6th Unit / Ch 25 Diabetes Mellitus Flashcards
Type 1 Diabetes 25 1.1
What are the three symptoms of T1D that typically accompany the progressive onset of clinical
disease, as shown?
Patients with T1D typically present with three Ps: (1) polyuria (frequent urination), (2) polydipsia (excessive thirst), and (3) polyphagia (excessive hunger) accompanied by fatigue and weight loss.
Progressive autoimmune pancreatic B-cell destruction results in
absolute insulin deficiency.
Type 1 Diabetes 25 1.2
How is the diagnosis of T1D confirmed?
- *T1D** diagnosis is confirmed by a HbA 1c level + 6.5 mg/dl, a FBG + 126 mg/dl, or a non-FBG
(random) + 200 mg/dl. T1D accounts for + 10% of the known cases of diabetes.
Type 1 Diabetes 25 1.3
What is the oral glucose tolerance test (OGTT)? For what reason is the test most typically used?
The OGTT reveals how quickly ingested glucose (75 g) is removed from the blood over a 2-hour period. The test is most typically used to screen those pregnant women at increased risk
for gestational diabetes and is done between 24 and 28 weeks of pregnancy. About 4% of pregnancies are affected.
Type 1 Diabetes 25 1.4
Why is dehydration a common symptom of hyperglycemia?
The renal tubules reclaim glucose via the SGLT-2, which is saturated at -180 mg/dl of glucose. Above this concentration, glucose “spills” into the urine causing increased urine output
( osmotic diuresis ), which can result in severe dehydration . It also accounts for the characteristic
polyuria and polydipsia of T1D.
Metabolic Changes in Type 1 Diabetes 25 2.1
What are the two causes of hyperglycemia in T1D?
Hyperglycemia in T1D is caused by (1) increased
gluconeogenesis because the fall in the insulin/glucagon ratio
makes glucose precursors available and (2) decreased glucose
uptake into muscle and adipose tissues because their insulin sensitive
GLUT-4s are not transported from intracellular vesicles to the cell surface.
Metabolic Changes in Type 1 Diabetes 25 2.2
Why is hypertriglyceridemia seen in T1D?
LPL degrades TAGs in circulating CMs and VLDLs.
Apo-CII on their surface activates the enzyme. In T1D,
the absence of insulin results
in downregulation of LPL expression in adipose, causing
hypertriglyceridemia.
Metabolic Changes in Type 1 Diabetes 25 2.3
Why does ketoacidosis occur in T1D?
In T1D, intracellular lipolysis by HSL is activated and FA
mobilization from adipose TAGs occurs. In hepatocytes, the
lack of insulin coupled with the increased supply of FFAs results in accelerated B-oxidation, the products of which are NADH, acetyl CoA, and ATP. The buildup of ATP and NADH inhibits
TCA cycle enzymes, pushing acetyl CoA to ketogenesis. Excessive KB production can result in DKA.
[ Note: FAs in excess of the liver’s capacity to oxidize
them are converted to TAGs and secreted as VLDLs, contributing to the hypertriglyceridemia.]
Type 1 Diabetes Treatment 25 3.1
Which of the three colored arrows shown represents the typical mean blood glucose value obtained with standard insulin therapy for T1D?
Standard insulin therapy (typically one or two injections of recombinant human insulin per day) for T1D is
represented by the blue arrow. The glucose levels obtained with this treatment range from 225 to 275 mg/dl,
with a HbA 1c level at 9% of the total Hb.
Type 1 Diabetes Treatment 25 3.2
Why does intensive insulin therapy result in a three-fold increase in the frequency of hypoglycemia? In spite of the risk, why might physicians choose intensive therapy in treating their patients with T1D?
The goal of intensive insulin therapy (red arrow) is to maintain tight control of blood glucose levels, accomplished with more frequent glucose readings and three or more injections of insulin per day. However, it is difficult to accurately titrate the appropriate dosage of insulin and hypoglycemia is a common complication
(shown). Nonetheless, the benefits of intensive therapy outweigh the risks in most populations. Patients on intensive
therapy show a +50% reduction in the long-term microvascular complications of diabetes (i.e., retinopathy ,
neuropathy, and nephropathy ) and lower HbA 1c values.
Type 1 Diabetes Treatment 25 3.3
What is “hypoglycemia unawareness”?
Patients with T1D develop glucagon secretion deficiency early in the disease and rely on epinephrine to prevent severe hypoglycemia. However, as the disease progresses, epinephrine secretion is impaired, creating a symptom-free and dangerous condition (hypoglycemia unawareness) when blood glucose falls.
Type 2 Diabetes 25 4.1
Most obese individuals are insulin resistant (as shown). Do most develop T2D?
Most obese individuals with insulin resistance do not develop T2D, the most common form of diabetes, because still-functional pancreatic B cells produce sufficient insulin to maintain normal blood glucose levels. [Note: Patients who do develop T2D have a combination of insulin resistance and dysfunctional B cells but do not require insulin to sustain life.]
Type 2 Diabetes 25 4.2
What is insulin resistance? How does obesity foster insulin resistance?
In insulin resistance, normal (or elevated) insulin levels fail to elicit the expected biologic response. Obesity fosters insulin resistance (shown) via changes in adipose secretions. The major
secretory changes include increased inflammatory cytokine (e.g., IL-6) and leptin production and decreased anti-inflammatory adiponectin production. Inflammation contributes to insulin resistance (and to CHD).
Type 2 Diabetes 25 4.3
What is an acute complication of T2D?
An acute complication of T2D is a hyperosmotic hyperglycemic state (most common in the elderly) that presents with very high blood glucose levels, severe dehydration, and altered mental
status. Coma and death can result.
Type 2 Diabetes 25 5.1
How is T2D development temporally related to the onset of insulin resistance and
the decline of B -cell function shown?
Obese individuals with insulin resistance may take + 10 years before they develop T2D. Initially, the B cells compensate by increasing insulin production. With time, however, they become increasingly dysfunctional and fail to produce enough insulin to correct the hyperglycemia.
Type 2 Diabetes 25 5.2
Why is dyslipidemia one of the metabolic changes associated with T2D?
Insulin resistance, coupled with decreased B-cell function, leads to decreased LPL expression in adipocytes and a decrease in TAG degradation in circulating VLDLs and CMs, causing hypertriglyceridemia (a dyslipidemia ).
Type 2 Diabetes Effects 25 6.1
Why is T2D progression, as shown, not generally associated with DKA development?
In T2D, the B cells have a diminished capacity to secrete insulin, but the amount is suffi cient to decrease glucagon secretion and prevent DKA.
Type 2 Diabetes Effects 25 6.3
How is T2D treatment different from that for T1D?
In diabetes, the treatment goal is glycemic control to reduce the development of long-term complications.
Oral medications are used to reduce hyperglycemia in T2D, whereas insulin therapy is used in T1D.
[Note: The risk for developing T2D, a metabolic disorder, can be significantly decreased by dietary modifications, exercise, and weight loss. In contrast, T1D results from autoimmune-mediated destruction of pancreatic B cells and no
preventive treatment exists currently.]
