One of the reasons we are seeing more and more patients with diabetes is because there is a very clear connection between obesity and type 2 diabetes. As the mean body weight in the population increases, so does the prevalence of diabetes, according to these data from 1990 to the year 2000. They both travel together. Unfortunately, our population is getting heavier. We are not following a very good lifestyle, and that is increasing not only the rates of obesity but also those of type 2 diabetes.

We live in a multicultural society. Data from the US 2000 census illustrate that the population is quite heterogeneous: 75% of the population is of Caucasian origin, but look at the numbers for the other racial/ethnic populations. These numbers have now actually changed. The most recent data show that the Latino population now comprises 13.9% of the US population, followed by the African American population. And as you can see, there are other minority populations in the country.

Why is that relevant? It is relevant because we recognize that type 2 diabetes affects different populations in different ways. In this graph, you can see that the prevalence of type 2 diabetes is significantly higher in most of these minority groups in comparison to the white population. In this case, the European population represents what we usually see in this country in the white population. Keep in mind that these data are in people between the age of 45 and 74 years, and the rates of diabetes are 1.5, 2, 3 times higher than in the white population, with the highest prevalence of diabetes in terms of percentage of the population being demonstrated in the Pima Indians.

The Pima Indians are an American Indian group (most live in the state of Arizona) that has the highest rates of diabetes in the world: 70% of all Pima Indians above the age of 35 years have type 2 diabetes. They have a tremendous genetic risk for the disease, and they develop diabetes at very high rates. There is a very interesting natural “study” that occurred many years ago. The Pima Indians represented just a single group at some point in the past, but they divided into two groups: one that resides in the state of Arizona and another group that migrated to the northern part of Mexico (Sonora state). Although the populations are genetically identical, their rates for diabetes are very different.

The group in Arizona has a lot more diabetes than the group in Mexico, and the reason is that their lifestyles are very different. The group in Mexico are more physically active, they are leaner, they have better meal planning in general--not perfect but a lot better than the group in Arizona, and the rates of diabetes for those in Arizona are probably 4 or 5 times higher than those for Pima Indians in Mexico. Still, Pima Indians in Mexico develop diabetes frequently because genetics is also a very important component of the risk for type 2 diabetes.

Therefore, the worst-case scenario occurs when a strong genetic predisposition is combined with improper lifestyle; then you can see escalating rates of type 2 diabetes, one of the reasons why minority populations have so much type 2 diabetes.

The rates for diabetes have increased tremendously in the last few years. These are data from 1990 to 1998, when it is very clear that diabetes increased in different age groups. But look at what happened in people between the age of 30 and 39 years; there was a 70% increase in the prevalence of diabetes. We are seeing younger and younger individuals with type 2 diabetes. I remember there was a time when we used to say “Let us only screen people for diabetes when they are above the age of 40 or 50 years.” That is no longer the case, because now young individuals get type 2 diabetes and even children and adolescents can have this condition.

Looking at the increase in the prevalence of diabetes in different groups, there was a higher increase in the prevalence for African Americans and Mexican Americans compared with the white population.

Not only do minority populations develop more diabetes, but they also develop more complications. In general, most of the studies suggest that minority populations develop more retinopathy, nephropathy, neuropathy, stroke, and sometimes cardiovascular disease.

Let us talk about the pathophysiology of type 2 diabetes so that you get a better sense of what is going on with this particular condition. It turns out that there are two main abnormalities that are present in most patients with type 2 diabetes. One is insulin resistance, defined as the inability of insulin to promote glucose uptake in peripheral tissues. It usually starts many years before the development of type 2 diabetes.

As insulin resistance develops, the pancreas needs to compensate by producing more insulin to keep up with that demand and maintain blood glucose at a normal level. That is why at the very beginning of the process, the beta cells are over-functioning, but eventually there is a point when beta cells cannot compensate any longer; beta-cell function declines and insulin production decreases. This is a process that is continuous, progressive, and, unfortunately, something that we do not really know how to stop. The first manifestation of an abnormality in glucose levels is postprandial hyperglycemia, which you may see even before you see any changes in fasting glucose levels in any individual.

