Type 2 Diabetes Update: How Sweet Life Is

1. Type 2 Diabetes Update:How Sweet Life Is Lt Col Tammy J Lindsay, MD, FAAFP Feb 2010

2. Objectives Prevention and screening guidance for T2DM Complication management strategies for T2DM Oral medication options for T2DM

3. Prevention and Screening: Take Home Points A1c is now listed as a screening method Lifestyle still leads the way in delaying the onset of T2DM in those with Insulin Resistance. Metformin helps, too. (A) ASA in men > 50 or women >60 with 1 other CAD risk factor. (C) As secondary prevention for CAD, ASA should be used at any age. (A) Up to 1/4 of people with T2DM don’t know it (because we haven’t diagnosed them).

4. Prevention and Screening:The Addition of A1c For screening/diagnosis of T2DM Cut off is >6.5% for DM, 5.7% for glucose intolerance Repeat for confirmation Caveats: This is not meant for office point of care testing Patients with hemoglobinopathies need diagnosis via glucose parameters The diagnosis of diabetes for the longest time has been reliant on sugar levels alone. There are some convenience factors that make A1c levels appealing. Now that the lab version of this test has become standardized the WHO and ADA have agreed that a cut off of equal to or greater than 6.5% is consistent with diabetes. Just like with the other tests for diabetes, this one will not always pick up the same individuals as will the FBS testing or the 2 hour glucose challenge testing. In fact, with this cut off the ADA suspects that about 1/3rd fewer patients will be identified with A1c testing. However, given the greater ease of testing, experts feel there will be a sort of balance achieved-- eg more people will get tested. Please remember, A1c testing is reliant upon hemoglobin. If you have a condition that effects hemoglobin (sickle cell, profound anemia, etc) you need to use standard glucose testing for diagnosis.The diagnosis of diabetes for the longest time has been reliant on sugar levels alone. There are some convenience factors that make A1c levels appealing. Now that the lab version of this test has become standardized the WHO and ADA have agreed that a cut off of equal to or greater than 6.5% is consistent with diabetes. Just like with the other tests for diabetes, this one will not always pick up the same individuals as will the FBS testing or the 2 hour glucose challenge testing. In fact, with this cut off the ADA suspects that about 1/3rd fewer patients will be identified with A1c testing. However, given the greater ease of testing, experts feel there will be a sort of balance achieved-- eg more people will get tested. Please remember, A1c testing is reliant upon hemoglobin. If you have a condition that effects hemoglobin (sickle cell, profound anemia, etc) you need to use standard glucose testing for diagnosis.

5. Prevention and Screening:Risk Factors BMI over 25 Physical Inactivity 1st degree relative with DM African American, Asian, Pacific islander, Native American, Latino GDM or women w/infants weighing more than 9 pounds HTN HDL<35; TRIG>250 PCOS or other signs of insulin resistance Prior IFG; IGT; or A1c >5.7% History of CAD W/O risk factors USPTF states there is insufficient evidence to rec for or against screening. With HTN or HLP, they rec screening. If overweight, then the ADA rec screening. If normal weight, they rec waiting until age 45. However, if the BMI is elevated and any of the other risk factors are presents--consider initial screening. After initial screening, if normal, every 3 yrs is sufficient. If abnormal, need more frequent monitoring may be warranted. One other issue worth mentioning is GDM. There may be more coming on this shortly. For the scope of this talk, it is sufficient to say that the recommendation is to screen all women at 6-12 weeks postpartum. W/O risk factors USPTF states there is insufficient evidence to rec for or against screening. With HTN or HLP, they rec screening. If overweight, then the ADA rec screening. If normal weight, they rec waiting until age 45. However, if the BMI is elevated and any of the other risk factors are presents--consider initial screening. After initial screening, if normal, every 3 yrs is sufficient. If abnormal, need more frequent monitoring may be warranted. One other issue worth mentioning is GDM. There may be more coming on this shortly. For the scope of this talk, it is sufficient to say that the recommendation is to screen all women at 6-12 weeks postpartum.

