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Our goals for today

Our goals for today

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Our goals for today

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  1. Our goals for today • Define diabetes and subtypes • Distinguish between the etiology of the prevalent forms of diabetes • Discuss basic features of gestational diabetes • Understand the pharmacological management of diabetes

  2. Strange but true……… • Greeks noticed that urine of diabetics attracted flies (linked this to increased sugar) • Chinese tested for diabetes by noticing whether ants were attracted to urine • Europeans tasted urine for sweetness

  3. Our eating habits have changed…..

  4. Soft Drinks…… • A 50 ml pop drink contains 10 teaspoons sugar • 360 ml can of pop contains 160 calories • (and same caffeine as in a cup of coffee) • Between 1985 and 1997: • Schools purchased 30% less milk and • 1,100% more soft drinks

  5. We exercise less…….

  6. Famous People & Diabetes

  7. Watch the units!

  8. Increased sugar in urine leads to loss of water—THIRST • Loss of sugar in urine=loss of calories—WEIGHT LOSS • Hunger • Dry mouth • Increased urination • Blurred vision • Frequent infections • Slow healing of cuts, bruises

  9. Type 1 Diabetes • Previously called “juvenile onset diabetes” or “insulin dependent diabetes” • Canadian connection (Charles Best, medical student partner in discovery of insulin)

  10. Insulin (1) Things to remember: • Glucose UNITS: multiply or divide by 18 (mg/dL is larger than mmol/L) • Normal pancreas secretes half of insulin as bolus after a meal. To replace this: need a short acting insulin Secretes other half gradually during day and night (basal secretion). To replace this: need long acting insulin

  11. Insulin (2) Insulin to cover meals: short or rapidly acting insulin. NOVOLOG (insulin aspartate) HUMALOG (lispro) For later meal: intermediate acting insulin NPH (neutral protamine of Hagedorn) For basal insulin: long acting insulin INSULIN GLARGINE (Lantus) ULTRALENTE

  12. Time-effect relationship for different types of insulin following subcutaneous injection.

  13. Extent and duration of various types of insulin Figure 41-2 from Katzung, 8th edition, 2001 HYPOGLYCEMIA is the most prominent adverse effect of insulin.

  14. Type 2 Diabetes • Previously called “adult onset diabetes” or “maturity onset diabetes” or “non-insulin dependent diabetes”

  15. Evolutionary Pathway ?

  16. Pancreatic alpha and beta cell dysfunction in T2DM

  17. First thing to do…………. Lifestyle modifications: • Exercise (actually the mere attempt to exercise regularly—no weight loss—can be beneficial) • Diet(work with nutritionist)

  18. Pharmacological management(1) Oral medications initiated when 2-3 months of lifestyle modifications cannot maintain optimal plasma glucose * SULFONYLUREAS: First generation: tolbutamide Second generation: glyburide, glipizide *BIGUANIDES: Metformin used as monotherapy

  19. Pharmacological management(2) • ALPHA-GLUCOSIDASE INHIBITORS: (Acarbose) inbibits pancreatic alpha-glycosidase hydrolase enzymes in intestine. • THIAZOLIDINEDIONES (Rosiglatone, Pioglitazone)—adjunct to exercise and diet or as monotherapy (PPAR activators—nuclear peroxisome proliferator-activated receptors)

  20. PAPR activators • Activation of genes that mediate a variety of characteristic actions of insulin • PAPR receptors: regulate storage and catabolism of dietary fats. • PAPRγ highly expressed in adipose tissue: leads to induction of adipocyte genes—e.g. lipoprotein lipase and fatty acid transporter 1…………improves insulin action in muscle and liver.

  21. DPP-4 inhibitors (Januvia®)Canada: Approved for one a day use in 2007 • DPP found in all major organs—esp kidney, liver (also capillary surfaces, circulation (soluble form) • No weight gain or hypoglycemia

  22. Complications of diabetes.. • MACROVASCULAR: coronary artery disease, peripheral vascular disease, cerebrovascular disease • MICROVASCULAR: leading cause of blindness, kidney failure and amputations

  23. Gestational Diabetes

  24. Definition : “any degree of glucose intolerance with onset or first recognized during pregnancy”. IncludesPatients that may previously have undiagnosed diabetes, or may develop diabetes coincidentally with diabetes.Occurs in 5-10% of all pregnancies

  25. Risk Factors • Previous diagnosis of GDM or impaired glucose tolerance • Glycosurea, history of glucose intolerance • Family history (first relative with type 2 DM) • Maternal age (>35yr) • Ethnicity • Overweight/obese: BMI> 30kg/m2 (increases risk 2-8X) • Previous high birth weight child (>4000g)

  26. Mechanisms • Largely unknown. Main feature is insulin resistance. • Pregnancy hormones may modify binding of insulin to IR…plasma glucose levels rise and insulin release is increased (feedback). • Insulin resistance: secures glucose supply to fetus? • Normal pregnancy: nearly doubled insulin release

  27. Mediators • Prolactin? Estradiol? • Fat (Obesity) • Immune system? • Gene Mutations • Placental cytokines(TNF-α, resistin, leptin) increase IR • Placental hormones ( cortisol, progesterone, human placental growth hormone) increase IR. • Human chorionic somatomammotropin increases throughout pregnancy and increases maternal insulin release

  28. Complications • Most women with GDM don’t remain diabetic after birth of child • Risk to baby: Growth abnormalities and chemical imbalances (admit to ICU?). Maternal hyperglycemia during week 6-7 of pregnancy: embryo toxicity (CNS, MSK, CV, spontaneous abortion). Hypoglycemia at birth. Jaundice. Increased RBC. Poorly developed lungs (respiratory distress). Later develop diabetes (~50% chance) • Risk for mother: Hypertension, UTI and type 2 diabetes (50% chance). Cesarean sections. Increased risk for developing GDM in later pregnancies.

  29. Treatment (1) Non-pharmacological: Cornerstone treatment • Medical nutritional therapy (MNT) –caloric and nutritional support for pregnancy but maintain target blood glucose without excess weight loss/gain (frequent, smaller meals, foods with low glycemic index etc) • 30 min daily exercise ( insulin sensitivity, weight loss) • If exercise and diet (2 weeks) does not help, use drug treatment

  30. Treatment (2) Pharmacologic • Insulin: during excessive fetal growth or when maternal glucose levels are not maintained. Use human insulin (least immunogenic)—INJECT—need oral medication. Increase dosage in 3rd trimester • Glyburide: minimal placental transfer. Not approved for GDM • Metformin: crosses placenta. Many women still need insulin. Not approved for GDM

  31. Take Away Messages………. Diabetes is a progressive disease: high rates of morbidity and mortality. Most diabetics die of cardiovascular complications. Treatment of diabetes is a partnership: patient, physician, home support, nutritionist….others. Insulin types and use (type 1 and type 2 diabetes). Oral hypoglycemics (type 2 diabetes). Gestational diabetes—risks for baby and also for mother.