Hi, I'm Jill Ellis, and welcome to this module. Today, we're going to be talking about type 2 diabetes and insulin resistance. And for the first module, we're going to focus on the epidemiology, clinical presentation, diagnosis, and management of type 2 diabetes. In the upcoming presentation, we'll talk a little bit about how we're going to put it all together, and then some more specialized management tools. These are my disclosures. Here's the instructional objectives for today's module. First, we'll discuss the basic pathophysiology of type 2 diabetes. We'll talk about some of the common risk factors in the clinical presentation. We'll talk about selecting and then also interpreting appropriate diagnostic testing and the evaluation of patients with hyperglycemia and or diabetes. We'll identify some treatment goals for diabetes. We will discuss non-pharmacologic and pharmacologic therapies to treat type 2 diabetes. And then we'll do a brief summary of the overall care of the diabetic patient, which will continue in the following module. First, we want to give you a little bit about the background of diabetes. So we all know about insulin and glucagon, but some of the newer hormones to hit the scene are the incretins. And so incretins, when we talk about those, we're talking about the glucose-dependent insulinotropic peptide, or GIP, and glucagon-like peptide 1, or GLP-1. And those names are probably familiar to you now because of the pharmacologic therapies that we're using to target the different aspects of diabetes. And what incretins do are, they're secreted by cells in the small intestine after an oral glucose load. And the way that we actually discovered these incretins was that it was found that when somebody ingests an oral carbohydrate load, their insulin response is much more robust than when someone is injected with some type of IV carbohydrate source. And we found that the reason for that was that the small intestine actually participated in the carbohydrate metabolism by secreting these incretins. So what incretins do is they actually help to increase insulin secretion. They help to suppress hepatic glucose production. They also suppress glucagon secretion. They suppress appetite, and they slow gastric emptying. And so all of these things together are very beneficial for diabetes, and that's why they've been a target for the treatments of diabetes because of their beneficial pathophysiologic effects that they have. Another quick slide, just about the background pathophysiology of diabetes. You've probably heard about the ominous octet. And what this does is it expands our focus from thinking about diabetes as just an insulin problem to recognizing that there's many pathophysiologic factors that contribute to the development of diabetes, which is important because then we want to focus on these different aspects when we're treating diabetes so that we're not just looking at the insulin. So you'll see at the top of the chart here, we have decreased insulin secretion, and that can either be an absolute or a relative decreased insulin secretion. So in type 1 diabetes, we have loss of the pancreatic beta cells. So there actually is a loss of insulin production, insulin secretion. In type 2 diabetes, it's not that we don't have insulin. In fact, we actually oftentimes have too much insulin, but it's a relative deficiency of insulin because it's just not enough to work to overcome those factors that are causing the insulin resistance. There's also increased lipolysis, and that can help to worsen insulin resistance, and it can contribute to the relative or absolute decrease in insulin secretion. There's an increased glucose resorption in the kidneys. So part of the pathophysiologic defects in diabetes is that instead of excreting some of that glucose out in the kidneys, the kidneys change the way they reabsorb that glucose, and that can contribute to hyperglycemia. There's decreased glucose uptake in skeletal muscle, and that's due to the hormonal changes such as the decreased insulin, the increased glucagon that leads to decreased uptake of the glucose into the skeletal muscles so that glucose remains in the circulation contributing to the hyperglycemia. There's a variety of neurotransmitters dysfunction that we've identified. There's increased hepatic glucose production by the liver. So not only do we have too much circulating glucose, but then the liver contributes by increasing glucose production, and that again has to do with the decreased insulin that's available. It has to do with the increased glucagon, and that's what the next bullet point there, the increased glucagon secretion, and then also the decreased incretin effect. So the incretins aren't secreted as well as they should be, and all of those factors together contribute to hyperglycemia. So if we focus just on the insulin aspect of diabetes, then we can miss some of those other pathophysiologic targets for treatment. There are many classifications for diabetes, and so type 1 and type 2 were the most common types of diabetes. There's also gestational diabetes, and then some other less common types of diabetes. But what I think the error sometimes can be in our thinking is that type 1 diabetes is just one set or classification of diabetes, or type 2 is a different set, where in reality, all of the diabetes, even within each of those groups is very heterogeneous. So one patient with type 1 diabetes can present one way and can have certain treatment requirements, whereas another patient also with type 1 diabetes has different treatment needs. So part of the treatment and focus on diabetes is looking at individualization of treatment targets and management of the diabetes. As we all know, diabetes is a common condition, and these statistics on this slide are from the National Diabetes Statistic Report in 2022. And what these numbers show is that there's 37.3 million cases of diabetes in the United States, and that's over 10% of the population. In addition to that, if you look down at the bottom of the slide, 96 million Americans over the age of 18 have prediabetes. So there's a huge population of patients either with diabetes or with prediabetes. And you'll see the majority of these cases are type 2 diabetes, and that's going to be the focus of these modules is that we'll talk about the type 2 diabetes and its associated insulin resistance. The majority of the remaining cases that aren't the type 2 diabetes are type 1, and then the minority of cases are going to be the gestational diabetes and some of those other genetic forms of diabetes and the rarer forms of diabetes. And of those 37.1 million cases of diabetes, there's 8.5 million patients who are undiagnosed. So recognition and screening for diabetes is also important. Not only is diabetes common, but it's also associated with significant morbidity and mortality. Diabetes is the seventh leading cause of death in the United States. And some studies have said that that number is actually underreported. It's the leading cause of end-stage renal disease, non-traumatic lower extremity amputations and adult blindness. And not only is it costly in terms of morbidity mortality, it's also costly