Managing the Patient with Diabetes

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Managing the Patient with Diabetes

• Cindy Brown, RN, MN, ANP, CDE

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Introduction

• Scope of the problem
• Number of people with Type 2 diabetes approaches
  21 million
• One third are as yet undiagnosed
• Typically have had the disease 7 years prior to
  diagnosis

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Introduction

• Often asymptomatic or exhibit subtle signs
• Puts the patient at risk for CAD, stroke, PVD,
  dyslipidemia, hypertension and obesity
• UKPDS study of gt5000 showed that tight glycemic
  control could reduce end-organ damage by 50-75

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Early Detection

• New guidelines released in 1997
• Lowered fasting BS from 140 mg/dL as diagnostic
  to 126 mg/dL
• Those with insulin resistance and/or impaired
  glucose tolerance may develop complications

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Diagnostic Criteria

• Symptoms casual BS gt/ 200
• Fasting BS /gt 126 on two occasions
• BS /gt 200 at the 2-hour mark of a glucose
  tolerance test

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Risk Factors

• Ethnicity African-American, Asian-American,
  Hispanic, Native American, Pacific Islander
• Family history in first-degree relative
• Hx GDM or a baby gt 9 pounds
• Hx FBS 110-125 mg/dL
• Hypertension
• Obesity, especially abdominal

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Pathophysiology of Type 2

• Genetic predisposition
• Abnormal beta cell function
• Impaired sensitivity of target tissues to insulin
  (insulin resistance)

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Abnormal Beta Cell Function

• Becomes evident when insulin resistance develops
• During pregnancy
• Steroid therapy
• Acute illness
• Increased central obesity

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Theory Behind Treatment

• Improved lifestyle oral medications
• Delay or prevention of Type 2 diabetes

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Signs and Symptoms

• Blurred vision
• Dizziness
• Excessive thirst
• Fatigue

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Signs and Symptoms

• Frequent urination
• Nocturia
• Weight loss
• Vaginitis

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Signs and Symptoms

• Weakness
• Impotence
• Weight gain, especially around the middle
• Excessive hunger

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Insulin Resistance

• Cells resist the effect of insulin
• Downgrades insulin receptors
• Blood sugar begins to rise
• Pancreas makes more insulin to overcome the
  resistance
• Insulin levels rise, leading to many symptoms

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Insulin Resistance

• Weight gain around the middle
• Inability to lose weight
• Fatigue
• Carbohydrate cravings
• Hypoglycemic symptoms with prolonged hunger or
  2-3 hours following a carb load

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Insulin Resistance

• Underlies many other disorders
• Type 2 diabetes
• Gestational diabetes
• Polycystic Ovarian Syndrome
• Syndrome X
• Raises risks of CAD, HTN, stroke even before
  overt diabetes diagnosed
• Leads to glucose intolerance

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Impaired Glucose Tolerance

• Fasting blood sugar gt110 but lt126
• 2 hour glucose .gt126 but lt200 on glucose
  tolerance test
• Represents step 2 on the road to diabetes
• Usually accompanied by insulin resistance
• Subset of lean persons who are not insulin
  resistant really do have low insulin production

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Goals of Treatment

• Optimal glycemic control
• Hgb A1c of 6.5
• Reduction of risks
• Control of lipid levels, esp. LDL lt70
• Control of BP lt130/80
• Taking low dose aspirin
• Taking an ACE-I

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Goals of Treatment

• Aimed at both insulin deficiency insulin
  resistance
• Most will need oral agents very soon after
  diagnosis
• Purpose of all treatment is to decrease the need
  for insulin

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Decline of Beta Cell Function

• Progressive despite treatment
• Single oral agent lifestyle changes has limited
  success
• Endogenous insulin production continues to
  decrease
• Secondary failure predicted for about 5 years out

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Treatment Options

• Modification of lifestyle
• Change of diet
• Increased physical activity
• Oral medications
• Injectable incretin mimetics
• Insulin
• Combination of oral and insulin

