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Diabetes Mellitus

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Title: Diabetes Mellitus


1
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2
  • Classification and diagnosis of Diabetes
    Mellitus
  • Fathy El-Sewy, MD
  • Professor of Internal Medicine and Diabetes
  • Faculty of Medicine
  • Alexandria University

3
  • DM is a group of chronic heterogeneous
    metabolic disorders characterized by
    hyperglycemia with disturbances of carbohydrate,
    fat and protein metabolism. It results from
    defects of insulin secretion, insulin action or
    both.
  • It is often accompanied by specific
    microvascular (retina, renal, peripheral nerves),
    and non-specific macrovascular (coronary,
    cerebral, peripheral blood vessels)
    complications.

4
CClassification of DM
  • Types of diabetes mellitus are
  • Type 1
  • - Autoimmune
  • - Idiopathic.
  • Type 2
  • - Predominantly insulin resistance
  • - Predominantly insulin secretory defect.

5
  • Gestational Diabetes Mellitus (GDM).
  • Other specific types
  • - Pancreatic diseases Pancreatitis
    pancreatectomy, neoplasia hemochromatosis.
  • - Endocrinopathies acromegaly, Cushing's
    syndrome, pheochromocytoma and hyperthyroidism
  • - Drugs or chemicals induced corticosteroids,
    thiazide diuretics, thyroid hormone, B-adrenergic
    agonists.

6
  • Diagnosis of DM
  •  
  • Diabetes is a very common disease many
    cases are undiagnosed, 10-20 of cases have
    serious vascular disease at presentation.

7
  • A- Clinical picture types of presentations are
  • a-Acute Young, 2-4 weeks.
  • - Polyuria ? urine output gt 2.5 liters/day due
    to osmotic diuresis.
  • - Polydipsia due to cellular dehydration.
  • - Polyphagia due to cellular starvation.
  • - Weight loss loss of fluids, ? catabolism.
  • - Ketoacidosis in 30 of type 1 diabetes.
  •  

8
  • b- Subacute older, several months
  • - Thirst, weight loss and polyuria.
  • - Lack of energy.
  • - Blurring of vision.
  • - Balanitis or pruritus vulvae.
  •  

9
  • c- Complications (only in type 2 diabetes)
  • - Repeated skin and fungal infections.
  • - Visual disturbances (? vision, frequent errors
    of refraction, and premature cataract).
  • - Abnormal gestation (e.g. macrosomic baby gt 4
    Kg).
  • - Unexplained peripheral neuropathy.
  • - Impotence.
  • - Premature arterial disease (MI, PVD).

10
  • d- Asymptomatic
  • - Accidentally discovered.
  • - Glycosuria.
  • - ? Blood glucose levels in routine checkup.

11
B- Physical signs
  • Type 1 diabetes
  • - No clinical signs related.
  • In fulminant cases signs of severe dehydration
    and acidosis.
  • Type 2 diabetes depend on the mode of
    presentation
  • - Pruritus vulvae or balanitis is common.
  • - Loss of ankle reflexes.
  • - ? Peripheral sensation.
  • - Hypertension and signs of atherosclerosis (weak
    pulsation of dorsalis pedis artery, bruit over
    the carotid).
  • - Signs of insulin resistance e.g. Acanthosis
    Nigricans or
  • Polycystic ovary syndrome.

12
C- Laboratory assessment
  • a-Urine testing
  • i- Glycosuria (ve urine for glucose), requires
    urgent blood glucose measurements
  • It is not used as a diagnostic tool of diabetes.
  • Renal threshold for glucose is about 180 mg/dl
    and shows individual variations.
  • ii- Ketonuria (ve urine for ketone bodies), may
    be found in
  • Prolonged fasting or starvation.
  • Heavy exercise.
  • Repeated vomiting
  • Alcohol intake.
  • So, it is not specific of diabetes.
  • iii-Glycosuria and ketonuria is diagnostic of
    diabetic ketoacidosis.

13
Blood glucose measurements using venous plasma.
  •  
  • The following 3 blood tests are used for
    diagnosis
  • Random plasma glucose sample taken any time of
    day.
  • Fasting plasma glucose (FPG) no caloric intake
    for 8 hours.
  • 2 hours post prandial (75gm oral glucose) plasma
    glucose (2h-PPPG) blood sample taken 2 hours
    after a person has consumed a 75 gm glucose
    powder dissolved in 250 ml water.

