11 Diabetes

Overview

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• Diabetes: meaning polydipsis/polyuria..

Diabetes Symptoms

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Complications:

Diabetes Diagnosis

_Diagnosis:..

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• Asymptomatic as in no polyuria/polydipsia..

Glucose Tolerance Test

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• Just measuring glucose level is not helpful because elevated in pregnancy

• Measuring glucose load response more helpful..

Hemoglobin A1C

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• 3 months because RBC lives for 3 months..

Type 1 Diabetes

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• aka insulitis

Islet cell antibodies are found in the vast majority of T1DM patients, as well as asymptomatic family members. Islet antigens that are the targets of autoimmune attack may include insulin and the β-cell enzyme glutamic acid decarboxylase (GAD).

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_Association with HLA-DR3 and DR4.,

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• lifelong insulin

• weight loss, low muscle mass, always wanting to eat

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Diabetic Ketoacidosis

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• Type 2 still has insulin, thus less common

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• Trauma/infection increases epinephrine

• Fruity breath from acetone

• Dehydration -> hypotension

• Ketones made from lipolysis

• Oxaloacetate depletion from high NADH pushing towards malate

• can get mild hyponatremia from loss of Na in urine

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• Patients with DKA and respiratory failure, always ckeck phosphate

_Symptoms:

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• Hyperglycemia long term > brain makes taurine molecules to match osmolarity (doesn't happen in type 2)

• Give fluid too fast > blood osmolarity drop

• Water goes to brain, brain edema

• Use IV mannitol to treat

_Associated with mucormycosis:.,

• classic case: DKA patient in recovery with new onset fever/headache/eye pain

_Treatment:

• K lost in urine. Add K after a few hours of insulin

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Type 2 Diabetes

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• more free FA bad because used for fuel instead of glucose

• Left: apple shape. Right: pear shape..

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Insulin Resistance

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• Type 2 associated with obesity

• Adipocytes make TNF-a and FA

• TNF-a and FA activates serine-threonine kinase

• serine-threonine kinase phosphorylates beta chain, inhibits tyrosine phosphorylation

• result is decreased number of available insulin receptors

Amyloid

_Histology

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• accumultates in type 2 diabetes islets

Acanthosis Nigerians

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• Insulin tells keratinocytes to grow

Hyperglycemic Hyperosmolar Syndrome, HHS

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• Similar to DKA of type

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• high serum osm from glucose

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Diabetic Complications

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Nonenzymatic Glycation

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• AGE cause problems

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• Macroangiopathy:..

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• Microangiopathy:..

• put on dialysis

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• Caused by AGE and hyperfiltration..

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Sclerosis of entire kidney:

• pyelonephritis and scarring with infection. Atrophic and smaller:

papillary necrosis, triangular necrosis:

Diffuse:

Nodular:

Kimmelstiel-Wilson Nodules

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Sorbitol

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Polyol pathway

_Alternative glucose pathway:..

• Little activity at normal glucose level but increased activity at chronic hyperglycemia

• End result is increased sorbitol because second step is slow

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• sensory loss more than motor

• distal more than proximal

• B12: equally proximal and distal

• diarhea

Diabetic Foot Disease

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• PVD: peripheral vascular disease

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• O2 chamber drives O2 into ulcer for healing

Diabetic Retinopathy

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• Both AGE and sorbitol involvement

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