Diabetes and Nephrology

8/13/2019 Diabetes and Nephrology

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DIABETIC NEPHROPATHY

DR PRASHANT BENDRE,DM(NEPHRO)


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COMPLICATIONS (ADA)

Eye 12,000-24,000 loose sight due to diabetes;leading cause of new blindness in 20-74 yrsage.

Kidneys 10-21% of diabetics have kidney disorder;

diabetic nephropathy-most common cause

of end stage renal disease.Heart 2-4 times more incidence of heart disease.

Stroke 2-4 times more incidence of stroke.

Nerve disease & amputation 60-70% pts have mild to severe nervedamage, most common cause of non

traumatic lower leg amputation.

Impotence 13% in Type 1

8% in Type 2

men 50 yrs, impotence rate 50-60%


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NEPHROPATHY


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NEPHROPATHY


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Intensive Therapy ReducesRisk of Retinopathy and Nephropathy

DCCT

Retinopathy MicroalbuminuriaCumulativepercent

progressing

DCCT Research Group. N Engl J Med. 1993;329:977-986

00

60

50

40

3020

10

0

-76%

P


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Intensive Insulin Therapy Reduces Risk ofRetinopathy and Nephropathy

Kumamoto Study

Ohkubo Y et al. Diabetes Res Clin Pract.1995;28:103-117

Cumulative

percent

progressing

40

30

2010

0

Years

0 1 2 3 4 5 6

Microalbuminuria

Secondary Intervention

-62%

P=0.032

-52%

P=0.044

Conventional therapyIntensive therapy

40

30

20

10

0

50

40

30

2010

0

50

40

30

20

10

0

0 1 2 3 4 5 6

Retinopathy

Secondary Intervention

-76%

P=0.039

-56%

P=0.049

Primary PreventionPrimary Prevention


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DCCT Research Group. N Engl J Med. 1993;329:977-986;Ohkubo Y et al. Diabetes Res Clin Pract.1995;28:103-117

Intensive Insulin TherapyMicrovascular Risk Reductionin Two Trials

Complication Reduction in Risk With 2%Reduction of A1C

Study DCCT Kumamoto

Retinopathy 63% 69%

Nephropathy 54%* 70%

Neuropathy 60% Significantlyimproved

* Albuminuria >300 mg/24 hrWorsening of albuminuria >300 mg/24 hr


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Relative Risk of the Development of

Diabetic Complications

Variable Relative risk P Value(95% CI)

Nephropathy 0.39 (0.17-0.87) 0.003Retinopathy 0.42 (0.21-0.86) 0.02

Autonomic 0.37 (0.18-0.79) 0.002neuropathy

Peripheral 1.09 (0.54-2.22) 0.66

neuropathy

IntensiveTherapyBetter

ConventionalTherapyBetter

0.0 0.51.0 1.5 2.0 2.5

Steno-2 Study, NEJM, Jan 2003


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Insulin Therapy Nephro Patients


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Subcutaneous Insulin Therapy in Hospitalized

Patients

Effective for in-hospital glycemic control

Patients can be transitioned from IV insulin tosubcutaneous insulin

Dose is easily adjusted to individual patient needs and

nutritional status Subcutaneous insulin is currently being studied as an

alternative to IV insulin in the management of patientswith diabetic ketoacidosis

Clement S et al. Diabetes Care. 2004;27:553-591.Umpierrez GE et al. Diabetes Care.2004;27:1873-1878.


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Limitations of Sliding Scale

Insulin Regimens

Dose in reaction to a single retrospective bloodglucose measurement

Does not provide basal insulin coverage

Provides supplemental insulin after hyperglycemia

occurs Does not consider nutritional changes or diurnal

insulin requirements

Nonphysiologic dosing places patients at risk of largefluctuations in blood glucose levels

- Increased incidence of hyperglycemic and hypoglycemic episodes

Queale WS et al.Arch Intern Med. 1997;157:545-552.


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Types of Subcutaneous Insulin for

Optimal Glycemic Control

Subcutaneous insulin scheduled to meet total dailyinsulin requirement

- Basal component

Continuous subcutaneous insulin infusion (CSII)

Long-acting insulin (insulin glargine)

Intermediate-acting insulin (NPH insulin)

- Prandial/nutritional componentshort-acting or rapid-

acting insulins

Humalog (insulin lispro), insulin aspart, insulin glulisine- Supplemental componentrapid-acting insulin

Adapted from: Clement S et al. Diabetes Care. 2004;27:553-591.


