Diabetes Dx & Pathophys

Question 1

diabetes - defined

Answer 1

*a disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both
*various types of diabetes:
-type 1 = beta cell destruction; no insulin secretion
-type 2 = insulin resistance; defect in insulin action
-gestational = beta cell dysfunction and insulin resistance during pregnancy
-miscellaneous = drug induced, exocrine pancreatic disease, monogenic diabetes (MODY), LADA

Question 2

diabetes - clinical presentation

Answer 2

1. often asymptomatic
2. the 3 P’s: polyuria, polydipsia, polyphagia
   -excess glucose causes osmotic diuresis → polydipsia
   -glucose cannot enter cells → low energy → polyphagia
3. weight loss (body is unable to utilize glucose as fuel; muscle & fat are broken down as alternatives)
4. blurry vision, distal paresthesias
5. diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS)

Question 3

diabetes - diagnosis

Answer 3

1. 8hr fasting plasma glucose 126+ mg/dL
2. 2hr glucose tolerance test 200+ mg/dL (check fasting plasma glucose, drink 75g glucose drink, then recheck glucose 2hrs later)
3. random plasma glucose 200+ AND hyperglycemia sx present
4. HbA1c 6.5% or higher
   *note - cannot rely on just one test: either repeat the same test or perform another to officially make the dx

Question 4

hemoglobin A1c (HbA1c) - overview

Answer 4

*glucose attaches to Hb by nonenzymatic glycosylating in a high glucose environment (more glucose in blood → more glucose attaches to Hb)
*A1c represents the average glucose over a 3-month period (average lifespan on an RBC)
*assumes stable Hb (blood transfusions, hemoglobinopathies, etc can change HbA1c)

Question 5

why do we treat diabetes?

Answer 5

*diabetes, when uncontrolled, can lead to multiple complications over time
*heart disease is the leading cause of death for pts with diabetes

Question 6

type 1 diabetes - overview

Answer 6

*characterized by autoimmune destruction of the pancreatic beta cells, resulting in absent insulin secretion
*most cases are diagnosed before age 18

Question 7

type 1 diabetes (T1DM) - pathogenesis

Answer 7

*beta cell destruction is mediated by both T and B lymphocytes:
-T lymphocytes - infiltrate the islets and destroy the beta cells (insulitis)
-B lymphocytes - autoantibody-mediated destruction of beta islet cells
*antibodies also target glutamic acid decarboxylase (GAD), an enzyme that controls insulin release from the beta cells
*a type IV cell-mediated hypersensitivity reaction

Question 8

type 1 diabetes (T1DM) - presentation

Answer 8

*often symptomatic at the time of dx as patients present with severe hyperglycemia
*polyuria, polydipsia, polyphagia

Question 9

type 1 diabetes (T1DM) - diagnosis

Answer 9

*diagnose with previous screening tests (fasting glucose, glucose tolerance test, HbA1c, etc) AND:
-anti-glutamic acid decarboxylase antibodies (GAD)
-other antibodies: islet cell cytoplasmic antibodies, insulin antibodies, etc

Question 10

type 1 diabetes (T1DM) - associations

Answer 10

*associated with mutations in HLA antigens: HLA-DR3 and HLA-DR4 but T1DM has a weaker genetic component than T2DM
*associated with other autoimmune conditions: hypothyroidism, vitiligo, celiac disease

Question 11

type 1 diabetes (T1DM) - prognosis

Answer 11

*without insulin, T1DM is fatal
*now, good prognosis

Question 12

type 2 diabetes (T2DM) - overview

Answer 12

*a “relative” insulin deficiency; a mismatch between insulin production and requirements driven by insulin resistance
*insulin resistance:
-a decrease in tissue responsiveness to insulin
-increased insulin levels required to maintain normal glucose

Question 13

type 2 diabetes (T2DM) - pathophysiology

Answer 13

*cause of insulin resistance unclear but correlates with obesity, sedentary lifestyle, high triglycerides, inflammation, and cytokines
*beta cells compensate initially with excess insulin secretion, but continued hyperglycemia can impair beta cell function and they fail → T2DM; a vicious cycle

