Chronic Disease Management- Diabetes

43 year old male presents with one month history of feeling very thirsty and hungry. Urinating 5 times every night. Feels tired and worn out. PMHx: HTN Meds: HCTZ 25 mg daily PE: AF P98 BP 128/88 BMI 36 Appears well. HEENT: dry mm CV tachy. RR.

What to do now? Diagnostic criteria for Diabetes: 1) Classic symptoms + casual blood glucose >= 200 2) Fasting glucose >= 126 3) 2h Plasma glucose>=200 after OGTT (75G ) 4) Hemoglobin A1c >6.5% (NEW ADA 2010)

His casual blood sugar is 203. His casual blood sugar is 203. Does he fulfill diagnostic criteria for diabetes? Does he fulfill diagnostic criteria for diabetes? YES. Symptoms and blood sugar>200 YES. Symptoms and blood sugar>200 What treatment do you advise at this time? What treatment do you advise at this time?

Biguanides (metformin) Decreases hepatic glucose production Decreases hepatic glucose production Decrease A1c 1-2% Decrease A1c 1-2% Advantages: weight loss, no hypoglycemia, improves microvascular and macrovascular risks, decreased lipids Advantages: weight loss, no hypoglycemia, improves microvascular and macrovascular risks, decreased lipids Disadvantages: GI upset, contraindications (hepatic disease, renal disease (cr >1.5 men/> 1.4 women), CHF, rare lactic acidosis Disadvantages: GI upset, contraindications (hepatic disease, renal disease (cr >1.5 men/> 1.4 women), CHF, rare lactic acidosis Optimal dose 2000mg/d Optimal dose 2000mg/d

Sulfonylureas (glipizide, glimepiride) Increased pancreatic insulin secretion Increased pancreatic insulin secretion Reduce A1c 1-2% Reduce A1c 1-2% Advantages: decrease microvascular risk, daily dose, glucose lowering effects plateau at ½ maximal daily dose Advantages: decrease microvascular risk, daily dose, glucose lowering effects plateau at ½ maximal daily dose Disadvantages: Weight gain (2-5kg), hypoglycemia, caution with renal or hepatic impairment Disadvantages: Weight gain (2-5kg), hypoglycemia, caution with renal or hepatic impairment

Alpha-glucosidase inhibitors(acarbose) Breaks down dissacharides and more complex carbs Breaks down dissacharides and more complex carbs Delays intestinal carbohydrate absorption and reduces postprandial glucose elevation Delays intestinal carbohydrate absorption and reduces postprandial glucose elevation Reduces a1c 0.5-1% Reduces a1c 0.5-1% Neg effects: flatulence, abd discomfort Neg effects: flatulence, abd discomfort

TZD (thiazolinediones)- rosiglitazone(avandia), pioglitazone(actos) PPAR gamma ligands, increase peripheral glucose disposal PPAR gamma ligands, increase peripheral glucose disposal Reduce a1c 1-2% Reduce a1c 1-2% Neg effects- weight gain, peripheral edema, anemia, chf, increased cv events (rosiglitazone) Neg effects- weight gain, peripheral edema, anemia, chf, increased cv events (rosiglitazone)

Non-sulfonylurea secretagogues Repaglinide(prandin), nateglinide(starlix) Repaglinide(prandin), nateglinide(starlix) Increased pancreatic insulin secretion Increased pancreatic insulin secretion Targets postprandial Targets postprandial Reduce a1c 1-2% Reduce a1c 1-2% Less weight gain Less weight gain Hard to dose (3 times a day), hypoglycemia, Hard to dose (3 times a day), hypoglycemia,

Exanetide (byetta) GLP-1 (glucagon like peptide) analog GLP-1 (glucagon like peptide) analog Augments insulin secretion Augments insulin secretion slows gastric emptying, slows gastric emptying, supresses inappropriately high glucagon levels supresses inappropriately high glucagon levels leads to weight loss leads to weight loss Reduces A1c by about 1% Reduces A1c by about 1% Neg: Nausea-dose dependent and gets better; injected Neg: Nausea-dose dependent and gets better; injected

Sitagliptin (Januvia) DPP-IV inhibitors; deactivates other peptides including GLP-1 DPP-IV inhibitors; deactivates other peptides including GLP-1 Oral Oral Reduce a1c 0.5% Reduce a1c 0.5% Reduce dose for renal insufficiency Reduce dose for renal insufficiency

Insulin Weight gain Weight gain Hypoglycemia Hypoglycemia A1c reduction 2% A1c reduction 2%

