1. Carbohydrates for Clinical Diagnosis
Linda D. Tamesis, MS, MD, FPSP

2. Carbohydrates

3. BASIC CHEMISTRY
CX(H20)Y
Contains
C=O OH

4. METABOLISM of CARBOHYDRATES
Absorbed by gut
Transported to liver
Only glucose can be used for energy

5. PANCREAS Amylase Breakdown of complex carbohydrates Insulin Glucagon
EXOCRINE
Amylase
Breakdown of complex carbohydrates
ENDOCRINE
Insulin
Glucagon
Somatostatin (GH)
Pancreatic polypeptide
Islet Amyloid Polypeptide (Amylin, IAPP)
Insulin- stimulates glucose uptake – decreases glucose in blood
Glucagon – stimulates glucose production – increase glucose in blood
Somatostatin inhibits the release of both insulin and glucagon
PP- reduces appetite and food intake

6. REGULATION OF BLOOD GLUCOSE
Insulin/ Glucagon
Increased
Anabolism
After eating
Decreased
Catabolism
Fasting

7. C peptide
As proinsulin is converted to its active form, insulin, a C chain is cleaved off. Measurement of this C chain or C peptide relates to the amount of insulin being made by the body or endogenous insulin.
Insulin

8. MEASUREMENT OF INSULIN
HYPOGLYCEMIA, due to:
Insulinoma
High insulin and high C peptide
Injected insulin
High insulin and low C peptide

9. MEASUREMENT OF C PEPTIDE
Etiology of DM
Low levels in DM1
Information of Beta cell secretory capacity
Differentiates endogenous insulin from exogenous insulin

10. C Peptide elevated lowered Insulinoma Type 1 diabetes mellitus
Sulfonylurea intoxication
Noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS)
Insulin resistance state (obesity, Cushing)
Chronic kidney disease
Type 1 diabetes mellitus
Exogenous insulin injection
(factitious) Hypoglycemia due to insulin-like growth factor secreting tumor
Insulin-independent hypoglycemia

11. DIABETES MELLITUS Hyperglycemia Increase in plasma glucose levels
Defect in insulin secretion, action or both
Polyuria, polydypsia, polyphagia
Microvascular and Macrovascular complications

12. Pre diabetes DM Type 1 IDDM DM Type 2 NIDDM Gestational GDM
CATEGORIES OF DM
Pre diabetes
DM Type IDDM
DM Type 2 NIDDM
Gestational GDM

13. DIABETES TYPE 1 TYPE 2 5-10 % Children Autoimmune destruction
Tx-Insulin
90-95 %
Adults
Insulin resistance
Tx-Oral
Lifestyle change

14. Impaired fasting glucose BP > 130/85 Waist circumference
METABOLIC SYNDROME
Impaired fasting glucose
BP > 130/85
Waist circumference
>102 men, >88 female
Triglycerides>150 mg/dL
HDL
<40mg/dL men, <50 mg/dL in females

15. History of impaired glucose tolerance
NIDDM SCREENING
Obesity (BMI>25)
Family history
High risk minority
History of GDM
>45 years old
Hypertension
Low HDL
High triglycerides
History of impaired glucose tolerance
Remember, screening is done on individuals who have no signs and symptoms of the disease in question

16. GLUCOSE MEASUREMENT
Plasma, serum, whole blood (from finger prick), CSF, urine, etc
Whole blood 15% lower than plasma
Liquid portion of blood must be separated within 30 minutes (cells consume glucose)
Gray top, with fluoride, stop glycolysis, so separation can take longer

17. TESTS FOR HYPERGLYCEMIA
Random blood sugar (RBS)
No patient preparation
Emergency room request
<140 mg/dl

18. TESTS FOR HYPERGLYCEMIA
Fasting Blood Sugar (FBS)
Requires at least 8 hour fast (8-12)
No drugs, water food
Patient usually starts fast after dinner and go to laboratory in the morning
Most often used for the screening and diagnosis of DM

19. TESTS FOR HYPERGLYCEMIA
2 hour Post Prandial (2hPP)
2 hours after eating
Used for screening and diagnosis of DM in patients who have difficulty fasting.

