1. Monitoring and Management Jennifer Danielson, PharmD, MBA, CDE Clinical Assistant Professor University of Washington School of Pharmacy

2. Learning Objectives 1.Identify patients who would benefit from self-monitoring of blood glucose (SMBG). 2.Recommend how often patients should SMBG. 3.I nterpret readings from SMBG. 4.Apply results of SMBG to recommending appropriate drug therapy (e.g. pattern management). 5.Relate results from glucose meters to HbA1c results. 6.Discuss use of continuous glucose monitoring (CGM) and interpret CGM trend results.

3. Treatment Guidelines Healthy eating Being active Monitoring Taking medication Problem solving Healthy coping Reducing risks

4. 10.0 9.0 8.0 7.0 6.0 A1c 5.0 ADA A1c Goal < 7% Pre-prandial 80-130 mg/dL Post-prandial (PPG) < 180mg/dL AACE A1c Goal < 6.5% Fasting plasma (FPG) < 110 mg/dL PPG < 140 mg/dL Upper range of normal Glycemic Goals ADA. Diabetes Care 2013: 36 (supp 1): S1-S10. AACE. Endocr Pract 2011; 17(supp 2): 1-53. Inpatient setting: Acute care 140-180mg/dL Critical care 110-140mg/dL Inpatient setting: Acute care 140-180mg/dL Critical care 110-140mg/dL

5. ADA Standards for SMBG SMBG for patients on multiple insulin injections or pumps –Prior to meals/snacks –Occasionally post-prandial –Bedtime –Prior to exercise –Hypoglycemia –Prior to critical tasks (such as driving) SMBG is a useful guide for less frequent insulin injections and non-insulin therapies When prescribing SMBG, ensure patients receive ongoing instruction & evaluation, plus follow-up to adjust therapy ADA. Diabetes Care 2013: 36 (supp 1): S1-S10.

6. CGM is a useful tool to lower A1c in adults ≥25yo on multiple injections per day or using a pump (Type 1) CGM may be useful for people younger than 25yo CGM is a supplemental tool for patients with hypoglycemia unawareness or frequent hypoglycemia ADA Standards for SMBG ADA. Diabetes Care 2013: 36 (supp 1): S1-S10.

7. AACE Standards for SMBG Patients using insulin: ≥2 times per day qnd before injections More often, if not at A1c goal or hypoglycemia Patients not using insulin: Recommended but the frequency of testing should be individualized In general, SMBG recommended for all patients with diabetes. AACE. Endocr Pract 2011; 17(supp 2). CGM is a good for obtaining better A1c control and for patients with hypoglycemia

8. StudyDesign(n)DurationResults Fontbonne et al. 1996 1 Randomized68 = SMBG 72 = urine 68 = control 6 months 50% compliance w/twice QOD A1c reduction 0.5% - 0.1% (not significant) Allen et al. 1990 2 Randomized27 = SMBG 27 = urine 6 months 87% compliance w/before meals QOD A1c reduction 2% both groups (not significant) Muchmore et al. 1994 3 Randomized12 = SMBG* 11 = control *more intensive nutrition counseling 40 weeks 25% compliance w/six times daily A1c reduction 1.5% & 0.8% (not significant) Schwedes et al. 2002 4 Randomized113 = SMBG* 110 = control *more intensive nutrition counseling 6 months 100% compliance w/6 times per day A1c reduction 1% & 0.5% (not significant) Guerci et al. 2003 5 Randomized345 = SMBG 344 = control 6 months* (but >40% drop out in both groups) Compliance unclear w/6 times per week A1c reduction 0.9% & 0.5% (significant) Davidson et al. 2005 6 Randomized43 = SMBG 45 = control 6 months (both received diet counseling/mgmt) 45% compliance w/before and after meals 6 days/wk A1c reduction 0.8% & 0.6% (not significant) Farmer A, Wade A, Goyder E, et al. Impact of self monitoring of blood glucose in the management of patients with non-insulin treated diabetes: open parallel group randomised trial. BMJ.2007; 335:132. N=453, 3 years, mean A1c 7.5%, A1c reduction 0.17% (not significant) Randomized Trials in Type 2 Patients Not Using Insulin