Question 14

type 2 diabetes (T2DM) - epidemiology

Answer 14

*diagnosed in adulthood, usually > 40yo
*age of onset is shifting to younger adults/kids with obesity on the rise

Question 15

type 2 diabetes (T2DM) - associations

Answer 15

*obesity increases the risk of metabolic syndrome: constellation of visceral or intra-abdominal adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, HLD, and low HDL
*metabolic syndrome, in turn, increases the risk of T2DM and CVD

Question 16

type 2 diabetes (T2DM) - presentation

Answer 16

*often asymptomatic early in dx, or BG only mildly elevated; as disease progresses and more profound hyperglycemia develops, sx develop
*signs of insulin resistance:
-acanthosis nigricans (hyperpigmentation in skin folds; high circulating insulin levels cross react with IGF-1 receptors in skin)
-skin tags
-central adiposity

Question 17

gestational diabetes - overview

Answer 17

*diabetes that is diagnosed during pregnancy
*increasing insulin resistance with progression of pregnancy, but mother’s pancreas is unable to secrete enough insulin to match her needs, causing hyperglycemia

Question 18

gestational diabetes - pathophysiology

Answer 18

*driver of insulin resistance and insulin secretion in pregnancy: human placental lactogen
*increased insulin resistance = pregnant women is less able to use glucose, causing postprandial glucose levels to increase and there is increased lipolysis in her body
*the glucose that she is not able to take up in her cells are instead taken up and used by the fetus

Question 19

gestational diabetes - risk factors

Answer 19

*age 25-30 or older
*Hispanic, African American, Native American, Asian, Pacific Islander
*obesity (BMI > 30)
*excessive gestational weight gain
*history of glucose intolerance, PCOS, prior GDM
*previous birth of a large infant (>9lbs)
*multiple gestations
*family history of diabetes

Question 20

gestational diabetes - maternal complications

Answer 20

*preeclampsia (HTN, protein in urine, potentially fatal)
*polyhydramnios (excess amniotic fluid):
-fetal malposition
-maternal respiratory compromise
-placental abruption
-preterm contractions/labor
-uterine atony
-umbilical cord prolapse

Question 21

gestational diabetes - fetal complications

Answer 21

*macrosomia (large for gestational age infants)
-risk of shoulder dystocia, brachial plexus injuries, clavicle fractures
*premature birth
*post-delivery complications:
-hypoglycemia, hypocalcemia, iron deficiency anemia, polycythemia, hyperbilirubinemia

Question 22

gestational diabetes - screening

Answer 22

*screen at 24-28 wks (1hr oral glucose tolerance test or 2hr OGTT)

Question 23

gestational diabetes - treatment

Answer 23

*lifestyle/diet changes
*insulin
*metformin or glipizide

Question 24

monogenic diabetes (MODY)

Answer 24

*aka maturity-onset diabetes of the young (MODY)
*onset of diabetes in late childhood or before the age f 25
*negative testing for diabetes autoantibodies
*defect is in glucose-stimulated insulin secretion
*autosomal dominant diabetes inheritance
*pts are usually not obese and do not have signs/symptoms of insulin resistance
*pts may not require insulin therapy

Question 25

drug-induced diabetes

Answer 25

*most commonly associated with glucocorticoids (prednisone, dexamethasone, hydrocortisone)
*glucocorticoids causes a supraphysiologic hypercortisolemic state which induces insulin resistance (steroid induced diabetes)
*checkpoint inhibitors such as monoclonal antibodies against PD-1 and CTLA-4 are associated with development of autoimmune diabetes

Question 26

latent autoimmune diabetes in adults (LADA)

Answer 26

*type 1 diabetes diagnosed later in life
*similar pathophys with autoimmune destruction of pancreatic beta islet cells; generally GAD antibodies are checked
*often misdiagnosed as T2DM b/c pts initially retain some beta islet cell function, but diminishes over time

Question 27

prediabetes

Answer 27

*impaired fasting glucose or impaired glucose tolerance but not to the degree of overt diabetes
*diagnosis:
-fasting plasma glucose 100-125 mg/dl
-oral glucose tolerance results 140-199 mg/dl
-HbA1c 5.7-6.4%
*focus on dietary modifications, weight loss (if applicable), and regular moderate intensity exercise as first line approach