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Diabesity Cheat Sheet (Rich Siegel presentation)

Rich Siegel, M.D., co-director, Tufts Medical Center's Diabetes Clinic, spoke on the Health Journalism 2013 panel "Diabetes: Latest in diagnosis, treatment, prevention."

Types of Diabetes

  • Type 1 diabetes – autoimmune destruction of pancreatic beta cells
  • Type 2 diabetes -  combination of insulin resistance and relative insulin deficiency with dysfunction of multiple organs including liver, fat, muscle, endocrine pancreas, kidney; most common type of diabetes
  • Gestational Diabetes -  diabetes which occurs during a pregnancy and resolves with delivery; very high risk for future type 2 diabetes
  • Maturity Onset Diabetes of Youth (MODY) – diabetes caused by a single gene defect, presenting usually under the age of 40 in multiple generations

Diagnosis of Diabetes

  • Fasting blood glucose (FBS) greater than or equal to 126 mg/dl
  • Hemoglobin A1C (HbA1C) greater than or equal to 6.5%
  • 2 hour blood glucose greater than or equal to 200 mg/dl after a 75 gram glucose challenge (oral glucose tolerance test)
  • Casual blood glucose greater than or equal to 200 mg/dl with symptoms
  • All tests should be confirmed by the same or a different test
  • “At risk for diabetes”
    • Impaired fasting glucose -  FBS 100-125 mg/dl
    • Impaired glucose tolerance – 2 hour blood glucose 140-200 mg/dl after glucose challenge
    • HbA1C 5.7-6.4%

Medications for Diabetes

Insulins

  • Basal (background) insulins – keeps glucose levels down between meals and overnight
    • NPH insulin (Humulin or Novolin N)
    • Insulin Glargine (Lantus)
    • Insulin Detemir (Levemir)
  • Bolus (mealtime) insulins – keeps glucose levels down after meals
    • Regular insulin (Humulin or Novolin R)
    • Insulin Lispro (Humalog)
    • Insulin Aspart (Novolog)
    • Insulin Glulisine (Apidra)
  • Premixed insulins – combination of basal and bolus insulins
    • Humulin or Novolin 70/30 – 70% NPH and 30% Regular
    • Humalog 75/25 – 75% Long acting Lispro and 25% Lispro
    • Humalog 50/50 -  50% Long acting Lispro and 50% Lispro
    • Novolog  70/30 -  75% Long acting Aspart and 25% Aspart

Non-insulin medications

  • Insulin secretagogues – oral meds increasing insulin secretion from pancreatic beta cells
    • Glyburide, Glipizide, Glimepiride (all generic) – once or twice daily
    • Repaglinide (Prandin), Nateglinide (Starlix) – dosed at each meal
    • Risk for hypoglycemia and weight gain
  • Biguanide – oral medication which reduces glucose production at the liver
    • Metformin (Glucophage and generic) as the only drug in the class
    • First line medication indicated with lifestyle in guidelines for type 2 diabetes
    • Weight neutral to minimal weight loss
    • No hypoglycemia risk by itself or with medications other than insulin or insulin secretagogues
    • ? Cardiovascular benefit, ? Benefit in selected cancers
  • Thiazolidinediones (TZDs) – oral medication which improves insulin resistance at fat and muscle
    • Pioglitazone (Actos and generic)
    • Rosiglitazone (Avandia) -  very restricted access making it effectively off the market; possible increased cardiovascular risk
    • Pioglitazone showed CV event benefit as secondary outcome in PROACTIVE trial
    • May lead to weight gain, especially together with insulin
    • Contraindicated in mid to late stage heart failure
    • Risk for bone loss; ? risk for bladder cancer (taken off the market in France and Germany)
  • Incretin related agents – on the market only since 2005; awaiting cardiovascular outcome trials
    • GLP-1 agonists – injectable medications which increase insulin release but only when sugars are high, slows stomach emptying and inhibit appetite working at endocrine pancreas, GI tract and brain
      • Exenatide (Byetta twice daily, Bydureon once weekly)
      • Liraglutide (Victoza)
      • Reduce glucose and weight
      • Expensive at $200-300 per month
      • Possible risk for pancreatitis, ? pancreatic cancer
      • DPP-IV inhibitors – oral medications increase insulin release but only when sugars are high
        • Sitagliptin (Januvia)
        • Saxagliptin (Onglyza)
        • Linagliptin (Tradjenta)
        • Alogliptin (Nesina)
        • Expensive at $200 per month
        • Minimal side effects but also possible pancreatitis risk
  • Other medication classes
    • Alpha glucosidase inhibitors – reduce postmeal glucose working in the intestines
      • Acarbose (Precose), Miglitol (Glyset)
      • Bile acid sequestrant – unknown mechanism of action
        • Colesevelam (Welchol) – primary effect is to lower LDL cholesterol
      • Amylin mimetic – reduce postmeal glucose by inhibiting glucagon, slowing gastric emptying
        • Pramlintide (Symlin)
      • Dopamine agonist – action in the brain though mechanism to lower glucose is not entirely clear
        • Bromocriptine mesylate (Cycloset)

Medications for Obesity

  • Appetite suppressants – works within the brain (mostly hypothalamus) to inhibit appetite
    • Phentermine (Adipex) – about 8-10% weight loss over 6 months
      • Generic
      • Not approved for long term use
      • Class IV drug with no clinical addiction potential
      • Requires monitoring for stimulant related side effects
      • Phentermine/Topiramate ER (Qsymia)
        • Greater weight loss potential (10 %) but also greater risk for side effects (mostly neuropsychiatric)
        • Expensive at $100 per month
        • Risk for birth defects (cleft palate)
        • Only available through selected mail order pharmacies
      • Lorcaserin (Belviq)
        • ? In pharmacies in March
        • About 5% average weight loss
      • Questions about long term safety lingers
      • Older meds used by some include diethylpropion, benzphetamine, mazindol, phendimetrazine
  • Gastrointestinal lipase inhibitor – works in the small intestine to limit fat absorption
    • Orlistat (Xenical, OTC Alli)
      • 5-8% weight loss
      • Effectiveness depends on baseline intake of fat
      • Side effects of malabsorption (fecal oiliness) unacceptable to many
      • Need multivitamin taken usually at bedtime

Surgeries for Diabetes and Morbid Obesity

  • Roux- N-Y Gastric Bypass
    • Combination restrictive and malabsorptive surgery
    • Usually 50-70% of excess weight loss(about 30-35% of absolute weight)
  • Vertical Sleeve Gastrectomy
    • Restrictive surgery with removal of over 75% of greater curvature of the stomach
  • Laparoscopic Adjustable Gastric Banding
    • Restrictive surgery
  • Biliopancreatic diversion with duodenal switch
    • Malabsorptive surgery