in terms of actual dollars. So it's estimated to cost the U.S. $327 billion in the year of 2017. And some of those costs are due to direct medical costs and some are due to reduced productivity as a result of diabetes, diabetes management and or diabetes complications. When we think about risk factors for diabetes, the most important modifiable risk factor in the United States is the obesity, sedentary lifestyle, high fat diet. We find that most, but not all patients with type two diabetes are either overweight or obese. And that contributes to insulin resistance, which is one of the underlying pathophysiologic defects in type two diabetes. And this is something that we can focus on and make a difference in the management of our patients is trying to identify strategies to reduce this risk factor. Number one, to prevent the development of diabetes, but then also if diabetes has developed to reduce its impact in terms of complications. Family history is a non-modifiable risk factor. So we can't do anything about that, but it is important to recognize its presence so that we can help to improve our ability to identify unrecognized diabetes in patients. Because as we mentioned in the last slide, there's many patients that have undiagnosed diabetes. There is a strong family history of patients have a family history of one or two parents of type two diabetes. There's also certain ethnic groups that are an increased risk for diabetes that are listed there. Female gender, increased age, tobacco use. Disordered sleep pattern is actually something that they've been looking at in the newer research where they find that disordered sleep patterns not only contributes to the development of diabetes, but it also can contribute to poorly controlled diabetes. And so it can lead to hyperglycemia. A prior history of gestational diabetes can increase the risk of type two diabetes. And then certain medications, glucocorticoids is a very common one that can lead to hyperglycemia. Other ones include thiazide diuretics, atypical antipsychotics. So again, just a little bit about type two diabetes to summarize some of the things we've talked about. We've already mentioned it's a heterogeneous group of conditions. What the patients with type two diabetes have in common is that they have insulin resistance, they have a relative insulin deficiency, and then they have resultant hyperglycemia. Now there can be some variations in their clinical presentation, in the treatments that they respond to, et cetera. But those are the three characteristics that patients with type two diabetes have. And the etiology of type two diabetes is complex. It's an interaction between genetic influences. And we've already talked about that strong family history. There's not, the majority of cases of type two diabetes are caused by complex genetic influences. There's multiple genes that interact to increase the risk of type two diabetes. And then environmental factors, again, most importantly, obesity. Type two diabetes is often accompanied by other conditions, including high blood pressure, high serum LDLs, low serum HDL concentrations. And it's the combination of those factors together that can increase the risk of complications, including the macrovascular complications, such as atherosclerotic cardiovascular disease. So the clinical presentation, like I mentioned, it can look different in different patients. Type two diabetes can present at all stages of life. We used to think of this as more of an adult onset type of diabetes, and that's no longer the case. There is an increasing incidence in the pediatric population. It is still uncommon in the pre-pubertal children. So under 10, it's uncommon. There have been rare case reports where there is a case of pre-pubertal onset of type two diabetes, but for the most part, it's going to be an adolescent, post-adolescent or adulthood. Oftentimes type two diabetes is asymptomatic and insidious. So patients are identified with the type two diabetes based on routine screening on a lab test. And then they're told that they have diabetes. Sometimes when you have patients who were diagnosed just asymptomatic on lab screening, when you retrospectively look back at their symptoms, they may endorse some of the classic symptoms of hyperglycemia, such as the polyuria, the polydipsia, the blurred vision, the weight loss, those types of things. But oftentimes they don't present asking for care because of those classic symptoms. Other signs and symptoms of hyperglycemia could include the weight loss, like I mentioned, fatigue, weakness, blurry vision. Sometimes type two diabetes actually presents with diabetic complications. So that could be neurovascular complications or cardiovascular complications. So you might have a patient who presents with acute coronary syndrome without a prior history of diabetes, but through the course of the diagnostic workup it is found that they actually have diabetes. And so that could be the initial presentation for type two diabetes. Some patients might present with dermatologic manifestations. So it could be recurrent or chronic skin infections. It could be the presence of acanthrosis nigricans, which we'll talk about on the next slide, or it could be other types of dermatologic manifestations, such as chronic itching. It might be slow healing of wounds after a minor trauma. Rarely patients could present with DKA or diabetic ketoacidosis or HHS or hyperosmolar hyperglycemic state. That is rare in type two diabetes to present that way, but that is a way that some patients could present. And on physical exam of patients with type two diabetes, oftentimes you may not see anything, but you might see evidence of some of the risk factors for insulin resistance in type two diabetes, including the presence of visceral obesity. You might also see acanthrosis nigricans. And that's a condition that, a dermatologic condition that's not specific to type two diabetes, but you may see evidence of underlying insulin resistance. And that's where you have, sometimes describe it as a dirty appearance to the skin. Sometimes patients describe it as like a velvety appearance to the skin, but you have some darkened areas of the skin that are hyperpigmented and sometimes even a little hyperkeratotic. So diagnostic testing. So if you have somebody that presents to you with symptoms that could be consistent with type two diabetes, such as the recurrent skin infections, or if they had some type of diabetic complication that made you think that they had underlying diabetes, how would you go about diagnosing those patients? Well, the diagnosis is based on fasting plasma glucose levels to our plasma glucose values during a 75 gram oral glucose tolerance test or hemoglobin A1c. And all of those tests are considered to be acceptable diagnostic tests to diagnose diabetes according to the American Diabetes Association. However, one thing that's important to know is that depending on which screening tool you use, you will identify a different set of patients. So for example, if you use fasting plasma glucose levels to diagnose patients with diabetes, you will diagnose more patients because it is more sensitive than if you use