1. Lucia M. Novak, MSN, ANP-BC, BC-ADM The Diabetes Institute Walter Reed Army Medical Center, Washington, DC Adjunct Assistant Professor, Graduate School of Nursing, Uniformed Services University of the Health Sciences, Bethesda, MD DIABETES AND CKD CASE STUDY

2. 57 yo African American man Presents for “routine DM f/u” Last appointment 6 months ago Concerned that his blood sugars are “all over the place.” Unhappy about “10 lbs. weight gain.” Needs refills of his meds, about 2 weeks left Too many pills, hopes you can stop some Has not eaten or taken any meds yet today, he figured you would want to send him to the lab DIABETES AND CKD CASE STUDY ~CHARLES~

3. Past Medical History: – Type 2 Diabetes Mellitus (5 years) – Hypertension (10 years) – Dyslipidemia (10 years) – Mild Osteoarthritis both knees (3 years) Social History: – Married – IT consultant – Nonsmoker – ~4 beers a week PERTINENT HISTORY

4. Medications: – Metformin XR (Glucophage XR) 2000 mg once daily (2005) (max) – Rosiglitazone (Avandia) 4 mg once daily (2007) (max is 8 mg/day) – Glyburide (Diabeta) 5 mg twice daily (2009) (max is 20 mg/day) Exercise: – Brisk walk every evening with his wife for 30-45 minutes – Goes to gym 2 days a week (weights) CURRENT DM MGMT

5. Breakfast (8:30) – bowl of oatmeal, ½ banana, cup of coffee Lunch (1-2pm) but skips at least 3x weekly – Turkey sandwich or soup, handful of chips and diet soda Dinner (6-7pm) – Baked chicken, greens, corn bread, veggie soup, water Snacks – “not if I have lunch, but if I don’t have lunch, then something from the vending machine late afternoon” – “Before bed or I will wake up with low sugars” 1-2 scoops Sugar-free ice cream or 2 cookies with ½ cup milk 24 HOUR DIET RECALL

6. aspirin Statin for cholesterol ACE-I for blood pressure Diuretic for blood pressure Supplements “natural remedies” – Cinnamon tablets and fish oil OTC – Ibuprofen or similar “when my knees act up” – (400 mg 2x daily, 4-5x weekly) – Self-initiated within the last 6 months OTHER MEDICATIONS

7. A1C: 6.3% Fasting Glucose: 103 mg/dL Scr: 1.0 mg/dL GFR: > 60mL/min/1.73 m 2 AST 32 U/L ALT: 24 U/L Microalbumin/creatinine: 10.6 mg/g CRT LDL-C: 86 mg/dL TG: 132 mg/dL LATEST LAB VALUES (6 MONTHS AGO)

8. BLOOD SUGAR RECORD DateBBABBLALBDADBT Sun76 Mon13852118 Tue61193 S Wed16498 NS Thu59179 S Fri123182 S Sat13562163 S Sun149104 NS Mon64 S = snack NS = no snack

9. General: – Feels well overall Eyes: – denies blurred vision or change in VA – last dilated exam was almost 1 yr ago: +mild NPDR OU CV: – Denies CP, SOB, DOE, postural dizziness – +edema to both ankles and feet “late in the day” Neuro: – Denies numbness/tingling/burning to feet/hands GU: – Denies polyuria, frequency, urgency, nocturia REVIEW OF SYSTEMS

10.  Vitals:  B/P: 168/92  B/P: 168/92, HR: 72 reg, RR: 12 unlabored BMI: 31.7 kg/m²  Ht: 70” Wt: 221 lbs BMI: 31.7 kg/m²  General:  Obese, well-developed, well-appearing, AAM, A&Ox4, NAD  CV:  S1S2, RRR, no murmur  Lungs:  CTA A-P  Extremities:  Both legs/feet warm  +2/4 PT DP pulses  +1/4 pitting pretibial edema bilat  Monofilament 5.07 (10 gm) intact to all dermatomes of both feet  Vibratory sensation 128 hz tuning fork fully intact both feet PE

11.  Hypoglycemia  Why occurring??  Contributing to weight gain?  Status of his renal function  AA ethnicity  Hx HTN, BP elevated today  Accounts for 30% ALL deaths in AA men and 20% in AA women  Known DM complication of retinopathy  Could he have nephropathy?  OTC NSAIDS  High salt diet WHAT ARE YOUR IMMEDIATE CONCERNS?

12.  The persistent and usually progressive reduction in glomerular filtration rate (GFR less than 60 mL/min/1.73 m 2 ), and/or  Albuminuria (more than 30mg of urinary albumin per gram of urinary creatinine) CKD: WHAT IS IT?

13. Diabetes and high blood pressure Diabetes and high blood pressure are the leading causes of kidney failure. one third The risk of developing CKD increases with the length of time a person has diabetes. About one third of people with diabetes will eventually develop CKD. Chronic kidney disease may also result from: – Hereditary factors, such as polycystic kidney disease (PKD) – A direct and forceful blow to the kidneys – NSAID use Relative risks compared to Whites: – African Americans 3.8 X – Native Americans 2.0 X – Asians 1.3 X CKD: WHO IS AT RISK?