6. Prevention and Screening:Lifestyle vs Medication? Lifestyle (58% reduction; NNT=7) Physical Activity--150 min a week (A) Physical Activity--strength training 3 times weekly (A) Diet--start with 5-10% (7%) weight loss (A) Encourage fiber (14gm/1000kcal) daily and whole grains (B) Metformin (31% reduction; NNT=14) in addition to the recs on the slide, follow up lifestyle counseling seems to be an important component When might activity not be ok--well for prevention this is less of a concern but these same recommendations are made for your active diabetics, So I thought I would comment just a moment. If you suspect CAD, evaluate that. Asymptomatic pts do not need to be tested prior to there regimen but should start slowly. For folks with active retinopathy, they may not be able to strength train or undergo vigorous aerobic activity without risk-talk to ophtho. With those with DM neuropathy such as charcot joint, walking is ok but pt should eval feet daily, wear proper footwear and at the first sign of breakdown seek care. Folks with autonomic neuropathy have greater risk of injury with exercise due to inappropriate cardiac response, orthostasis, hypoglycemia, or temperature dysregulation. Metformin is currently the only drug that is recommended in “prevention” of DM (and for only high risk individuals with more than one risk factor)--some others have shown promise but either cost and side effects make their use not as advantageous.in addition to the recs on the slide, follow up lifestyle counseling seems to be an important component When might activity not be ok--well for prevention this is less of a concern but these same recommendations are made for your active diabetics, So I thought I would comment just a moment. If you suspect CAD, evaluate that. Asymptomatic pts do not need to be tested prior to there regimen but should start slowly. For folks with active retinopathy, they may not be able to strength train or undergo vigorous aerobic activity without risk-talk to ophtho. With those with DM neuropathy such as charcot joint, walking is ok but pt should eval feet daily, wear proper footwear and at the first sign of breakdown seek care. Folks with autonomic neuropathy have greater risk of injury with exercise due to inappropriate cardiac response, orthostasis, hypoglycemia, or temperature dysregulation. Metformin is currently the only drug that is recommended in “prevention” of DM (and for only high risk individuals with more than one risk factor)--some others have shown promise but either cost and side effects make their use not as advantageous.

7. Lifestyle tools www.fitday.com www.nutrimirror.com www.sparkpeople.com This is not an endorsement for any of these sites or the information on them--but they each have a free area for calorie counting, fitness entry and mets calculation. There are advertising at each. This is not an endorsement for any of these sites or the information on them--but they each have a free area for calorie counting, fitness entry and mets calculation. There are advertising at each.

8. Complication Management:Take Home Points Ask about hypoglycemic episodes every visit. Individualize A1c levels Bariatric surgery is an option for T2DM patients with a BMI over 35, mortality data however is so far lacking (B) Tight lipid control decreases CVD mortality in diabetic patients (A) Tight BP control decreases complications and deaths from DM (A) Tight glucose control helps with microvascular complications but not macrovascular complications or mortality (A) Smoking cessation should be a primary treatment goal (A)

9. Complication Management:Hypoglycemic Management Hypoglycemia is frequently the major limiting factor to glycemic control Treatment with pure glucose preferred, though any carbohydrate acceptable. Combining fat will slow absorption. Severe hypoglycemia should be treated with glucagon. Prevention is critical. Ask each visit if your patient is having them, if they know the symptoms and if they have a plan on what to do. Anyone on insulin should have glucagon rescue kit and family should be taught how to use Hypoglycemic unawareness can persists for several weeks--relax glucose targets during this time Know that exercise can decrease insulin needs and in some pt on SU may need a snack. Ask each visit if your patient is having them, if they know the symptoms and if they have a plan on what to do. Anyone on insulin should have glucagon rescue kit and family should be taught how to use Hypoglycemic unawareness can persists for several weeks--relax glucose targets during this time Know that exercise can decrease insulin needs and in some pt on SU may need a snack.

10. Complication Management:A1c Goals Most non-pregnant adults <7% is a good target If meeting goals, measure every 6 months; otherwise, every 3 months. More intensive control does not seem to provide improved macrovascular or mortality benefit. Microvascular benefit exists. Things that could adjust the target (loosen or tighten) age and life expectancy, duration of disease, frequency of hypoglycemic episodes, known CAD, other co-morbid conditions, other individual patient factors. Preprandial glucose 70-130; post<180Things that could adjust the target (loosen or tighten) age and life expectancy, duration of disease, frequency of hypoglycemic episodes, known CAD, other co-morbid conditions, other individual patient factors. Preprandial glucose 70-130; post<180

