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Introduction to Diabetes 4/3/2013
1
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
Introduction to Diabetes 4/3/2013
2
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
Introduction to Diabetes 4/3/2013
3
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
4
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
Introduction to Diabetes 4/3/2013
5
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.