14. Cardiovascular disease is linked to CKD Cardiovascular disease is linked to CKD Annual mortality from CVD is increased 10 - 100 times with kidney failure Risk of CVD is increased 1.4 - 2.05 times with creatinine >1.4 - 1.5 mg/dl Risk of CVD is increased 1.5 - 3.5 times with microalbuminuria. (>30) Increased incidence of hypoglycemia with insulin secretagogues and exogenous insulin CKD: WHY SHOULD I CARE?

15.  Normal kidney function – GFR above 90mL/min/1.73m 2 and no proteinuriaproteinuria  1) CKD1 – GFR above 90mL/min/1.73m 2 with evidence of kidney damage  2) CKD2 (Mild) – GFR of 60 to 89 mL/min/1.73m 2 with evidence of kidney damage  3) CKD3 (Moderate) – GFR of 30 to 59 mL/min/1.73m 2  4) CKD4 (Severe) – GFR of 15 to 29 mL/min/1.73m 2  5) CKD5 (Kidney failure) - GFR less than 15 mL/min/1.73m 2  Some clinicians add CKD5D for those stage 5 patients requiring dialysis  many patients in CKD5 are not yet on dialysis. STAGES OF CKD

16. Address the hypoglycemia – Hold Glyburide – Instruct to test blood sugars at least twice daily: AM FBG and 2 hr post meal Address renal concerns – Take BP meds, never skip even when fasting for labs – Hold NSAIDs, use acetaminophen – Diet counseling, Refer to RD for MNT Referral for dilated eye exam Send to the lab TODAY and schedule f/u within 1 week Address all medications at next visit as they may need to be changed pending labs WHAT DO I DO TODAY WITH THE AVAILABLE INFORMATION?

17.  “I’m a mess now, my blood sugars are all over the place.”  “Please tell me I don’t have to take the needle … I am not ready for that.”  Has not been walking as much to rest his knee, feels better  But is very frustrated that he cannot exercise RETURNS FOR 1 WEEK F/U

18. Metformin and rosiglitazone only (no glyburide) BLOOD SUGAR RECORD SINCE LAST APPOINTMEMENT DateBBABBLALBDADBT Sun149104 NS Mon74165 Tue132210 Wed148196 Thu153161 Fri149173 Sat166202 Sun154215 Mon169

19. 6 months ago A1C: 6.3% Fasting Glucose: 103 mg/dL Scr: 1.0 mg/dL GFR: >60 mL/min/1.73 m 2 AST: 32 U/L ALT: 24 U/L Microalb/creatinine: 10.6 mg/g CRT LDL-C: 86 mg/dL TG: 132 mg/dL This past week A1C: 7.8% A1C: 7.8% Fasting Glucose: 146 mg/dL Scr: 1.6 mg/dL Scr: 1.6 mg/dL GFR: 45 ml/min/1.73 m 2 GFR: 45 ml/min/1.73 m 2 AST: 32 U/L ALT: 24 U/L Microalb/creatinine: 58.6 mg/g CRT Microalb/creatinine: 58.6 mg/g CRT LDL-C: 93 mg/dL TG: 162 mg/dL TG: 162 mg/dL LABS VALUES UPDATE

20.  Vitals:  B/P: 146/90  B/P: 146/90, HR: 72 reg, RR: 12 unlabored BMI: 31.7 kg/m²  Ht: 70” Wt: 221 lbs BMI: 31.7 kg/m²  General:  Obese, well-developed, well-appearing, AAM, A&Ox4, NAD, but anxious  No edema today PE

21. Renal function and metformin: YOUR CONCERNS

22.  What to do about metformin?  Relatively Contraindicated in patients with impaired renal function (RISK OF LA):  SCr > 1.4 mg/dL for women, or > 1.5 mg/dL for men  However, Scr will not be raised above the normal range until 60% of total kidney function is lost.  AAs, (both men and women) have a higher amount of muscle mass than Caucasians  AAs will have a higher Scr level at any level of CrCl.  eGFR better indicator of renal function  measured whenever renal disease is suspected or careful dosing of nephrotoxic drugs is required. ≥60no restrictions  eGFR: ≥60 mL/min, no restrictions 30-59CAUTION (50% dose)  eGFR 30-59 mL/min: CAUTION (50% dose) <30 ABSOLUTE contraindication  eGFR <30 mL/min: ABSOLUTE contraindication RENAL FUNCTION AND METFORMIN Herrington, W.G & Levy, J.B. (2008). Metformin: effective and safe in renal disease? Int Urol Nephrol, 40: 411-417. Shaw, J.S. et al. (2007). Establishing pragmatic estimated GFR thresholds to guide metformin prescribing. Diabetic Medicine, 24: 1160-1163.

23. Renal function and metformin: Controversial meds – rosiglitazone: – Increased Risk of CV events, to include MI – REMS (Risk Evaluation and Mitigation Strategy) SEVERELY RESTRICTED USE YOUR CONCERNS

24. AVANDIA: REMS As of February 2011: INDICATIONS AND USAGE After consultation with a healthcare professional who has considered and advised the patient of the risks and benefits of AVANDIA®, this drug is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who either are: 1)already taking AVANDIA, or 2) not already taking AVANDIA and are unable to achieve adequate glycemic control on other diabetes medications and, 3) in consultation with their healthcare provider, have decided not to take pioglitazone (ACTOS®) for medical reasons.