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Medical Nutritional Therapy

• Low calorie, carbohydrate controlled meal plans
• No longer a diabetic diet
• Recent research has led to realization that the
  source of the carbohydrate is not as important
  as the quantity
• There are no bad foods

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Oral Hypoglycemic Agents

• Insulin sensitizing agents
• Biguanides
• TZDs
• Sulfonylureas
• Alpha glucosidase inhibitors
• DPP-4 Inhibitor
• Combinations

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Oral Hypoglycemic Agents

• Incretin mimetics

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Insulin Sensitizing Agents

• Metformin (biguanide)
• No stimulation of insulin secretion
• Increases glucose utilization
• Decreases glucose production (liver)
• Increases uptake of glucose in peripheral tissue
• Decreases GI absorption of glucose
• Has an anorexiant effect

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Metformin

• Currently available as Glucophage, Glucophage XR,
  Glucovance, Fortamet , Glumetza and Riomet
• Now have ActoplusMet, Avandamet, Janumet
• Has become available in generic form

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Metformin

• Advantages
• Reduction of insulin resistance
• Weight loss
• Decrease of triglycerides improvement of lipid
  profile
• No increase in insulin secretion
• No hypoglycemia when used as monotherapy

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Metformin

• Disadvantages
• GI side effects diarrhea, nausea, gas
• Lactic acidosis in presence of impaired renal or
  liver function
• Should be avoided when creatinine gt1.4 in
  females, gt1.5 in males in presence of liver
  dysfunction (elevated ALT/AST) or binge drinking

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Metformin

• Withhold in conditions that predispose to renal
  insufficiency and/or hypoxia
• Acute MI or CHF
• Shock or acute hypotension
• Severe infection
• Major surgical procedure
• Use of iodinated contrast media
• DKA

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Metformin

• Start slowly with 500 mg once daily _at_ supper
• Titrate upwards by one pill per week until taking
  TID with meals
• Ingested with food decreases GI side effects
  increases effectiveness

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Metformin

• Max dose2550 mg/day
• Available in 500 mg, 850 mg and 1000 mg tablets
• XR formulation available in 500 mg 750 mg
  tablets can take total dose once daily with
  supper

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Metformin

• Glucovance a combination of glucophage and
  glyburide
• Good choice for newly diagnosed
• Glyburide reduces BS and smaller doses of
  Glucophage easier on stomach
• Available in 1.25/250, 2.5/500, 5/500

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Thiazolidinediones (TZDs)

• Enhance insulin action
• Increase glucose utilization in peripheral
  tissues
• May suppress gluconeogenesis
• Mediated via stimulation of PPARy - increase
  expression of genes that encode for glucose
  transporter proteins

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TZDs

• May exhibit lipid-lowering and anti-hypertensive
  effects
• Work well in combination with other oral
  hypoglycemic agents
• Recent animal studies suggest that they can
  regenerate beta cell function

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TZDs

• Available as pioglitazone (Actos) and
  rosiglitazone (Avandia)
• Chemically related to troglitazone
• LFTs must be monitored q2 months first year of
  therapy

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TZDs

• Advantages
• Reduction of insulin resistance
• Once-daily dosing
• No risk of hypoglycemia
• Additive effect with other agents
• Can be used with renal impairment
• Favorable lipid profile

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TZDs

• Disadvantages
• Rare risk of liver damage
• Necessity of frequent liver function monitoring
• Slower onset of action
• Possible weight gain and fluid retention
• Lower doses reduce above side effects

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TZDs

• Actos available in 15 mg, 30 mg, and 45 mg
• Avandia available in 2mg, 4mg, 8 mg
• May be dosed QD or BID
• DREAM study implies diabetes prevention

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Sulfonylureas

• Related to sulfonamide drugs
• Lower BG predominantly via stimulation of insulin
  secretion
• Potentiate the action of insulin in liver,
  muscle, adipose tissue
• Insulin levels return to pretreatment levels
  after several months of treatment