hemoglobin A1c. Hemoglobin A1c is a little bit less sensitive in diagnosing patients with type two diabetes. However, the ADA has endorsed the use of all of the tests because they have found that all of them are predictive of the complications that can occur from diabetes. And most of the complication studies have been based on hemoglobin A1c. So they established a set point for hemoglobin A1c diagnosis of diabetes, above which there is an increased risk of diabetic complications. So again, either of these tests, any of these tests, all three of these tests are available as diagnostic testing. However, you just need to be aware that which test you use may influence who is ultimately diagnosed with diabetes in your patient populations. There are other diagnostic tests available, including fructosamine. Fructosamine is a test that's not commonly ordered. It is a test that assesses blood glucose control over the past two weeks. So that might be useful if you have a patient that has some type of hemoglobinopathy or rapid blood turnover that makes their hemoglobin A1c, that is reliable. Or if you have a patient where recent control of their blood glucose over the past two weeks, as opposed to the past three months with hemoglobin A1c would be helpful. A urinalysis may also be helpful. You can have the presence of glucose in the urine or even the presence of ketones if there's some ketosis occurring. It's not gonna be specific enough to diagnose diabetes, but it could indicate the presence of a potential diagnosis of diabetes. Sometimes we also have to measure insulin levels or C-peptide levels to try and establish the type of diabetes because sometimes the difference between type 1 diabetes and type 2 diabetes can be a little bit unclear. So you might order insulin levels to see if they are increased, which would be consistent with insulin resistance, or if they're decreased, which would be more consistent with type 1 diabetes. And then C-peptide levels is actually a byproduct of insulin when it's produced in the body by the pancreas. So C-peptide can help us to distinguish between endogenous and exogenous insulin production. If you have a patient that is being treated with insulin, if you're uncertain if they've had some insulin, then sometimes C-peptide levels can be useful. So if you have endogenous production of insulin, you would expect both the insulin levels and the C-peptide levels to be increased. And so taking those levels, we'll look at each of those three diagnostic criteria in the plasma glucose levels, the oral glucose tolerance test, and the hemoglobin A1C to kind of establish the specific diagnostic values that are associated with that. So for plasma glucose testing, a fasting glucose greater than or equal to 126 milligrams per deciliter is indicative of diabetes. If you have a fasting glucose between the normal range of 100 and that diagnostic threshold of diabetes at 125, what we call that is impaired fasting glucose. And that would be one of the causes of prediabetes. So prediabetes can include impaired fasting glucose, impaired glucose tolerance, both of those. So with the fasting glucose, we could identify the impaired fasting glucose. And then if you have a random plasma glucose, so non-fasting that's greater than or equal to 200 milligrams per deciliter in a patient that has classic symptoms of hyperglycemia, so polyuria, polydipsia, weight loss, that would be diagnostic for diabetes just with that one lab value. The other values, so for instance, the fasting blood glucose or the hemoglobin A1C, you will have to repeat those tests to confirm the diagnosis of diabetes. However, the exception to that is the random plasma glucose greater than or equal to 200. And that is diagnostic on its own without confirmatory testing. Hemoglobin A1C, more useful in diagnosis of type 2 diabetes as opposed to type 1 diabetes. Plasma glucose is equivalent in diagnosing both type 1 and type 2. But because the onset of type 1 diabetes is more rapid, generally, and there's more abrupt loss of insulin and then subsequent hyperglycemia, because the hemoglobin A1C measures three months of glucose control, it can be a little bit less helpful in type 1, but it's very helpful in the diagnosis of type 2. It's also nice because fasting isn't required. So if you have a patient who presents for an office visit, you can obtain the hemoglobin A1C there regardless of their last oral intake. Or if you have a hospitalized patient upon admission, you can obtain the hemoglobin A1C upon admission without waiting for fasting. And so just like we had with the fasting blood glucose, we have a level that suggests pre-diabetes and a level that is indicative of diabetes. So a hemoglobin A1C between 5.7 and 6.4 is pre-diabetes or an increased risk for developing diabetes. And then a hemoglobin A1C of 6.5% or greater is indicative of diabetes. And this chart just shows a comparison between the hemoglobin A1C and the mean plasma glucose level, which can be helpful for both providers and patients because sometimes they're not as familiar with what does a hemoglobin percentage mean. So this shows that if you have a hemoglobin A1C value of 6%, that actually equates to a mean plasma glucose level of 126 milligrams per deciliter of glucose. And so that is the diagnostic threshold for diabetes if you use a plasma glucose level. But if you look at the diagnostic criteria for hemoglobin A1C, it's actually 6.5%. So this further illustrates the point of, regardless of which test you use, you will diagnose a different set of patients. So if you use the plasma glucose, you'll diagnose more patients with type 2 diabetes. If you use the A1C value, you will diagnose fewer patients with type 2 diabetes. And then this is talking about how I mentioned that you do have to have confirmatory testing. So if you have a lab test that indicates the presence of diabetes, you do have to repeat that lab test or repeat or order one of the other diagnostic tests that's acceptable for the diagnosis of diabetes. So confirming diagnosis of diabetes requires two abnormal test results from the same samples or in two separate test samples. And these can be combined in whatever way you prefer. So you could have two fasting plasma glucose levels. You could have a fasting plasma glucose level in the hemoglobin A1C, or you can have two hemoglobin A1Cs. Oftentimes providers will use a fasting plasma glucose and an A1C recognizing that those two pieces of information will give you different information about the patient. So that can be helpful. If you have two tests that do not say the same thing. So for instance, if you order a fasting plasma glucose and a hemoglobin A1C on a patient and the fasting plasma glucose is in the diagnostic range for diabetes, but the hemoglobin A1C value is not, what the American Diabetes Association guidelines recommend is that you repeat the test that was diagnostic of diabetes. So in that instance, you would repeat the fasting plasma glucose. And if that fasting plasma glucose is in the diagnostic range, the patient would be considered to have diabetes. If the repeat test is in the pre-diabetes range or not in the diagnostic range, then it's recommended