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Diabetes mellitus - (Part-3) -- Laboratory diagnosis and management

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Laboratory diagnosis-
1) Urine Analysis
2) Blood biochemistry
3) Immuno assays
4) Additional tests
a) Management of Type 1 DM
b0 Management of type 2 DM

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Diabetes mellitus - (Part-3) -- Laboratory diagnosis and management

  1. 1. Diabetes Mellitus- Laboratory Diagnosis and Treatment (Part-3) Biochemistry for medics www.namrata.co
  2. 2. Contents 1) Laboratory Diagnosis o Urine Analysis o Blood Biochemistry o Immunological Assays 2) Management o Management of type 1 DM o Management of type 2 DM 3) Summary
  3. 3. URINE ANALYSIS a) Detection of urinary glucose (Glucosuria) o First-line screening test for diabetes mellitus o Normally glucose does not appear in urine until the plasma glucose rises above 160180 mg/dl. o In certain individuals due to low renal threshold glucose may be present despite normal blood glucose levels. o Conversely renal threshold increases with age so many diabetics may not have Glycosuria despite high blood sugar levels. Positive Benedict’s test
  4. 4. URINE ANALYSIS (Contd.) o Detection of Glucosuria- A specific and convenient method to detect glucosuria is the paper strip impregnated with glucose oxidase and a chromogen system (Clinistix, Diastix), which is sensitive to as little as 0.1% glucose in urine. o Diastix can be directly applied to the urinary stream, and differing color responses of the indicator strip reflect glucose concentration. o Benedict’s and Fehling’s test can also detect glucosuria. DiastixReagent strips
  5. 5. URINE ANALYSIS (Contd.) b) Ketonuria o Qualitative detection of ketone bodies can be accomplished by nitroprusside tests (Acetest or Ketostix), Rothera’s test etc. oThese tests do not detect Beta-hydroxy butyric acid, which lacks a ketone group o Ketone bodies may be present in a normal subject as a result of simple prolonged fasting. Positive Rothera’s test KetostixReagent strips
  6. 6. URINE ANALYSIS (Contd.) c) Microalbuminuria o May be defined as an albumin excretion rate intermediate between normality (2.5-25 mg/day) and macroalbuminuria (250mg/day). oThe small increase in urinary albumin excretion is not detected by simple albumin stick tests and requires confirmation by careful quantization in a 24 hr urine specimen.
  7. 7. URINE ANALYSIS (Contd.) o The importance of microalbuminuria in the diabetic patient is that it is a signal of early reversible renal damage. o Performing an albumin-tocreatinine ratio is probably easiest. o Microalbuminuria is a common finding (even at Gradation of turbidity is linked to diagnosis) in type 2 protein concentration diabetes mellitus and is a risk factor for macro vascular (especially 11/7/2013 coronary heart) disease. Biochemistry For Medics 7
  8. 8. BLOOD BIOCHEMISTRY 1) Blood Glucose Estimation Choice of sample • Plasma or serum from venous blood samples has the advantage over whole blood of providing values for glucose that are independent of Haemtocrit and that reflect the glucose concentration to which body tissues are exposed. • Plasma and serum are more readily measured on automated equipment, 11/7/2013 Biochemistry For Medics they are used in most laboratories. 8
  9. 9. BLOOD BIOCHEMISTRY Choice of sample (contd.) • If serum is used or if plasma is collected from tubes that lack an agent to block glucose metabolism (such as fluoride), samples should be refrigerated and separated within 1 hour after collection. • The glucose concentration is 10–15% higher in plasma or serum than in whole blood because structural components of blood cells are absent. 11/7/2013 Biochemistry For Medics 9
  10. 10. BLOOD BIOCHEMISTRY Fasting blood Glucose o Fasting blood glucose is measured after an overnight fast of 10 hrs. o Fasting blood glucose estimation is better than random blood glucose. o FPG < 5.6 mmol/L (100 mg/dL) is considered normal; o FPG = 5.6–6.9 mmol/L (100–125 mg/dL) is defined as IFG; and o FPG >7.0 mmol/L (126 mg/dL) warrants the diagnosis of DM.
