Pathophysiology of Type 2 Diabetes

Question 1

Type II diabetes

Answer 1

Decreased insulin secretion, aka β cell dysfunction + decreased insulin sensitivity, aka insulin resistance

Can be characterized by:

High blood glucose levels (hyperglycemia)

Microvascular and neuropathic complications: degenerative changes in the eyes (retinopathy), kidneys (nephropathy), peripheral and autonomic nerves (neuropathy)

Macrovascular complications: accelerated atherosclerosis affecting coronary and peripheral blood vessels

Question 2

What clinical features suggest type 2 diabetes?

Answer 2

Central (abdominal) obesity, glucose intolerance, hypertension, atherosclerosis, polycystic ovary syndrome (PCOS)

Question 3

Lab values for prediabetes (impaired glucose tolerance IGT or impaired fasting glucose IFG)

Answer 3

HbA1c 5.7-6.4 (DCCT assay)

Fasting plasma glucose (FPG) levels greater than 100 mg/dL but

Question 4

Recommendations for pre-diabetics

Answer 4

Yearly screening for diabetes, intervention with diet and exercise

Only pharmacological intervention is metformin

Question 5

Normal plasma glucose values in healthy, non-pregnant adults

Answer 5

Fasting plasma glucose

Question 6

Criteria for diabetes

Answer 6

HbA1c >6.5% (assay standardized to the DCCT assay)

OR

FPG 126 mg/dL = provisional diagnosis of diabetes (the diagnosis must be confirmed).

OR

2-hr post-load glucose 200 mg/dl = provisional diagnosis of diabetes (the diagnosis must be confirmed)

Question 7

2 key factors in the pathophysiology of type 2 diabetes

Answer 7

Insulin resistance and Beta Cell dysfunction

Patients with type 2 diabetes or impaired glucose tolerance have both decreased β-cell function and decreased insulin sensitivity (i.e. insulin resistance).

Must have decreased insulin secretion (genetic predisposition to β-cell dysfunction) and insulin resistance (lifestyle, high fat diet, obesity, genetic, aging) to develop Type-2 diabetes.

The pancreatic β-cells are unable to compensate for the defects in insulin action, and fail to secrete enough insulin. It is at this point that hyperglycemia develops.

Question 8

Role of genetics in the development of type 2 diabetes

Answer 8

Increased risk:
Familial aggregation
African American, Hispanic, Pima Indians of Arizona, Pacific Islander
Twins

Type 2 diabetes is:
Polygenic
No association with HLA

Question 9

What interventions have been shown to prevent type 2 diabetes in high risk subjects?

Answer 9

Yearly screening for diabetes
30 mins. of exercise 5 days a week (150 minutes/week) and loss of 3 - 5% of body mass equals a 60% reduction in risk.
Weight maintenance or loss
Diet affects glucose production and glucose absorption
Metformin
Full CVD risk profiles and intervention
Diet and exercise is optimal treatment for diabetes

Question 10

Insulin secretion in pts with type 2 diabetes

Answer 10

Insulin secretion is diminished in nearly all patients with type 2 DM for more than 10 years, making insulin necessary for optimal glycemic control

Question 11

Diabetic Ketoacidosis

Answer 11

Severe insulin deficiency leading to extreme hyperglycemia (usually glucose >300mg/dl), an increased anion gap metabolic acidosis (usually pH 5 mM)

Lack of insulin plus an increase in counter-regulatory hormones.

The low insulin/glucagon ratio also promotes/permits ketogenesis in the liver

Both increased production and decreased utilization of glucose and ketones, increase their serum levels

As the dehydration progresses the decrease in renal blood flow and resultant decrease in GFR reduces the kidney’s ability to excrete glucose and hyperosmolality is thus worsened.

Question 12

What is the most common precipitation cause of DKA?

Answer 12

Infection often accompanied by misguided omission of insulin

Question 13

Presentation of hyperglycemia

Answer 13

polyuria, polydypsia, weight loss, weakness

acutely: abdominal pain, nausea, vomiting

Question 14

Treatment of DKA

Answer 14

Insulin and fluid replacement

Question 15

Hypoglycemia in diabetes

Answer 15

Most common acute complication of diabetes

Symptoms can be divided into two categories: adrenergic (excessive secretion of epinephrine), and neuroglycopenic (due to dysfunction of the central nervous system (CNS) because of hypoglycemia)

2-3 times more common in patients trying to normalize blood glucose with intensive insulin regimens

Question 16

Symptoms of hypoglycemia

Answer 16

Adrenergic:
Sweating
Tremor
Tachycardia
Anxiety 
Hunger

Neuroglycopenic:
Confusion
Convulsions
Loss of consciousness
Dizziness 
Headache
Decreased mental activity
Clouding of vision

Question 17

What is the primary defense against hypoglycemia in type 1 diabetes

Answer 17

epinephrine