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Comparison of Human Insulins

and Analogues

Insulin Onset of Duration ofPreparations Action Peak (h) Action (h)

Lispro/Aspart/Glulisine 5-15 min 1-2 3-6

Regular

human 30-60 min 2-4 6-10HumanNPH/Lente 1-2 h 4-8 10-20

HumanUltralente 2-4 h 10-16 16-20

Insulin glargine 1-2 h flat ~24

Time course of action of any insulin can vary in different people or atdifferent times in the same person; thus, time periods indicated here shouldbe considered general guidelines only.

Mudaliar S et al. Endocrinol Metab Clin North Am. 2001;30:935-982.

Th Ri k f S H l i i I t i l T t d T 1


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The Risk o f Severe Hypoglyc emia in Intensiv ely Treated Type 1

(DCCT)

62

19

H

ypoglycemic

events

per100pt-y

ears Intensive

Conventional

Both arms received human insulin in non-hospital setting


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Regular Insulin Has Significant Activity

Beyond Four Hours After Injection

Time (hours)

0 1 2 3 4 5 6 7 8 9 10 11 12

M

eanglucoseinfu

sionrate

(mg/min)

500

400

300

200

100

0

600

46% of total activity of regular

insulin occurs after 4 hours

Glucose

Regular

Human

Insulin


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Insulin lispro Insulin glargine

Basal-Bolus Insulin Therapy

( Should Mimic the normal physiology)

Breakfast DinnerLunch Bedtime

InsulinEffect

Leahy JL. Insulin Therapy. Marcel Dekker Inc; 2002:87-112.


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ANALOGS


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[Lys (B28), Pro (B29)] - Human Insulin Analog (recombinantDNA origin)

B28

LYS

B29

PRO

S

S

S S

S

S

A-chain

B-chain

1

1

21

30

Humalog (insulin lispro injection [rDNA origin])

Analog insulins

Modify time action of human insulin toward a more physiologic

profile

Improve patient convenience

See Important Safety Information included in this presentation.


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Dissociation of Insulins

Regular Human Insulin

10-3M 10-3M 10-5M 10-8M

Formulation

Capillary membranHumalog

10-3M 10-3M 10-3M

Formulation Transient

Peak time

1 hr

Peak time

2-4 hr

Ciszak E et al. Structure1995;3:615-622.


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0 1 2 3 4 5 6 7 8

9 10 11 12

5

4

3

2

1

0

Time (Hours)

Humalog (insulin lispro injection [rDNA origin])

Regular human Insulin

SerumI

nsulinLevels(ng/mL)

(N=10)

Howey DC, et al. Diabetes1994; 43:396-402.

Serum Insulin Levels After

Subcutaneous Injection in Healthy Volunteers

Humalog Resulted in Rapid Increase


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Data derived from Heinemann L et al. Diabetic Medicine.1996;13:625-629.

HumalogResulted in Rapid Increasein Insulin After Test Meal

Baseline insulin concentration was maintained by infusion of 0.2 mU/min/kg human insulin.

Mean SEM

Time (minutes)

HumalogHumulinR

Plasm

ainsulinconcentration(ng/mL)

0.0

0.5

1.0

1.5

2.0

2.5

3.0

-60

SC insulin injection + meal

60 120 180 240 300 360 420 480

With Humalog, insulin concentrations peaked at

68 18 min vs. 116 27 min with regular human

insulin after a high-fat, high-calorie meal

(pizza, cola, dessert) and returned to baseline

faster

0

N=10 type 1 pts


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Limitations of Human NPH,

Lente, and Ultralente

Do not mimic normal basal insulin secretion profile

- Variable absorption

- Pronounced peaks

-


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Switching from IV to Subcutaneous Insulin

IV insulin has a short half-life (


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Switching from IV to Subcutaneous Insulin

Initiate prandial doses of rapid-acting analog with the first dietarytray, even if patient is on an intravenous insulin infusion

Establish 24-hour insulin requirement

Calculate the total daily dose of subcutaneous insulinat 80% of the projected 24-hour insulin requirement

Stop intravenous infusion of insulin 2 hours after first basalinsulindose of insulin glargine

Monitor BG preprandially, 2 hours postprandially, at bedtime, andat 3:00 AM

Adjust total 24-hour dose of insulin daily

Campbell KB et al. Clinical Diabetes. 2004:22:81-88.

