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

Carbohydrates

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

GLUCOSE CURVE

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

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%

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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