to follow that patient closely because you do wanna recognize that diabetes does develop on a continuum. So you go from a period of relative insulin deficiency without hyperglycemia, oftentimes to a period of impaired glucose tolerance and then to fasting hyperglycemia. So that patient with those indeterminate diagnostic tests would be at high risk to progress to diabetes in the near future. So you do wanna repeat those labs within three to six months. And then the only exception to needing to repeat or confirm those diagnostic tests is if you have a random plasma glucose that's greater than or equal to 200 with the classic symptoms of hyperglycemia, like I mentioned. So after diagnosis is confirmed, there are additional lab tests that you would wanna order. So that can include baseline renal and liver function testing, and that's gonna be helpful both for medication dosing and to identify the presence of comorbidities that can commonly occur with type 2 diabetes. You also wanna get a fasting lipid profile and this can be helpful to determine the patient's 10-year atherosclerotic cardiovascular disease risk. And then that can help to direct further management of comorbidities. You wanna obtain a spot urinary albumin to creatinine ratio to identify the presence of diabetic kidney disease. It's helpful to get a thyroid stimulating hormone or a TSH for patients who have concurrent dyslipidemia and for women who are 50 years of age or older. And then to consider an electrocardiograph if that's clinically indicated. And for type 2 diabetes, these diagnostic tests are recommended to be obtained at the time of diagnosis. So you don't wait for a period of time to see if complications develop, you order them right at the time of diagnosis because it is anticipated that many patients with type 2 diabetes have actually had the condition undiagnosed for a period of years. And so patients with type 2 diabetes are at risk for complications right at the time of diagnosis, which is a little bit different than patients with type 1 diabetes, who we generally wait about three to five years to start screening for comorbidities because they oftentimes have had a shorter period of hyperglycemia before diagnosis. And then moving on to treatment goals. When we think about treatment goals, we wanna think about the care plan, engaging with the patient and using a multidisciplinary approach. So the care plan should be individualized based on the age of a patient. I talked about how type 2 diabetes is no longer just an adult disease. So you may be treating a pediatric population, which would include the family and other caregivers in the care plan. You might have to consider school schedules, work schedules, cultural dietary impact, health literacy, a variety of factors and thinking how can I treat diabetes in this individual patient? It's no longer a one size fits all care plan for patients. And you definitely want to engage with the patient to formulate that care plan because if you don't have the patient involved, you oftentimes will have poor compliance with the treatment plan that you established. And that's gonna lead to difficulty managing the diabetes effectively. And it's also difficult to manage diabetes on your own. So a single healthcare provider is going to have a very hard time managing all of the different aspects that need to be addressed for patients with type 2 diabetes. So you need to include the patients, like I already mentioned, and then it's gonna be a primary care physician. There may be subspecialty physicians based on the presence of complications. So it might be an ophthalmologist, a neurologist, a cardiologist, or a vascular specialist, a variety of different specialists who need to become involved in the care of the patient. It can include nurse practitioners, physician assistants, nurses, dietitians, exercise specialists, pharmacists to help with the increasing complexity of medication needs, dentists to ensure that patients are having proper oral care, podiatrists, mental health professionals to screen for commonly occurring psychosocial disorders, mental health disorders, diabetes, distress. And you want to make sure that all of these aspects are addressed so the patient can be effectively treated. Overall treatment goals. The initial goal that we oftentimes focus on for patients with type 2 diabetes is to restore euglycemia while minimizing the risk of hypoglycemia. And we'll talk about what does that mean as far as specific glycemic targets in the upcoming slides. But the main limiting factor to achieving glycemic goals is hypoglycemia because we don't want to cause hypoglycemia which has a number of adverse effects for patients both acutely and over time for patients with type 2 diabetes. So we lower the blood glucose to a level that does not increase that risk. We also want to minimize acute complications. So those acute complications can include hypoglycemia but they can also include acute hyperglycemic crises such as the DKA, diabetic ketoacidosis or the HHS or hyperosmolar hyperglycemic state. We want to delay, prevent and identify early any chronic complications that might occur. And that can include atherosclerotic cardiovascular disease. It can include a variety of neurologic complications. It can include chronic kidney disease. It can involve retinopathy. We want to prevent, ideally prevent or if they develop minimize their progression of those complications. We want to provide comprehensive non-pharmacologic therapy and appropriate pharmacologic therapy. So sometimes the urge can be to rush right to pharmacological therapy, which is important because we want to start these patients on medications right away but we don't want to miss all of the non-pharmacologic opportunities that we have to address some of the underlying pathophysiologic defects and diabetes as well. Once patients have developed comorbid conditions we want to aggressively treat them. And then we also want to consistently address and have a concern for psychosocial concerns because these do commonly occur in patients with diabetes. And if they're not adequately addressed it can lead to poor glycemic management and reduced outcomes for these patients. So a little bit more information on the glycemic targets. Like I said, we want to restore the euglycemia. And so what does that mean exactly? Well, they're glycemic targets. And again, these are based on the American Diabetes Association. There are other guidelines that are more stringent. For instance, if you look at some of the clinical endocrinology guidelines they have a more stringent guidelines. So there is some variation but these are good starting points for patients with type two diabetes. So fasting plasma glucose levels are recommended to be between 80 and 130 milligrams per deciliter. They've raised the lower end of that for children and adolescents with type one diabetes to 90 to 130 milligrams per deciliter. And that's just to minimize the risk of hypoglycemia in those patients because they are high risk for hypoglycemia. We also want to look at peak postprandial glucose levels less than or equal to 180 milligrams per deciliter. And they no longer separate that out