  11. 11. BLOOD BIOCHEMISTRY(contd.) Random blood Glucose o Random is defined as without regard to time since the last meal. o RBG measurement is required only during emergency. oThe current criteria for the diagnosis of DM emphasize that the FPG is the most reliable and convenient test for identifying DM in asymptomatic individuals. o A random plasma glucose concentration >11.1 mmol/L (200 mg/dL) accompanied by classic symptoms of DM (polyuria, polydipsia, weight loss) is sufficient for the diagnosis of DM
  12. 12. BLOOD BIOCHEMISTRY(contd.) Glucose tolerance test o When the fasting plasma glucose level is 126 mg/dL or higher on more than one occasion, further evaluation of the patient with a glucose challenge is unnecessary. oHowever, when fasting plasma glucose is less than 126 mg/dL in suspected cases, a standardized oral glucose tolerance test may be done .
  13. 13. BLOOD BIOCHEMISTRY(contd.) Glucose tolerance test Methodology 75 g of glucose dissolved in 300 mL of water is given after an overnight fast to a person who has been receiving at least 150–200 g of carbohydrate daily for 3 days before the test.
  14. 14. BLOOD BIOCHEMISTRY(contd.) Glucose tolerance test- Data InterpretationThe Diabetes Expert Committee criteria for evaluating the standard oral glucose tolerance test. Normal Glucose Tolerance Impaired Glucose Tolerance Diabetes Mellitus Fasting plasma < 110 glucose (mg/dL) 110–125 >126 Two hours after < 140 140–199 >200 glucose load
  15. 15. Concentration in mg/dl Glucose Tolerance Test (mg/dl) Time in minutes 11/7/2013 Normal Glucose tolerance curve Biochemistry For Medics 15
  16. 16. BLOOD BIOCHEMISTRY(contd.) b) Glycated hemoglobin (Hb1C) measurements o HbA1c comprises 4–6% of total hemoglobin A 1. o Since glycohemoglobins circulate within red blood cells whose life span lasts up to 120 days, they generally reflect the state of glycemia over the preceding 8–12 weeks, thereby providing an improved method of assessing diabetic control. o Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (eg, recovery from acute blood loss, hemolytic anemia) will falsely lower HbA1c irrespective of the assay method used.
  17. 17. BLOOD BIOCHEMISTRY(contd.) Glycated hemoglobin (Hb1C) measurements Methods for measuring HbA1c include electrophoresis, cationexchange chromatography, boronate affinity chromatography, and immunoassays. 11/7/2013 Biochemistry For Medics 17
  18. 18. BLOOD BIOCHEMISTRY(contd.) c) Serum fructosamine estimation oSerum fructosamine is formed by nonenzymatic glycosylation of serum proteins (predominantly albumin). oSerum albumin has a much shorter half-life than hemoglobin, serum fructosamine generally reflects the state of glycemic control for only the preceding 1–2 weeks.
  19. 19. BLOOD BIOCHEMISTRY(contd.) Serum fructosamine Estimation o Normal values vary in relation to the serum albumin concentration are 1.5–2.4 mmol/L when the serum albumin level is 5 g/dL. o When abnormal hemoglobins or hemolytic states affect the interpretation of glycohemoglobins or when a narrower time frame is required, such as for ascertaining glycemic control at the time of conception in a diabetic woman who has recently become pregnant, serum fructosamine assays offer some advantage. 11/7/2013 Biochemistry For Medics 19
  20. 20. BLOOD BIOCHEMISTRY(contd.) Self-monitoring of blood glucose o Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful. o In type 1 patients in whom "tight" metabolic control is attempted, they are indispensable. oThere are several paper strip (glucose oxidase, glucose dehydrogenase, or hexokinase) methods for measuring glucose on capillary blood samples. A reflectance photometer or an amperometric system is then used to measure the reaction that takes place on the reagent strip.
