Glucose Metabolism and Diabetes - PowerPoint PPT Presentation

1 / 33
About This Presentation
Title:

Glucose Metabolism and Diabetes

Description:

Glucose Metabolism and Diabetes Mariel Arvizu, MD Review session – PowerPoint PPT presentation

Number of Views:540
Avg rating:3.0/5.0
Slides: 34
Provided by: maa130
Category:

less

Transcript and Presenter's Notes

Title: Glucose Metabolism and Diabetes


1
Glucose Metabolism and Diabetes
  • Mariel Arvizu, MD
  • Review session

2
Carbohydrate Metabolism
  • Glucose most important
  • Monosaccharide
  • Oxidation 1 g Glu 4 kcal of energy
  • Energy stored in the form of ATP
  • Mytochondria aerobic respiration were Glu
    becomes carbon dioxide and water

3
Glucose Metabolic pathways
  • Glycolysis oxidation produces ATP and pyruvate
    from Glu enter Krebs cycle (citric acid cycle)
  • ATP produced 8-10 glycolisis is anaerobic
    process
  • ATP in Krebs cycle 25 this is aerobic
  • TOTAL about 36 ATP
  • Glycogenesis conversion of excess Glu to
    Glycogen
  • Glycogenolysis breakdown of glycogen into Glu
    (opposite to glycogenesis)
  • Gluconeogenesis de novo synthesis of glucose
    from e.g. amino acids main source in human body
    lactate, glycerol, alanine, glutamine
  • Pentose-phosphate pathway hexoses into pentose
    and NADPH generation prevents oxidative damage
    in cells.
  • Carbon fixation known as photosynthesis were
    CO2 is reduced to glucose

4
Glucose regulation
Insulin Glucagon
5
Other hormones in Glucose
Amylin Glucagon-like peptide (GLP-1) Gastric
inhibitory peptide (GIP)
  • Amylin is released along with insulin from beta
    cells.
  • It has much the same effect as GLP-1
  • It decreases glucagon levels decrease glucose
    production in liver
  • slows the rate at which food empties from your
    stomach
  • and makes your brain feel that you have eaten a
    full and satisfying meal.
  • The overall effect of these hormones is to reduce
    the production of sugar by the liver during a
    meal to prevent it from getting too high.

6
Epinephrine, cortisol, and growth hormone
  • Epinephrine - promotes glycogenolysis, also
    promotes the breakdown and release of fat
    nutrients that travel to the liver where they are
    converted into sugar and ketones.
  • Cortisol makes fat and muscle cells resistant to
    the action of insulin, and enhances the
    production of glucose by the liver. Under normal
    circumstances, cortisol counterbalances the
    action of insulin. Under stress or if a synthetic
    cortisol is given as a medication (such as with
    prednisone therapy or cortisone injection),
    cortisol levels become elevated and you become
    insulin resistant. keep your blood sugar under
    control.
  • Growth Hormone Like cortisol, growth hormone
    counterbalances the effect of insulin on muscle
    and fat cells. High levels of growth hormone
    cause resistance to the action of insulin.

7
Diabetes mellitus (DM)
  • High glucose levels due to pancreatic dysfunction
    and/or insulin resistance
  • Insulin resistance(insensitivity) condition in
    which cells do not respond properly to insulin

8
Classification of Diabetes
9
Dm type 1 vs Dm type 2
  • T1DM- characterized by insulin DEFICIENCY
  • T2Dm characterized by insulin resistance with
    relative insulin deficiency
  • Body habitus patients with T2DM are usually
    obese
  • Age very important, children with T2DM usually
    after puberty
  • Family history stronger in T1Dm approx 10 have
    a relative affected

10
(No Transcript)
11
T2DM vs T1DM
12
Type I Diabetes
  •  Type 1 diabetes mellitus (T1DM), one of the most
    common chronic diseases in childhood
  • 2/3 diagnosis of diabetes in 19 years
  • 1/3 of diagnosis are in adults
  •  destruction of the insulin-producing pancreatic
    beta cells

13
Epidemiology DM I
  • Genetic susceptibility  The lifetime risk of
    developing T1DM is significantly increased in
    close relatives of a patient with T1DM
  • No family history 0.4 percent
  • Offspring of an affected mother 1 to 4 percent
  • Offspring of an affected father 3 to 8 percent
  • Offspring with both parents affected reported
    as high as 30 percent
  • Non-twin sibling of affected patient 3 to 6
    percent
  • Dizygotic twin 8 percent
  • Monozygotic twin 30 percent within 10 years of
    diagnosis of the first twin and 65 percent
    concordance by age 60 years

14
Other risk factors
  • Viral infections enterovirus infections
  • Immunizations
  • Diet cow's milk at an early age
  • Higher socioeconomic status
  • Obesity
  • Vitamin D deficiency increases mortality rates
  • Perinatal factors maternal age, history of
    preeclampsia, and neonatal jaundice.
  • Low birth weight decreases the risk of developing
    T1DM

15
Clinical presentation
  • Classic new onset chronic polydipsia, polyuria,
    and weight loss with hyperglycemia and ketones
    (urineketonuriabloodketonemia)
  • Diabetic ketoacidosis
  • Silent (asymptomatic)

