Lowering the blood glucose below 50 mg%.

Mild = 60-70 mg%

Severe = <40 mg%

1. Insulin shock

2. Alcohol

3. Exercise

1. Adrenergic (neurogenic)

2. Neuroglucopenic = cellular malnutrition

1. Early warning signs

2. Tachycardia

3. Pallow

4. Sweating

5. Hunger

(mediated by release of catecholamines)

1. headache

2. Hypothermia

3. Irritability

4. Visual disturbances

5. Seizure

6. Coma

(mediated by lack of glucose to the brain)

Getting low

Is Low

stressful situations

(infection, trauma)

1. Increase insulin requirements

2. Increase gluconeogenic hormones like glucocorticoids and catecholamines

1. Hyperglycemia (>250mg/dl)

2. Ketosis (acetone breath)

3. Metabolic acidosis (ph<7.3)

1. Kussmaul respiration

2. Acetone breath

3. Tachycardia

4. Dry mouth

5. Headache

6. Polydipsia, Polyuria

7. Dehydration

8. Ab pain

9. Coma

1. Insulin therapy

2. Fluid and electrolyte replacement

(goal is to: restory circulatory volume, decrease serum glucose, and correct acidosis and ion imbalance)

HyperOsmolar Hyperglycemic NonKetotic Coma

Elderly Type 2 Diabetics with renal failure

1. Insulin resistance and excessive carb intake

2. Advanced age

3. Trauma, infection

4. Meds that elevate glucose

1. Hypovolemia

2. Hypotension

3. Weight loss

4. Dehydration (more severe than in DKA)

5. Hypothermia

6. Polyuria (5-13 L/hr), Polydipsia

7. Weakness

Glucose = > 600-1000 mg%

pH > 7.3 (no ketosis)

70-90 mg/dl

> 310 mOsm/L

1. Decrease in renal function due to hyperomolarity and osmotic dehydration. 

2. Increase in liver production of glucose

1. Hypoglycemia

2. DKA

3. HHNK

1. Increased polyol pathway

2. Increased sorbitol that can alter singal transduction pathways

What enzyme converts glucose to sorbitol?

What about sorbitol to fructose?

(In the polyol pathway)

1. aldose Reductase

2. Sorbitol Dehydrogenase

1. Aldose reductase inhibitors

2. Acarbose = A-glucosidase inhibitor

1. Make platelets more sticky = accelerated atherosclerosis

2. Alter lipid metabolism = accelerated atherosclerosis

3. Formation of advanced gycation end products which increase the binding of glucose to proteins

1. Change the permeability

2. Change the basement membrane

1. Increase endothelin

2. Increase coagulation

3. Reduce NO

(Get enothelial damage, vasoconstriction, more clotting so more atherosclerosis)

1. cytokine release (TNF-a)

2. Increase in PKC

3. Increase in ROS = tissue damage

What type of patients did the DCCT test on?

(Diabetes control complications trials)

Control:  Gluc = 110 mg% w/ A1C of 6%

Regular: Gluc = 231 mg% w/ AlC of 9%

Tight: Gluc = 155 mg% w/ AlC of 7%

1. 3x higher in hypglycemia

2. Weight gain

3. May not be good for very young and old.

1. 60-70% decrease in neuropathy, retinopathy and nephropathy

2. 40% decrease in macrovascular complications

1. Age of patients were from 13-39 (no young or old)

2. No racial diversity (96% were white)

Epidemiology of Diabetes Intervention and Complication

It is the follow up study on the 'tight' control group. Followed for 11 yrs

U.K. Prospective Diabetes Study

Type 2 Diabetics = 20 yr study with 11 yr follow up.  Found for every % drop in HbA1c, there was a 25-40% decrease in complications.

What are the basic types of neuropathy that you can have with diabetes?

Which is the most common?

At specific sites?

1. Distal Symmetric Polynueropathy - most common

2. Autonomic

3. Ischemic or focal neuropathy- specific sites

1. Usually seen in lower extremeties

2. Burning followed by pain at night

3. Diminished perception of vibration, pain, temperature

4. GI disturbances

5. Erectiles dysfunction

Loss of myelin (Schwann cell abnormality)

May be due to thicnkening of vessel wall and ischemia to nerve tissue.

1. Dying back neuropathy

2. Conduction velocity decreases

1. Altered sorbitol pathway = increases osmolarity and leads to tissue damage

2. Hypoxia/ischemia

3. Glycation of proteins

4. Decrease in growth factors

5. Autoantibodies

1. Increase in capillary permeability

2. Capillary basement membrane thickening

3. Tissue hypoxia

1. Asymptomatic/nonproliferative

2. Intermediate/pre-proliferative

3. Proliferative

1. Intimal thickening

2. Some increase in permeability

3. Microaneurysms

"bening" - no visual impairment

1. Progressive ischemia (cotton wool spots)

2. Some areas of infarct, hemorrhage

3. Some non functioning capillaries

Neovascularization = new blood vessels and fibrous tissues form over the surface of the retina.

The new vessels are weak and are at risk to rupture and lead to retinal detachment

Will fill eye with blood if it bursts!

Protein changes induced by high glucose

Adverse effects of intraglomerular hypertension

Microalbuminuria which is btwn 30-300 mg/day

Usually asymptomatic

1. Hyperglycemia

2. Endothelial damage

3. Elevated lipids

4. Abnormal blood coagulation

5. Tissue anoxia

6. Autoantibodies to glycated lipoproteins

7. Isulin effects

8. Hypertension/smoking

Decreases NO

Increase endothelin

More free radicals

Subendothelial proliferation  = increase atherosclerosis

1. CAD

2. Stroke

3. PVD

2

Duration

1. Hair loss

2. Cold feet

3. Intermittent claudication

1. Poor blood flow

2. Impaired senses

3. Bacteria like sugar

4. WBC compromised

5. Increase in glycosylated Hb = Hypoxia

Miscarriage

Pre-eclampsia

Because of morning sickness

and the fetus also has glucose requirment

(hihger risk at night)

Diabetes Prevention Program

Divided into 3 groups:

Lifestyle changes

Placebo

Metformin

1. Lost 5-7% body weight

2. 30 min exercise/day

3. Include diet rich in whole grain fruits and veggies

4. Low calories, low fat meals