DIABETES MELLITUS: ETIOLOGY, CLASSIFICATION, AND DIAGNOSIS

Question 1

What is diabetes mellitus?

Answer 1

A term that encompasses a heterogeneous group of metabolic disorders characterized by elevated blood glucose levels.

Question 2

What is the origin of the term diabetes mellitus?

Answer 2

The term diabetes comes from Arateus and the Greek word ‘diabainein’, meaning ‘siphon’, while ‘mellitus’ was coined by Thomas Willis in 1675 due to the sweet nature of urine in affected individuals.

Question 3

What is the epidemiology of diabetes?

Answer 3

Approximately 1.5 million Americans are diagnosed each year; 30 million Americans had diabetes in 2015, with 1.25 million having type 1 diabetes. 7.2 million adults remain undiagnosed and about 84 million have prediabetes.

Question 4

Which population has the highest rate of diabetes?

Answer 4

American Indians and Alaskan Natives have the highest rate of diabetes (15.1%).

Question 5

What are the underlying pathophysiological differences between type 1 and type 2 diabetes?

Answer 5

Type 1 diabetes results from autoimmune destruction of pancreatic beta cells causing insulin deficiency. Type 2 diabetes is characterized by excessive hepatic glucose production, tissue insulin resistance, and relative insulin deficiency.

Question 6

Why do people get diabetes?

Answer 6

Type 1 diabetes has an inherited susceptibility and environmental triggers; type 2 diabetes has a stronger genetic influence and established triggers like obesity and physical inactivity.

Question 7

How is diabetes diagnosed?

Answer 7

Diabetes is diagnosed through laboratory testing using criteria such as:
* Hemoglobin A1c (HbA1c) ≥ 6.5%
* Fasting plasma glucose ≥ 126 mg/dL
* Random plasma glucose ≥ 200 mg/dL with classic symptoms
* Oral glucose tolerance test with 2-hour plasma glucose ≥ 200 mg/dL after a 75-g load.

Question 8

What is the current classification for different types of diabetes?

Answer 8

The current classification includes:
* Type 1
* Type 2
* Type 3c (pancreatogenous)
* Gestational (type 4)
* Latent autoimmune diabetes of adulthood (LADA)
* Maturity-onset diabetes of the young (MODY).

Question 9

What are the five clusters proposed by European investigators for classifying diabetes?

Answer 9

The five clusters are:
* Cluster 1: Severe autoimmune diabetes
* Cluster 2: Severe insulin-deficient diabetes
* Cluster 3: Severe insulin-resistant diabetes
* Cluster 4: Mild obesity-related diabetes
* Cluster 5: Mild age-related diabetes.

Question 10

What does the classification based on antibody status and beta cell function include?

Answer 10

It includes:
* A1/b1: Presence of autoantibodies but preserved beta cell function (e.g., LADA)
* A1/b2: Presence of autoantibodies and absent beta cell function (e.g., type 1 DM)
* A2/b1: Absence of autoantibodies and preserved beta cell function (e.g., type 2 DM)
* A2/b2: Absence of autoantibodies with absent beta cell function (e.g., type 3c DM).

Question 11

What is the lifelong requirement for type 1 diabetes?

Answer 11

Insulin therapy

Patients with type 1 diabetes require insulin therapy for life to manage their condition.

Question 12

What is the ‘honeymoon phase’ in type 1 diabetes?

Answer 12

A period when beta cells produce small amounts of insulin

During this phase, patients may still require insulin but at smaller doses.

Question 13

What life-threatening condition can develop without insulin therapy in type 1 diabetes?

Answer 13

Diabetic ketoacidosis (DKA)

DKA is a severe complication of uncontrolled diabetes.

Question 14

What chronic complications can arise from uncontrolled hyperglycemia in type 1 diabetes?

Answer 14

Retinopathy, diabetic kidney disease, neuropathy

Chronic complications are serious and can lead to significant health issues.

Question 15

What typically occurs in the natural history of type 2 diabetes?

Answer 15

Insulin resistance followed by insulin deficiency

Over time, the ability of pancreatic beta cells to produce insulin diminishes.

Question 16

What is a common initial treatment for type 2 diabetes?

Answer 16

Noninsulin medications

These medications can help restore normal blood sugar levels initially.

Question 17

What may be added to the treatment regimen if glycemic control is not achieved in type 2 diabetes?

Answer 17

Insulin

Insulin may be required if multiple noninsulin agents are insufficient.

Question 18

What is an effective strategy to reduce insulin resistance in type 2 diabetes?

Answer 18

Weight loss

Losing weight can help improve insulin sensitivity.

Question 19

Who is more likely to develop ketosis-prone diabetes?

Answer 19

Nonwhite individuals

This form of diabetes is less commonly encountered.

Question 20

What happens to beta cell function after DKA resolution in ketosis-prone diabetes?

Answer 20

Function is often recovered

Patients may be able to taper off insulin therapy after recovery.

Question 21

What is LADA?

Answer 21

Latent autoimmune diabetes in adults

LADA is an autoimmune form of diabetes that presents later in life.

Question 22

What distinguishes LADA from type 2 diabetes?

Answer 22

Presence of positive antibodies (usually GAD Ab)

Patients with LADA may initially require noninsulin agents.

Question 23

What is a common non-diabetes-related cause of hyperglycemia?

Answer 23

Glucocorticoid administration

Steroids can lead to elevated blood sugar, especially in those with glucose intolerance.

Question 24

What critical conditions can cause hyperglycemia?