Insulin Insulin Name OnsetPeakDuration Humalog (Lispro) 5 – 15 mins 30 – 75 mins 2 – 3 hrs Novolog (Aspart) 10 – 20 mins 1 – 3 hrs 3 – 5 hrs Regular 30 mins 2 – 5 hrs 5 – 8 hrs NPH (N) 1 – 3 hrs 6 – 12 hrs 16 – 24 hrs Lente (L) 1 – 3 hrs 6 – 12 hrs 16 – 24 hrs Lantus (Glargine) 1 hour Evenly x 24 hrs 24 – 28 hrs NPH/Regular 70/30 or 50/50 30 – 60 mins 2 – 12 hrs Up to 18 hrs RAPID INTER MED LONG MIX

Summary of Insulin Action Profiles Short (regular) Rapid (lispro, aspart, glulisine) Intermediate (NPH) Long (Glargine) Time (hours) Insulin concentration

Returns in 3 months…. Stopped drinking a gallon of sweet tea every day. No more Mcdonalds. Stopped drinking a gallon of sweet tea every day. No more Mcdonalds. Taking metformin 1000mg po bid Taking metformin 1000mg po bid BP 122/68 BP 122/68 A1c improved from 8% to 6.9% A1c improved from 8% to 6.9% What would you do differently if his blood sugar was 300 at presentation? What would you do differently if his blood sugar was 300 at presentation? Metformin not enough…start metformin and insulin, taper insulin later once well controlled Metformin not enough…start metformin and insulin, taper insulin later once well controlled

2 years later.. Doing well…blood sugars running higher. Doing well…blood sugars running higher. Meds- ASA, Statin, metformin Meds- ASA, Statin, metformin BP 144/90 BP 144/90 A1c 8.2%, cr 1.2 A1c 8.2%, cr 1.2 What are you going to do now? What are you going to do now? Htn- add ACEI Htn- add ACEI Glycemic control- add sulfonylurea Glycemic control- add sulfonylurea

2 years later…. On ASA, metformin 1000 bid, glipizide 10 bid, enalapril 20 qd, simvastatin 40 daily On ASA, metformin 1000 bid, glipizide 10 bid, enalapril 20 qd, simvastatin 40 daily BP 128/72 BP 128/72 A1c 9% A1c 9% What now? What now?

Start insulin…don’t be afraid What do you prescribe and how? What do you prescribe and how? Basal insulin Basal insulin Use NPH or lantus Use NPH or lantus Start with 10 units Start with 10 units Increase by 2-5 units every 3-5 days if Blood sugar > 150 Increase by 2-5 units every 3-5 days if Blood sugar > 150

6 months later... Doing well with glargine (lantus) 55 units daily Doing well with glargine (lantus) 55 units daily Fasting blood sugars Fasting blood sugars A1c 8.4% A1c 8.4% What is up with that? What is up with that? Check postprandials and add short acting insulin to largest meal Check postprandials and add short acting insulin to largest meal

Other things to think about with diabetic patients Reducing CV risk Reducing CV risk ASA ASA Statin Statin Blood pressure Blood pressure ACEI ACEI Reducing microvascular risk Reducing microvascular risk Eye exam Eye exam Microalbumin Microalbumin ACEI ACEI Foot exam Foot exam Immunizations Immunizations Influenza Influenza Pneumococcal Pneumococcal

Foot Exam Risk factors for diabetic foot ulcers Risk factors for diabetic foot ulcers Previous foot ulceration Previous foot ulceration Prior lower extremity amputation Prior lower extremity amputation Long duration of diabetes (>10 yrs) Long duration of diabetes (>10 yrs) Poor glycemic control (A1c >9%) Poor glycemic control (A1c >9%) Impaired vision Impaired vision

What are components of foot exam? REMOVE SHOES AND SOCKS REMOVE SHOES AND SOCKS Inspect for Inspect for Structural abnormalities Structural abnormalities Reduced joint mobility Reduced joint mobility Dryness, fissures, tinea Dryness, fissures, tinea Palpate the posterior tibialis and dosalis pedis pulses Palpate the posterior tibialis and dosalis pedis pulses Inspect footwear for proper fit Inspect footwear for proper fit Test sensation- Test sensation- Best done with ten gram monofilament Best done with ten gram monofilament

Copyright restrictions may apply. Singh, N. et al. JAMA 2005;293: Monofilament Test for Light Touch Sensation

Monofilament Test at four sites on each foot for 1-2 seconds, until the filament buckles to a “C” Test at four sites on each foot for 1-2 seconds, until the filament buckles to a “C” 90% sensitivity 90% sensitivity Increasing the testing to 10 locations on each foot increases sensitivity but more time consuming Increasing the testing to 10 locations on each foot increases sensitivity but more time consuming Tuning fork Tuning fork Lower sensitivity (55-61% sensitive) Lower sensitivity (55-61% sensitive)