into one hour and two hour postprandial levels. They just say peak postprandial levels checked between one and two hours should be less than or equal to 180 milligrams per deciliter. And you will definitely encounter more patients using continuous glucose monitoring. And that's an area of increasing interest and some expanding knowledge. And so if you have patients using continuous glucose monitors, additional glycemic targets that can be used include the time with the glucose in the target range and then the frequency of hypoglycemia. And those can be additional tools that can help you to further adjust therapy to reach goals. When we look at glycemic targets we can also consider hemoglobin A1C targets. And a good starting point for a hemoglobin A1C target is less than 7%. You may have some patients who could qualify for more stringent hemoglobin A1C targets such as less than six and a half percent if it can be achieved without significant hypoglycemia because remember that's the most significant factor limiting glycemic lowering therapy. You can also consider some patients to have less stringent hemoglobin A1C goals for instance, less than 8% if you're having difficulty achieving those more stringent goals. So that might be a patient who has had diabetes for a long period of time, patient who has significant comorbidities, patients with limited life expectancy, et cetera. And then also pediatric goals may be more or less stringent based on the risk for hypoglycemia. That's the primary factor limiting glycemic lowering therapy and some pediatric patients may be experiencing significant hypoglycemia due to the reduced ability of some of the pediatric patients to recognize hypoglycemia. But then you might have some patients who are on continuous glucose monitoring and you're easily able to identify their hypoglycemia and you can have a more stringent glycemic target for those patients because you do want to reduce their risk of long-term complications. And now one of the areas in diabetes that has expanded its focus in recent years is not just focusing on glycemic targets but also thinking about other risk factors that we want to target to reduce overall risk. And so this includes blood pressure goals. Recently, the ADA and the American Heart Association aligned their blood pressure goals so that both agree that a blood pressure goal of less than 130 over 80 for most patients is reasonable. And so that is a target that we want to focus on for the majority of your patients with type 2 diabetes. Also looking at lipid goals. And if you think about treatment for primary prevention, we'll initiate treatment based on calculated overall ASCBD risk. As we mentioned, we do want to calculate their ASCBD risk after diagnosis. And then if you have a patient who has established ASCBD then you will treat to specific targets to minimize their risk of recurrent ASCBD events. This next section is going to look at kind of all of the tools we have available to treat diabetes. So we have a lot of different options. And so we're going to focus just on discussing those options here. And then in the next presentation, we'll talk about putting those various options together and how that would look like for an individual patient. And like I mentioned before, non-pharmacologic treatment is a key component of treatment of type 2 diabetes. And there's many different components and aspects of that. This slide gives a brief overview of those aspects of pharmacologic treatment, excuse me, those aspects of non-pharmacologic treatment. And then the upcoming slides will give a little bit more detail about each of these. So first, physical activity, dietary modification, weight reduction, diabetes self-management education, diabetes self-management support, blood glucose monitoring, making sure that your patients have up-to-date immunizations and preventive care, encouraging patients who smoke to stop smoking to reduce their risk, and then family planning for women of reproductive age. So a little bit more about physical activity. And these physical activity goals from the American Diabetes Association do align with general recommendations from the U.S. Department of Health. And the overall goal is to have 150 minutes or more per week of moderate to vigorous intensity activity for adults. And children are encouraged to engage in 60 or more minutes of moderate or vigorous physical activity daily, and overall for all patients to reduce sedentary time. So these should be familiar to you just for general recommendations for healthy lifestyle modifications, which would include your patients with type 2 diabetes. In addition to the aerobic activity, patients are also recommended to engage in resistance training at least two or more times a week. Children are encouraged to have strength training three or more times a week. And you can work with your patient to find out a way that this can be incorporated into their lifestyle that works for them. So this does not mean that all of your patients have to get a gym membership. This can be resistance training using body weight. And so there's different ways that you can incorporate this into a way that is feasible for your individual patient. For older adults, it's important to include flexibility and balance training two to three times a week to help reduce the risk of falls. Keep activity levels consistent. This is something that is a little bit more specific to patients with diabetes because as they have different levels of activity, they can have different glycemic excursions associated with that. So you want to keep those activity levels relatively constant so that you can then treat your diabetes according to whatever that anticipated activity level is gonna be. And it can also be important for patients to monitor their blood glucose levels closely during times of altered activity levels because that can put them at risk actually both for hyperglycemia in some instances and hypoglycemia. For dietary modifications, we definitely recommend that patients should see a trained medical nutrition therapist, ideally a provider who is specialized in the management of diabetes because there can be a lot of different factors to consider. But some overall principles to think about when we're looking at dietary modifications for patients with type two diabetes is that we do want to have an individualized approach. There's no longer a thing such as just an American Diabetes Association diet. We have to look at the individual patient and find out what their food preferences are, what their lifestyle is, and then how does the diabetes management fit into that? We overall want to emphasize healthy food choices and portion control. And just like for the physical activity, those are good recommendations for all patients, including your patients with diabetes. We want to encourage nutrient-dense carbohydrates that are high in fiber and minimally processed. And overall, it is recommended to reduce overall carbohydrate intake because there is some evidence that will improve glycemia levels in patients with diabetes. So it really is a focus on overall healthy diet management, a referral to a provider who is specialized in