Unfortunately, the progression of these two abnormalities continues over time so that we always see escalating A1C levels in our patients with type 2 diabetes. This is coupled precisely with a decline in beta-cell function. Thus, the treatment of type 2 diabetes needs to be based on the pathophysiology that we are talking about right now.

Let me talk in more detail about insulin resistance. Insulin resistance is somehow genetically determined; unfortunately, we do not know exactly what goes wrong in our patients with diabetes. We know that there are some rare mutations that have been described in insulin action, but the common scenario is that, for most of our patients, there is probably not just a single abnormality; it is a multiplicity of derangements that happen inside the different target cells. It is the intracellular signaling cascade that is abnormal, and there are many abnormalities that have been described. That is why we say that these forms are largely unidentified.

Insulin resistance also gets worse as a result of the presence of other factors. As we get older, if we eat more, if we do not exercise, insulin resistance gets worse. But two components have become very relevant. As glucose levels increase, people develop impaired glucose tolerance, and hyperglycemia makes insulin resistance even worse. At the same time, the elevated free fatty acids that circulate as the result of insulin resistance also enhance insulin resistance even further. These are the concepts of glucotoxicity and lipotoxicity that have been demonstrated to affect insulin function. They may also affect the ability of the pancreas to produce insulin.

One of the abnormalities that has been consistent in people with type 2 diabetes is the presence of intra-abdominal fat. We now recognize that visceral fat, or intra-abdominal fat, is very deleterious for metabolism and vascular function. Most people with type 2 diabetes have increased levels of visceral fat in comparison with healthy individuals.

Visceral fat releases different substances -- cytokines, substrates, hormones -- that result in two main abnormalities. One is that many of these substances will lead to more insulin resistance. Therefore, there is a connection between having increased weight, increased abdominal fat, and more insulin resistance. That is the reason why being overweight increases the risk for type 2 diabetes. The other abnormality is that at the same time, many of these substances also lead to endothelial dysfunction and an increase in cardiovascular risk. Obviously, if someone has insulin resistance or type 2 diabetes, there are other abnormalities that are frequently associated with insulin resistance that can also lead to cardiovascular disease.

There is one hormone that is actually a good hormone among all these elements, adiponectin. Adiponectin is a hormone that is produced in adipose tissue and increases insulin sensitivity. In other words, it reduces insulin resistance. It also protects the vasculature. It is an anti-inflammatory hormone. The problem is that as we get heavier and we get more visceral fat, adiponectin levels go down. Therefore, insulin resistance is associated with decreased adiponectin levels that seem to be related to increased cardiovascular risk in the general population.

Coming back to insulin resistance, we have discussed that there is a genetic influence and there are also lifestyle issues. But if you have insulin resistance, does that mean that you will develop type 2 diabetes? Not necessarily. If you were provided with very good beta cells in the pancreas, those cells will compensate and will produce more insulin and will keep blood glucose at a normal level all the time. However, if you do not have good beta cells, they will not be able to compensate for that insulin resistance, and then hyperglycemia will appear, leading to type 2 diabetes. That is why in the pathophysiology of type 2 diabetes, we talk about the dual abnormality: insulin resistance and beta-cell dysfunction. As you will hear in the second lecture, there are therapies that specifically target insulin resistance and others that specifically target beta-cell dysfunction. We usually combine therapies to help our patients with type 2 diabetes.

A big problem is that beta-cell function continuously declines over time. According to the United Kingdom Prospective Diabetes Study (UKPDS), by the time someone is diagnosed with diabetes, at least 50% of beta-cell function has been lost. If we extrapolate that back in time, we could probably speculate that it is 10 to 15 years before the diagnosis of diabetes that beta cells are starting to fail, not producing enough insulin.

This means that diagnosing someone with type 2 diabetes represents a late stage in the development of all these metabolic and vascular abnormalities that happen many, many years before someone develops hyperglycemia. This is something for you to reflect on in terms of how early we should intervene in our patients who are moving in that direction.