11. Complication Management:CAD risk factor control Treat HTN Goal <130/80; check every visit 1st line meds: ACE-I or ARB; Diuretic; B-blockers are safe (esp after MI) Treat HLP LDL <100; non HDL chol <130; if overt CAD, LDL goal <70; non HDL chol goal <100 Treat with a statin; if goals not reached may add fibrate or niacin ASA therapy for high risk individuals Encourage smokers to stop certainly focus on lifestyle --For HTN: dash diet, lower Na, higher K, physical activity, weight loss, ETOH in moderation only. For HLP: plant sterols/stanols, omega 3 fatty acids, fiber, wt loss, and physical activity For HTN: do not use Ca channel blockers first line (not as effective as ACE for nephropathy), do not use ace and arb together--increased acute dialysis risk Original goals with chol: treat all DM over 40 and those with CAD; goal -- 30-40% reduction in LDL, LDL < 100 or 70 if overt CAD, then secondary goals can be targeted, nonHDL chol, HDL>40, Trig <150 ASA--high risk over 50 in men or 60 in women and one other risk factor--smoking, htn, hlp, fam hx, albuminuria (primary)--if this is secondary prevention--just do it unless there is contraindications, and if there are consider clopidogrelcertainly focus on lifestyle --For HTN: dash diet, lower Na, higher K, physical activity, weight loss, ETOH in moderation only. For HLP: plant sterols/stanols, omega 3 fatty acids, fiber, wt loss, and physical activity For HTN: do not use Ca channel blockers first line (not as effective as ACE for nephropathy), do not use ace and arb together--increased acute dialysis risk Original goals with chol: treat all DM over 40 and those with CAD; goal -- 30-40% reduction in LDL, LDL < 100 or 70 if overt CAD, then secondary goals can be targeted, nonHDL chol, HDL>40, Trig <150 ASA--high risk over 50 in men or 60 in women and one other risk factor--smoking, htn, hlp, fam hx, albuminuria (primary)--if this is secondary prevention--just do it unless there is contraindications, and if there are consider clopidogrel

12. Complication Management:CAD Management in setting of T2DM Reassess risk factors (and treat) at least annually ASA (A), ACE-I or ARB (C), and Statin (A) With prior MI, B-Blocker for first 2 yrs (can cont if in setting of hypertension) TZDs are contraindicated in CHF patients Metformin can be used in stable CHF patients but if renal function is changing or CHF is uncontrolled it should be avoided Once nephropathy develops the risk for CAD increases (B)

13. Complication Management:Nephropathy Screen annually with spot albumin/creatinine ratio (C) Measure GFR (MDRD is most accurate) annually--if below 60... Restrict protein (0.8 gm/kg) Screen for anemia Screen for metabolic bone disease Screen for malnutrition Consider Hep B vaccine for those at high risk of ESRD. ACE-I or ARB for microalbuminuria treatment and prevention, not both (A) DM kidney dz is the most common cause of ESRD in the US at 45% ACE-I and ARB together led to increased need for acute dialysis--NNH 565 ACE-I and ARB considered equivalent if one not tolerated may try other class mdrd = modification diet in renal disease (2 of 3 samples should be positive prior to dx of persistent microalbuminuria; 30-299 microgram/mg or macroalbuminuria >300 microgram/mg)DM kidney dz is the most common cause of ESRD in the US at 45% ACE-I and ARB together led to increased need for acute dialysis--NNH 565 ACE-I and ARB considered equivalent if one not tolerated may try other class mdrd = modification diet in renal disease (2 of 3 samples should be positive prior to dx of persistent microalbuminuria; 30-299 microgram/mg or macroalbuminuria >300 microgram/mg)

