Clinical Presentation



Clinical Presentation






Introduction

While most people think only of type 1 and type 2 diabetes, there are actually many forms of diabetes. Diabetes types are generally unified by hyperglycemia, but their pathogenesis can be quite distinct. Because primary care clinicians provide the overwhelming majority of diabetes care, it is essential that they know how to identify and treat the various forms. This first chapter examines the value of clinical presentations. When the clinician is aware of the different forms of diabetes, they are better able to identify key features and make correct diagnoses.




case questionsCASE QUESTIONS



1. Does he indeed have diabetes mellitus?

View Answer

1. While the diagnosis of diabetes usually requires two tests separated by time, the fact that he has an elevated random glucose well above 200 mg/dL and hemoglobin A1c at 8.4% confirms that he has had hyperglycemia for a minimum of 3 months prior to the lab test. Repeating any of the qualifying labs to confirm the diagnosis is an option including a fasting glucose, a 2-hour postprandial glucose, a glucose tolerance test (GTT), or a hemoglobin A1c. However, considering his current levels, this is largely unnecessary (Table 1.1 and Figure 1.1).



2. Is his presentation common for type 2 diabetes mellitus?

View Answer

2. More than 10% of the US adult population had diabetes mellitus in 2020. Another 35% had prediabetes.3 Importantly, more than 20% of those individuals with active diabetes mellitus did not know they had diabetes (undiagnosed).4

The most common presentation of type 2 diabetes is an asymptomatic finding on a routine screening lab. It is also worth noting that one-third of people with diabetes find out that they have diabetes in association with the presentation of a diabetes-related complication. It has also been reported that 25% of people who present with a heart attack find out that they have diabetes at that time.3



3. Did the statin give him diabetes?

View Answer

3. While there have been reports that statins can raise glucose levels and even tip someone into new onset type 2 diabetes, it is very unlikely in this case. Prior to his hospitalization, he was not taking any medications and his glucose and A1c were elevated. The short period of time he took the statin in the hospital would not have had a significant impact on his glucose and HbA1c.

A 2009 study looked at changes in glucose from statin use in people with and without diabetes. The net increase in fasting glucose was 7 mg/dL in people with known diabetes and 2 mg/dL in people without diabetes.5,6 While this is a significant increase, the benefits from statins far outweigh the potential adverse effect of hyperglycemia. It is unlikely that statins will increase this risk in people who do not have insulin resistance already.7 It is worth noting that this study was completed within the Veterans health system, which is known to have substantially higher rates of diabetes and prediabetes.6



4. How to tell your patient that he does in fact have type 2 diabetes?

View Answer

4. Denial, fear, and anger are common reactions to being diagnosed with a serious health condition, like diabetes. If the diagnosis is unexpected, as in the case for this patient, he may try to find an alternative explanation or minimize its importance. This is a normal way of coping when first diagnosed; however, if the denial or minimization of diabetes goes on too long, your patient will increase the likelihood of serious diabetes complications. This is particularly relevant for this case given adult men tend to have the most difficulty accepting a diagnosis of diabetes. As a clinician, the best coping strategies you can offer your patient are to go slow with recommendations for diet and physical activity modification (everything does not need to be fixed overnight), manage stress and anxiety, refer to diabetes education, identify the right support network, and involve family members in the management plan.8















5. What are the next steps for this patient?

View Answer

5. His recovery should start with cardiac rehabilitation including diabetes education, medical nutrition therapy, moderation of alcohol intake, and encouragement to participate in at least 150 minutes of moderately vigorous physical activity per week.