Insulin sensitivity is decreased in minority populations. I like this study because they studied people who do not have diabetes and who are not obese. Their body mass index (BMI) is between 23 and 26.5 kg/m². They are young individuals, and, therefore, they do not have other factors that could affect insulin sensitivity. Yet you can see that minority populations have lower insulin sensitivity in comparison with the white group. This means that genes play a role to decrease insulin action. This is one of the reasons why minority populations may have a higher risk of developing type 2 diabetes. Perhaps therapies that target insulin resistance may be even more appropriate for minority populations, as they do have decreased insulin action.

We know that in most patients from minority populations, as shown here for the Hispanic population, there is an increased tendency toward decreased insulin action in peripheral tissues, skeletal muscle, and also in the liver. There may also be increased abdominal obesity with the release of all the substances that I told you about; and there may also be abnormalities in beta-cell function that we do not understand very well, which in combination lead to more abnormalities, leading to impaired glucose tolerance and eventually type 2 diabetes. We can then say that genes and environment do play a role in the development and course of type 2 diabetes.

Let us now discuss how type 2 diabetes is related to the development of cardiovascular disease. First of all, it is important to recognize that cardiovascular disease is the number one cause of death in the general population, and it is also the number one cause of death in people with type 2 diabetes.

The best way to illustrate the high risk that our patients with type 2 diabetes face is showing you the data from this study conducted in Scandinavia, following people for 7 years and assessing their risk of developing a myocardial infarction.

What you can see here is that the lowest risk, at 7 years, is for those people who had no history of heart disease and did not have diabetes, and that makes perfect sense. In concordance, the highest risk is for people with type 2 diabetes who already had a heart attack; close to 45% to 50% in 7 years; very high.

But look at the two groups in the middle. The risk of developing a myocardial infarction is the same in people with type 2 diabetes who have no history of cardiovascular disease as it is in people without diabetes who already had a heart attack. In other words, just by having type 2 diabetes, the risk is the same as anyone without diabetes who already had cardiovascular disease as a diagnosis. Therefore, type 2 diabetes equals cardiovascular disease as a risk factor for the development of a new heart attack.

This is precisely why we should consider all our patients with type 2 diabetes at a very high risk for developing cardiovascular disease. Therefore, treatment strategies should be very aggressive and the goal should be to control all risk factors in the best possible way to minimize cardiovascular risk.

The metabolic syndrome, a constellation of abnormalities that increase cardiovascular risk, is very common in the general population, according to data from the National Cholesterol Education Program (NCEP). Approximately 32% of Mexican Americans qualify as having the metabolic syndrome, about 24% in the white population, and about 22% in the African American group. As you can see, this is a very common abnormality in people in the general population.

An interesting area of research and clinical practice is the extent to which ethnicity plays a role in the development of some of these factors. This slide shows data on the metabolic syndrome by race and ethnicity. It can be seen that 36% of Mexican American women have the metabolic syndrome. Remember that this classification included people who had at least three abnormalities such as high fasting plasma glucose, high triglycerides, low high-density lipoprotein (HDL) cholesterol, high blood pressure, or increased abdominal obesity. These data show that one in three of these Hispanic women have three or more of these abnormalities, a very high proportion. But in the other groups, it is also significant; as you can see, at least one in four or one in five individuals.

Men frequently have these abnormalities as well. However, only 16% of African American men qualify to have the metabolic syndrome, this is explained by better lipid profiles in many individuals from this group when compared with their other racial/ethnic counterparts.

There was a time when people said that the Hispanic population had a lower risk of developing cardiovascular disease. I have mentioned that Latinos or Hispanics have more diabetes, more insulin resistance, more metabolic syndrome, and more obesity, therefore there should be more cardiovascular disease. Well, there were some studies, such as the San Antonio Heart Study, that reported lower rates for heart disease among Latinos in comparison with the white population. But after looking at this study more carefully and learning from what some of the investigators in this important study have reported, there may be some migration factors that influence the results by capturing lower rates for cardiovascular disease.

We can then say that there is no evidence of any proven factor that protects Latinos or Hispanics from cardiovascular disease, and, therefore, we should treat every population as aggressively as possible to reduce cardiovascular risk.

