go up because it has nowhere to go. If you maintain a healthy weight and do sufficient exercise, this loss of sensitivity is less likely to occur. But as you put on weight, changes occur in your body that result in decreasing sensitivity to insulin and a rising blood glucose.
In the early stages of type 2 diabetes the pancreas compensates for the insulin resistance by pumping out more insulin. Later on, the pancreas begins to fail, meaning that it can’t make enough insulin to maintain normal blood glucose any longer, and the blood glucose rises above the levels that define diabetes: 126 mg/dl (7 mmol/L) or greater after an overnight fast, or 200 mg/dl (11.1 mmol/L) or greater after eating.
When high levels of glucose in the blood are maintained for ten or more years, the following damage may result:
Changes in the eye that can lead to the formation of cataracts (clouding of the eye lens) and glaucoma (a disease involving high fluid pressure within the eye that can cause blindness).
Changes in the back of the eye (retinopathy) that involve leaks forming in the existing blood vessels as well as new blood vessel formation (neovascularization). These changes can lead to blindness and retinal detachment.
Changes in the kidneys may lead to kidney failure.
Changes in the nerves of the body may lead to a variety of abnormalities of sensation or movement, the most common of which is tingling and numbness, as well as loss of sensation in the feet.
Changes in the heart and blood vessels may lead to heart attack, stroke, or decreased or absent blood flow to the legs and feet.
The combination of nerve damage and peripheral vascular disease leads to ulcers and infections in the feet that do not heal. These infections can progress to gangrene and may require amputation.
Type 2 diabetes used to be known as adult-onset diabetes or non-insulin-dependent diabetes. The last name is a little misleading . . . type 2 diabetes is still a problem with insulin, and many people end up being treated with it. The name derived because it’s not immediately life-threatening to go without insulin treatment in this condition, whereas it is life-threatening to go without insulin in type 1 diabetes.
Looking at the characteristics of type 2 diabetes
As mentioned earlier, type 2 diabetes has much in common with type 1 diabetes — but also much that’s different. The two types of diabetes aren’t generally confused, but some overlap occurs, especially when a person with type 2 diabetes is thin, young, or very sick at the time of diagnosis.
Type 2 diabetes differs from type 1 in the following major ways:
Obesity is characteristic of type 2 diabetes. The diabetes used to develop in the fourth or fifth decade of life, but now that overweight and obesity are becoming an epidemic in children, symptoms of type 2 diabetes are emerging earlier in life.
Type 2 diabetics have fat that is distributed around the waist instead of in the hips and legs. This is called visceral fat because it surrounds the internal organs of the abdomen, the viscera. It is this fat which causes the insulin resistance and also the high cholesterol and triglycerides which predisposes a person to cardiovascular disease.
The high blood glucose levels result not from a total lack of insulin, but from an insensitivity to the body’s own insulin. The pancreas tries to overcome this insensitivity by making more insulin, but at some point the pancreas can’t make enough insulin to overcome this insulin resistance.
People with type 2 diabetes often have modestly elevated blood glucose levels of 200 to 250 mg/dl (11.1 to 13.9 mmol/L). In contrast, patients with type 1 diabetes are more likely to have high blood glucose levels (300 to 400 milligrams per deciliter (mg/dl) or 16.7 to 22.2 mmol/L) and elevated ketone levels in the blood and urine.
At diagnosis many patients with type 2 diabetes appear well and may only have high blood glucose levels. A patient with type 1 diabetes is very sick or sometimes critically ill at the time of diagnosis.
Usually another family member has type 2 diabetes or is overweight or obese.
The rate of type 2 diabetes is fastest growing in ethnic minorities, including African Americans, Mexican Americans, and Native Americans.
No autoantibodies are found in the blood.
Treatment doesn’t require insulin from day 1 unless the glucose is extremely high, such as over 450 mg/dl (25 nmol/L).
As a result of increasing obesity in younger children, more cases of type 2 diabetes are emerging at younger ages, as young as 10 years of age. This is a medical crisis — if the diabetes isn’t controlled in these children, they’ll develop complications by 20 or 30 years of age. They may be the first generation with a shorter lifespan than the previous generation.