Concomitant pharmacotherapy should also be initiated. Historically, this approach includes the use of metformin as foundational therapy, which certainly could be used in this case. However, in light of recent cardiovascular outcome trials and changes in guidelines, this patient also has a compelling indication for a medication that has been shown to have benefit to reduce secondary atherosclerotic cardiovascular events. These medications could include one of the SGLT-2 (sodium-glucose cotransporter-2) inhibitors or GLP (glucagon-like peptide)-1 receptor agonists with proven benefit in cardiovascular risk reduction.9 We will discuss this topic much more later in the book (see Chapter 4 for further discussion on this point).



answers and explanationsANSWERS AND EXPLANATIONS

1. While the diagnosis of diabetes usually requires two tests separated by time, the fact that he has an elevated random glucose well above 200 mg/dL and hemoglobin A1c at 8.4% confirms that he has had hyperglycemia for a minimum of 3 months prior to the lab test. Repeating any of the qualifying labs to confirm the diagnosis is an option including a fasting glucose, a 2-hour postprandial glucose, a glucose tolerance test (GTT), or a hemoglobin A1c. However, considering his current levels, this is largely unnecessary (Table 1.1 and Figure 1.1).

2. More than 10% of the US adult population had diabetes mellitus in 2020. Another 35% had prediabetes.3 Importantly, more than 20% of those individuals with active diabetes mellitus did not know they had diabetes (undiagnosed).4

The most common presentation of type 2 diabetes is an asymptomatic finding on a routine screening lab. It is also worth noting that one-third of people with diabetes find out that they have diabetes in association with the presentation of a diabetes-related complication. It has also been reported that 25% of people who present with a heart attack find out that they have diabetes at that time.3

3. While there have been reports that statins can raise glucose levels and even tip someone into new onset type 2 diabetes, it is very unlikely in this case. Prior to his hospitalization, he was not taking any medications and his glucose and A1c were elevated. The short period of time he took the statin in the hospital would not have had a significant impact on his glucose and HbA1c.

A 2009 study looked at changes in glucose from statin use in people with and without diabetes. The net increase in fasting glucose was 7 mg/dL in people with known diabetes and 2 mg/dL in people without diabetes.5,6 While this is a significant increase, the benefits from statins far outweigh the potential adverse effect of hyperglycemia. It is unlikely that statins will increase this risk in people who do not have insulin resistance already.7 It is worth noting that this study was completed within the Veterans health system, which is known to have substantially higher rates of diabetes and prediabetes.6

4. Denial, fear, and anger are common reactions to being diagnosed with a serious health condition, like diabetes. If the diagnosis is unexpected, as in the case for this patient, he may try to find an alternative explanation or minimize its importance. This is a normal way of coping when first diagnosed; however, if the denial or
minimization of diabetes goes on too long, your patient will increase the likelihood of serious diabetes complications. This is particularly relevant for this case given adult men tend to have the most difficulty accepting a diagnosis of diabetes. As a clinician, the best coping strategies you can offer your patient are to go slow with recommendations for diet and physical activity modification (everything does not need to be fixed overnight), manage stress and anxiety, refer to diabetes education, identify the right support network, and involve family members in the management plan.8













5. His recovery should start with cardiac rehabilitation including diabetes education, medical nutrition therapy, moderation of alcohol intake, and encouragement to participate in at least 150 minutes of moderately vigorous physical activity per week.

Concomitant pharmacotherapy should also be initiated. Historically, this approach includes the use of metformin as foundational therapy, which certainly could be used in this case. However, in light of recent cardiovascular outcome trials and changes in guidelines, this patient also has a compelling indication for a medication that has been shown to have benefit to reduce secondary atherosclerotic cardiovascular events. These medications could include one of the SGLT-2 (sodium-glucose cotransporter-2) inhibitors or GLP (glucagon-like peptide)-1 receptor agonists with proven benefit in cardiovascular risk reduction.9 We will discuss this topic much more later in the book (see Chapter 4 for further discussion on this point).


Case Summary and Closing Points

Type 2 diabetes is a common and, for many, a silent condition. Since most people have no symptoms early in the disease, it is common for clinicians to find and diagnose people at the time of a complication. This may be microvascular (retinopathy,
nephropathy, neuropathy) or macrovascular (acute coronary syndrome or stroke). The key to identifying type 2 diabetes as early as possible is to know the risk factors and use the evidence-based screening recommendations.