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Sulfonylureas

• Second generation drugs now used over first
  generation
• Available as glipizide, glyburide, glimepiride
• No advantage to using two of this class
• With failure, no reason to try another of same
  class

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Sulfonylureas

• Best to start at lowest dose and work up
• No advantage to exceeding max doses
• If BS not controlled at max dose, add an agent
  from a different class
• Major side effecthypoglycemia, esp. in elderly
  with renal insufficiency, with alcohol ingestion
  or skipped meals

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Secretagogues

• Stimulate insulin secretion
• Release of insulin glucose-dependent
• Effect maximized post-prandially
• Rapid onset of action
• Targets post-prandial rise of BS
• Can be used as monotherapy or in combination with
  metformin

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Secretagogues

• May be used with renal insufficiency and liver
  dysfunction
• May cause mild-moderate hypoglycemia, nausea,
  diarrhea, constipation , vomiting
• Lower risk of nighttime hypoglycemia

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Alpha-glucosidase Inhibitors

• Inhibit enzymatic conversion of dietary starches
  to oligosaccharides
• Delay absorption of glucose from the GI tract
• Reduces post-prandial BS excursions

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Alpha-glucosidase Inhibitors

• Advantages
• Targets post-prandial BS
• No risk of hypoglycemia when used alone
• Additive effect when used with sulfonylureas
• Lack of weight gain

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Alpha-glucosidase Inhibitors

• Disadvantages
• Less potent effect on BS
• Multi-dosing
• Very high incidence of GI side effects
• Complicates treatment of hypoglycemia when used
  with insulin or sulfonylureas pure glucose
  effective treatment

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Alpha-glucosidase Inhibitors

• May cause elevations in liver enzymes
• May exacerbate lactose intolerance

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Incretins

• Hormone that
• Originates in GI tract
• Released during feeding
• Augments insulin secretion (beta cells)
• Some also decrease glucagon secretion (alpha
  cells)
• Actions are glucose dependent

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Incretins

• Effect greatly diminished in Type 2 diabetes
• Major incretins
• Glucagon-like peptide 1 (GLP-1)
• Glucose-dependent insulinotropic polypeptide
  (GIP)
• Both increase insulin secretion
• Only GLP-1 suppresses glucagon secretion
• Both rapidly inactivated by DPP-4

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Incretin Mimetics

• Byetta (exenatide)
• Gut derived peptides secreted in response to
  meals
• Glucagon-like peptide-1 (GLP-1)
• Glucose dependent stimulation of insulin
• Supression of glucagon secretion
• Delay of gastric emptying
• Promotion of satiety

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Incretin Mimetics

• Byetta
• OK to use with sulfonylureas, metformin, insulin
• Being studied with TZDs
• Promotes weight loss
• Major side effect nausea
• Increased risk of hypoglycemia with insulin use

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Incretin Mimetics

• Byetta
• Start at 5 mcg BID before breakfast and supper
• Increase to 10 mcg after one month
• Pre-filled disposable pens
• Needs refrigeration
• Appears to preserve beta cell function

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Incretin Mimetics

• Symlin (pramlintide)
• Pancreatic islet peptide secreted in response to
  food
• Suppresses glucagon secretion
• Delays gastric emptying
• Promotes satiety
• Use in Type 1 diabetes and Type2, insulin using

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Incretin Mimetics

• Symlin
• Given before meals along with insulin, but
  separate sites
• Major role decrease post-prandial glucose
  excursions
• Can induce weight loss
• Side-effect nausea

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Incretin Mimetics

• Symlin
• In Type 1 diabetes, start with 5 units in an
  insulin syringe
• Every 3-5 days without nausea, titrate dose
  upward by 5 units until taking max of 20 units
  TID
• In Type 2 diabetes, start with 10 units, titrated
  up to 40 units.

