Diabetes Mellitus Type I and Type II atf

Type I and Type II Diabetes Mellitus
ENDOCRINE PATHOLOGY: Note #1.
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1. TYPE I AND TYPE II DIABETES MELLITUS
Diabetes Mellitus | Type I and Type II Diabetes Mellitus
Medical Editor: Ilia-Presiyan Georgiev
OUTLINE
I) TYPE I DIABETES MELLITUS
II) TYPE II DIABETES MELLITUS
III) CLINICAL MANIFESTATIONS
IV) DIAGNOSIS
V) CHRONIC COMPLICATIONS
VI) TREATMENT
VII) CONTENT FORMATTING
VIII) APPENDIX
I) TYPE I DIABETES MELLITUS
(A) CAUSES
(1) Diabetes mellitus type I is an autoimmune disease
There are two components to an autoimmune disease
o Environmental component
o Immune component
(2) The environmental component is
believed to be an unknown virus
o This virus is thought to infect specific cells in the body
 Viral proteins get expressed onto MCH-1
complexes in those cells
Cytotoxic T-cells recognize the foreign antigen
o Generate an immune response against it
(3) Immune component
The immune system reacts inappropriately the
environmental factor
o Due to susceptibility genes
 HLA-DR3
 HLA-DR4
These genes lead to inappropriate immune response
o T-cells release cytokines
 Stimulate plasma cells
o Plasma cells produce antibodies
These HLA susceptibility genes are associated with other
autoimmune diseases
o Rheumatoid arthritis
o Systemic lupus erythematosus
o Celiac disease
o Vitiligo
These antibodies attack particular portions of cells
o In diabetes they attack the pancreatic beta cells
Figure 1 Causes of diabetes mellitus type I.
(B) EFFECTS ON THE CELLS
(1) The glucose goes
inside a beta cell
o Via a glucose transporter (GLUT)
Inside it undergoes aerobic metabolism
o Produce ATP
These ATP molecules bind to K+ sensitive channels
(2) There is an enzyme
called glutamic acid decarboxylase
o Converts glutamic acid into GABA
 GABA is another molecule that is associated with
the stimulation of insulin production
 Has protective effects on the beta cells
(3) There are three sets of antibodies
associated with diabetes mellitus type 1
Anti-islet cell antibodies
o Target specific self-antigens present on our
pancreatic islet cells
Anti-glutamic acid antibodies
o Target glutamic acid decarboxylase
Anti-insulin antibodies
o Target the insulin
As these antibodies attack the beta cells or the proteins
inside they start destroying the cells
(4) Insulin binds to insulin receptors
on the different cells in the body
Triggers an intracellular cascade
o Increases the expression of glucose transporters on
the cell membrane
o That allows glucose to enter the cell
If the insulin production is decreased
Figure 2 Effects of diabetes mellitus type I on the cells.
Last edited: 9/11/2021

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ENDOCRINE PATHOLOGY: Note #1.
Type I and Type II Diabetes Mellitus
II) TYPE II DIABETES MELLITUS
(A) CAUSES
(1) Metabolic syndrome is
believed to be responsible for diabetes type II
Signs and symptoms of metabolic syndrome
o For diagnosis are required 3 or more of these
1. Fasting glucose level ≥ 100mg/dl
2. Triglycerides ≥ 150mg/dl
3. HDL ≤ 50 (for females) and 40 (for males)
4. Blood pressure ≥ 130/85 mmHg
5. BMI ≥ 35 (for females) and 40 (for males)
(2) Metabolic syndrome is
believed to be responsible for insulin resistance
There are researches that suggest two genetic
components are high risk
o Having a first-degree relative with
o Certain ethnicities
 Pacific islanders
Figure 3 Causes of diabetes mellitus type 2.
(B) EFFECTS ON THE CELLS
(1) The glucose goes
inside a beta cell
o Via a glucose transporter
Inside it undergoes aerobic metabolism
o Produce ATP
These ATP molecules bind K+ sensitive channels
(2) There is an enzyme
called glutamic acid decarboxylase
o Converts glutamic acid into GABA
 GABA is another molecule that is associated with
the stimulation of insulin production
 Also has protective effects on the beta cells
(3) Insulin binds to insulin receptors
on the different cells in the body
o To increase the glucose transport
(4) With diabetes type II
there is decreased intracellular response
 In order to get the glucose into the cells
Over time the beta cells decrease their activity
(5) Alongside insulin
another protein is released – amylin
Amylin accumulates in the tissue space around the beta
cells
o Causes amyloid deposition
 Damages the beta cells
 Decrease their activity
Figure 4 Effects of diabetes mellitus type 2 on the cells.
III) CLINICAL MANIFESTATIONS
(1) Hyperglycemia causes
a lot of glucose to be filtered into the kidney tubules
o Through glomerular filtration
Kidney tubules can’t reabsorb such amounts of glucose
 Called glycosuria
Glucose is osmotically active
o Pulls water with it
• Called polyuria
Hyperosmolar blood
o Low water and high glucose
 Large volumes of urine
 Glucose blood levels remain high
Hyperosmolar blood stimulates osmoreceptors in the
hypothalamus
o Trigger an increase in thirst
 Trying to replenish the lost water volume
o Called polydipsia