References

1. American Diabetes Association. Standards of Medical Care 2022. Classification and Diagnosis and of Diabetes; 2021. https://diabetesjournals.org/care/article/45/Supplement_1/S17/138925/2-Classification-and-Diagnosis-of-Diabetes

2. CDC. Prevalence of Both Diagnosed and Undiagnosed Diabetes; 2021. https://www.cdc.gov/diabetes/data/statistics-report/diagnosed-undiagnosed-diabetes.html

3. Norhammar A, Tenerz A, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet. 2002;359(9324):2140-2144. doi:10.1016/S0140-6736(02)09089-X

4. CDC. Diabetes Fact Sheet. https://www.cdc.gov/diabetes/data/statistics-report/diagnosed-undiagnosed-diabetes.html

5. Sukhija R, Prayaga S, Marashdeh M, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Invest Med. 2009;57:495-499.

6. Liu Y, Sayam S, Shao X, et al. Prevalence of and Trends in diabetes among Veterans, United States, 2005-2014. Prev Chronic Dis. 2017;14:E135. doi:10.5888/pcd14.170230

7. Chogtu B, Magazine R, Bairy KL. Statin use and risk of diabetes mellitus. World J Diabetes. 2015;6(2):352-357. doi:10.4239/wjd.v6.i2.352

8. Mathew R, Gucciardi E, De Melo M, Barata P. Self-management experiences among men and women with type 2 diabetes mellitus: a qualitative analysis. BMC Fam Pract. 2012;13:122. doi:10.1186/1471-2296-13-122

9. American Diabetes Association. Standards of Medical Care 2022. Pharmacologic Approach to Glycemic Control. https://diabetesjournals.org/care/article/45/Supplement_1/S125/138908/9-Pharmacologic-Approaches-to-Glycemic-Treatment




case questionsCASE QUESTIONS



1. What is the problem list for this patient?

View Answer

1. The problem list for this patient includes:

a. Obesity

b. Metabolic syndrome

c. Type 2 diabetes

d. Suspected nonalcoholic fatty liver disease

e. Albuminuria

f. Concern about depression



2. Does he have diabetes? If so, what type?

View Answer

2. His glucose value and hemoglobin A1c clearly indicate that he has diabetes. Given that he has a family history of type 2 diabetes, his body habitus matches type 2 diabetes. Further, the fact that he has dyslipidemia and presents with physical characteristics of insulin resistance, the overwhelming likelihood is that he has type 2 diabetes. While it is often thought that children only get type 1 diabetes, we now know that a sizable proportion of children diagnosed with diabetes actually have type 2 diabetes.1 Pediatric obesity is becoming an increasingly common scenario and a significant public health challenge. We are seeing more and more obese adolescents and young adults being diagnosed with metabolic-related diseases such as type 2 diabetes.1,2

Given the clinical presentation, there is no need to do any additional evaluation at this time. If he were to develop catabolic symptoms later, he could be tested for type 1 diabetes (Figure 1.3).



3. What is causing the rash?

View Answer

3. The skin changes are from acanthosis nigricans, a problem related to insulin resistance. It is most commonly seen on the neck, especially the posterior aspect of the neck in the axilla and sometimes in the groin. It may also occur on extensor surfaces.3

The pathophysiology of acanthosis is believed to be related to the excessive stimulation of epidermal keratinocytes and dermal fibroblasts. This stimulation is felt to be a result of excess endogenous insulin and insulin-like growth factor.4 These hormones rise with obesity and insulin resistance. Insulin is itself a growth factor, and it stimulates growth of many cell lines including melanin cells in the epidermis. The skin changes of plaque formation and hyperpigmentation appear when the growth rate exceeds the sloughing of cells causing the skin to thicken and becomes darker.