  21. 21. BLOOD BIOCHEMISTRY(contd.) Lipid profile o Serum Total cholesterol is elevated o Serum triglycerides are high o Serum HDLc is low o Qualitative change in LDL particles, producing a smaller dense particle whose membrane carries supranormal amounts of free cholesterol. oThese smaller dense LDL particles are more susceptible to oxidation, which renders them more atherogenic
  22. 22. BLOOD BIOCHEMISTRY(contd.) Additional Tests o The patient should be screened for DMassociated conditions (e.g., kidney, liver and thyroid dysfunction). o Individuals at high risk for cardiovascular disease should be screened for asymptomatic CAD by appropriate cardiac stress testing, when indicated. oThe classification of the type of DM may be facilitated by laboratory assessments.
  23. 23. BLOOD BIOCHEMISTRY(contd.) Insulin Luminescence assay kit C-Peptide Luminescence assay kit Serum insulin or C-peptide measurements do not always distinguish type 1 from type 2 DM, but a low Cpeptide level confirms a patient's need for insulin. 11/7/2013 Biochemistry For Medics 23
  24. 24. IMMUNOLOGICAL ASSAYS o Antibodies to insulin, islet cells, or Glutamic acid decarboxylase (GAD) can be estimated to differentiate between the types of diabetes mellitus oThey are absent in type 2 diabetes mellitus. o Latent autoimmune diabetes of adults, or LADA, is a form of slow-onset type 1 diabetes that occurs in middle-aged (usually white) adults. oIt can be differentiated from type 2 diabetes by measuring anti-GAD65 antibodies.
  25. 25. Management of Diabetes Mellitus The goals of therapy for type 1 or type 2 DM are to: (1)eliminate symptoms related to hyperglycemia, (2)reduce or eliminate the long-term micro vascular and macro vascular complications of DM, and (3)allow the patient to achieve as normal a lifestyle as possible.
  26. 26. Management of Type 1 Diabetes Mellitus o Because individuals with type 1 DM partially or completely lack endogenous insulin production, administration of basal, exogenous insulin is essential for regulating glycogen breakdown, gluconeogenesis, lipolysis, and ketogenesis. o Likewise, insulin replacement for meals should be appropriate for the carbohydrate intake and promote normal glucose utilization and storage.
  27. 27. Management of Type 1 Diabetes Mellitus Insulin Preparations oInsulin is indicated for type 1 diabetes as well as for type 2 diabetic patients with insulinopenia whose hyperglycemia does not respond to diet therapy either alone or combined with other hypoglycemic drugs. oWith the development of highly purified human insulin preparations, immunogenicity has been markedly reduced, thereby decreasing the incidence of insulin allergy, immune insulin resistance, and localized lipoatrophy at the injection site.
  28. 28. Management of Type 1 Diabetes Mellitus oInsulins can be classified as short-acting or long-acting oThe short-acting preparations are regular insulin and the rapidly acting insulin analogs . oThey are dispensed as clear solutions at neutral pH and contain small amounts of zinc to improve their stability and shelf life. oThe long-acting preparations are NPH insulin and the long-acting insulin analogs. oNPH insulin is dispensed as a turbid suspension at neutral pH with protamine in phosphate buffer. oThe long-acting insulin analogs are also dispensed as clear solutions.
  29. 29. Management of Type 1 Diabetes Mellitus Mixed insulin preparations oSince intermediate insulins require several hours to reach adequate therapeutic levels, their use in patients with type 1 diabetes requires supplements of regular or rapidly acting insulin analogs preprandially. oFor convenience, regular or rapidly acting insulin analogs and NPH insulin may be mixed together in the same syringe and injected subcutaneously in split dosage before breakfast and supper.
  30. 30. Management of Type 1 Diabetes Mellitus Methods of insulin administration 1) Insulin syringes and needles-Plastic disposable syringes are available in 1-mL, 0.5-mL, and 0.3-mL sizes. 2) Insulin pen injector devices-Insulin pens eliminate the need for carrying insulin vials and syringes. 3) Insulin pumps-Insulin infusion pumps are used for subcutaneous delivery of insulin. These pumps are small (about the size of a pager) and very easy to program. 4) Inhaled insulin-A novel method for delivering a pre-prandial powdered form of insulin by inhalation (Exubera) has been approved by the FDA.
