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Dr tasnim dm

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an overview on DM and Hypoglycemia

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Dr tasnim dm

  1. 1. An Overview On Diabetes Mellitus &Hypoglycemia Dr.Tasnim Ara Jhilky MD Part II Phase A Department of Biochemistry Sir Salimullah Medical College Midford ,DhakA
  2. 2. Insulin secretion Increasing blood glucose increases metabolic flux through glycolysis, the citric acid cycle and the generation of ATP The increase in [ATP] inhibits ATP-sensitive K+ channels causing depolarization of the cell membrane That increases Ca2+ influx via voltage-sensitive Ca2+ channels, stimulating exocytosis of insulin.
  3. 3. C -Peptide • The connecting peptide is a short 31 AA protein that connects insulin A chain to its B chain in proinsulin molecule. • C- peptide & native insulin are secreted in equimolar proportion. It has no biological activity. • Normal fasting con 1-2 ng/ml • C-peptide may be used for determining the possibilities of gastrinomas associated with multiple endocrine neoplasome syndrome. • C- peptide levels are used to determine the level of insulin resistance
  4. 4. . •Indication of measurement • Fasting hypoglycemia • B cell tumor • Monitor pt after pancreatic surgery •Advantage • Good indicator of insulin production & secretion • Longer half life than insulin(6min) • No hepatic degradation • Measurement in urine can be done to distinguish type 1, 2, & maturity onset DM • Do not cross react with insulin
  5. 5. INSULIN RESISTANCE Reduced sensitivity of target cells to respond properly to insulin to show the metabolic effects of insulin. It is a state in which a given con. of insulin produces a less than expected biological effect Cause •Mutation to insulin receptor •Autoantibodies to insulin receptor •Reduecd number &/or binding of insulin receptor •Obesity with receptor defect •Prolonged steroid therapy •Excess GH •GDM •PCOS
  6. 6. Diabetes Mellitus Diabetes mellitus is the commonest metabolic disorder. It may be defined as a metabolic disorder resulting hyperglycemia from defects in insulin secretion; insulin action or both that arise from genetic as well as environmental factors It is defined by documenting raised blood glucose in fasting ( ≥7.00mmol/l) and/or 2 hrs after an std. oral glucose drink ( ≥11.1mmol/l)
  7. 7. Etiological Classification of Diabetes Mellitus I. Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency) A. Immune-mediated B. Idiopathic II. Type 2 diabetes It is due to insulin resistance& relative insulin deficiency ,usually develops with increasing age. Evironmental factors like obesity & physical inactivity are known strong determinents in genetically susceptible individual.
  8. 8. Etiological Classification of Diabetes Mellitus (contd.) III. Other specific types of diabetes A. Genetic defects of β cell function B. Genetic defects in insulin action (Characterized by Insulin resistance) eg o Pancreatitis o Pancreatectomy o Neoplasia o Cystic fibrosis o Hemochromatosis o Fibrocalculous pancreatopathy
  9. 9. IV.Gestational diabetes mellitus (GDM ) Is glucose intolerance of any severity detected in a pregnant women who was not known to have this abnormality prior to conception. Etiological Classification of Diabetes Mellitus (contd.)