Answer 24

Infections, stress-induced cortisol increase

Critical illnesses can exacerbate blood sugar levels.

Question 25

What syndrome is associated with endogenous hypercortisolism?

Answer 25

Cushing syndrome ## Footnote It can result from various tumors leading to excess cortisol production.

Question 26

What rare causes of hyperglycemia are associated with hormone-secreting tumors?

Answer 26

Acromegaly, pheochromocytoma, paraganglioma ## Footnote These tumors can lead to elevated glucose levels through hormonal effects.

Question 27

What is a risk factor for hyperglycemia in hospitalized patients?

Answer 27

Receiving intravenous dextrose or enteral nutrition ## Footnote Nonphysiologic nutrition methods can elevate blood sugar levels.

Question 28

What is type 3c diabetes?

Answer 28

Type 3c diabetes, also known as pancreatogenic or pancreatogenous diabetes, is a form of diabetes that develops when nonautoimmune disorders of the pancreas compromise pancreatic endocrine function, resulting in decreased insulin production. ## Footnote Patients most likely to develop type 3c diabetes include those with recurrent acute pancreatitis, chronic pancreatitis, abdominal trauma, or those who have undergone pancreatectomy.

Question 29

Who should be screened for diabetes?

Answer 29

Screening for diabetes is recommended for: * Overweight and obese adults ages 40 to 70 years * Individuals with a family history of diabetes * Those with a history of gestational diabetes or polycystic ovarian syndrome * Members of certain racial/ethnic groups (African American, American Indian or Alaskan Native, Asian American, Hispanic or Latino American, Native Hawaiian/Pacific Islander). ## Footnote The USPSTF recommends screening for abnormal fasting plasma glucose levels, while the ADA suggests screening every 3 years starting at age 45.

Question 30

Can diabetes be prevented?

Answer 30

Diabetes can be prevented through: * Intensive lifestyle modifications in patients with prediabetes * Pharmacotherapy for high-risk individuals with multiple risk factors * Lifestyle changes for those with persistently elevated HbA1c levels. ## Footnote No therapies have been shown to effectively prevent the progression of type 1 diabetes.

Question 31

What is monogenic diabetes?

Answer 31

Monogenic diabetes results from single gene mutations causing pancreatic beta cell dysfunction or insulin signaling defects, typically diagnosed in young patients who do not require insulin and lack autoantibodies. ## Footnote Common forms include neonatal diabetes and MODY, which are treated differently based on the specific genetic mutation.

Question 32

How can insulin resistance be assessed clinically?

Answer 32

Insulin resistance can be assessed through: * Clinical manifestations such as acanthosis nigricans, skin tags, hirsutism, ovarian hyperandrogenism, and androgenic alopecia * Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score using fasting blood glucose and serum insulin levels. ## Footnote Acanthosis nigricans is the most recognized sign, characterized by symmetric, velvety, thickened skin.

Question 33

What is metabolic syndrome?

Answer 33

Metabolic syndrome is diagnosed when a patient has at least 3 out of 5 of the following: * Hyperglycemia * Hypertension * Hypertriglyceridemia * Low levels of high-density lipoprotein (HDL) * Increased abdominal circumference. ## Footnote It is associated with increased risk of heart disease, stroke, and diabetes, requiring intensive lifestyle modifications and often medication.

Question 34

What is diabetes a result of?

Answer 34

Absolute or relative insulin deficiency.

Question 35

What happens in type 1 diabetes?

Answer 35

Beta cells are destroyed, resulting in complete insulin deficiency.

Question 36

What occurs in type 2 diabetes?

Answer 36

Beta cells cannot produce enough insulin to compensate for underlying insulin resistance.

Question 37

How is diabetes diagnosed?

Answer 37

Via blood testing with abnormal results on two separate occasions.

Question 38

What are the diagnostic criteria for diabetes?

Answer 38

HbA1c ≥ 6.5%, fasting plasma glucose ≥ 126 mg/dL, random plasma glucose ≥ 200 mg/dL, or plasma glucose ≥ 200 mg/dL after a 75-g glucose load during an OGTT.

Question 39

List the types of diabetes according to one classification method.

Answer 39

* Type 1 * Type 2 * Type 3c * Gestational (Type 4) * Other

Question 40

How can diabetes be conceptualized beyond traditional classifications?

Answer 40

As falling on a spectrum of autoimmunity and beta cell function (A1/b2).

Question 41

What recent proposal has been made regarding diabetes classification?

Answer 41

Dividing diabetes into five distinct groups to predict diabetes-related outcomes.

Question 42

What therapy do patients with type 1 diabetes require?

Answer 42

Lifelong insulin therapy.

Question 43

What is a 'honeymoon phase' in type 1 diabetes?

Answer 43

A short-lived initial phase where pancreatic beta cells can still produce a small amount of insulin.

Question 44

What characterizes the natural history of type 2 diabetes?

Answer 44

Insulin resistance develops before beta cell dysfunction.

Question 45

What percentage of type 2 diabetes patients in the U.S. are on insulin therapy?

Answer 45

Approximately half.

Question 46

What should be considered when evaluating a patient with hyperglycemia?

Answer 46

A new diagnosis of diabetes or preexisting diabetes.

Question 47

What are some causes of stress hyperglycemia?

Answer 47

* Glucocorticoids * Critical illness * Medical therapies (enteral or parenteral nutrition)

Question 48

What are rare causes of hyperglycemia and diabetes?

Answer 48

* Acromegaly * Pheochromocytoma