25. Renal function and metformin: Controversial meds – rosiglitazone: – Increased Risk of CV events, to include MI – REMS (Risk Evaluation and Mitigation Strategy) SEVERELY RESTRICTED USE – glyburide: – impaired Ischemic Preconditioning YOUR CONCERNS

26. SFU CONCERNS  INCREASED CARDIAC MORTALITY  FDA-required warning KATP  INHIBITING KATP channels in heart (MOA)  Precise role in the heart not fully understood  IMPAIRMENT of Ischemic Preconditioning (IP) Lee, T.-M. & Chou, T.-F. (2003). Impairment of myocardial protection in type 2 diabetic patients. J Clin Endocrinol Metab, 88(2), 531-537.  Exposure of myocardium to brief episodes of mild myocardial ischemia PRECONDITIONS and reduces impact of subsequent prolonged ischemia  REDUCES size of infarct  Arrhythmias  Increases intracellular Ca ⁺⁺  Accelerates cell death  Delay re-polarization Glyburide  1 st gen SFU and Glyburide most problematic, non-selective  SUR1 (pancreas), SUR2A (cardiac), SUR2B (vascular) Simpson, S., et al. (2006). Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ, 174(2), 169-174.

27. Renal function and metformin: Controversial meds – rosiglitazone: – Increased Risk of CV events, to include MI – REMS (Risk Evaluation and Mitigation Strategy) SEVERELY RESTRICTED USE – glyburide: – impaired Ischemic Preconditioning He needs PRANDIAL SUPPORT, but recent hypoglycemia OPTIONS? Suboptimal BP control Acute renal damage Obesity High salt diet, not yet seen RD, but has stopped eating canned soups Knee pain YOUR CONCERNS

28.  Afraid of needle (insulin or otherwise)  Weight gain  Inability to exercise/knee pain  Too many pills/simplify regimen CHARLES’ CONCERNS

29. Metformin at ½ the dose: 1000 mg once daily Switch to pioglitazone (Actos) 15 mg once daily Add DPP4 inhibitor – Sitagliptin (Januvia) 50 mg once daily OR – Saxagliptin (Onglyza) 2.5 mg once daily Add Glimeperide (Amaryl)1 mg once daily If pt tolerates new meds without problems consider: Combinations available to simplify regimen DPP4 +metformin (both) Pioglitazone + metformin Pioglitazone + glimeperide DIABETES MGMT DECISIONS

30.  Only 45% of AAs have controlled BP  Overwhelming majority will require combination drugs  Combinations MUST have either diuretic or CCB for best effect  Pt already taking ACE-I plus diuretic  PLAN:  Add CCB to ACE-I and diuretic  use combination meds when possible  ACE-I + CCB  ACE-I and HCTZ  Repeat all labs in 3 months  renal fx should improve with good glycemic and BP control  Refer to nephrology if no improvement no-impact  Encourage lifestyle: diet and no-impact exercise BLOOD PRESSURE MGMT DECISIONS

31.  “I feel fantastic!! I am not claiming dialysis!!”  “My blood sugars look great!”  Denies any problems tolerating his medications and is pleased with his current regimen.  Denies any problems with hypoglycemia  “I went to the lab like you told me to last week and I can’t wait to see how I am doing.” 3 MONTH F/U

32.  Vitals:  B/P: 122/64, HR: 72 reg, RR: 12 unlabored Wt: 216 lbs (loss of 5#)  Ht: 70” Wt: 216 lbs (loss of 5#) BMI: 31 kg/m²  General:  Obese, well-developed, well-appearing, AAM, A&Ox4, NAD  No edema 3 MONTH F/U

33. 3 months ago A1C: 7.8% Fasting Glucose: 146 mg/dL Scr: 1.6 GFR: 45 cc/min AST: 32 ALT: 24 Microalb/creatinine: 58.6 mg/g CRT LDL-C: 93 mg/dL TG: 162 mg/dL This past week A1C: 6.7% Fasting Glucose: 96 mg/dL Scr: 1.2 GFR: 56 cc/min AST: 32 ALT: 24 Microalb/creatinine: 28.6 mg/g CRT LDL-C: 82 mg/dL TG: 124 mg/dL LABS VALUES

34. BLOOD SUGAR RECORD DateBBABBLALBDADBT Sun102132 Mon96128 Tue80114 Wed93128 Thu89137 Fri100119 Sat91122 Sun101135109118 Mon86

35. He had his eye exam last week, no change from previous year He and his wife met with RD, CDE – Lower sodium foods (DASH diet) – Portion control (plate method) when not at home – Weight loss He and his wife now goes to pool 2x weekly, reduced walking to 2x weekly and his knees feel better Self-expressed goal of < 200 lbs. by next visit in 3 months with ultimate goal of 180 lbs within 2 years. OTHER