  10. 10. TYPE 2 DIABETES •Family history of diabetes (i.e., parent or sibling with type 2 diabetes) • Obesity (BMI >25 kg/m2) • Habitual physical inactivity • Previously identified IFG or IGT • History of GDM or delivery of baby >4 kg (>9 lb) • Hypertension (blood pressure >140/90 mmHg) • HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L) • Polycystic ovary syndrome or acanthosis nigricans • History of vascular disease
  11. 11. Points Type-1 DM (IDDM) Type-2 DM (NIDDM) Age of onset Before 35 years (juvenile onset DM) After 35 years (maturity onset DM) Defect β-cell destruction β-cell dysfunction Insulin Status Absolute deficiency (β-cell loss) Inadequate insulin (β-cell Dysfunction) or insulin resistance Insulin sensitivity Normal Decreased Plasma insulin Low or Nil Normal or high Islet cell auto antibody Positive Negative Genetic predisposition Moderate Strong
  12. 12. Methods and criteria for diagnosing diabetes Symptoms of hyperglycemia plus: a random venous plasma glucose concentration ≥ 11.1 mmol/l(200mg%)  a fasting plasma glucose concentration ≥ 7.0 mmol/l (126mg%) Plasma glucose conc. ≥ 11.1 mmol/l two hours after 75g anhydrous glucose in an oral glucose tolerance test (OGTT). HbA1c ≥6.5%
  13. 13. Continue Islets cell auto antibodies – freuently present in type I, but absent in type II C- peptide level present in type II but absent in type I Urine: ketone bodies present in type I but usually absent in type II . Urine for glucose is not mandatory for diagnosis of diabetes.
  14. 14. Pre-Diabetes •It is the intermediatory metabolic stage of glucose between normal glucose homeostasis & DM •Components IFG IGT Importance/ consequence: •Risk of developing DM later •Increased risk of vascular complications •It is an useful message to decide on preventive measure through dietary and life style modification to avoid develop DM
  15. 15. Lab.dx:WHO criteria-done by OGTT FASTING(mmol/l) 2hr after OGTT(mmol/l) diagnosis 6.1-6.9 <7.8 IFG <7.0 7.8 to 11.0 IGT
  16. 16. Methods and criteria for diagnosing diabetes: OGTT Assesment of enogenous insulin response to physiological glucose challence Indication •fasting plasma glucose <7mmol/l (6.1-6.9) •Dx of pre diabetes & GDM •RBG 7.8-11.0 mmol/l •Obesity,dyslipidemia,and other risk factors of DM
  17. 17. . • . Procedure • Collection of fasting blood sample in the morning after previous overnight fasting • 75 gm of glucose are given to the patient with 300ml of water within 5 min of fasting blood collection • At the end of 2 hrs of oral glucose take,another blood sample ollected for glucose estimation This is a more accurate test for glucose utilization if the fasting glucose is borderline
  18. 18. Diagnostic criteria for oral glucose tolerance test (WHO 1999) Condition Plasma glucose concentration as mmol/l (mg/dl) Normal Impaired Fasting glucose (IFG) Impaired glucose tolerance (IGT) Diabetes Fasting <6.1(<110) (3.6-6.1) <7.0(<126) (6.1-6.9) <7.0(<126) (6.1-6.9) ≥7.0(≥126) 2hours after 75 gm glucose <7.8 (<140) <7.8 (<140) <11.1(<200)( 7.8-11.0) ≥11.1 (≥200)
  19. 19. . Assessment for the glycemic control of DM: It is done by estimation of 1. Glycosylated hemoglobin A1c (HbA1c) 2.Plasma fructosamine con.
  20. 20. Glycosylated hemoglobinA1 c •Glycosylated hemoglobin A1c (HbA1c) HbA1c is Glucose derived products of normal adult Hb (HbA) • It is produced by non enzymatic condensation of glucose with N terminal valine of each Beta globin chain of adult Hb, formation is proportional to the blood glucose concentration. •1% rise of plasma glyco- HbA1c con. Corresponds to an average increase of blood glucose con. By 2mmol/l • Normal value of glyco- HbA1c is 4-6% of total hemoglobin.
  21. 21. (HbA1c)
  22. 22. continued HbA1c Status <5.7% Normal 5.7%-6.4% IGT ≥6.5% DM Importance : Monitoring of diabetes control Mean blood glucose level over 3-4 months period
  23. 23. Pros and Cons of measurement of HbA1c to dx DM PROS CONS • Pt does not have to fast • HbA1C is more closely associated with chronic complication • Pre analytic stability of HbA1c superior to glucose • Using the same marker to dx & monitor more seamless • HbA1C has comparatively poor sensitivity in dx of DM • HbA1C not as closely associated with cardiovascular disease • HbA1C is unreliable in conditions where red cell turnovetr is increased.eg.chronic anaemia,haemolysis,haemogl obinopathes • Standardization of HbA1C
  24. 24. Plasma fructosamine con.  It is formed by non enzymetic glycosylation of plasma protein (albumin)  Normal value = 1.5-2.4 mmol/L  It reflects the glycemic control for preceeding two weeks.