14. Complication Management:Retinopathy Optimal BP control is essential in reducing progression (A) Glycemic control is also important (B) ASA therapy is safe (although it does not effect eye disease progression) Fenofibrate can reduce the need for photocoagulation (A) Photocoagulation is the mainstay of therapy Screening with initial diagnosis in T2DM. Follow-up depends on findings. May be accomplished with experienced eye practitioner or photos. In patients with DM and HTN, 8% with tight BP control required photocoagulation c/w 12% with less tight control. NNT=25 (from the 1998 UKPDS) Furthermore, vision loss occurred in 2.4 % of DM with tight control vrs 3.1% with usual care--NNT =200 for 5 yrs and were less likely to have deterioration NNT=8 (from Jan 2005 UKPDS update) For glucose control, there has been noted to be a decrease in the laser treatments needed in the tight glycemic control group over the control (NNT = 323) there was however, no mortality or macrovascular complication benefit realized In type 2 DM, there was a modest reduction over 5 yrs when treated with fenofibrate in the need for 1st photocoagulation--the impact was greatest if the pt had baseline retinopathy. NNT=67 and 17 respectivelyIn patients with DM and HTN, 8% with tight BP control required photocoagulation c/w 12% with less tight control. NNT=25 (from the 1998 UKPDS) Furthermore, vision loss occurred in 2.4 % of DM with tight control vrs 3.1% with usual care--NNT =200 for 5 yrs and were less likely to have deterioration NNT=8 (from Jan 2005 UKPDS update) For glucose control, there has been noted to be a decrease in the laser treatments needed in the tight glycemic control group over the control (NNT = 323) there was however, no mortality or macrovascular complication benefit realized In type 2 DM, there was a modest reduction over 5 yrs when treated with fenofibrate in the need for 1st photocoagulation--the impact was greatest if the pt had baseline retinopathy. NNT=67 and 17 respectively

15. Complication Management:Neuropathy--Peripheral &Autonomic Symptomatic Painful Diabetic Peripheral Neuropathy is associated with overall QOL and can lead to depression. Screen at diagnosis and at least annually. Screen for PAD Provide good foot care education. Some useful treatments for PDPN include: TCAs, anticonvulsants, duloxetine, gabapentin, and capsacin. Autonomic DN affects all organ systems How do you screen? Simple in office testing will suffice--10g monofiliament, vibratory testing, and superficial pain testing are all equal according to a 2001 Lancet article. The ADA rec choosing 10g monofiliment testing plus one other, throwing ankle reflex testing in with the other options. cardiac tachyarhythmias can be the first sign, orthostatsis, gastroparesis, constipation, hypoglycemic unawareness, the list goes on...these can all lead to management issues. It is enough for the scope of this talk to you to be aware, to watch for, to treat symptoms. How do you screen? Simple in office testing will suffice--10g monofiliament, vibratory testing, and superficial pain testing are all equal according to a 2001 Lancet article. The ADA rec choosing 10g monofiliment testing plus one other, throwing ankle reflex testing in with the other options. cardiac tachyarhythmias can be the first sign, orthostatsis, gastroparesis, constipation, hypoglycemic unawareness, the list goes on...these can all lead to management issues. It is enough for the scope of this talk to you to be aware, to watch for, to treat symptoms.

16. Complication Management Tools

17. Complication Management Tools

18. Oral Medications:Take Home Points Most T2DM patients will require medications: along with lifestyle change, initiate metformin at time of diagnosis unless contraindicated. Diabetes is a progressive disease. Therapy modification will be required. Take action when glycemic goals are not being met. Utilize medications with varying MOA to get best results. Involve a team approach--nurse educator, nutritionist, patient and physician.

19. Oral Medications:ADA/EASD Tier approach american diabetes assoc and the european assoc of study of diabetes have put out guidelines on what meds should be started when... We will go thru each of these with the exception of insulin--that is next houramerican diabetes assoc and the european assoc of study of diabetes have put out guidelines on what meds should be started when... We will go thru each of these with the exception of insulin--that is next hour

20. Oral Medication: Metformin- Tier 1 Sulfonylureas- Tier 1 GLP-1 Mimetics- Tier 2 (actually injectable, I know) TZD- Tier 2 Acarbose- Other Amylin analogs- Other (Also injectable) DPP-4 inhibitors- Other Meglitintides- Other

21. Oral Medication:Metformin MOA: insulin sensitizer A1c reduction expected: 1-2% Advantages: low risk of weight gain, hypoglycemia, is available generically, LOWERS all cause MORTALITY Disadvantages: GI side effects; cannot use in renal dysfunction (Cr Cl <30) Peripheral uses: restores fertility in PCOS, lowers lipids, delays T2DM onset Other comments: Careful with your elderly, those with CHF, and alcoholics...General rule of thumb: Stop the medication on admission

22. Oral Medication:Sulfonylureas MOA: enhances insulin secretion A1c reduction expected: 1-2% Advantages: rapid acting, inexpensive Disadvantages: weight gain, hypoglycemia Other comments: less durable than the other oral agents at maintaining target glucose levels glyburide and chlorpropamide significantly higher risk of severe hypoglycemiaglyburide and chlorpropamide significantly higher risk of severe hypoglycemia