This rash is often mistaken for dirt or poor hygiene. It is important to recognize that there is no specific agreed upon treatment for acanthosis other than interventions that improve insulin resistance.



4. What are the next steps?

View Answer

4. There is much to consider here. It is important to explain to the patient and his family that acanthosis is a marker of high genetic risk for insulin resistance and type 2 diabetes. This helps to direct attention away from issues about weight and focus on the genetic component of type 2 diabetes. It is important to reinforce that the rash is not hygiene related. It is also important to communicate that there are no simple or direct solutions for the skin changes. The best approach is to address the underlying cause and provide accurate medical information and psychosocial support. Diabetes care guidelines recommended screening adolescents for depression at diagnosis and routine follow-up. Adolescents with type 2 diabetes are at higher risk for depression compared to the general adolescent population. Your patient indicates that he has been more socially withdrawn this year in school, which suggests potential psychosocial concerns. Screening and diagnosing depression is critical given symptoms of depression interfere with the ability to engage in self-care behaviors, like physical activity, following a healthy diet, managing weight, and monitoring blood glucose levels.






This adolescent and family need a family-based comprehensive approach to address the items noted above with a particular focus on mental health and healthy coping. (This approach will be explored in Chapter 2, Case 2.)



answers and explanationsANSWERS AND EXPLANATIONS

1. The problem list for this patient includes:

a. Obesity

b. Metabolic syndrome

c. Type 2 diabetes

d. Suspected nonalcoholic fatty liver disease

e. Albuminuria

f. Concern about depression

2. His glucose value and hemoglobin A1c clearly indicate that he has diabetes. Given that he has a family history of type 2 diabetes, his body habitus matches type 2 diabetes. Further, the fact that he has dyslipidemia and presents with physical characteristics of insulin resistance, the overwhelming likelihood is that he has type 2 diabetes. While it is often thought that children only get type 1 diabetes, we now know that a sizable proportion of children diagnosed with diabetes actually have type 2 diabetes.1 Pediatric obesity is becoming an increasingly common scenario and a significant public health challenge. We are seeing more and more obese adolescents and young adults being diagnosed with metabolic-related diseases such as type 2 diabetes.1,2

Given the clinical presentation, there is no need to do any additional evaluation at this time. If he were to develop catabolic symptoms later, he could be tested for type 1 diabetes (Figure 1.3).

3. The skin changes are from acanthosis nigricans, a problem related to insulin resistance. It is most commonly seen on the neck, especially the posterior aspect of the neck in the axilla and sometimes in the groin. It may also occur on extensor surfaces.3

The pathophysiology of acanthosis is believed to be related to the excessive stimulation of epidermal keratinocytes and dermal fibroblasts. This stimulation is felt to be a result of excess endogenous insulin and insulin-like growth factor.4 These hormones rise with obesity and insulin resistance. Insulin is itself a growth factor, and it stimulates growth of many cell lines including melanin cells in the epidermis. The skin changes of plaque formation and hyperpigmentation appear when the growth rate exceeds the sloughing of cells causing the skin to thicken and becomes darker.

This rash is often mistaken for dirt or poor hygiene. It is important to recognize that there is no specific agreed upon treatment for acanthosis other than interventions that improve insulin resistance.

4. There is much to consider here. It is important to explain to the patient and his family that acanthosis is a marker of high genetic risk for insulin resistance and type 2 diabetes. This helps to direct attention away from issues about weight and focus on the genetic component of type 2 diabetes. It is important to reinforce that the rash is not hygiene related. It is also important to communicate that there are no simple or direct solutions for the skin changes. The best approach is to address the underlying cause and provide accurate medical information and psychosocial support. Diabetes care guidelines recommended screening adolescents for depression at diagnosis and routine follow-up. Adolescents with type 2 diabetes are at higher risk for depression compared to the general adolescent population. Your patient
indicates that he has been more socially withdrawn this year in school, which suggests potential psychosocial concerns. Screening and diagnosing depression is critical given symptoms of depression interfere with the ability to engage in self-care behaviors, like physical activity, following a healthy diet, managing weight, and monitoring blood glucose levels.







