Diabetes Mellitus

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

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• 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.

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CClassification of DM

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

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• 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.

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

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• 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.
•  

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

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• 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).

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

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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.

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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.

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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.

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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.
•  

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• 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
•  

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• 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)
•  

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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.

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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.

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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.

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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.

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B) Type 2 diabetes

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

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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.

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Comparative clinical features of type 1 and type
2 diabetes
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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.

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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.

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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
•  

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• 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.

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• II- Average risk of GDM
• Screening should be performed between 24th-28th
  week of gestation.
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• Method Two-step approach
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• 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
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• 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
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• GDM is diagnosed if two or more of these
  plasma glucose values are found.

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• 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.
•  

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Screening of diabetes
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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.

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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

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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.

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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.

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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

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Thank you