Pathophysiology of Type II Diabetes

Question 1

1. List the clinical features that suggest type 2 diabetes.

Answer 1

usually greater than 40, 
90% obese, 
\+ family history, 
insulin resistant, 
usually eventually requires insulin Tx

Question 2

2. List the criteria used to define diabetes, impaired glucose tolerance, impaired fasting glucose and gestational diabetes.

Answer 2

CRIERIA FOR DIABETES MELLITUS
1. HbA1c >6.5% (assay standardized to the DCCT assay)
OR
2. The diagnostic categories using fasting plasma glucose
• FPG less than 100 mg/dL = normal fasting glucose
• FPG 100–125 mg/dL = IFG (impaired fasting glucose)
• FPG 126 mg/dL = provisional diagnosis of diabetes (the diagnosis must be confirmed, as described below).
OR
3. The corresponding categories when the OGTT is used
• 2 hr post-load glucose

Question 3

3. Discuss the 2 key factors in the pathophysiology of type 2 diabetes (insulin resistace and beta cell dysfunction).

Answer 3

, β-cell dysfunction is critical in the pathogenesis of type 2 diabetes.

. Insulin resistance is the second key element in the pathogenesis of hyperglycemia in type 2 diabetes.

Question 4

4. Describe interventions that have been shown to prevent type 2 diabetes in high-risk subjects

Answer 4

LIFESTYLE

Question 5

5. Describe the role of genetics in the development of type 2 diabetes.

Answer 5

• Familial aggregation of type 2 DM is much more common than is the case with type 1 DM. Diabetes or abnormalities of glucose tolerance can be found in up to 38% of siblings and about 1/3 of the offspring of individuals with type 2 DM.
• Prevalence is increased 1 to 3-fold in African-Americans and Hispanics. In the Pima Indians of Arizona, the prevalence of type 2 DM is >40%, the highest in the world.
• The concordance rate for type 2 DM in identical twins is 90-100% compared to

Question 6

6. Recognize the acute complications of diabetes including Diabetic Ketoacidosis

Answer 6

DKA- severe insulin deficiency leading to extreme hyperglycemia (usually glucose >300mg/dl), an increased anion gap metabolic acidosis (usually pH 5 mM).
The pathogenesis of DKA involves a lack of insulin plus an increase in counter-regulatory hormones. The low insulin/glucagon ratio also promotes/permits ketogenesis in the liver
Thus, there is both increased production and decreased utilization to increase serum glucose and ketones in DKA.
Hyperglycemia results in glycosuria and polyuria, resulting in an osmotic diuresis with loss of fluid and electrolytes. Polydypsia and polyphagia also result. As a result of the osmotic diuresis, there is weight loss and severe dehydration. 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.

Physical Findings:
altered mental state, dehydration including loss of skin turgor, hypotension, and weakness.
Postural hypotension
tachycardia will likely be present.

Precipitating Causes:
infection –>misguided omission of insulin.
Noncompliance and deliberate omission of insulin is common in younger patients.
In older patients serious underlying causes such as myocardial infarction, CVA or pneumonia should be searched for.

Establishing the Diagnosis:
Blood glucose >200 mg/dl is considered necessary for diagnosis of DKA. Urinary ketones can be detected by a urine dipstick in ER if urine is available. Serum β-hydroxybutyrate is positive in ketoacidosis with a turn-around time of one hour.

Treatment of Diabetic Ketoacidosis (INSULIN and VOLUME REPLACEMENT):
Insulin will inhibit both gluconeogenesis and ketogenesis while promoting utilization of glucose and ketoacids.

Fluid replacement will help restore blood volume and improve kidney perfusion. In doing so the kidney is better able to clear glucose and restore bicarbonate. Restoration of normovolemia will also decrease the stimuli to counter regulatory proteins.

GENERAL THERAPEUTIC GOALS IN THE TREATMENT OF DKA:
» Improve circulatory volume and tissue perfusion
» Decrease serum glucose
» Clear the serum and urine of ketoacids
» Decrease counter-regulatory hormones
» Correct electrolyte imbalance
» Avoid cerebral edema in children

Question 7

CRITERIA for PRE-DIABETES

Answer 7

One of the following must be met: HbA1c 5.7-6.4% OR fasting plasma glucose of 100-125 mg/dL, OR a 2 hr OGTT plasma glucose value >140 and 200 mg/dl, need to be repeated to confirm dx.

Question 8

major environmental risk factor

Answer 8

sedentary lifestyle and the development of obesity

Question 9

metabolic syndrome

Answer 9

• Waist circumference >40 inches in men and >35 inches in women
• Triglycerides >150 mg/ld.
• HDL men 130/88
• FBG >100 mg/dl

Question 10

Hypoglycemia Unawareness

Answer 10

Hypoglycemic unawareness occurs when the patient no longer has the adrenergic warning signs of diabetes and may go into an altered mental state with no warning symptoms at all. This is more common in patients who have frequent hypoglycemia. The cause is uncertain, but it is more common in well-controlled patients and may be caused by alterations in delivery of glucose to the brain. The treatment of hypoglycemic unawareness is scrupulous avoidance of hypoglycemia for 3 or more weeks. Hypoglycemic unawareness is different than the loss of epinephrine-induced symptoms because of autonomic neuropathy in long-standing diabetes, which is not reversible.