23. Oral Medication:GLP-1 Mimetics MOA: potentiates insulin secretion A1c reduction expected: 0.5-1.0 % Advantages: weight loss, no hypoglycemia, decrease SBP and lipids Disadvantages: associated with GI side effects including post marketing pancreatitis, contraindicated if Creatinine clearance <30, expensive Dosing: an injectable (2x daily) Other comments: better durability, able to combine with metformin, TZD or sulfonylurea it also suppresses glucagon and slows gastric motilityit also suppresses glucagon and slows gastric motility

24. Oral Medications:TZDs MOA: insulin sensitizers A1c reduction expected: 0.5-1.4% Advantages: lipid panel improves Disadvantages: weight gain, significant fluid retention, increased risk of CHF, possibly CAD, fractures, caution in liver disease Other comments: the CAD findings have been in rosiglitazone; pioglitazone more favorable--thus the consensus panel only recommended pioglitazone use it is an insulin sensitizer--watch with concommittent insulin use...it is an insulin sensitizer--watch with concommittent insulin use...

25. Oral Medications:Alpha Glucosidase Inhibitors (Acarbose) MOA: reduce the rate of digestion of polysaccarides in SI A1c reduction expected: 0.5-0.8% Advantages: weight neutral Disadvantages: TID dosing, costly, GI side effects Other comments: given overall lower efficacy and higher costs did not make the tier 2 listing but may work for an individual patient

26. Oral Medications:Amylin agonists MOA: slows gastric emptying, inhibits glucagon A1c reduction expected: 0.5-1.0% Advantages: weight loss Disadvantages: 3 injections daily, GI side effects, costly Other comments: only used as adjunct care

27. Oral Medications:DPP-4 Inhibitors-Sitagliptin MOA: increases insulin secretion and suppresses glucagon A1c reduction expected: 0.5-0.8% Advantages: weight neutral, generally well tolerated, decreased SBP, improved lipids Disadvantages: costly, increased URI, some reports of anaphylaxis, angioedema, and dermatitis

28. Oral Medications:Meglitintides: Glinide MOA: stimulate insulin secretion A1c reduction expected: 0.5-1.5% Advantages: rapid acting Disadvantages: weight gain, tid dosing, some risk of hypoglycemia, expensive

29. Oral Medications:ADA/EASD Tier approach american diabetes assoc and the european assoc of study of diabetes have put out guidelines on what meds should be started when... We will go thru each of these with the exception of insulin--that is next houramerican diabetes assoc and the european assoc of study of diabetes have put out guidelines on what meds should be started when... We will go thru each of these with the exception of insulin--that is next hour

30. A Word about Special Populations Kids: Kids are getting T2DM at an alarming rate. The distinction of is this T1DM or T2 DM is critical to make: education, medication, screenings are different. If there is a question, get help. Start screening overwt kids at 10 if 2 risk factors present. Pregnant women (and those that want to be) Strict control is needed before and during the pregnancy for pre-existing diabetic patient. Evaluation for retinopathy should be accomplished. Many of the medications that are used for maintenance treatment need to be discontinued during pregnancy. Geriatric Population Treat life expectancy not age alone. Remember to look at med list and evaluate contraindications kids: EEP--risk factors include fam hx, ethicity other than white, signs of insulin resistence, and mom with gdmkids: EEP--risk factors include fam hx, ethicity other than white, signs of insulin resistence, and mom with gdm

31. Medication Tools Nurse assisted “pill card” creation AHRQ has a step by step process for individual med list creation at www.ahrq.gov Publication No. 08-MO16 Creatinine Clearance (MDRD) GFR (mL/min/1.73 m2) = 186 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African-American) (conventional units)

32. Conclusion: 57.1% of Americans with DM reach an A1c goal of <7% 45.5% reach a BP goal of <130/80 46.5% reach a total chol goal of under 200 Only 12.2% reach all 3 Hopefully, you now have additional tools to partner with you patients to increase this number in your clinic. taken from cheung bm am j med 2009;122:443-453 taken from cheung bm am j med 2009;122:443-453

33. Acknowledgements Special thanks to.... Capt Jason McCarthy Capt Christopher Jonas Major Blake Rodgers Nutritional Medicine Department at Scott AFB

34. Questions????