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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. Strange but true……….

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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


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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



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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




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Watch the

units!


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Type 1 Diabetes

  • Previously called “juvenile onset diabetes” or “insulin dependent diabetes”

  • Canadian connection (Charles Best, medical student partner in discovery of insulin)


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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


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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



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Extent and duration of various types of insulin following subcutaneous injection.

Figure 41-2 from Katzung, 8th edition, 2001

HYPOGLYCEMIA is the most prominent adverse effect of insulin.


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Type 2 Diabetes following subcutaneous injection.

  • Previously called “adult onset diabetes” or “maturity onset diabetes” or “non-insulin dependent diabetes”


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Evolutionary Pathway following subcutaneous injection. ?


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Pancreatic alpha and beta cell dysfunction in T2DM following subcutaneous injection.


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First thing to do…………. following subcutaneous injection.

Lifestyle modifications:

  • Exercise (actually the mere attempt to exercise regularly—no weight loss—can be beneficial)

  • Diet(work with nutritionist)


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Pharmacological management(1) following subcutaneous injection.

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


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Pharmacological management(2) following subcutaneous injection.

  • 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)


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PAPR activators following subcutaneous injection.

  • 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.


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DPP-4 inhibitors (Januvia®) following subcutaneous injection.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


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Complications of diabetes.. following subcutaneous injection.

  • MACROVASCULAR: coronary artery disease, peripheral vascular disease, cerebrovascular disease

  • MICROVASCULAR: leading cause of blindness, kidney failure and amputations


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Gestational Diabetes following subcutaneous injection.


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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


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Risk Factors or first recognized during pregnancy”.

  • 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)


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Mechanisms or first recognized during pregnancy”.

  • 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


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Mediators or first recognized during pregnancy”.

  • 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


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Complications or first recognized during pregnancy”.

  • 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.


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Treatment (1) or first recognized during pregnancy”.

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


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Treatment (2) or first recognized during pregnancy”.

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


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Take Away Messages………. or first recognized during pregnancy”.

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.


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