  25. 25. Other Tests- 1. Lipid profile 2. Renal function test. 3. Liver function test.
  26. 26. Metablic dearrangment in DM: ↙Lack of insulin↘ low Glucose uptake ↓ Inhibition of LPL stimulation of HSL by tissues proteolysis ↓ ↓ ↓ ↓ glycogenolysis ↑ plasma amino acid ↓catabolism of VLDL lipolysis ↓ & chylomicron ↓ Hyperglycemia gluconeo genesis ↑plasma FFA Hypertriacylglyceridemia Hyperglycemia β oxidation & KB formation glycosuria, osmotic diuresis ,electrolyte depletion ketoacidosis
  27. 27. . • . Acute complication related to immediate & rapid changes in metabolism that arise within a short time(hrs to wks) 1.Diabetic coma due to Diabetic ketoacidosis Hyperosmolar non ketotic coma Hypoglycemia 2.Acute circulatory failure 3.Lactic acidosis
  28. 28. HONK • It is a combination of • Hyperglycemia • Dehydration • Hyperosmolarity,without significant ketonuria • Here residual insulin reserve prevents ketosis. • Precipitating factor include..severe illness,dehydration,diuretics,diaysis,glucorticode • Develops slowly • Impairment of consciousness is common • Type 2 dm,elderly are sufferer.
  29. 29. Difference between DKA and HONK POINTS HONK DKA Blood glucose Very high(>30mmol/l) High(>15mmol/l) Ketone body none present acidosis normal Moderate /severe Volume depletion marked mild Plasma anion gap normal increased Present in Type 2 type1 ECE osmolarity Very high Usually normal Serum insulin Mild to moderate lack Severe lack hyperventilation absent present dehydration marked mild
  30. 30. . •Chronic complication of DM •After a long period of uncontrolled DM ,these develops A.Microvascular complications •Microangiopathy •Retinopathy-cataract-blindness •Nephropathy •Neuropathy •B.Macrovascular complication •Coronary artery disease;IHD •Cerebrovascular disease;Stroke,Ischemic attack •Peripheral vascular disease;feet gangrene
  31. 31. . •Approximately 60% of diabetic pt die of vascular disease & 35% of coronary heart disease . •Blindness is 25 times & CRF 17 times more common in diabetic pt •There is increasing evidence that tight glycemic control delays the onset of these sequlae
  32. 32. GDM(gestational diabetes mellitus) • Any degree of glucose intolerance with onset or detection for the first time during pg is called GDM. • Charactrised by hyperglycemia developed first time during pregnancy, women who had no DM before pregnancy Causes: insulin antagonistic activity of progesterone & human placental lactogen
  33. 33. . Women who are high risk of GDM • H/O of GDM • H/O unexplained fetal loss or malformation • Delivery of baby >9 ibs • Maternal age > 25 yrs • Excessive wt gain during pg • Genereal risk factors ..obesity,pre diabetes,family history etc
  34. 34. Screening for GDM • In all pg –screening at 24-28 wks of gestation • If there is one or more risk factors –screening earliar (1st visit),if negative then repeat at 24-28 wks gestation • Screening by 1 hr 50g glucose • Irrespectative of food intake ,50 gm glucose is given orally and at the end of 1 hr blood glucose is measured • Blood glucose ≥7.8 mmol/l……..suspected for GDM & advised OGTT.