The African American population is at a very high cardiovascular risk. African Americans have the highest rate of strokes, among different populations in this country. They have very high rates of hypertension, which certainly increase the risk for cardiovascular disease and many of these abnormalities.

Let us look at the prevalence of some of the elements in the metabolic syndrome across ethnic groups. First, if we look at BMI above 25 kg/m², the definition of being overweight, we can see that 50% to 60% of all adults in the general population are overweight. And for some groups, such as African American and Hispanic women, the number is about 65%. And look at what happens in men. The majority of the adult population is overweight. This is, again, one of the reasons why we have escalating levels of type 2 diabetes.

There are different criteria to consider abdominal obesity, based on the cutoff levels established for waist circumference. For the general population, it is above 88 cm in women and 102 cm in men. If you use that as a cutoff point to assess what is happening in the general population, it turns out that at least one in five or one in four individuals in the male population has abdominal obesity. And these numbers are even higher for women. This is something that we have seen more recently; there are more women who are developing obesity, and particularly abdominal obesity, in the general population. That is why the rates for diabetes are increasing in women as well.

If we look at fasting glucose levels, we see the same trends; a very large number of individuals, particularly those from the Hispanic population, who have higher levels of fasting hyperglycemia; again, consistent data in terms of the higher predisposition for type 2 diabetes.

High triglyceride levels are also very prevalent in different groups. This is something very common in the Hispanic population. But for the first time you see that there is a factor that is lower in a minority group in comparison with the white population, and that is for the African American group. This is something very consistent. If you go back and look at charts on your patients, you may see that, in general, many African Americans have better lipid profiles than the white population. They usually have lower rates of high triglycerides.

They also have lower rates of low HDL cholesterol. This is because lipid metabolism is different across ethnic groups; African Americans tend to have better lipid profiles.

I said that African Americans have the highest rates of strokes. How could that be if they have good lipid levels, at least in terms of triglycerides and HDL cholesterol? An important factor is that African Americans have the highest rates of hypertension among different groups, being one of the reasons why they develop so much cardiovascular disease and stroke. In other words, hypertension probably overpowers whatever beneficial effects they may be having from better lipid profiles.

Another issue is that African Americans, in general, when compared with other groups with the same degree of BMI, the same degree of obesity, usually have lower visceral fat content, which may be beneficial. But hypertension is so powerful that, again, it probably increases the risk despite all the other factors that we may see in the African American population.

Unfortunately, Asian Americans are developing more diabetes as well, particularly Asian Americans living in this country for several years. This is probably the best way to illustrate that. If you look at prevalence of diabetes for Japanese living in Tokyo and you compare that with Japanese Americans living in Seattle, Washington, the rates for diabetes are 4 or 5 times higher for that population in the U.S. I could show you similar data for Chinese in China and Chinese Americans, Vietnamese in Vietnam and Vietnamese Americans. Unfortunately, genetic predisposition combined with the improper lifestyle that some members of these populations have acquired tremendously increases the risk for type 2 diabetes.

One thing that is important for you to keep in mind when we look at ethnicity issues is that the different criteria that have been established in terms of obesity may not be applicable to all groups in the same way. For instance, for BMI, if you try to define obesity in the same way for the Asian American population, you will have a hard time; you will not see the same degree of obesity among Asians. People in the Asian American population may develop insulin resistance and type 2 diabetes at much lower BMI levels, and that is the reason why there is this suggestion about modifying the BMI criteria.

For instance, for the general population, we say that someone is overweight if the BMI is between 25 and 30 kg/m²; above 30 kg/m² is obesity. For the Asian American population, the numbers should be lower. Someone is overweight if their BMI is between 23 and 25 kg/m², and anything above 25 kg/m² for that population is considered obesity.

This is something that the International Diabetes Federation (IDF) has also suggested. You can access this information at the IDF Web site (www.idf.org). There are some different guidelines for different groups, with the idea that for some populations the numbers should be completely different.

What about the American Indian population? I told you about the Pima Indians. But the Pima Indians are just one of many tribes of American Indians in this country. Many of them share a genetic risk for type 2 diabetes and cardiovascular disease. Most American Indian groups have a very high rate for diabetes and also for cardiovascular disease.