Doctors diagnose type 2 diabetes in exactly the same way as they do type 1 diabetes: by finding blood glucose levels in the same ranges as mentioned in the earlier section “Making a diagnosis.”
Treatment and prognosis
Because the pancreas is intact but failing in type 2 diabetes, treatments range from making the body more sensitive to its own insulin, to boosting insulin production even further, to suppressing glucagon production, to slowing carbohydrate absorption in meals. A major way to accomplish this at the start is lifestyle change. The patient must lose weight and begin a lifelong habit of daily exercise. By doing this a person can delay or prevent all the blood glucose abnormalities and the complications of diabetes. The problem is that many people cannot sustain the lifestyle changes necessary to slow type 2 diabetes.
All treatment in type 2 diabetes begins with weight loss, consuming a nutritional diet, and exercise.
I’ve seen diet and exercise successfully reverse the abnormal blood glucose in type 2 diabetes even 20 years after diagnosis. It’s never too late to have an effect on the blood glucose, but it can prove too late to reverse the chronic complications of the disease.
If diet and exercise aren’t completely successful, options include numerous classes of pills and injections, up to and including insulin, to bring blood glucose under control.
People with type 2 diabetes don’t have to measure their blood glucose to the same extent as people with type 1 diabetes, but occasional blood glucose measurements and tests after eating questionable foods can help keep them focused on adjusting their lifestyle and nutrition to achieve optimal blood glucose levels.
The life expectancy for type 2 diabetes is about 10 to 12 years shorter than people the same age who do not have diabetes. This is because type 2 diabetes includes not only high blood sugars but abnormal cholesterol, high blood pressure, and other changes that accelerate the development of cardiovascular and kidney disease, which in turn lead to early death. Type 2 diabetes is a leading cause of adult blindness, kidney failure, amputations, heart attacks, and strokes. Unfortunately many people with type 2 diabetes think of it as simply a blood sugar disease and an annoyance for their lifestyle, when in fact it is far deadlier than that.
If you bring diabetes under control with diet and exercise, you generally bring high blood pressure and high cholesterol under control as well. It’s like killing three birds with one stone.
Not everyone with type 2 diabetes is overweight or obese. In lean individuals with type 2 diabetes, insulin resistance may be due to genetic reasons and their pancreas may be failing even more rapidly in its ability to make insulin.
Checking out vitamin D’s role in type 2 diabetes
Type 2 diabetes is a lifestyle disease linked closely to overweight and obesity. Because obesity leads to lower serum 25-hydroxyvitamin D levels, it becomes harder to link vitamin D status directly to type 2 diabetes risk. In fact, one recent small study concluded that all of the effects of low vitamin D on type 2 diabetes risk were due to being overweight. It might be impossible to separate these effects in simple association studies. Nonetheless, there are still some interesting studies that suggest maintaining high vitamin D status may be important for protection from type 2 diabetes.
Type 2 diabetes results from insulin insensitivity and a relative lack of insulin:
Calcitriol (activate vitamin D) increases insulin production in cultured pancreatic beta cells and increases insulin sensitivity in cultured muscle cells.
A drug similar to calcitriol, an analog, reduced the development of complications associated with type 2 diabetes in a mouse model of the disease; however, this effect was not due to the ability of the vitamin D drug to control blood glucose levels.
African Americans, who have the lowest levels of vitamin D because of their skin pigmentation, have the highest levels of type 2 diabetes. However, they also have a higher prevalence of overweight and obesity — two well-established risk factors for the disease.
High vitamin D status is associated with a lower risk of developing type 2 diabetes. For example, in one study women with serum 25-hydroxyvitamin D levels greater than 30 ng/ml (75 nmol/L) had the lowest rates of type 2 diabetes — 50 percent lower than women with levels of 15 ng/ml (37.5 nmol/L). However, weight status, nutrition, and other factors confound analyses like this.
Normal levels of vitamin D are associated with control of many things that cause complications in diabetes: higher levels of HDL-C, lower levels of LDL-C, better blood pressure control, and reduced hemoglobin A1c levels.