14
Interpretation
  • A- Diagnostic criteria of DM
  • a- Classical symptoms of DM any one of three
    positive tests
  • 1- Random plasma glucose ? 200
    mg/dl.
  • Or 2- Fasting plasma glucose ? 126
    mg/dl.
  • Or 3- 2h-PPPG ? 200 mg/dl
  • b- Absence of classical symptoms of
    hyperglycemia Any abnormal test must be
    confirmed on a subsequent day by any one of the
    three tests.
  •  

15
  • B- Prediabetes include individuals who have
  • FPG 100-125mg/dl (called impaired fasting
    glucose)
  • 2.2h-PPPG 140-199 mg/dl (called impaired glucose
    tolerance).
  •  
  • C- Normoglycemia include individuals
    who have
  • 1. FPG lt 100 mg/dl
  • 2. 2h-PPPG lt 140 mg/dl
  •  

16
  • The old OGTT requiring half hourly blood
    glucose measurements has been replaced by
    Modified OGTT fasting plasma glucose (FPG) and 2
    hours-post prandial (75 gm oral glucose) plasma
    glucose (2h-PPPG)
  •  

17
Categories of glucose intolerance
  • Diabetes mellitus (Type 1, Type 2 GDM).
  • Prediabetes (IFG and IGT).
  • I- Diabetes mellitus
  • A) Type 1 diabetes
  • 1- Autoimmune
  • a- Rapidly progressive ? young.
  • b- Slowly progressive ? LADA (Late onset
    Autoimmune Diabetes in the Adulthood).
  • 2- Idiopathic non immune mediated.

18
Features of rapidly progressive type 1 autoimmune
diabetes
  • a- Clinical markers
  • - Young lt 30 years.
  • - Classical, acute and severe presentation.
  • - Never obese.
  • - Ketosis prone.
  • - Insulin requiring for survival.
  •  
  • b- Laboratory markers
  • - Plasma insulin and c-peptide levels are absent
    or very low.
  • - GAD-Abs, ICA, insulin autoantibodies.
  • - HLA- DR3, and or DR4 associated.

19
Features of slowly progressive autoimmune type 1
diabetes(LADA)
  • Age at onset usually gt 35 years.
  • Clinical presentation as non-obese type 2
    diabetes.
  • Initial control with diet or oral agents.
  • Progressive deterioration of insulin secretion.
  • Positive markers of autoimmunity to the
    ?-cells.

20
Idiopathic non immune mediated
  • - Atypical type 1 diabetes, called type 1.5.
  • - Difficult to distinguish form type 1.
  • - FH is positive for early onset diabetes in
    many relatives.
  • - Ketoacidosis may occur.
  • - Metabolic control is difficult without
    insulin.

21
B) Type 2 diabetes
  • - Obese (80) predominantly insulin
    resistant.- Non obese (20) predominantly
    insulin secretory defect. - MODY Maturity Onset
    Diabetes in the Young.

22
MODY( Maturity Onset Diabetes in the Young)
  • - Rare form of diabetes in children.
  • - Monogenic defects in ? cell function
    (glucokinase gene).
  • - Inherited as an autosomal dominant.
  • - Broad clinical spectrum from asymptomatic
    hyperglycemia to severe acute presentation.
  • - Molecular diagnostic testing is available only
    in research laboratories.

23
Comparative clinical features of type 1 and type
2 diabetes
24
Prediabetes
  • A metabolic stage intermediate between
    normal glucose homeostasis and diabetes.
  • This stage include individuals who have
  • 1- Impaired fasting glucose (IFG) when
    FPG 100-125 mg/dl.
  • 2- Impaired glucose tolerance (IGT) when
    2h-PPPG 140-199 mg/dl.
  • Also called, borderline, subclinical or early
    diabetes.
  • IFG and IGT are not clinical entities but are
    risk factors for
  • 1- Progression to diabetes.
  • 2- Macrovascular disease.