the care of diabetes so that they can help your diabetic patient to make healthy lifestyle choices that will have a positive impact on their glucose levels. And then we move into weight management, which is another aspect of non-pharmacologic treatment. And I think it's important to educate your patients that modest weight loss has been shown to have improved glycemic control. So it's not that patients have to get all the way to their ideal body weight. A weight loss of just five to 7% has been shown to have durable, beneficial glycemic effects and reduction in risk of complications for patients with diabetes. More is better. So more intensive weight loss goals, for instance, 15% of total body weight can be appropriate if it's able to safely be achieved. But it can be helpful to start with those smaller incremental goals and then move on to more intense goals if the patient is able to achieve those goals. And then it's important that during those periods of weight loss that you monitor the BMI height and weight to assess the adequacy of dietary intake and glycemic control. And it is now recommended to consider pharmacologic therapy to achieve those weight loss goals. And that pharmacologic therapy can include medications specifically indicated for weight loss, but also it can include glycemic lowering medications that have a beneficial side effect of weight loss. And we'll talk about that coming up as well. So the ADA recommends that when you select medications for treatment of diabetes, you consider their side effects profile and individualize that according to the patient. So if you have a patient that is overweight or obese, picking one of those agents, such as a GLP-1RA, which we'll talk about coming up here, that may be a beneficial option for your patient because you will have the dual benefit of glycemic lowering and weight loss. Another aspect of non-pharmacologic treatment is the diabetes self-management education and diabetes self-management support. Diabetes is a complicated disease. It's complicated for providers, but it's also complicated for patients. So we want them to have the tools and the education that they need to be able to manage their diabetes on a day-to-day basis at home and empower them to have the tools to improve their glycemic control. So they should have a basic understanding of the pathophysiology of diabetes, the importance of maintaining a daily schedule, importance of blood glucose monitoring or recording, the importance of their dietary instructions, making sure that they know how to take their medications correctly, ketone urea monitoring for some patients, predominantly patients with type 1 diabetes, but patients with type 2 diabetes can also get DKA. So some patients with type 2 diabetes may also be recommended to have ketone urea monitoring. Important that patients recognize signs and symptoms of hypoglycemia. That is a complication that the ADA recommends that we ask every patient with diabetes about every visit because of the risk and concerns for hypoglycemia. And then what patients should do if they become sick, what they should do when they exercise, and just making sure that the patients have all the tools that they need to successfully manage their diabetes. A little bit more about the blood glucose monitoring. We want to make sure that patients know how to take their blood glucose, but also that you appropriately recommend to your patients when they should do blood glucose monitoring. And this is an area where there's been a lot of increase in technology, especially with the continuous blood glucose monitoring, like I mentioned previously. But even just with the non-continuous, the intermittent blood glucose monitoring, there's many different types of monitors, devices, many different costs. And so you want to make sure that you are familiar with some of those models for your patients so that you can make some recommendations for that. If you have patients that are on intensive insulin therapy, we'll talk about the different types of intensive insulin therapy coming up. But if you have a patient that's on intensive insulin therapy, blood glucose monitoring is a key component of their diabetes management. So you will have to have them monitor their blood glucose. Patients who are not on intensive insulin therapy is actually an area where the APA does not make clear guidelines. There's no consensus recommendation for blood glucose monitoring for your patients that are not on intensive insulin therapy. What they found is that many patients with diabetes, not on the intensive insulin therapy, will check their blood glucose, but will not do anything based on those results. And so the actual act of checking your blood glucose does not do anything to alter the overall course of your diabetes. But if you have a patient who is checking their blood glucose to inform their overall control, for instance, what does activity do to their blood glucose levels? Or what does this dietary modification do to their blood glucose levels? Then it can be helpful for your patients to do blood glucose monitoring. So it's really an individualized decision between the patient and the provider, if you have a patient that is on non-intensive insulin therapy or oral therapy for their diabetes, if they should be checking their blood glucose, and if so, how often. And then continuous blood glucose monitoring should be offered for diabetes management in youth and adults on insulin therapy if capable of safely using the device. And that's a stronger recommendation from the American Diabetes Association that has been previously made just because of the increased availability and efficacy of those therapies. So you will definitely encounter more patients on continuous blood glucose monitoring. It's important that your patients with diabetes maintain immunizations that are up-to-date according to the CDC schedule. So annual influenza vaccine. Adults with diabetes do qualify for the pneumococcal vaccination. Hepatitis B vaccination is recommended for patients with type 2 diabetes and then COVID-19 vaccinations and subsequent boosters. Patients with diabetes are at an increased risk of cancer. The risks are complex and it's not clearly a causal factor, but it is recommended that patients have routine cancer screening according to the United States Preventative Service Task Force recommendations. There's no increased frequency of screening recommended, however, they just want to make sure that your patients are up-to-date according to the guidelines. Patients with diabetes should have regular ophthalmologic, dental, podiatry, and audiology referrals, and then mental health professional referrals as needed. Moving on from the non-pharmacologic therapy options to the pharmacologic treatments. Commonly used oral agents include metformin. For many, many years, that was recommended as the initial treatment for all patients with type 2 diabetes, unless there was some type of contraindication. The American Diabetes Association has softened their recommendation on that and still generally say that metformin is recommended as initial therapy. However, due to some of the benefits of the other newer agents, including