Introduction to Diabetes 4/3/2013

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Fed State – Insulin dominates

↑ Glycolysis↑ Glycolysis↑ Glycogenesis↑ Lipogenesis↑ Protein synthesis

Fasting state – Glucagon dominates

↑ Glycogenolysis↑ y g y↑ Gluconeogenesis↑ Proteolysis↑ Lipolysis↑ Fatty acid utilization↑ Ketogenesis

Relationship between Plasma Glucose and Insulin Secretion

Major stimuli insulin secretionPlasma GlucosePlasma Glucose

Other stimuli for secretionGI hormonesVagal Stimuli-ACh

From Berne, Levy, Koeppen, & Stanton, Physiology, fourth edition, Mosby Inc.

Classification of Diabetes

• Type 1A. Immune-mediatedA. Immune mediatedB. Idiopathic

• Type 2Insulin Resistance: decreased ability of the body to clear glucose from the circulation in response to insulin

Oth S ifi T• Other Specific Typese.g. Genetic defects, diseases of exocrine pancreas, drugs or

chemicals, infections, etc.

• Gestational Diabetes

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Euglycemia

Circulating GlucoseIslet β-cells

Insulin

Modified from Rosen et al. / Nature (2006) 444, 847-853 & Doyle et al. / Diabetes (2007) 56 (8) p. 1999-2007

Glucose Uptake Glucose Output

Type 2 diabetes - Insulin resistance & β-cell dysfunction

Circulating GlucoseIslet β-cells

Insulin: initially hyperinsulinemia, years later β-cell dysfunction

Modified from Rosen et al. / Nature (2006) 444, 847-853 & Doyle et al. / Diabetes (2007) 56 (8) p. 1999-2007

Glucose Uptake Glucose Output

Diagnosing Diabetes and Pre-diabetes

American Diabetes Association

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Diagnosing Diabetes

• Fasting BG > 126 mg/dL (no caloric intake for at least 8 hours)

OR• Random BG > 200 mg/dL in a patient with classic

symptoms (thirst, polyuria, wt loss, visual blurring)OR

• 2 hour BG > 200 mg/dL during an OGTTAll to be confirmed on a subsequent occasion

Diagnosing Diabetes

• Hemoglobin A1c 6.5%

Excess glucose is taken up by RBCs and is attached (glycates) to hemoglobin Higher blood glucose levels means increase in % of

l tiglycationMemory is retained till RBCs die – about 120 days

Oral Glucose Tolerance Test

250

300

100

150

200

250

sma

gluc

ose

(mg/

dL)

Subject 1Subject 2Subject 3

0

50

Fasting 0.5 1 1.5 2

Plas

Time after oral glucose (hours)

24 hour Glucose Profile in Normal and Obese Individuals

From Berne, Levy, Koeppen, & Stanton, Physiology, fourth edition, Mosby Inc.

Introduction to Diabetes 4/3/2013

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24 hour Plasma Insulin Profile in Normal and Obese Individuals

From Berne, Levy, Koeppen, and Stanton, Physiology, fourth edition, Mosby Inc.

Hyperglycemia

What are the consequences of hyperglycemia?Short termShort term• Increase thirst, appetite and urination• Fatigue, blurred vision, weakness

Long term• Micro and macro vascular disease such as

ti th th h th di lretinopathy, neuropathy, nephropathy, cardiovascular disease and stroke

• Increased risk of cancer

Hypoglycemia

What are the consequences of hyperglycemia?Short termShort term• Hunger, weakness, dizziness • Nausea, headache, sweating

Long term• Confusion, unusual behavior, hallucinations

S i l i l bl• Seizures, neurological problems• Coma • Death

Recap: Type 1 versus Type 2

Type 1: Hyposecretion of Insulin, immuno-destruction of beta cellsTreatment = Insulin injections j

Type 2: Hyporesponsive Endocrine Disorder; Insulin InsensitivityTreatment varies and may include any of the following: Lifestyle modifications! weight management and exercise Oral medications Insulin injections (usually later in the disease process)

At-risk for Diabetes: impaired fasting blood glucose or abnormal OGGTTreatment: lifestyle modifications! weight management and exercise

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Effects of Muscle Contraction on Glucose Uptake

• Muscle contraction increases GLUT4 mobilization to the plasma membrane and transverse tubules ofthe plasma membrane and transverse tubules of skeletal muscle

• Rate of glucose transport correlates with the frequency of muscle contractions

• Protective effect of physical fitness against DM and IGTIGT– Increases insulin sensitivity– Increase glucose transport

Euglycemia:Endocrine Response to Aerobic Exercise in

Changes in Plasma Levels of Hormones

Increase • Glucagon• Epinephrine and Norepinephrine• Growth hormone-IGF1• Cortisol

Decrease in Insulin

Beneficial Effects of Exercise

• Improves insulin sensitivity• Lowers cardiovascular risk• Lowers cardiovascular risk• Lowers HbA1c• Decrease the risk of vascular disease or

atherosclerotic complications• Lowers BP• Improves blood lipid profiles• Promotes weight loss (intraabdominal fat)• Improves sense of wellbeing

Exercise Considerations

• Exercise increases insulin sensitivity following exercise Especially important for individuals with Insulin Especially important for individuals with Insulin

Resistance, i.e. the individual with pre-diabetes or Type 2

• Insulin injection may need to decreased prior to exercise bout especially for the individual with Type 1 who would be at risk for Hypoglycemia

Careful self-monitoring of blood glucose during and followingexercise should help to determine the most advantageousapproach. A combination of altered insulin dosage and CHO feedings may give the best results.