25
Gestational Diabetes Mellitus (GDM)
  • Any degree of glucose intolerance with
    onset or first recognition during pregnancy. It
    may or may not disappear after delivery and
    liable to recur with following pregnancies.
  • It appears in about 2-5 of all
    pregnancies.

26
Detection and diagnosis
  • Pregnant women are classified into high,
    average, and low risk of GDM, and time and method
    of screening depend on the degree of risk.
  • I- High risk of GDM factors that increase the
    risk of GDM are
  • 1- Marked obesity.
  • 2- Strong FH of DM.
  • 3-Previous history of GDM.
  • 4- Old age gt 30 years.
  • 5- Glycosuria.
  • 6- History of macrosomic baby
  •  

27
  • Screening blood glucose testing should be
    performed as early as possible during the first
    trimester using venous plasma glucose
  • Diabetes is diagnosed if
  • Fasting plasma glucose ? 126 mg/dl
  • Or Random plasma glucose ? 200 mg/dl
  • The test should be confirmed on a
    subsequent day unless symptoms of hyperglycemia
    are present.
  • High risk women not found to have GDM at
    the initial screening should be reassessed
    between 24-28th week of gestation, the same as
    women with average risk of GDM.

28
  • II- Average risk of GDM
  • Screening should be performed between 24th-28th
    week of gestation.
  •  
  • Method Two-step approach
  •  
  • Step 1 1h-GCT(Glucose Challenge Test)
  • - 24th 28th week
  • - No fasting
  • - 50 gm oral glucose load.
  • - Plasma glucose level after one hour
  • lt 140 mg/dl ? normal
  • gt 140 mg/dl ? go to the next step
  •  

29
  • Step 2 if screening is positive ? 3 h-OGTT
  • - Fasting
  • - 100 gm oral glucose load dissolved in 250 ml
    water
  • - Diagnostic criteria for the 100 gm OGTT are as
    follows
  • Plasma glucose level
  • Fasting ? 95 mg/dl
  • 1 hour ? 180 mg/dl
  • 2 hour ? 155 mg/dl
  • 3 hour ? 140 mg/dl
  •  
  • GDM is diagnosed if two or more of these
    plasma glucose values are found.

30
  • III- Low risk of GDM No screening is needed for
    any woman fulfilling all the following criteria
  • 1- Normal body weight.
  • 2- -ve FH of DM in 1st degree relatives.
  • 3- -ve history of abnormal glucose tolerance.
  • 4- Age lt 25 years.
  • 5- -ve history of poor obstetric outcome.
  •  

31
Screening of diabetes
32
Criteria define screening for a particular
disorder
  • 1-It should be an important public health
    problem.
  • 2-Has an early asymptomatic stage.
  • 3-There is a suitable screening test.
  • 4-An accepted treatment should be available.
  • 5-There is evidence that early treatment improves
    long term outcome.

33
Screening tests
  • Fasting plasma glucose is currently recommended
    for diabetes screening
  • 1- It is quick.
  • 2- It is easy.
  • 3- It is acceptable to patients in clinical
    setting
  • Categories of FPG concentrations are
  • Less than 100mg / dl Normal
  • 101 to 125 mg /dl IFG
  • Greater than 125 mg/dl DM

34
Screening recommendations
  • The two approaches are
  • 1- To screen the entire population above a
    certain age.
  • 2- To screen certain high risk groups.
  • The ADA recommends that people be screened by
    measurement of FPG every 3 ys. beginning at age
    45 ys.
  • Screening should be considered at an earlier
    age or be carried out more frequently if diabetes
    risk factors are present.

35
Diabetes risk factors
  • Age 45 years.
  • Overweight.
  • Family history of DM in a first degree relative.
  • Habitual physical inactivity.
  • History of delivering a large babygt4kg or of
    GDM.
  • Hypertension.
  • Dyslipidemia.
  • Previously identified IFG or IGT
  • PCOS
  • History of vascular disease.
  • Belonging to a high risk ethnic or racial group.

36
Recommendations
  • If the FPG is 100mg/dl , the test should be
    repeated.
  • Requirements to make the diagnosis of DM are
  • - Two FPG values 126 mg/dl,
  • - Or, Two post-glucose values 200mg/dl
  • - Or, one of each, or a random glucose 200mg/dl
    with symptoms of hyperglycemia

37
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