Type I and Type II Diabetes Mellitus
ENDOCRINE PATHOLOGY: Note #1.
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Figure 5 Clinical manifestations part I.
(2) Decreased glucose utilization
leads to decreased ATP production
The body is forced to use other metabolic sources of fuel
Lipolysis in the adipose tissue
o Breakdown of triglycerides into free fatty acids and
glycerol
 Both can be used in the cellular pathway to make
energy
Proteolysis in the muscles
o Breakdown of proteins into amino acids
 Can be used to make energy
↑ lipolysis and proteolysis lead to unexplained weight
loss
 To replenish the calories
 Called polyphagia
Figure 6 Clinical manifestations part II.
IV) DIAGNOSIS
(1) Blood work
Fasting glucose ≥ 126mg/dl
o If the patient hasn’t eaten in a certain amount of time,
the blood glucose is expected to be lower
 Sign of diabetes especially if there are other
symptoms present
Random glucose ≥ 200 mg/dl
o Regardless of the patient eating or fasting
 Alongside other symptoms is diagnostic of
diabetes
2-hour oral glucose tolerance test – glucose ≥ 200
mg/dl
o Glucose is given and is supposed to stimulate insulin
production
 Insulin is supposed to push glucose into the cells
• Diabetics don’t have the insulin or are insulin
resistant → blood glucose levels remain high
o Need two tests to confirm diabetes
Hemoglobin A1c ≥ 6.5%
o Used for diagnosis and for monitoring glucose
control over three months
o High blood glucose levels make the glucose
conjugate to the hemoglobin
 Produces glycated hemoglobin
o It is informative for the period of three months
 This is the lifespan of the red blood cells
• Hemoglobin is located in them
(2) Antibodies
can also be taken into consideration
o Anti-islet cell antibodies
o Anti-glutamic acid antibodies
o Anti-insulin antibodies
 Age and risk factors should be taken into
consideration
Figure 7 Diagnostic criteria for diabetes mellitus.
V) CHRONIC COMPLICATIONS
(A) NON-ENZYMATIC GLYCATION
(1) High blood glucose levels make
the glucose conjugate with different molecules
o Mainly proteins and lipids
No enzyme is used
o Called non-enzymatic glycation
Non-enzymatic glycation of lipids and proteins creates
very potent inflammatory molecules
o Can cause inflammation of the blood vessels
 A lot of LDL deposit to that tissue
• Leads to atherosclerosis
o Some protein deposits can occur in the vessels and
around the basal membrane
 Leads to hyaline arteriolosclerosis
(2) The combination of
these two effects leads to
o ↓ blood flow distal to these plaques and the
arterioles
o ↓ gas exchange across the tissues
 Due to the thickened basal membrane
o Physical manifestations of particular types of diseases
are associated with non-enzymatic glycation
Figure 8 Non-enzymatic glycation.

