Diabetes Mellitus

Question 1

Type 1: Age of Onset

Answer 1

Peak in early childhood and adolescence

Question 2

Type 2: Age at Onset

Answer 2

Post-pubertal

Question 3

Type 1: Ketosis at Onset

Answer 3

Common

Question 4

Type 2: Ketosis at Onset

Answer 4

Uncommon

Question 5

Type 1: Family Hx

Answer 5

5-10%

Question 6

Type 2: Family Hx

Answer 6

> 50%

Question 7

Type 1: Pathophysiology

Answer 7

Autoimmune disease

Question 8

Type 2: Pathophysiology

Answer 8

Insulin resistance

Question 9

Type 1: Associated Conditions

Answer 9

• Autoimmune thyroid disease
• Celiac disease
• Addison’s disease

Question 10

Type 2: Associated Conditions

Answer 10

• Obesity
• Lipid abnormalities
• PCOS
• NAFLD
• Sedentary/inactive

Question 11

Type 1: Blood Glucose

Answer 11

Overtly elevated

Question 12

Type 2: Blood Glucose

Answer 12

Mild to moderate elevation

Question 13

Type 1: Insulin

Answer 13

Absent

Question 14

Type 2: Insulin

Answer 14

Elevated until later in progression

Question 15

Type 1: C-Peptide

Answer 15

Absent

Question 16

Type 2: C-Peptide

Answer 16

Elevated until later in progression

Question 17

Obesity’s Role in Development of T2DM

Answer 17

• Adipose tissue is inflamed and recruits M1 macrophages –> adipose tissue releases more inflamatory markers –> disruption of adipokines –> release of FAs
• Associated with IL-6 and other pro-inflammatory markers (TNF alpha, IFN gamma, CRP)

Question 18

T2DM stems from an initial ___ ____

Answer 18

Insulin resistance

Question 19

Incretin Effect is abolished in:

Answer 19

T2DM
- Release of GI peptides is lost and thus insulin release is primarily due to glucose alone

Question 20

Timeline of Insulin Resistance Progressing to T2DM

Answer 20

(1) Peripheral systemic insulin resistance
(2) Reactive hyperinsulinemia – postprandial glucose levels are not normal but more insulin is required to do the job (reactive hyperinsulinemia)
(3) Postprandial hyperglycemia
(4) Disrupted response to oral glucose tolerance test
(5) Blunted incretin release
(6) Chronic elevated insulin levels
(7) Mild to moderate chronically elevated glucose levels
(8) Frank hyperglycemia

Timeline of development can be 5-30 years

Question 21

Pre-Diabetes

Answer 21

Timeline: -10 years to 0 years (time of Dx)
- Gradual decrease in beta cell function
- Gradual increase in insulin resistance
- Sharp increase in insulin secretion that starts to decrease when near time of dx
- Increasing postprandial glucose levels
- Increasing fasting glucose

Question 22

T1DM: Patient Characteristics

Answer 22

• Skinny
• Polydipsia
• Polyuria
• High blood glucose levels
• DKA

Question 23

Type 1 DM

Answer 23

• Disease of inadequate insulin secretion
• T-cell mediated destruction of beta cells, often from autoimmune disease (no insulin or C-Peptide produced)
• Increased blood glucose, FAs, ketoacids, AAs, increased conversion of FA to Ketoacids

Question 24

Decreased utilization of Ketoacids results in:

Answer 24

Diabetic Ketoacidosis (DKA)

Question 25

T1DM: Osmotic Diuresis / Glucosuria

Answer 25

- Increased blood glucose increases filtered load of glucose, exceeds reabsorptive capacity of proximal tubule - Water and electrolyte reabsorption also blunted - Polyuria and thirst (polydipsia)

Question 26

T1DM: Hyperkalemia (Shift of K+ out of Cells)

Answer 26

- Intracellular concentration of K+ is low - Lack of insulin effect on Na/K ATPase - Plasma levels may be normal, total K+ is usually low due to polyuria and dehydration

Question 27

Development of T1DM: HLA Class II Alleles

Answer 27

- DQ2/DQ8 found in more than 90% of individuals - Heterogenous genotypes DR3/DR4 are most common in children diagnosed prior to age 5 - HLA Class II that lack Asp57 of the beta chain a

Question 28

Purpose of Insulin Injections

Answer 28

- Goal is to recreate normal physiology (basal and bolus insulin) - Timing insulin dose to meal consumption helps mimic physiological response

Question 29

T1DM: Environmental Causes

Answer 29

- Obesity - Viral infections - Too few childhood infections dampening the effectiveness of the immune system - Wheat gluten - Vitamin D deficiency - Early exposure to cows milk

Question 30

Complications from DM:

Answer 30

- Increased risk of CVD and ischemic vascular disease - Increased risk of non-fatty liver disease (NFLD) - Steatohepatitis - Increased risk of kidney failure - Risk of blindness - Skin ulcers and amputations - Reduced wound healing