weight loss, cardiovascular benefits, renal benefits, now there may be some patients who metformin is no longer the initial recommended therapy anymore. Other agents that can commonly be used are sarfonylureas. Those have been around for a very long time. They're very inexpensive. However, they don't have as good of a side effect profile as metformin or some of the newer agents that are available. TZDs are still sometimes used, not as commonly used, but those are still considered commonly used medications according to the American Diabetes Association. DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1RAs are newer therapies that do have some beneficial side effect profiles that we'll talk about in the upcoming presentation. Here's some less commonly used oral agents. You may encounter these, but these would not commonly be started in therapy. And then injectable agents. So GLP-1RAs, the majority of them are injectable. You did see there was the one oral agent on the slide a couple of slides ago, but the majority of those are injectable. And again, those are focusing on the incretin defects in diabetes. And then there's a newer medication that's a GLP-1RA and a GIP combination incretin drug that has been shown to be very effective in glycemic lowering therapy and in weight loss. And then also insulin. And we'll talk a little bit more about insulin on the upcoming slide here. Many different forms of insulin, rapid acting, both injectable and inhaled, short acting, intermediate acting, long acting, ultra long acting, and mixed insulin preparations. The most common types of insulin that you're gonna encounter at this time are gonna be rapid acting, injectable, and then the long acting. Those are definitely the most commonly used insulin forms at this point. A variety of different insulin regimens that we just want to make sure you're familiar with the terms. So sliding scale insulin is a very old term. It's a reactive approach to hyperglycemia where a rapid acting or a regular insulin is given for an elevated blood glucose level. And it's without regard to the timing of food ingestion, without regard to the preexisting insulin administration or individualization of the dose to the patient's insulin sensitivity. So sliding scale insulin is no longer recommended. What is now recommended is correction insulin. So correction insulin is where we administer rapid acting or regular insulin based on the blood glucose readings obtained either before a meal or at regular intervals. So whereas the sliding scale insulin does not account for the timing of the food ingestion, the timing of the last insulin injection or the individualization of the dose to the patient's insulin sensitivity, correction insulin does. Other types of insulin regimens are scheduled insulin therapy. And this is where you have a combination of intermediate or long acting insulin with or without a prandial insulin administration of regular acting insulin or rapid acting insulin. And then basal only scheduled insulin therapies where you have a long acting, intermediate acting or continuous infusion of regular or rapid acting insulin. So basal only scheduled insulin is a subtype of scheduled insulin therapy, but the patient takes the same dose of insulin every day and the patient takes just a long acting insulin. And when you have somebody on basal only scheduled therapy, that's gonna be a patient with type two diabetes who is using that long acting insulin to supplement their other non-insulin therapies. So for basal only scheduled insulin therapy, that's a subtype of scheduled insulin therapy where you only have the long acting insulin and you'll have patients who are taking a once a day dose or sometimes a twice a day dose if they're using intermediate acting of insulin to help supplement their other glycemic lowering therapies. So you might have a patient with type two diabetes who is on metformin or maybe even another oral glycemic lowering agent, but they're not yet meeting their glycemic targets. So the provider may add on a basal insulin dose to help further lower their glucose levels and help them reach their glycemic targets. Another type of insulin regimen is bolus insulin therapy. And this is where you give either rapid acting or regular insulin before meals in fixed or flexible dosing. And so this can include corrective insulin only if you have a patient that's not eating, or if you have a patient that's eating, you'll give corrective and nutritional coverage. So if you have a patient that's on bolus insulin therapy only, that means they're only receiving short acting or rapid acting insulin. They're not receiving that long acting basal insulin therapy. And this can either be given in fixed dosing. For instance, you have a patient that you give five units of rapid acting insulin before each meals, and then you have flexible dosing based on the glucose levels and the carbohydrate intake. So if it's flexible dosing, you'll have the patient check their blood glucose before the meals. And then you'll also have them calculate their anticipated carbohydrate intake. And based on their glucose level and their anticipated carbohydrate intake, they will give themselves an amount of insulin that you tell them based on their scale. So it can either be the same dose with each meal or a variable dose with each meal. You can also have conventional fixed basal bolus insulin. So this just combines the basal fixed dose and the bolus fixed dose. So you'll have a basal insulin, which is long acting or intermediate acting. Or if you're on a pump, it could be continuous infusion of regular rapid acting insulin. And then bolus insulin using their rapid or short acting insulin with fixed dosing. So an example of this would be that you have a patient that takes 20 units of long acting insulin every night. And then before each meal, they take five units of rapid acting insulin. So they take the same amount of insulin each day, and that is their set amount. They'll check their blood glucose levels just to make sure that they're not becoming hypoglycemic or hyperglycemic. And they'll report back to their provider to determine if changes need to be made if either hypoglycemia or hyperglycemia is occurring. And then intensive basal bolus insulin is where you have both a basal component and a bolus component, but the dose of the bolus component changes. So the basal insulin will still be the same dose every day. So for instance, our patient that I described in the last slide, if you have a patient that takes 20 units of long acting insulin at night, they would still take that same 20 units. But instead of having five units with each meal, they would now calculate their insulin dose before each meal. So they would take 20 units of the long acting at night. And then in the morning, they would check their blood glucose levels. And if their blood glucose was above their glycemic target, they would give themselves a certain amount of insulin for that. They would also calculate the amount of carbohydrates they plan to eat for breakfast and give themselves a certain amount of insulin for that. So this patient may calculate that they need four units of rapid acting insulin