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DPP 4 Inhibitors

• Januvia (sitagliptin)
• New class of oral medications
• Dipeptidyl peptidase-4 blocker
• Inactivates gt50 GLP-1 in 1 minute
• Inactivates gt50 GIP in 7 minutes
• Blocking action of DPP-4 allows GLP-1 and GIP to
  increase insulin secretion and suppress glucagon
  secretion

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DPP-4 Inhibitors

• New on market Onglyza
• Very similar to Januvia

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Insulins

• Use of insulin in Type 2 diabetes growing
• Excess hepatic glucose production found in the
  unfed stateelevated FBG
• Glucose toxicity caused by secretion defect and
  hyperglycemia
• Insulin can partially reverse these processes

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Insulins

• Can counteract insulin resistance glucose
  toxicity
• Results in recovery of insulin secretion
  improvement of postprandial glucose excursions
• Preprandial injections of rapid-acting insulin
  reduces postprandial BS

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Insulins

• Rapid-acting
• Lispro (Humalog)
• Onset 5-10 min
• Peak 1 hour
• Duration 2 hours
• Aspart (Novolog)
• Onset 5-10 min
• Peak 0.5-1 hour
• Duration 3-5 hours

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Insulins

• Rapid-acting
• Glulisine (Apidra)
• Onset lt30 minutes
• Peak 30-90 minutes
• Duration lt6 hours

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Insulins

• Short-acting
• Regular
• Onset 0.5-1 hour
• Peak 2-4 hours
• Duration 4-6 hours

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Insulins

• Intermediate-acting
• NPH
• Onset 1-4 hours
• Peak 4-12 hours
• Duration 14-24 hours
• Lente off US market

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Insulins

• Long-acting
• Ultralente now off US market
• Levemir
• Onset 1 hour
• Peak slight
• Duration 22-24 hours
• Less weight gain
• Lantus
• Onset 1 hour
• Peak - none
• Duration 22- 24 hours

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Insulins

• Others
• 70/30 (70 NPH/30 Reg)
• 50/50 (50 NPH/50 Reg)
• 75/25 (75 lispro protamine/25 lispro)
• U-500 Regular (concentrated)

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Insulins

• Goal is to mimic natural insulin production as
  closely as possible
• Long acting _at_ bedtime rapid acting before meals
  mother nature

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Exercise

• Increases tissue sensitivity to insulin
• Reduces dosage of medications
• Reduces cardiovascular risk factors
• Lowers LDL
• Raises HDL
• Lowers BP
• Improves collateral flow
• Decreases central obesity

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Exercise

• Change mindset about exercise vs. physical
  activity
• All activity counts
• Need not be done in one session
• Can be effective even if done in chair

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Considerations in the Elderly

• Particularly susceptible to hypoglycemia,
  especially with renal insufficiency
• Many more co-morbidities requiring poly-pharmacy
• More risk of interactions and side-effects
• Loss of hypoglycemia awareness
• BS goals usually higher

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Considerations in the Elderly

• Good BS control aids cognition
• Medications expensive leads to choosing which
  ones can be taken
• Often opt for the cheapest solution
• Social isolation, depression , illness may cause
  skipped meals and hypoglycemia which can lead to
  personality changes, falls, car accidents

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Recommendations

• Goals
• Hgb A1c6.5 (AACE) lt7.0 (ADA)
• FBG110
• Postprandial BG lt 140
• BP lt 130/80
• Annual eye exam
• Daily aspirin

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Recommendations

• ACE inhibitor, even prior to microalbuminuria
• Lipids
• LDL lt70 (esp. with CAD)
• HDL gt45 (men) gt 50 (women)
• Triglycerides lt150
• Cholesterol lt200

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Recommendations

• Modest weight loss of 10-15 body weight brings
  big results

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Medications to Avoid

• Beta-blockers may mask hypoglycemia warning
  signs
• Steroids markedly increase blood sugar
• HCTZ increases blood sugar
• Niacin increases insulin resistance

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Conclusion

• Type 2 diabetes difficult to control
• Treatment regimens complicated
• Good BS control takes enormous amounts of work on
  a daily basis
• Need all the encouragement they can get