Clement S et al. Diabetes Care.2004;27:553-591.Bode BW et al. Endoc Pract. 2004;10(suppl 2):71-80.


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Guidelines for Supplemental Insulin

Insulin glulisine, lispro, or aspart are administered onlyat mealtime(s)

- Prevent or correct blood glucose levels outside 120 to

180 mg/dL

Type 1 diabetes: add 1 unit of insulin for every 50mg/dL over 180 mg/dL

Type 2 diabetes: add 1 unit for every 30 mg/dL over180 mg/dL*

Insulin-resistant patients: initially add 1 unit for every

20 mg/dL over 180 mg/dL

Hirsch IB. Insulin in the Hospital Setting. Adelphi Inc; 2002.

*Same dose as type 1 for conservative approach.


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Efficacy of Humalog

Compared to regular insulin

Humalog returns glucoseconcentrations to premealvalues in half the time1

The rise in 2-hourpostprandial glucose was53% lower with Humalogcompared toregular insulin2

Humalog produces 40%fewer nocturnalhypoglycemic episodes3

1. Heinemann L et al. Diabet Med.1996;13(7):625-629.2. Anderson JH Jr et al.Arch Intern Med.1997;157(11):1259-1255.3. Anderson JH Jr, et al. Diabetes.1997;46(2):265-270.

Time (Minutes)

BloodGlucose

(mg/dL)1

0 30 60 90 120 150 180 210 240

Regularinsulin

N=1020

0

15

0

10

0

Meal+sc insulin injectionHumalog

Baseline insulin concentration was maintained by infusion of 0.2 mU/min/kg human insulin


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Humalog vs Regular: A1C Reduction

Patients using

CSII

Superior A1C

reduction with

Humalog vs

regular

Humalog Regular

(N=39)

-0.6

-0.3

-0.7

-0.6

-0.5

-0.4

-0.3

-0.2

-0.1

0

Dec

reaseinA1C(%)

1. Patients in the Humalog group had greater reductions in A1C than patients who

remained on regular insulin.

2. When used in and external insulin pump, Humalog should not be diluted or mixed

with any other insulin.

3. Use of Humalog with pumps improves glycemic control without an increase in risk

of hypoglycemia.

2-Hour Postprandial Glucose Excursions With


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HumulinR / Humalog(n = 467)

Humalog/ HumulinR (n = 455)

GlucoseExcursion(mmol/L)

ean 95% C.I.

Months

2-Hour Postprandial Glucose Excursions WithInsulin Lispro and Regular Human Insulin in T 1DM

***p


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Hospital Discharge Transition:

Patients With Diabetes

Start new insulin regimen prior to discharge

- Stabilize blood glucose prior to discharge

- Obtain A1C for discharge planning if result not available for the

previous 2-3 months

- Refer patient to a certified diabetes educator (CDE)

- Provide specific instructions on medication use

- Provide instruction on glucose monitoring

- Provide instruction on hypoglycemia prevention

- Schedule a follow-up visit

Initiation of insulin at discharge can improve woundcontrol

Clement S et al. Diabetes Care. 2004;27:553-591.Lien LF et al. Med Clin North Am.2004;88:1085-1105.


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Summary

Aggressive glycemic management and follow-up ofhospitalized patients with elevated blood glucose

levelsis critical for

- Optimal glycemic control while in the hospital

- Improved hospital outcomes

- Early detection of diabetes in patients with hyperglycemia after

discharge Insulin should be used as the treatment of choice for

optimal management of hyperglycemia in the hospital


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Summary (cont)

Maintaining tight glycemic control with IV orsubcutaneous (SC) insulin in the hospital can

-Significantly improve outcomes for mortality and morbidity

- Significantly reduce direct and indirect costs currently associated

with uncontrolled hyperglycemia in the

hospital setting

Diabetes education, medical nutrition therapy, and

discharge planning are also essential components ofhospital care


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Humalog offers particular advantages in hospitalized Nephro patients

Rapid acting, therefore less chances of hypoglycemia relative to regular human insulin

because of shorter residence time

Better postprandial control compared to regular human insulin

Flexible Dosing

Can be injected immediately before meals; convenient in hospital setting

Can be injected after meals. This is of particular advantage in situations where food

intake is erratic or unpredictable

Available in easy and simple to use disposable pens

Summary (cont)

Documents

Diabetes and Nephrology