The impact of vitamin D supplements is just starting to be explored in small clinical trials. On the positive side, Southeast Asian women with average vitamin D levels given a large supplement with vitamin D (4,000 IU) showed improvement in their indicators of type 2 diabetes; however, several other small studies giving vitamin D3 supplements for four to six months raised serum 25-hydroxyvitamin D significantly but didn’t reduce symptoms of type 2 diabetes. These studies all started with subjects whose vitamin D levels were around 20 ng/ml ml (50 nmol/L). Bigger studies are needed with more vitamin D doses and with subjects ranging from vitamin D deficient to vitamin D insufficient to really understand what vitamin D can do for people with type 2 diabetes.
So where are we when it comes to vitamin D and type 2 diabetes? Because it’s so hard to separate the effects of obesity and vitamin D status, we have good reason not to trust the studies that associate serum 25-hydroxyvitamin D and type 2 diabetes risk. Also, no large, well-controlled, clinical trials have yet been done to confirm that raising vitamin D status reduces the risk of type 2 diabetes or improves the symptoms of diabetes in people with the disease.
Still, there are some who claim that if you take large amounts of vitamin D and raise your serum 25-hydroxyvitamin D levels to more than 30 or even 40 ng/ml (75 or 100 nmol/L), that you’ll be protected from the disease. With the evidence we have in hand I think that the better choice is to keep your weight under control and not assume that vitamin D will cure everything.
When you see ads for people trying to sell vitamin D as a cure for type 2 diabetes you could also follow the example of German poet Otto Hartleben. He was feeling very ill and sought a diagnosis from a physician, who told him that he needed to stop drinking and smoking. As Hartleben started to leave, the doctor called after him, “My advice will cost you $25.” “But I’m not taking it,” he said, and left without paying.
Metabolic Syndrome: A Dangerous Precursor to Heart Disease and Diabetes
Metabolic syndrome is a collection of signs that are associated with increased risk for diseases like diabetes and heart disease. It’s most often associated with accumulation of fat around your abdominal organs, or viscera, and gives you a large waistline. However, people with metabolic syndrome aren’t necessarily obese. Up to 25 percent of the American population is believed to have metabolic syndrome. Many patients with metabolic syndrome go on to develop diabetes, but some don’t. All are at high risk for a fatal heart attack.
Metabolic syndrome consists of a group of abnormalities that include high blood LDL-C and triglycerides with low blood HDL-C, increased blood pressure, raised blood glucose, central obesity (high visceral fat), and insulin insensitivity that may lead to diabetes. The presence of all these abnormalities in one person may result in a significant increase in heart attacks, strokes, and blood vessel disease, even if diabetes doesn’t develop.
Determining who’s at risk for metabolic syndrome
A number of characteristics increase your risk of developing metabolic syndrome:
Genetic predisposition: Metabolic syndrome runs in families.
Increasing age: The condition is much more common in older individuals.
Increasing weight: Heavier people have a much higher incidence.
Postmenopausal status: Premenopausal hormones protect against metabolic syndrome.
Tobacco exposure: People who smoke have increased metabolic syndrome.
Low socioeconomic status: Poor food choices and the stress of poverty are likely contributors.
High-carbohydrate diet: Normally, about 45 to 65 percent of your daily calories should come from carbohydrates. A high-carbohydrate diet is one in which more than 65 percent of calories come from carbohydrates.
No alcohol consumption: People who drink no alcohol are at higher risk. Men who have one to two glasses of wine, or its equivalent, per day (up to ten a week), and women who have one glass of wine a day (up to five a week) are at lower risk for metabolic syndrome.
Hispanic American ethnicity: Females, in particular, are affected.
Recognizing major signs and symptoms
Many signs and symptoms point to metabolic syndrome. These indicators are the most important:
Central obesity, with a waist circumference of 40 inches or more in males and 35 inches or more in females
Abnormal blood fats, with high triglyceride levels of more than 150 mg/dl (1.7 mmol/L), and HDL cholesterol levels of less than 40 mg/dl (1.0 mmol/L) in men and less than 50 (1.28 mmol/L) in women
Blood pressure greater than 130/85
Fasting blood glucose greater than 110 mg/ dl (6.1 mmol/L)
Presence of polycystic ovary syndrome in women (see the next section)
Microalbuminuria, more than 20 mg/dl of albumin, a blood protein, in the urine
Elevated levels of C-reactive protein, the inflammation protein already discussed
Dealing with metabolic syndrome
You can take these steps (literally) to deal with metabolic syndrome:
Lose weight.