The Strong Heart Study integrated data on 13 different American Indian tribes. The prevalence of the metabolic syndrome is significantly higher than that observed in the general population per the National Health and Nutrition Examination Survey (NHANES). So American Indians also have high rates for obesity, metabolic syndrome, and type 2 diabetes.

What about the South Asian population? Unfortunately, they also develop diabetes more frequently. I was fortunate enough to be in India recently and I was impressed by the escalating rates of diabetes in that population. You will not see the same degree of obesity that you see in other populations. However, even though you see lean individuals, they have the tendency to develop abdominal obesity very easily, to accumulate internal or visceral fat that increases insulin resistance and, therefore, results in higher rates for type 2 diabetes. They also have significantly high rates for cardiovascular disease.

What I was telling you about visceral fat is illustrated in this very interesting study conducted in Boston, Massachusetts, in which two populations were matched (people from the Asian Indian population and Caucasians) for the same degree of BMI. These are what we would consider lean individuals. But look at the visceral fat content in Asian Indians in comparison with the white population; twice as high -- a highly significant difference. That means that you may see people with a BMI of just 23 or 24 kg/m², yet insulin resistance and increased visceral fat may be present. So it is not a surprise that you see people with type 2 diabetes who are not considered overweight according to our general standards. As previously mentioned, the definition of obesity has to be specific to each racial and ethnic population.

The other population that is growing very quickly in this country is the Arab population. We do not have data about Arab Americans, but I wanted to illustrate that according to different data put together from different countries, the rates for diabetes in different areas are very, very high among the Arab populations, with Bahrain having very high rates, perhaps because the westernized influence has been more clear in this population, again reflecting the genetic predisposition coupled with lifestyle issues. Again, this is something that we need to learn more about. Data on Arab Americans are needed.

I have talked about cardiovascular disease. There is one important connection that I want you to be aware of, and that is about endothelial dysfunction connected with insulin resistance and inflammation. It is very simple. The endothelium, which is the inner layer of the vessels, used to be considered just a mechanical barrier between the blood and the tissues. Now we know that it is a very active organ that does a lot of different things.

A healthy endothelium maintains a balance between all these different forces. It is normal to have a certain level of constriction, of inflammation, but it should be in balance with all the other functions.

Endothelial dysfunction appears when that balance is lost, and that may be the result of an injury from high blood glucose, high blood pressure, high cholesterol, smoking, or those cytokines and substances released from visceral fat, all of them leading to endothelial dysfunction.

There are many ways to assess endothelial dysfunction. This is something that we do more in clinical research, but I just wanted to share all these options as you may find them in multiple articles throughout the medical literature. Most of these elements have been shown to be abnormal in people with type 2 diabetes and many in those at risk for the disease.

It is very clear that people with type 2 diabetes have profound endothelial dysfunction. They have a markedly decreased vascular reactivity when compared with healthy individuals who are not overweight.

We published a study several years ago showing that not only people with diabetes have decreased endothelial function, but also people with impaired glucose tolerance and even relatives of people with type 2 diabetes; individuals who had one or both parents with type 2 diabetes, normal glucose tolerance tests, normal blood pressure levels, and very close to normal lipids. They were overweight with a BMI of 27 or 28 kg/m². They had significantly decreased endothelial function, suggesting that the process of inflammation and vascular dysfunction does not start when people get diabetes. It usually starts many years before someone develops diabetes, and is very closely related to the presence of insulin resistance.

Atherosclerosis is considered to be an inflammatory disease. In response to an injury, an inflammatory response is generated, which evolves to form a plaque that may ultimately rupture, mostly due to the presence of endothelial dysfunction, hyperglycemia, dyslipidemia, etc.

There are some important enzymes, called metalloproteinases (e.g., matrix metalloproteinase-9 [MMP-9]) that are responsible for breaking that plaque. We know, for instance, that by reducing insulin resistance, we stabilize the plaque, and that may be one of the ways to prevent future cardiovascular abnormalities in our patients with type 2 diabetes. So we are looking at different ways to improve cardiovascular disease/reduce inflammation in our patients.