16
Classic New Onset most common
  • Polyuria occurs when Glu rises 180 mg/dL
    exceeding the renal threshold for glucose, which
    results in glycosuria diuretic osmosis
  • Bed wetting (Nocturia)
  • Day time incontinence (previously continent)
  • Polydipsia increased serum osmolality from
    hyperglycemia.
  • Weight loss due to hypovolemia and increased
    catabolism, because insulin deficiency impairs
    glucose use in skeletal muscle and increases fat
    and muscle breakdown

17
Diabetes ketoacidosis (DKA) in T1DM
  • 2nd most common presentation 30
  • Fruity-smelling breath
  • Drowsiness and lethargy
  • 50 if children age lt 3 years old
  • More likely to happen in lower socio-economic
    status

18
Diagnosis criteria for DM I American Diabetes
Association (ADA criteria)
  • Fasting plasma glucose 126 mg/dL (7 mmol/L) on
    more than one occasion. Fasting is defined as no
    caloric intake for at least eight hours.
  • Random venous plasma glucose 200 mg/dL (11.1 mmol
    /L) in a patient with classic symptoms of
    hyperglycemia.
  • Plasma glucose 200 mg/dL (11.1 mmol/L) measured
    two hours after a glucose load of
    1.75 g/kg (maximum dose of 75 g) in an oral
    glucose tolerance test (OGTT). Most children and
    adolescents are symptomatic and have plasma
    glucose concentrations well above
    200 mg/dL (11.1 mmol/L) thus, OGTT is seldom
    necessary to diagnose T1DM.
  • Glycated hemoglobin (A1C) 6.5 percent (using an
    assay that is certified by the National
    Glycohemoglobin Standardization Program). This
    criterion is more useful to diagnosis of type 2
    diabetes mellitus (T2DM) in adults, and should be
    confirmed by hyperglycemia.

19
Physical exam?
20
Glycated hemoglobin (A1C)
  • Type of Hb used to indirectly calculate the
    average plasma glucose concentration
  • Once Hb becomes glycosilated it remains that way
  • Half-life Hb 4 weeks 3 months
  • Normal range 6.5

21
Normal range Hb1AC
22
Diabetes Type 2
  • characterized by
  • Hyperglycemia
  • insulin resistance
  • relative impairment in insulin secretion
  •  prevalence rises with increasing degrees of
    obesity
  • Genetic predisposition 39 have at least one
    parent
  • Ethnicity 2-6 fold in African-American,
    Hispanics, Native Americans in the U.S.
  • Understanding the pathogenesis of type 2 diabetes
    is complicated by several factors

23
(No Transcript)
24
Prevalence of T2DM in the U.S. in 2010
CDC. National diabetes fact sheet national
estimates and general information on diabetes and
prediabetes in the United States, 2011. Atlanta,
GA US Department of Health and Human Services,
CDC 2011. Available at http//www.cdc.gov/diabete
s/pubs/factsheet11.htm. Accessed September 20,
2012.
25
Global Prevalence of Type 2 Diabetes in 2000 and
estimated prevalence in 2030.
26
(No Transcript)
27
Pathophysiology
  • Usually accompanied by other METABOLIC SYNDROME
  • Hypertension
  • High cholesterol LDL HDL
  • Hyperinsulinemia effects
  • Increased circulating free- fatty acids
  • Inflammatory cytokines from excess fat and
    oxidative factors

28
Insulin secretion in T2DM
  • beta cells requires glucose transport into the
    cell
  • Animal models suggest mediated by the glucose
    transporter 2 (GLUT-2).

29
Insulin resistance
  • Best predictor of DM 2
  • severe with increasing age and weight, thereby
    unmasking a concurrent defect in insulin
    secretion in susceptible subjects
  • In normal-weight nondiabetic subjects at high
    risk for T2DM, both fasting and post-glucose
    hyperinsulinemia predict future weight gain,
    which in turn predisposes to hyperglycemia

30
Genetic Susceptibility
  • monozygotic twin pairs with one affected twin
    90 of unaffected twins eventually develop the
    disease 
  • First-degree relatives of patients have impaired
    nonoxidative glucose metabolism (indicative of
    insulin resistance)
  • beta cell dysfunction, as evidenced by decreases
    in insulin and amylin release in response to
    glucose stimulation

31
(No Transcript)
32
Diagnosis criteria for DM 2
  • classic symptoms of hyperglycemia (thirst,
    polyuria, weight loss, blurry vision)
  • random blood glucose value of 200 mg/dL
  •  Fasting plasma glucose (FPG) values
    126 mg/dL (7.0 mmol/L)
  •  two-hour post oral glucose challenge values of
    200 mg/dL
  • glycated hemoglobin (A1C) values 6.5 percent
    (48 mmol/mol)

33
Criteria for T2Dm criteria
  • WHO -  FPG 126 mg/dL (7.0 mmol/L) or a two-hour
    post glucose challenge value 200 mg/dL 
  • ADA Same as previous slide but they add A1C
Write a Comment
User Comments (0)
About PowerShow.com