  31. 31. Management of Type 1 Diabetes Mellitus Methods of insulin administration 11/7/2013 Biochemistry For Medics 31
  32. 32. Management of Type 1 Diabetes Mellitus An insulin pump is an alternative to Inhaled Insulin-The FDA multiple daily injections of insulin by approved the first inhaled insulin syringe or an insulin pen and version of insulin allows for intensive insulin therapy when used in conjunction with blood called Exubera from Pfizer 11/7/2013 monitoring. Biochemistry For Medics glucose Inc. 32
  33. 33. Management of Type 1 Diabetes Mellitus o Complications of Insulin Therapy Hypoglycemia, Insulin allergy, immune insulin resistance and lipodystrophy at the injection site are some of the complications of insulin therapy. o Besides insulin therapy, life long dietary and life style modifications are required to be done to achieve euglycemia. Injection site Lipodystrophy
  34. 34. Management of Type 1 Diabetes Mellitus o Islet cell transplantation is a minimally invasive procedure, wide application of this procedure for the treatment of type 1 diabetes is limited by the dependence on multiple donors and the requirement for potent longterm immunotherapy. Islet cell transplantation
  35. 35. Management of Type 1 Diabetes Mellitus Stem cell therapyStem cell therapy is one of the most promising treatments for the near future. It is expected that this kind of therapy can ameliorate or even reverse some diseases. 11/7/2013 Biochemistry For Medics 35
  36. 36. Management of Type 2 Diabetes Mellitus oThe goals of therapy for type 2 DM are similar to those in type 1. oThe care of individuals with type 2 DM must also include attention to the treatment of conditions associated with type 2 DM (obesity, hypertension, dyslipidemia, cardiovascular disease) and oDetection/management of DM-related complications.
  37. 37. Management of Type 2 Diabetes Mellitus a) Weight reduction o Treatment is directed toward achieving weight reduction, and prescribing a diet is only one means to this end. o Behavior modification to achieve adherence to the diet o Increased physical activity to expend energy—is also required. 11/7/2013 Biochemistry For Medics 37
  38. 38. Management of Type 2 Diabetes Mellitus b) Hypoglycemic agents • If the patient is not able to achieve target glycemic control with weight management and exercise, then pharmacologic therapy is indicated. • Based on their mechanisms of action, glucoselowering agents are subdivided into agents that increase insulin secretion, reduce glucose production and increase insulin sensitivity 11/7/2013 Biochemistry For Medics 38
  39. 39. Management of Type 2 Diabetes Mellitus 1) Insulin Secretagogues o Insulin Secretagogues stimulate insulin secretion by interacting with the ATPsensitive potassium channel on the beta cells. o These drugs are most effective in individuals with type 2 DM of relatively recent onset (<5 years), who have residual endogenous insulin production. 11/7/2013 Biochemistry For Medics 39
  40. 40. Management of Type 2 Diabetes Mellitus a) Sulfonylurea—first b) Sulfonylurea— generation second generation   Chlorpropamide   Glimepiride c) Non sulfonylureas   Repaglinide   Tolazamide   Glipizide   Nateglinide    Tolbutamide   Glipizide (extended  release)   Glyburide  Glyburide (micronized) 11/7/2013 Biochemistry For Medics 40
  41. 41. Management of Type 2 Diabetes Mellitus • Insulin Secretagogues are generally well tolerated.  • All of these agents, however, have the potential to  cause profound and persistent hypoglycemia, especially  in elderly individuals. • Hypoglycemia is usually related to delayed meals,  increased physical activity, alcohol intake, or renal  insufficiency. 11/7/2013 Biochemistry For Medics 41