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ENDOCRINE PATHOLOGY: Note #1.
Type I and Type II Diabetes Mellitus
(B) ATHEROSCLEROSIS
(1) Within the vessels in the heart
can lead to coronary artery disease
o Potentially leading to myocardial infarction
(2) Within the vessels of the lower extremities
can lead to peripheral artery disease
o Potentially presenting with
 Claudication
 Decreased blood flow to the tissues
(3) Within the vessels supplying the nervous tissue
can lead to an ischemic stroke
(4) Within the vessels of the retina
can lead to retinopathy
o Three things are associated with diabetic retinopathy
 Microaneurysms
 Cotton wool spots
 Flame hemorrhages
o Those can affect the vision
Figure 9 Atherosclerosis.
(C) HYALINE ARTERIOLOSCLEROSIS
(1) Within the vessels of the glomeruli
Damages the glomeruli
 Like albumin
• It enters the urine
o Called microalbuminuria
(2) Over time consistent microalbuminuria
can lead to chronic kidney disease
o The most common cause of chronic kidney disease
The proteinaceous deposits that form within the glomeruli
are called Kimmelstiel-Wilson nodules
Figure 10 Hyaline arteriolosclerosis.
(D) OSMOTIC CELL DEATH
(1) Glucose gets taken up into the cells
If there are increased amounts of glucose some gets
converted to sorbitol
o By aldose reductase
Sorbitol is converted into fructose
o By sorbitol dehydrogenase
Certain tissues lack sorbitol hydrogenase
o They can’t convert sorbitol into fructose.
Sorbitol is extremely osmotically active
o Pulls water inside different cells that don’t have
sorbitol dehydrogenase
 This can cause osmotic cell death
(2) Cells inside the lens of the eye
Leads to cataracts
(3) Cells of the proximal convoluted tubule
or other tubular cells
Leads to progression of the nephropathy
(4) The Schwann cells of the peripheral nerves
Causes demyelination that affects:
Autonomic nerves
a. Supplying the stomach
 The stomach can’t contract properly
o Inability of the stomach to contract and
push chyme into the duodenum
b. Supplying the bladder
 Called neurogenic bladder
c. Supplying the blood vessels
o And promoting vasoconstriction when a person
stands up and needs blood to be able to get up to the
right side of the heart
 Patients become lightheaded and dizzy
• Called orthostasis
Peripheral nerves
o Most commonly – the oculomotor nerve
 The third cranial nerve
 Helps control extra ocular movement
o If affected
 The eye is moved laterally and downward
 Pupil function is preserved
Somatic nerves
o Most commonly the somatic sensory nerves that
supply the distal extremities bilaterally
o Cause
 Loss of sensation
 Burning sensation
• Called dysesthesia
 Tingling sensation
• Called paresthesia
o Over time patients with sensory deficits can endure
wounds and be unaware of that
o Hyperglycemia impairs wound healing
 This condition can progress to foot ulcers
Figure 11 Osmotic cell death.

Type I and Type II Diabetes Mellitus
ENDOCRINE PATHOLOGY: Note #1.
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VI) TREATMENT
(A) DIABETES TYPE 1
Treated with insulin
(B) DIABETES TYPE 2
(1) Promotion of weight loss
through exercise and dietary changes
Diabetes type II is caused by metabolic syndrome
o The patients are obese and with bad diets
(2) Diabetes medication
Metformin - first-line medication
Other types of medications:
o GLP-1 agonists
o DPP-4 inhibitors
o SGLT2 inhibitors
o Thiazolidinediones
o Sulfonylureas
o Glucosidase inhibitors
o Meglitinides
Sometimes insulin is given to type 2 diabetics
o If they are on multiple diabetes medications
o And their hemoglobin A1c > 7%
Figure 12 Diabetes treatment.
(C) CHRONIC COMPLICATIONS
(1) Neuropathy
Gabapentin and pregabalin - first line medications
o Decrease the numbness, pain and tingling
Yearly podiatry visits for overall foot care
o Very important
(2) Nephropathy
ACE inhibitors and ARBs - first line medications
o Decrease the proteinuria
Kidney function should be monitored
o The can progress to chronic kidney disease.
The basic metabolic panel (BMP) should be checked for
o ↑ creatinine
o ↑ blood urea nitrogen
The amount of albumin in the urine should be monitored
(3) Retinopathy
Vascular endothelial growth factor inhibitors (VEGF
inhibitors) – first line medication
Laser photocoagulation
Vitrectomy
Yearly optometry visits
o Very important
(4) Atherosclerosis
Aspirin
o As prophylactic measure
If the atherosclerotic disease risk is very high (≥7.5%)
o Lipid panel is monitored
o Statin may be given to reduce the risk of
complications
(5) Glucose control
Hemoglobin A1c (HbA1c) should be kept below 7%
o Uncontrolled HbA1c (>7%)
 Should be checked every 3 months
o Well controlled HbA1c (≤7% or less)
 Should be checked every 6 months
Figure 13 (C) Chronic complications treatment.