  35. 35. Diagnostic criteria for GDM •The 75-g OGTT should be performed in the morning after an overnight fast of at least 8 h with measurement of plasma fasting glucose and at 1 and 2 h, at 24–28 weeks of gestation in women not previously diagnosed with overt diabetes •The diagnosis of GDM is made when any of the following plasma glucose values are exceeded: • 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)
  36. 36. Complication Maternal •Pg loss,abortion,iud •Preeclamsia,eclampsia •development of maternal diabetes after pregnancy. Fetal complication Macrosomia •Congenital anomalis • ed risk of birth trauma •Still birth,IUGR •Neonatal hypoglycemia
  37. 37. .• Follow up : women who are obese & whose GDM was diagnosed before 24 weeks of gestation should be evaluated for diabetes at 6 to 12 weeks of post parterm period. • And if diabetes is not present, re -evaluate for diabetes at least every 3yrs.
  38. 38. Hypoglycemia • Defined as low blood glucose concentration with symptoms that is relived by ingestion of food or CHO. • In adult it is diagnosed by blood glucose con.<63mg% (3.5mmol/l) • Symptom develops when glucose falls below 2.2mmol/l • The diagnosis is established when 3 criteria (whipple”s triad) are satisfied • There must be symptoms consistent with hypoglycemia • There must be lab. Conformation of hypoglycemia • Symptoms must be relieved by the adminintration of glucose
  39. 39. Blood glucose conc. & it’s effect: ≥3.5 mmol/L ≥2.5 mmol/L ≥2.0 mmol/L ≥1 mmol/L <1mmol /L normal Counter regulatory response Cognitive disturbanc e EEG changes COMA
  40. 40. . Symptoms- Hypoglycemia normally leads to suppression of insulin secretion,an increase in catecholamine secretion and stimulation of glucagon ,cortisol,GH. • Adrenargic(warning symptom) – • when blood glucose fall abruptly mediated by Catecholamine –  Anxiety sweating Feeling weak palpitation Tremor nausea
  41. 41. . • Neuroglycopenic--- when blood glucose fall gradully, impair delivay of glucose to brain (As CNS consumes approx. 50% of glucose used by the body) Headache Confusion  slurred speech Poor concentration convulsion Coma Death Type: I ) Post prandial: (reactive hypoglycemia ) 2) Fasting hypoglycemia
  42. 42. Hypoglycemic Symptoms
  43. 43. Reactive hypoglycemia caused by • an exagerated insulin release following a meal. A transient fall may occurs 1.5-2hrs after ingestion of an oral glucose load. • Insulin induced…inappropriate or excessive insulin produce hypoglycaemia.(exogenous/endogenous differentiated by Cpeptide) • Drug-induced….Sulphonylureas,salisylate,b blocker can produce hypoglcemia • Alcohol…..excessive dose alcohol cause increase insulin secretion • Dumping syndrome.. Rapid gastric emptying following partial gastrectectomy →rapid absorption of large amounts of glucose.
  44. 44. . Fasting hypoglycemia Causes • Insulinoma • Malignncy • Hepatic &renal disease • Addisions disease • sepsis
  45. 45. . •In diabetic pt precipitating factor for hypoglycemia •Insufficient CHO intake •Excess insulin or sulphonylureas •Strenuous exercise •Excessive alcohol intake
  46. 46. . Neonatal hypoglycemia:  Mean blood glucose con. appox. 40 mg/dl(normal) Declines shortly after birth when liver glycogen stores are depleted. In first week of life is diagnosed by blood glucose con. <25%(1.4mmol/l) for preterm or LBW baby <45%(2.5mmol/l) for full term baby • Certain groups of neonate vernable to hypoglycemia • Small for gestational age • Babies of diabetic mother • Inborn error of metabolism • Toxaemia of pg
  47. 47. Lab.investigation in hypoglycemia • Blood glucose con…………….low • Serum insulin con……………..high • Serum C peptide con…………high in insulinoma • absent in exogenous insulin therpy • Liver function test Hormonal assay……………….cortisol,gh etc.
  48. 48. 65 Treatment General approaches - Medications - Dietary and exercise modification - Regular complication monitoring - Self monitoring of blood glucose - Control of BP and lipid level
  49. 49. THANK YOU.