  42. 42. Management of Type 2 Diabetes Mellitus 2) Biguanides • Metformin is representative of this  class of agents.  • It reduces hepatic glucose production  through an  undefined mechanism and  improves peripheral glucose utilization  slightly. • Metformin reduces fasting plasma  glucose and insulin levels, improves the  lipid profile, and promotes modest  weight loss. • The major toxicity of metformin, lactic  acidosis, can be prevented by careful  patient selection. 11/7/2013 Biochemistry For Medics 42
  43. 43. Management of Type 2 Diabetes Mellitus 3) α-Glycosidase Inhibitors o α -Glycosidase inhibitors (acarbose  and miglitol) reduce postprandial  hyperglycemia by delaying glucose  absorption; they do not affect  glucose utilization or insulin  secretion. o These drugs, taken just before each  meal, reduce glucose absorption by  inhibiting the enzyme that cleaves  oligosaccharides into simple sugars  in the intestinal lumen.   o The major side effects (diarrhea,  flatulence, abdominal distention)  are related to increased delivery of  oligosaccharides to the large bowel  11/7/2013 Biochemistry For Medics 43
  44. 44. Management of Type 2 Diabetes Mellitus 4) Thiazolidinediones •Thiazolidinediones reduce insulin  resistance.  •Rosiglitazone, Pioglitazone belong to this category. •Thiazolidinediones promote a  redistribution of fat from central to  peripheral locations. •Circulating insulin levels decrease  with use of the thiazolidinediones,  indicating a reduction in insulin  resistance 11/7/2013 Biochemistry For Medics 44
  45. 45. Management of Type 2 Diabetes Mellitus 5) Insulin Therapy in Type 2 DM o Insulin should be considered as the initial therapy in  type 2 DM, particularly in lean individuals or those with  severe weight loss, in individuals with underlying renal  or hepatic disease that precludes oral glucose-lowering  agents, or in individuals who are hospitalized or  acutely ill.  o Insulin therapy is ultimately required by a substantial  number of individuals with type 2 DM because of the  progressive nature of the disorder and the relative  insulin deficiency that develops in patients with longstanding diabetes.  11/7/2013 Biochemistry For Medics 45
  46. 46. Summary Of Type 1 DM 1) Diabetes mellitus type 1 (Type 1 diabetes, IDDM, or juvenile  diabetes) is a form of diabetes mellitus that results from  autoimmune destruction of insulin producing beta cells of the  pancreas.  2) The classical symptoms of Type 1 diabetes are polyuria,  polydipsia, polyphagia and weight loss.  3) Type 1 diabetes is fatal unless treated with insulin.  4) Injection is the most common method of administering  insulin; insulin pumps and inhaled insulin has been available  at various times. 5) Diabetic keto acidosis is the commonest complication of  Type 1 DM. 11/7/2013 Biochemistry For Medics 46
  47. 47. Summary of Type 2 DM 1)Type 2 DM is characterized by impaired insulin secretion,  insulin resistance, excessive hepatic glucose production,  and abnormal fat metabolism. 2) While many patients with type 2 diabetes present with  increased urination and thirst, many others have an  insidious onset of hyperglycemia and are asymptomatic  initially. 3) Hyperglycemic hyperosmolar state (HHS) is an acute  complication of Type 2 diabetes. Chronic complications are  micro and macro vascular involving small and large blood  vessels respectively. 11/7/2013 Biochemistry For Medics 47
  48. 48. Summary of Type 2 DM(contd.) 4) Glucose lowering agents that either increase insulin  secretion, reduce glucose production, increase insulin  sensitivity, and enhance GLP-1 (Glucagon like peptide)  action are used to treat hyperglycemia. 5) The care of individuals with type 2 DM must also  include attention to the treatment of conditions  associated with type 2 DM (obesity, hypertension,  dyslipidemia, cardiovascular disease) and  detection/management of DM-related complications. 11/7/2013 Biochemistry For Medics 48
  49. 49. For further details •Refer A Case oriented Approach Towards  Biochemistry •A Book Of Clinical BiochemistryJay pee Brothers Medical  Publishers. •http://www.jaypeebrothers.com/pgDetails.aspx?cat=s&book_id=978   11/7/2013 Biochemistry For Medics 49