20. GLUCOSE CURVE

21. ORAL GLUCOSE TOLERANCE TEST
Patient fasts 8 hours
Baseline blood sample taken
75gms of glucose consumed within 5 minutes
Blood extracted at 1 and 2 hours
Used to differentiate Pre diabetes from DM, GDM

22. AMERICAN DIABETES ASSOCIATION
DIABETES MELLITUS
At least 2 occasions
FBS > 126 mg/dl (7.0 mmol/L)
2hPP > 200 mg/dl (11.1 mmol/L)
Symptoms of diabetes
RBS > 200 mg/dl
A1c > 6.5%

23. AMERICAN DIABETES ASSOCIATION
Pre diabetes / impaired glucose tolerance
FBS = 100 mg/dl to 125 mg/dl

24. GLUCOSE CHALLENGE TEST
Screening for GDM
Done between 24th and 28th wk
Screening for pregnant who
Has had GDM during a previous pregnancy
Gave birth to a baby who weighed > 8.8 lbs
>25 yo
Overweight before pregnancy

25. GLUCOSE CHALLENGE TEST
Plasma glucose measured 1 hour after a 50 gram glucose load
No fasting
(+) > 140 mg/dl

26. CAPILLARY BLOOD GLUCOSE (CBG) (HGT)
Self monitoring of glucose levels
Not accurate
Very precise
3-4 times a day
Useful in type I

27. GLYCOSYLATED HEMOGLOBIN (HbA1c)
Glucose over threshold blood level binds to hemoglobin
Binding irreversible
Compound remains in blood until RBC dies, 120 days

28. GLYCOSYLATED HEMOGLOBIN
For every 1% change in HgA1c there is a 35 mg/dl change in mean glucose level

29. Glycosylated Hemoglobin (HbA1c)
Best use is to monitor glucose control
Should be done every 3-6 months for DM1 and DM2
Now included for diagnosis of DM

30. MONITORING FOR DIABETIC CONTROL
HbA1c
Fructosamine
3-6% reference range
Control in preceding 3-5 weeks
Cannot be used if hemoglobin is less than 6gm/dl
No reference range
Control in previous 2-3 weeks
Not affected with anemia
Best for GDM
Rapid changes in diabetic treatment

32. KETONES Products of FFA metabolism Beta hydroxybutyric acid
Acetoacetic acid
Acetone
Important for DM1 to detect ketoacidosis
Abdominal pain, nausea, electrolyte imbalance, dehydration
1st 2 usually found in equal concentrations

33. KETONES Increase in/with Ketoacidosis High fat diet Starvation
No method of measurement can be used for all 3 ketones
Acetoacetic acid (strips and tablets)
B hydroxybutyric acid (analyzer)

34. MICROALBUMINURIA First sign of diabetic nephropathy
Micral test, dipstick test for urine

35. Islet Autoantibody OTHER TESTS Glutamic acid decarboxylase (GAD65)
Insulin autoantibodies (IAA)
Islet cell antigen 512 autoantibodies (ICA 512)
For DM1

36. HYPOGLYCEMIA NEUROGENIC Tremors, palpitation, anxiety
Diaphoresis, hunger, parathesias
NEUROGLYCEMIC
Dizziness, tingling difficulty in concentration, blurred vision, confusion, seizures, coma

37. HYPOGLYCEMIA < 50 mg/dL In adult, absence of DM requires evaluation
In child, immediate evaluation
Conditions
Drugs Autoimmune diseases
Alcohol Neoplasia
Severe illness Hormone deficiencies

38. LACTIC ACIDOSIS DIAGNOSIS High levels of lactic acid in blood
Increased anion gap
Low blood pH
CAUSES
Tissue hypoxia Tumors
Inborn errors of metab Drugs
Metabolic conditions