Lucia M. Novak, MSN, ANP-BC, BC-ADM

The Diabetes InstituteWalter 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

• 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~

• 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

• 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

• 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

• 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

• A1C: 6.3%• Fasting Glucose: 103 mg/dL• Scr: 1.0 mg/dL • GFR: > 60mL/min/1.73 m2

• 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)

BLOOD SUGAR RECORD

Date

BB AB BL AL BD AD BT

Sun 76

Mon 138 52 118

Tue 61 193 S

Wed 164 98 NS

Thu 59 179 S

Fri 123 182 S

Sat 135 62 163 S

Sun 149 104 NS

Mon 64

S = snackNS = no snack

• 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

Vitals: B/P: 168/92B/P: 168/92, HR: 72 reg, RR: 12 unlabored Ht: 70” Wt: 221 lbs BMI: 31.7 kg/m²BMI: 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

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?

The persistent and usually progressive reduction in glomerular filtration rate (GFR less than 60 mL/min/1.73 m2),

and/orAlbuminuria (more than 30mg of urinary albumin per gram of

urinary creatinine)

CKD: WHAT IS IT?

• Diabetes and high blood pressure Diabetes and high blood pressure are the leading causes of kidney failure.• The risk of developing CKD increases with the length of time a

person has diabetes. About one third 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 useNSAID use

• Relative risks compared to Whites:– African Americans 3.8 XAfrican Americans 3.8 X– Native Americans 2.0 X– Asians 1.3 X

CKD: WHO IS AT RISK?

• Cardiovascular disease is linked to CKDCardiovascular 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?

Normal kidney function – GFR above 90mL/min/1.73m2 and no proteinuria

1) CKD1 – GFR above 90mL/min/1.73m2 with evidence of kidney damage

2) CKD2 (Mild) – GFR of 60 to 89 mL/min/1.73m2 with evidence of kidney damage

3) CKD3 (Moderate) – GFR of 30 to 59 mL/min/1.73m2

4) CKD4 (Severe) – GFR of 15 to 29 mL/min/1.73m2

5) CKD5 (Kidney failure) - GFR less than 15 mL/min/1.73m2 Some clinicians add CKD5D for those stage 5 patients

requiring dialysis many patients in CKD5 are not yet on dialysis.

STAGES OF CKD

• 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?

“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 betterBut is very frustrated that he cannot exercise

RETURNS FOR 1 WEEK F/U

Metformin and rosiglitazone only (no glyburide)

BLOOD SUGAR RECORDSINCE LAST APPOINTMEMENT

Date

BB AB BL AL BD AD BT

Sun 149 104 NS

Mon 74 165

Tue 132 210

Wed 148 196

Thu 153 161

Fri 149 173

Sat 166 202

Sun 154 215

Mon 169

6 months ago• A1C: 6.3%• Fasting Glucose: 103 mg/dL• Scr: 1.0 mg/dL• GFR: >60 mL/min/1.73 m2

• 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/dLScr: 1.6 mg/dL• GFR: 45 GFR: 45 ml/min/1.73 mml/min/1.73 m22

• AST: 32 U/L• ALT: 24 U/L• Microalb/creatinine: 58.6 Microalb/creatinine: 58.6

mg/g CRTmg/g CRT• LDL-C: 93 mg/dL• TG: 162 mg/dLTG: 162 mg/dL

LABS VALUESUPDATE

Vitals: B/P: 146/90B/P: 146/90, HR: 72 reg, RR: 12 unlabored Ht: 70” Wt: 221 lbs BMI: 31.7 kg/m²BMI: 31.7 kg/m²

General: Obese, well-developed, well-appearing, AAM, A&Ox4, NAD, but

anxious No edema today

PE

• Renal function and metformin:

YOUR CONCERNS

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 functioneGFR better indicator of renal function measured whenever renal disease is suspected or careful dosing of

nephrotoxic drugs is required. eGFR: ≥60≥60 mL/min, no restrictionsno restrictions eGFR 30-5930-59 mL/min: CAUTION (50% dose)CAUTION (50% dose) eGFR <30 <30 mL/min: ABSOLUTE contraindicationABSOLUTE 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.

• 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

AVANDIA: REMSAVANDIA: 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.

• 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

SFU CONCERNS

INCREASED CARDIAC MORTALITY FDA-required warning INHIBITING KATP 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

1st gen SFU and GlyburideGlyburide 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.

• 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

Afraid of needle (insulin or otherwise)Weight gain Inability to exercise/knee painToo many pills/simplify regimen

CHARLES’ CONCERNS

• 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 dailyOR– 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

Only 45% of AAs have controlled BPOverwhelming majority will require combination drugsCombinations MUST have either diuretic or CCB for best

effectPt already taking ACE-I plus diureticPLAN:

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

Encourage lifestyle: diet and no-impactno-impact exercise

BLOOD PRESSURE MGMT DECISIONS

“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

Vitals: B/P: 122/64, HR: 72 reg, RR: 12 unlabored Ht: 70” Wt: 216 lbs (loss of 5#) 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

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

BLOOD SUGAR RECORD

Date

BB AB BL AL BD AD BT

Sun 102 132

Mon 96 128

Tue 80 114

Wed 93 128

Thu 89 137

Fri 100 119

Sat 91 122

Sun 101 135 109 118

Mon 86

• 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