This adolescent and family need a family-based comprehensive approach to address the items noted above with a particular focus on mental health and healthy coping. (This approach will be explored in Chapter 2, Case 2.)


Case Summary and Closing Points

This is a case wherein the initial presentation of type 2 diabetes is not glucose-related. It is worth remembering that skin changes are commonly the first signs of diabetes especially in at-risk populations. Further, it is important to remember that when type 2 diabetes is diagnosed in adolescents and young adults the condition is more severe and should be treated promptly and thoroughly. Optimally, this includes a team-based approach that addresses the health needs of the entire family.



References

1. Mayer-Davis EJ, Lawrence JM, Dabelea D, et al. Incidence Trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med. 2017;376(15):1419-1429.

2. Divers J, Mayer-Davis EJ, Lawrence JM, et al. Trends in incidence of type 1 and type 2 diabetes among youths—selected counties and Indian reservations, United States, 2002-2015. MMWR Morb Mortal Wkly Rep. 2020;69(6):161-165. doi:10.15585/mmwr.mm6906a3

3. Duff M, Demidova O, Blackburn S, Shubrook JH. Cutaneous manifestations of diabetes. Clin Diabetes. 2015;33(1):40-48.

4. Hines A, Alavi A, Davis MDP. Cutaneous manifestations of diabetes. Med Clin North Am. 2021;105(4):681-697. doi:10.1016/j.mcna.2021.04.008

5. Anderson BJ, McKay SV. Psychosocial issues in youth with type 2 diabetes mellitus. Curr Diab Rep. 2009;9:147-153.




case questionsCASE QUESTIONS



1. What is making him sick?

View Answer

1. This child has the “polys,” a presentation of polyuria, polydipsia, and polyphagia with weight loss. This is the classic presentation of type 1 diabetes. According to clinical presentation and labs, he is in an anion gap ketoacidosis—mostly likely diabetic ketoacidosis (DKA).

When severe hyperglycemia arises from an absolute deficiency of insulin, the body starts to use alternate fuels such as ketones to fuel the brain and other key areas. This process causes unopposed lipolysis and oxidation of free fatty acids and thereby results in ketone body production and a subsequent increased anion gap metabolic acidosis. If insulin deficiency is persistent and hyperglycemia becomes prominent, the body starts to develop catabolic symptoms (the “polys”) and weight loss. If this persists, the body becomes acidotic. Acidosis can commonly lead to symptoms such as nausea, abdominal pain, and vomiting. Most people who present with DKA as their initial finding of diabetes assume that something else is causing these symptoms such as a stomach flu.

Once the acidosis is treated, his gastrointestinal symptoms are likely to get better. He also needs fluid resuscitation. Once the fluid deficit is treated and he receives an adequate amount of insulin to prevent catabolic symptoms, his “polys” will improve.



2. Does he have diabetes? If so, what type?

View Answer

2. Glucose screening for diabetes when a child is sick is not optimal as children can have substantial hyperglycemia under severe stress.1 In this case, with a concomitant HbA1c of 9.6%, we know that the patient has been hyperglycemic for 3 months—even longer than his poly symptoms. We can confidently diagnose him with diabetes based on this and his presentation in DKA.

DKA is one of the most common presentations of new diagnosis of type 1 diabetes. Based on his lack of family history of diabetes and the presentation at age 8 with DKA, with no signs of insulin resistance, he likely has type 1 diabetes. However, there are a couple of factors to keep in mind. There is a ketosis-prone (DKA-prone) form of type 2 diabetes, albeit this is more common in young adults who are phenotypically more like type 2. Further, COVID-19 infections have been shown to increase rates of type 1 and type 2 diabetes as well as cases of sustained hyperglycemia that eventually completely resolve.2,3

His presentation is most consistent with type 1 diabetes. He should be treated as having type 1 diabetes in both the inpatient and outpatient setting until further evaluation can be completed when he is more stable.