Become physically active.
Stop smoking.
Eat fewer refined carbohydrates (carbohydrates that have been processed into white flour or simple sugar).
If you drink alcohol, do so sparingly.
Take a drug to lower blood glucose.
Take a drug to lower blood pressure.
Connecting metabolic syndrome and vitamin D
Similar to type 2 diabetes, the close relationship between body fat and serum 25-hydroxyvitamin D makes it hard to use simple association to show a relationship between the metabolic syndrome and vitamin D status. For example, consider the following two points:
In large groups of people, the lower the level of vitamin D, the more often a diagnosis of metabolic syndrome is made.
Metabolic syndrome has a high incidence in the elderly, who have low levels of vitamin D. Subjects with a level below 20 ng/ml (50 nmol/L) are much more likely to have metabolic syndrome. They are especially prone to a large waist circumference and low levels of HDL cholesterol.
These studies could both be seen to support the idea that low vitamin D is just a marker of being overweight. Because of this you can’t automatically conclude that the low serum 25-hydroxyvitamin D levels have caused the metabolic syndrome; as opposed to being a consequence of the overweight and obesity. Still, there are a lot of interesting relationships that suggest vitamin D may have a role in the development of metabolic syndrome. For example, all of the evidence I already showed you relating vitamin D to blood pressure, insulin production or action, and cardiovascular disease risk is still relevant to the question of metabolic syndrome. In addition, there are some specific studies that are worth thinking about:
In older South Koreans, those who had the lowest 25-hydroxyvitamin D levels were more likely to develop high blood pressure and metabolic syndrome.
Patients with elevated levels of parathyroid hormone tend to have increased insulin resistance and metabolic syndrome. Remember, low vitamin D status is one of the reasons for high PTH levels.
Obese adolescent females with a low vitamin D level had insulin resistance and metabolic syndrome. When they took supplemental vitamin D to raise their level, their insulin resistance improved.
Low serum 25-hydroxyvitamin D levels are common in Arab American males who also have high levels of insulin resistance, high blood glucose, and metabolic syndrome.
We don’t know if low vitamin D is a cause for metabolic syndrome, but we do know that being overweight increases metabolic syndrome and reduces vitamin D status. Keep your weight under control, and you might not have to worry about either of these problems.
Mark Twain said, “Be careful in reading health books. You may die of a misprint.”
Polycystic Ovary Syndrome: A Leading Cause of Female Infertility
Polycystic ovary syndrome (PCOS) is the most common reason for infertility in women. Ten percent or more of all women have PCOS during the reproductive years, and the incidence is increasing along with our waistlines. The name isn’t quite appropriate because it implies the presence of many cysts (polycystic) in the ovaries. In fact, often the diagnosis is made without any cysts present. The name originally derived from women who had extensive beards and whose ovaries looked like sacs of grapes, but in the modern era, women with PCOS tend to have normal-looking ovaries (perhaps a cyst or two at most) and a far milder problem with excess facial hair (hirsutism) and acne.
PCOS is increasing in frequency because it is associated with obesity and the frequency of obesity is rising rapidly. The link between PCOS and obesity is insulin resistance that develops in people with excess weight. The excess insulin in the blood that accompanies insulin resistance is thought to make a woman’s ovaries produce more of the male sex hormones (androgens) and less of the female sex hormone (estrogen). This is what leads to a disrupted menstrual cycle and a more masculine appearance of women with PCOS.
The big surprise is that a condition associated with fertility and menstrual function is also associated with insulin resistance, metabolic syndrome, hypertension, abnormal cholesterol, and diabetes. As a result, many of the things I told you earlier in this chapter about vitamin D status and diabetes, metabolic syndrome, or diabetes may also relate to PCOS. In a very real sense, PCOS is a form of prediabetes and should serve as an indicator that a woman is destined to have diabetes in the next 5 to 10 years unless preventative measures are taken now. Unfortunately for men, the prediabetic stage is completely silent.