9. Non-Randomized Trials in Type 2 DM At least 8 trials, consistently showing relationship between SMBG and A1c reduction but not all randomized, many with flaws 2 Still, A1c reduction range: 0.16% to 0.88% (significant in all cases) Non-randomized trials –Over dozen studies, most showing no relationship between monitoring and A1c reduction –Those that show difference have flaws with uneven treatment or self-selection 1 Meta-analyses & Reviews –Conflicting results but suggest that SMBG may be helpful in gaining better glycemic control –Significant reduction in A1c of (depending on time measured and statistical model used) 2,3 Using InsulinNot Using Insulin 1 McAndrew, et al. Does patient blood glucose monitoring Improve diabetes control? Systematic Review. Diabetes Educator 2007 33: 991. 2 Welschen, Bloemendal, Nijpels, et al. SMBG in patients with Type 2 diabetes not using insulin: a systematic review. Diabetes Care 28:1510-1517, 2005. 2 Ramachandra, Ellis. SMBG in insulin-requiring type 2 diabetes. Diabetes Tech and Thera 2008;10:S1. 3 Fullerton B, et al. SMBG in patients with Type 2 diabetes who are not using insulin. Cochrane Review: Jan 2012. Fullerton B, et al. SMBG in patients with Type 2 diabetes who are not using insulin. Cochrane Review: Jan 2012. 12 trials included in meta analysis, N=3259, A1c reduction 0.3% (significant at 6mos but not at 12mos)

10. SMBG in Type 2 Diabetes Diagnosis Knowledge Skills Awareness Understanding in Cultural Context Interpretation Response Achieve glycemic control Reduce complications Less symptom distress Improved quality of life Improved patient attitudes Pre-requisitesConsequences MK Song, TH Lipman. Concept analysis: Self-monitoring in type 2 diabetes mellitus. Intnl Jour Nurs Stud. 45 (2008) 1700-1710.

11. ADA Standards for A1c Testing Patient at goal: A1c at ≥2 times/yr Patient not at goal: A1c quarterly Use point of care technology to provide opportunity for timely changes http://wilburnmedicalusa.com/-c-0/siemens-dca-vantage-analyzer-p-149274?clid=CJK59qb7k8MCFVSSfgodnnkASQ

12. Cases 1 and 2

13. Pattern Management Applying results of home blood glucose monitoring to drug therapy management. Recognizing highs/lows that occur in patterns. Adjusting drug therapy to address the patterns of highs and lows seen. Follow-up on results for changes made.

14. Glucose Triad Fasting blood glucose Postprandial blood glucose A1c Lower Higher

15. Effect on Blood Glucose Basal drugs  Fasting Metformin TZDs Sulfonylureas Intermediate and long- acting insulin –Lantus® –Levemir® –NPH Bolus drugs  Postprandial Short and rapid acting insulin –Regular –Humalog ® –Novolog ® –Apidra ® Sulfonylureas Meglitinides Acarbose DPP-4 inhibitors GLP-1 analogues

16. Effect on Blood Glucose Basal drugs  Fasting Metformin TZDs Sulfonylureas Intermediate and long- acting insulin –Lantus® –Levemir® –NPH Bolus drugs  Postprandial Short and rapid acting insulin –Regular –Humalog ® –Novolog ® –Apidra ® Sulfonylureas Meglitinides Acarbose DPP-4 inhibitors GLP-1 analogues

17. Slide adapted from Zane Brown, MD Professor UW Medicine

18. Case Example BLDHS 104146110176 106136164 118132126 120222 126148134 122138116212

19. Case Example BLDHS 104146110176 106136164 118132126 120222 126148134 122138116212

20. Case Example BLDHS 110126118196 987256202 118110126188 112120164 9664100212 102 194

21. Estimated Average Glucose (eAG) eAG (CI 95%)A1c 97 (76-120)5% 126 (100-152)6% 154 (123-185)7% 183 (147-217)8% 212 (170-249)9% 249 (192-282)10% 269 (217-314)11% 298 (240-347)12% Formula: 28.7 x A1C – 46.7 = eAG wide CIs weighted most to last 30 days Diabetes Care 2008. 31:1473-1478 http://professional.diabetes.org/GlucoseCalculator.aspx

22. What if you saw it like this? SD

23. Actual Download Print-Out Print out image from: CliniPro by Numedics

24. Cases 3 through 5

25. Continuous Glucose Monitoring Alternative site testing –Measures subcutaneous fluid not blood –~10 minute delay in results –Must know the caveats with hypoglycemia Continuous Glucose Monitoring Systems –Medtronic Guardian REALtime CGMS –Dexcom SEVEN –Minimed Paradigm –Abbott FreeStyle Navigator

26. Daily Use Glucose change is gradual. Glucose is increasing moderately. Glucose is increasing rapidly. Glucose is decreasing moderately. Glucose is decreasing rapidly.

27. CGM Interpretation What should the patient do to respond? 72 mg/dL 11:10 am

28. CGM Interpretation What should the patient do to respond? 72 mg/dL 11:25 am

29. CGM Interpretation What should the patient do to respond? 118 mg/dL 12:20 pm

30. CGM Interpretation What should the patient do to respond? 196 mg/dL 2:02 pm