3. What are best practices for communicating with the family regarding a new diagnosis of diabetes?

View Answer

3. Receiving a lifelong diagnosis like type 1 diabetes can be a traumatic experience for the family as well as the child. The most important thing to communicate while the child is in DKA is the child appears to have type 1 diabetes; the most immediate concern is to stabilize them; and there will be an opportunity to discuss their condition and its implications once the child is stabilized—typically the next day. Providing more information on the first day is not likely to be beneficial, as the shock of the diagnosis and the child’s condition fully occupies the family’s attention. Waiting to start diabetes education when the child is more stable is important as it allows all relevant family members to be present, improves their ability to hear the messaging, and allows everyone in the family to take in the same information. This is especially important as there are many misconceptions about what causes type 1 diabetes and what constitutes optimal treatment.

Important messages on day 2 (when the family can be assembled with the child and the child is feeling better) include the following: (1) the type of diabetes (if known); (2) how it will be treated; (3) information about whether or not it can be cured; and (4) the specific and likely impacts on the child’s and family’s daily activities. Related to message 4, the child and his family may experience a variety of feelings—fear, anger, guilt, helplessness, anxiety, etc.—about the diagnosis and what’s to come. As a provider, you can help the child and family cope with the diagnosis by acknowledging their feelings and reinforcing that the child will continue to be a contributing member of society.

Common education and treatment goals before discharge include (1) the ability of the child and key family members to check glucose, inject insulin, and check ketones; (2) knowledge of common symptoms of hyperglycemia and hypoglycemia; and (3) knowledge of how to treat hyperglycemia and hypoglycemia. There is much more to learn, but these basics are most critical to help the family feel safe enough to go home.



4. What are the next steps?

View Answer

4. Both the child and their family will have to learn many new skills and incorporate them into their daily lives for the rest of the child’s life. Recognizing the enormity of this situation, it is essential to practice patience while providing instruction for small steps that the family can achieve in a timely manner. These new skills include learning about carbohydrates, glucose monitoring, and calculating and injecting insulin—this will include basal insulin, mealtime insulin, and correction insulin. The child and family members will need to learn how to identify and treat hyperglycemia and hypoglycemia (as stated above).

All of the organizations that interact with the child will also need written instructions on how to assist the child (school, day care, extracurricular activities). A newly diagnosed child can expect to be seen every 3 to 5 days for the first 2 weeks. Children and family members should be encouraged to bring in questions with the goal of honing their abilities incrementally. Early diabetes education, in the hospital and at home, is critically important to build a strong set of diabetes self-care skills increasing the comfort and confidence of the child and family.


answers and explanationsANSWERS AND EXPLANATIONS

1. This child has the “polys,” a presentation of polyuria, polydipsia, and polyphagia with weight loss. This is the classic presentation of type 1 diabetes. According to clinical presentation and labs, he is in an anion gap ketoacidosis—mostly likely diabetic ketoacidosis (DKA).

When severe hyperglycemia arises from an absolute deficiency of insulin, the body starts to use alternate fuels such as ketones to fuel the brain and other key areas. This process causes unopposed lipolysis and oxidation of free fatty acids and thereby results in ketone body production and a subsequent increased anion gap metabolic acidosis. If insulin deficiency is persistent and hyperglycemia becomes prominent, the body starts to develop catabolic symptoms (the “polys”) and weight loss. If this persists, the body becomes acidotic. Acidosis can commonly lead to symptoms such as nausea, abdominal pain, and vomiting. Most people who present with DKA as their initial finding of diabetes assume that something else is causing these symptoms such as a stomach flu.

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Jun 17, 2023 | Posted by in ENDOCRINOLOGY | Comments Off on Clinical Presentation

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