Recognizing major signs and symptoms
The diagnosis of polycystic ovary syndrome is based on infrequent or irregular menses (such as going 2 to 6 months or more without a period) along with signs of too much male hormone (androgen) in a female. Androgen excess results in hair production in areas where females don’t usually have hair, such as the face, arms, legs, and breasts. It also results in acne. The irregular menses indicate that ovulation is infrequent (if occurring at all), and so women with PCOS often have a problem with fertility. A more ominous problem is that those irregular menses increase the risk for endometrial cancer (cancer of the uterus).
Blood levels of androgens in women with PCOS are usually normal, but the levels of testosterone or androstenedione can be a little above normal. But because facial hair and acne are usually present, we know that the androgen levels are inappropriately high for the affected individual, even if the blood level doesn’t exceed the normal range. Androgen excess happens because follicles that contain eggs in the ovaries grow to a certain point and then stop growing (follicular arrest). After that the tissue around the follicles (stroma) starts producing androgens in abnormal amounts.
When women who don’t have PCOS take androgens, they develop insulin resistance and produce excessive amounts of insulin — exactly what happens in metabolic syndrome and type 2 diabetes.
A diagnosis of PCOS results from the following characteristics:
Overweight or obesity (although about 10 to 15 percent of patients with PCOS aren’t obviously overweight)
Hirsutism (excess hair on face, chin, sideburn area, and between the breasts)
Irregular menstrual function
Note that no blood tests are required to make the diagnosis, nor is an ultrasound or CT scan of the ovaries required. It doesn’t matter what the ovaries look like; what’s important is what the ovaries are doing (causing the irregular menses, facial hair, etc.). Unfortunately many patients and doctors do an ovarian ultrasound whenever the diagnosis is considered, and when the radiologist describes the ovaries as looking normal, they mistakenly conclude that the woman doesn’t have PCOS. This shouldn’t happen.
Dealing with polycystic ovary syndrome
Polycystic ovary syndrome has been traditionally managed in several effective ways. The major forms of treatment for PCOS include:
Weight loss, which is accomplished by diet and exercise.
Medications, the best of which is metformin, which improves insulin insensitivity, and often restores ovulation. There is some evidence that the insulin sensitizers (pioglitazone and rosiglitazone) may work even better, but their use is restricted because of the concerns mentioned earlier in this chapter.
Oral contraceptives, which protect against uterine cancer, and improve the acne and hirsutism but not, of course, infertility, elevated cholesterol, and high blood pressure. Also, the concern is that oral contraceptives may worsen the weight gain and insulin resistance of PCOS.
Clomiphene, a drug that restores fertility by inducing ovulation but doesn’t affect the other signs and symptoms.
Laser surgery on the ovaries — this helps some women by bringing some follicles closer to the surface where the egg can be released.
The prognosis for PCOS is fairly good in the short term. Treatment can restore fertility and improve the hirsutism and acne. However, these women have a high chance of developing type 2 diabetes and metabolic syndrome (and all their associated cardiovascular complications) later in life. Anything that may prevent this is of great value, and vitamin D may be a key tool.
Connecting polycystic ovary syndrome and vitamin D
There hasn’t been much research on the relationship between PCOS and vitamin D. The major observation is that women with PCOS tend to have low blood levels of 25-hydroxyvitamin D. The real question is whether supplementing with vitamin D will clear up some of the problems associated with PCOS. Consider some of the key evidence:
A recent small study showed that a large single dose of vitamin D administered to women with PCOS and low vitamin D status improved a measure of insulin sensitivity.
Another small study of just 13 women with PCOS and low vitamin D status showed that a supplement with vitamin D and calcium normalized menstrual cycles in 7 subjects. This suggests that some of the problems of PCOS may be due to poor calcium metabolism and the lack of vitamin D.
These studies, although small, are very promising. At the minimum they say that women with PCOS should make sure their serum 25-hydroxyvitamin D levels stay over 20 ng/ml (50 nmol/L); however, more research is needed to say whether low vitamin D is really a significant cause for PCOS or whether the low blood levels simply reflect that most women with PCOS are overweight or obese.