Derangement of Glucose Homeostasis - III PDF

DERANGEMENT OF GLUCOSE HOMEOSTASIS - III Dr. S.P.R.P. Prematilake Lecturer (probationary) Dept. of Biochemistry At the end of this lecture, small-group discussion and practical demonstration, the student should be able to define and explain impaired glucose tolerance, impaired fasting glucose,...

DERANGEMENT OF GLUCOSE HOMEOSTASIS - III Dr. S.P.R.P. Prematilake Lecturer (probationary) Dept. of Biochemistry At the end of this lecture, small-group discussion and practical demonstration, the student should be able to define and explain impaired glucose tolerance, impaired fasting glucose, diabetes and diabetic ketoacidosis describe the laboratory diagnosis of the above conditions describe the oral glucose tolerance test describe the significance of the analysis of glycated Hb in blood and microalbumin in urine Outline Tests for diagnosis of DM Tests for monitoring of control of DM Tests for detection of complications of DM DIAGNOSIS OF DM Diagnosis of Diabetes Mellitus Is based on, Clinical features of long-standing or acute hyperglycemia Evidence of hyperglycemia (or a directly related effect of it) by laboratory testing Clinical features + one abnormal lab result or Abnormal lab results at two separate occasions Normal Blood Glucose Curve Since blood glucose level varies throughout the day, how can we decide on a cut-off value? Random Blood Glucose level (RBS) Venous blood glucose level is measured without considering the time of the last meal Normal: < 100 mg/dl or  5.6 mmol/l Diabetes:  200 mg/dl or  11.1 mmol/l Fasting Blood Glucose level (FBS) Venous blood glucose level is measured at a fixed time from the last meal (defined as no caloric intake for 8 hrs) Normal: < 100 mg/dl or  5.6 mmol/l Diabetes:  126 mg/dl or  7.0 mmol/l Post-prandial Blood Glucose level (PPBS) Venous blood glucose level is measured at a fixed time after a meal, usually 2hrs afterwards Normal: < 140 mg/dl or < 7.8 mmol/l Diabetes:  200 mg/dl or  11.1 mmol/l Oral Glucose Tolerance Test (OGTT) Venous blood glucose level is measured at a fixed time after a fixed load of glucose, i.e. at 1hr/ 2hrs afterwards OGTT 2hr Normal: < 140 mg/dl or < 7.8 mmol/l Diabetes:  200 mg/dl or  11.1 mmol/l In simple, Fasting for 8 – 12 hrs Fasting blood glucose sample taken 75g of glucose ingested by patient Blood glucose level tested at fixed times, mostly at 2hrs HbA1c Test (Glycated Hb levels) Glycation is non-enzymatic binding of glucose to other substrates. It is directly proportionate to glucose concentration in blood. The percentage of HbA1c that is glycated is assessed as an indirect measure of blood glucose level. (Of glycated Hb, about 80% is HbA1c.) Normal: < 5.7% Diabetes:  6.5%  Advantages No need of fasting or timed samples Measures the average blood glucose concentration over a period of 2 – 3 months Also used to monitor control Disadvantages Standardized only for adults Cannot be used in increased red cell turnover or hemoglobinopathies, pregnancy What is this in-between group? Normal Diabetes Natural Progression of Type II DM Prediabetes Category for those whose blood sugar or HbA1c test results are neither diabetic nor “normal” Prediabetes is not a disease or a condition. They are a high-risk group to develop DM in future. Impaired Fasting Glucose: FBS is 100 – 125 mg/dl or 5.6 – 6.9 mmol/l Impaired glucose tolerance: OGTT is 140 – 199 mg/dl or 7.8 – 11.0 mmol/l Summary WHO criteria for diagnosis of DM Test Normal Prediabetes Diabetes RBS < 100 mg/dl -  200 mg/dl  5.6 mmol/l  11.1 mmol/l FBS < 100 mg/dl 100 – 125 mg/dl  126 mg/dl  5.6 mmol/l 5.6 – 6.9 mmol/l  7.0 mmol/l (IFG) OGTT < 140 mg/gl 140 – 199 mg/dl  200 mg/dl < 7.8 mmol/l 7.8 – 11.0 mmol/l  11.1 mmol/l (IGT) HbA1c < 5.7% 5.7 – 6.4  6.5% Urine testing for glucose Glucose will appear in urine only when blood glucose levels exceed the renal threshold for glucose. Therefore, testing for glucose in urine is not a good diagnostic test. However, it is used as a screening test. The commonly used Benedict test is a test for reducing substances, which includes glucose. OGTT in Pregnancy 75g OGTT is done and venous blood is tested at just before the test (fasting), 1hr and 2hrs afterwards. GDM is diagnosed in the presence of any of the following: Fasting:  92 mg/dL (5.1 mmol/L) 1 h:  180 mg/dL (10.0 mmol/L) 2 h:  153 mg/dL (8.5 mmol/L) C-peptide levels C-peptide is a by-product of insulin synthesis. C-peptide levels can therefore be used as a measure of insulin production (beta cell function). Can be tested in fasting state or after a standard meal. Antibody testing Specific antibodies can be detected in Type I DM, especially during the early stage of the disease. Islet-cell antibodies (IA2) Antibodies against glutamic acid decarboxylase (Anti- GAD65) Anti-insulin antibodies MONITORING CONTROL OF DM Which of the following is best for monitoring blood glucose control in a DM patient? RBS FBS OGTT HbA1c HbA1c level HbA1c levels is a good test for monitoring glycemic control. Based on the value, it is concluded if the control is good or poor. Fructosamine test Measures glycated proteins/ albumin levels in serum It is an indicator of the average glucose level over past 2 – 3 weeks. Can be used when HbA1c levels are not reliable. But it is dependent on serum albumin levels. Blood Sugar Series A blood sugar series is often carried out during pregnancy to decide on sugar control. Before and after breakfast Before and after lunch Before and after dinner DETECTION OF COMPLICATIONS OF DM Diabetic nephropathy Albumin loss in urine is a feature of diabetic nephropathy. A loss of < 30mg of albumin per day is considered normal. At early stages of kidney damage, daily loss of albumin in urine starts to rise gradually above 30 mg. At this range of 30 – 300 mg loss of albumin per day is called microalbuminuria.  Microalbuminuria can be tested in different samples of urine. 24hr sample 30 – 300 mg Less than 24hr sample 20 – 200 mcg/min Spot sample (expressed as 30 – 300 mg/g albumin:creatinine ratio) DKA Ketoacidosis Arterial blood gas testing for pH, pCO2, HCO3- and base excess Ketonuria Urine for ketone bodies Hyperosmolality Plasma osmolality References “Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia”, 2006 – World Health Organization “Standards of Medical Care in Diabetes – 2017”, American Diabetes Association “Management of Diabetes Mellitus” – National Clinical Practice Guidelines, Sri Lanka