We recognize, unfortunately, that there are some populations that are lagging behind in their healthcare. The Institute of Medicine reported that there are some health disparities between the white population and minority groups in this country, and some of them are applicable to the diabetes arena as well. I do not think that people are being discriminated against intentionally; I think that the disparities are a reflection and the result of many factors on the side of the patient, (social, cultural, and language issues), the side of the healthcare provider (general lack of cultural awareness) and multiple healthcare issues, including access to care.

But I think that at the same time, we as healthcare providers probably need to recognize that we may not be doing a great job in providing care to some groups in particular, because we may not understand what to do differently, how to address cultural issues. And that is one of the goals of this program; not for you to be instantly culturally competent, because that is a process that takes a long time, but just be aware of the fact that we collectively may be able to improve the way we provide services to other patients. This is not about white providers seeing Latinos or African Americans; this is about any of us that practice in this country, because most of us care for patients from other cultures.

The issue is that all these populations are rapidly growing, that there are many cultural and social and healthcare issues that are related to diabetes, and that we need to understand a little bit more about what is going on to better design culturally oriented programs.

This is a partial list of different things that we have identified in the Hispanic/Latino population that may influence diabetes care, such as: family orientation, fatalism, faith/religion, body image, of course nutrition/physical activity, acculturation, language, and myths. It is important to recognize how these elements play a role in the development of diabetes and its complications.

Another important aspect in diabetes care is cultural competence among ourselves as providers. We need a more culturally oriented focus to our activities in diabetes care.

For instance, we need culturally oriented patient education materials. This is an example of the work that we are doing in the Latino Diabetes Initiative at Joslin. This is a patient education material that we just developed called Rosa's Story. This is the result of information from focus groups in our research. We gathered a lot of different people together and we asked them how they would like to learn about diabetes care, and many of them said that they did not want to read printed materials, they wanted to listen to stories, something more attractive. Patients learned more and better remembered the information presented in audio-based material than with printed information.

Based on these responses, we created this audio novella, which presents the story of a Latino woman from Latin America who does not speak any English. She has to face the challenges of being diagnosed with diabetes and having to take care of the disease within the context of typical social and cultural issues that Latinos live with in this country. There are obviously other very good materials available from different organizations where you can find information for different cultural groups. Perhaps you already have some in your practice, in your group, in your hospital, but if not, then you should look at other things that are available so that you can improve the care of your patients.

Let me come back to this point: for many years we have blamed patients. Sometimes we say, “My patient does not want to follow my instructions. I have a noncompliant patient. What can I do?” Even though I recognize there are people who do not follow our recommendations, I would ask you to think in a different way. Perhaps the questions to ask are: “Have I done the best in terms of providing care to my patients? Have I been able to communicate my messages in the best possible way? If not, what can I learn and what can I do differently so that I can help my patients?” I think that is something that we need to slowly try to implement in a better way.

The American Medical Association has written a definition of cultural competence. Cultural competence is not a matter of speaking another language. It is about developing skills that allow us to understand, appreciate, and work with individuals from cultures other than our own. It involves an awareness and acceptance of cultural differences, self-awareness, and knowledge of patients' culture and adaptation of skills. Again, it is a process that takes time, but it is something very important.

There are now two states in the country, California and New Jersey, that have made it mandatory for physicians to get continuing education credits in programs that address cultural issues because of the importance of this aspect. I anticipate that this will happen in every state in our country in the short-term, and I honestly think that that will be beneficial for many of us and obviously for many of our patients.

This is a list of different resources: the American Diabetes Association, which has different information for culturally oriented materials, the National Diabetes Education Program, and the National Institutes of Health. We have two initiatives at Joslin, the Asian American Initiative and the Latino Diabetes Initiative, with some pieces that may be helpful. Not listed here but important to mention is the National Dietetics Organization, which also has information in terms of nutrition.

To summarize, we are facing the challenge of type 2 diabetes in the general population, and in minority patients, who also have high rates of cardiovascular disease and have multiple challenges from cultural perspectives. I think it will be very important for all of us to work collectively to integrate this information to provide better care to our patients.