before breakfast. They might calculate that they need six units of rapid acting before lunch, and maybe they need eight units of rapid acting before dinner. And sometimes you can also add in a bedtime dose as well. So there's some flexibility here. The benefit of that is it allows the patient to have more flexibility in their day. So if they don't eat the same thing every day, if they don't have the same activity levels, this insulin regimen will allow for the flexibility in their life. The downside is that it does require more management from the patient, and they have to be able to understand the dosing of the insulin. You can also achieve this with a continuous insulin infusion. So if you have somebody who has a continuous insulin infusion through an insulin pump, what their basal insulin will be a steady infusion of regular insulin. And then when they get ready to eat, they will input what they're eating into the pump so they can give themselves a bolus of that regular insulin. Or if they check their blood glucose level, they can input what their insulin they should give themselves based to correct their increased glucose levels. And as insulin pumps become more and more sophisticated, there are now some closed loop systems where you have an insulin pump and a continuous glucose monitor that can talk to each other. And some of that dosing and management can be taken care of for the patient through that technology. So again, this is an area that just continues to expand as our technology expands. Thinking about insulin dosing, whether you use fixed dosing or flexible dosing, you are going to base that on weight. So if you are using the fixed dosing, you'll calculate out what dose the patient will take every day based on their weight. If you're using the flexible dosing, you will use their weight to determine what their total insulin requirements are. And that will help guide you to tell them what types of corrective insulin ratios they should use and what type of carbohydrate ratios they should use. In general, you want to start low with your insulin dosing and then titrate up according to the glucose levels. So you want to undershoot your glucose levels a little bit, meaning that you will sometimes let the patients have a little bit of hyperglycemia while you're adjusting down with the main principle that you keep in your mind is that you want to avoid hypoglycemia. And then if you are providing both basal and bolus coverage, the ultimate goal is to provide about half of the insulin as basal insulin and about half of the insulin as bolus insulin. So for instance, in the examples where I said we had a patient that was taking 20 units of long acting insulin at night, our goal would be for those patients to have about 20 units of rapid acting insulin during the day. So they might do five before breakfast, five before lunch, five before dinner, and maybe they take three before bedtime. Now that's not exactly a 50-50 ratio, but it's pretty close. And that's always going to be kind of your goal. So sometimes you have to readjust insulin therapies where you'll maybe bring the bolus down a little bit and the basal up or vice versa. We bring the basal down a little bit and the bolus up just to try and recalibrate to that 50-50 ratio. And that can take a lot of time to ultimately get to that. As you're titrating one up and one down, it just takes time to get to that. Another thing about insulin is insulin issues. So there could be a variety of times where patients say they're eating the same thing, they're doing the same activity, and they're taking their medications, but their blood glucose levels are just not what they expect. They might be too low, they might be too high, and they're just confused about why that is. So you want to make sure that first of all, the patient has adequate tools to do the diabetes self-management education and support. But if they seem to be doing everything correctly, sometimes there is just variable absorption of insulin. They've done some studies that have shown that a single dose of insulin can have a variable rate of absorption in the same patient of up to 50% day to day. So sometimes the insulin is absorbed differently and it may work differently in your patient. It also can vary based on the amount of subcutaneous depot. So if you're giving a patient a very large amount of long acting insulin, for instance, if you're giving 100 units of long acting insulin at one time, the way that that is absorbed can be different if you're giving a very small dose or a much reduced dose. So sometimes we do have patients split up their dosing if that seems to be an issue or to give half their dose in one spot and half in the other. Making sure that patients are using the correct injection technique. So again, going back to the diabetes, self-management, education, making sure that they're doing things correctly. Asking patients where they're injecting their insulin. So fastest absorption will happen in the abdominal wall. So if you have a patient who's injecting rapid acting insulin, so on a basal bolus regimen, for the rapid acting insulin, it might be helpful to have them inject into the abdominal wall for the rapid acting insulin, but then maybe into their buttock or their leg for their long acting insulin where it's a more slow absorption. And so kind of finding out from patients, did they change their injection site? That might lead to some variability in insulin issues as well. Another type of treatment that you might not initially think about for diabetes is surgical treatment. So we have the non-pharmacologic treatment, we have the pharmacologic treatment, and then now there's an increasing emphasis on surgical treatment or metabolic surgery. So metabolic surgery should be recommended as an option to treat type 2 diabetes in appropriate surgical candidates that have a BMI over 40. And that's any type of diabetes, regardless of the level of complexity of their glucose lowering regimens, regardless of their control. If they have a BMI over 40, they would qualify for metabolic surgery for the diabetes. And then you can consider metabolic surgery for patients that have lower BMIs and inadequately controlled diabetes. And you'll notice that the thresholds for BMI in Asian Americans is lower. And like I mentioned back at the beginning of the presentation, diabetes is a heterogeneous disease and it presents differently in different patients. And so the form of diabetes that presents in patients with Asian Americans appears to have higher rates of complications at lower BMIs, which is why the indications for metabolic surgery are a little bit lower for Asian Americans with diabetes. Other surgical options besides metabolic surgery can include whole pancreas and pancreas islet transplantation, but that's primarily for patients with type 1 diabetes. And that's the end of this presentation. In the next presentation, we'll talk a little bit more about putting all of those different pieces together. Thank you.

type 2 diabetes

insulin resistance

hyperglycemia

risk factors

individualized care plans

non-pharmacologic treatments

pharmacologic treatment options

insulin regimens

metabolic surgery