Inpatient Management of Diabetes Mellitus

William Harper, MD, FRCPC

Endocrinology & Metabolism

Assistant Professor of Medicine, McMaster University

BS > 11.1 mmol/L

Renal threshold for glycosuria (normal GFR)

Decreased WBC functionChemotaxsisPhagocytosis

Decreased Wound Healing

Evidence to support Inpatient BS control?

DIGAMI• 620 patients AMI, prior dx DM or BS > 11 mM• IV insulin gtt started @ 5 U/h• Titrated to keep BS 7-10.9 mM• Insulin IV > 24h MDI > 3 months• No in-hospital mortality benefit.• Rx Increased hospitalization by 1.8d• 0.5% reduction HbA1c @ 3 months• @ 1 year % on Insulin: 72% Rx Group 49% Cntrl Group• 1 year mort: ARR 7.5% NNT 13• 3.4 y mort: ARR 11% NNT 9

Evidence to support Inpatient BS control?

Leuven, Belgium Study• 1548 ICU patients (63% CV Sx)• If BS > 6.1 mM: Rx with IV insulin gtt & TPN +/- tube feeds• Start IV insulin @ 2-4 U/h, titrated to BS 4.4-6.1 mM• Ave insulin dose: Rx group 3.0 U/h Cntrl group 1.4 U/h• Once out of ICU relaxed treatment goal to < 11.1 mM• Mortality in ICU: ARR 3.4% NNT 29• Mortality in-hospital: ARR 3.7% NNT 27• Greatest reduction in mortality was sepsis-related.• Insulin Rx reduced: bacteremia, ARF needing HD, need for PRBC,

critical illness polyneuropathy, duration of ventilation and length of stay in ICU

• To what extent were benefits nutrition related as opposed to insulin related?

Goals of Inpatient DM Management

• “Avoid hypoglycemia and marked hyperglycemia”

• Target BS: 7.0 - 11.0 mM (5.0 – 10.0 mM)

• Avoid Hypoglycemia

• Precipitating arrhythmia or other cardiac events

• Inducing seizure, focal or cognitive defects periop

• Avoid Marked Hyperglycemia (BS > 11.1 mM)

• Treat (and avoid) DKA, HONC

DM Inpatient Management

1. Eating

2. NPO: temporary (for a test or surgery)

3. NPO: prolonged

DM Inpatient Management

1. Eating Diet (T2DM)

OHA (T2DM)

Insulin (T2DM and T1DM)

2. NPO: temporary (for a test or surgery)

3. NPO: prolonged

Pathophysiology of T2DM

Blood glucose

diet

Hepatic glucose output INSULIN

PeripheralTissueUptake

+

_

GLUCOSE ABSORPTION

GLUCOSE PRODUCTION

Metformin Thiazolidinediones

MUSCLE

PERIPHERAL GLUCOSE UPTAKE Thiazolidinediones Metformin

PANCREAS

INSULIN SECRETION Sulfonylureas: Glyburide, Gliclazide, Glimepiride Non-SU Secretagogues: Repaglinide, Nateglinide

ADIPOSE TISSUELIVER

Alpha-glucosidase inhibitors

INTESTINE

Sites of Action of Currently Available Therapeutic Options

OHAs: Drug BG HbA1c Side-effects

Sulfonylurea FBG 20% 1.0-2.0% Hypoglycemia

Weight gain

Biguanide FBG 2.8-3.9 mM 1.0-2.0% Lactic acidosis

GI intolerance

TZD FBG 2.2-3.6 mM 1.0-1.5% Edema

Weight gain

Liver monitoring

Meglitinide FPG 4 mM

PPG 5.6 mM1.0-2.0% Hypoglycemia

(50% < SU)

α-glucosidase Inhibitor

FPG 14%

PPG 25%0.5-1.0% GI intolerance

Drug Trade Dose Cost ODB

Glyburide Diabeta Start 1.25-5 mg od

Spit dose bid > 10mg/d

Max 10 mg bid

$14/mos Yes

Gliclazide Diamicron Start 80 mg bid

Max 160 mg bid$90/mos No

Gliclazide

MRDiamicron

MR

Start 30 mg od

Max 120 mg od$30/mos Exp Sect 8

Glimepiride Amaryl Start 1-2 mg od

Max 8 mg od$30-40/mos No

Repaglinide Gluconorm Start 0.5 mg tid-qid

Max 4 mg qid$45/mos Exp Sect 8

Nateglinide Starlix Start 60-120 mg tid

Max 180 mg tid$45/mos Exp Sect 8

Metformin Glucophage Start 500 mg od-bid

Max 1000 mg bid$14/mos Yes

Pioglitazone Actos Start 15 mg od

Max 45 mg od $115/mos

Exp Sect 8

Rosiglitazone Avandia Start 4 mg od

Max 4 mg bid$ 60/mos

$ 120/mos

Exp Sect 8

TZD adverse effects

• Edema• 4-5% of patients get mild-moderate edema• 15% if TZD used in combo with insulin

• Mild anemia (dilutional)• Weight gain

• Increase in subcutaneous not visceral fat

• Myalgia (pioglitazone only)• Myalgia 5.4% pioglitaz. versus 2.7% placebo• Few patients with unexplained CK > 10x ULN

• Contraindicated in class II, III and IV CHF

• Contraindicated if ALT > 2.5x ULN or active liver disease

Metformin

• Contraindications:• Creatinine >133 uM (men), >124 uM (women), CrCl < 1.17 mL/s

• CHF symptomatic (> NYHA class III, E.F. < 35-40%)

• Liver failure

• Alcoholism

• Hypoxic respiratory condition

• Active moderate to severe infection

• Radiocontrast or Surgery with GA:– Hold metformin for 24-48h

– Restart after documented preservation of renal function

Metformin

• Side effects:• Lactic acidosis (metformin 0.03 cases/1000 patient years)

– Phenformin 10-20X higher rates of lactic acidosis

• GI: diarrhea, flatulence, abdominal discomfort– Usually disappear within 2 weeks

– Dose dependent: avoided by slow titration & in some cases dose reduction

– 5% of patients can’t tolerate metformin due to GI S/E’s

• Starting dose: 500 mg with largest meal (prevent GI S/E’s)

• Increase by 500 mg increments q1-2 wk

• Maximal hypoglycemic affect: 1000 mg bid

Insulin

Type Starts Peaks Duration

Humalog

NovoRapid

5-10 min 0.5-1hrs 3.5 hrs

Regular 30 min 2-4 hrs 6-8 hrs

NPH

Lente

1-2 hrs 6-10 hrs 16-24 hrs

Ultralente 4-6 hrs 8-24 hrs 24-36 hrs

Glargine 1.5h None Up to 24 hrs

BIDS Therapy

• T2DM: “Introduction to insulin”

• Keep on OHAs

• Start NPH 0.2 U/kg SC qhs

• Increase by 2-4 U q4d until FBS 4-7

• If dose > 30-40U or if BS high late in day despite OK FBS than split into 2 injections with 2/3 acB and 1/3 qhs

Starting Insulin Regimen• TDD = 0.5-0.7 U/kg

• “2/3, 1/3” Regimens• 2/3 of TDD acB, 1/3 acD

• 2/3 of TDD as Long-acting, 1/3 as short acting

• Pre-mix: acB 30/70 acD 30/70

• MDI Regimens• 2/3, 1/3 Regimen: move acD long acting to qhs

• i.e. acB N, H acD H qhs N

• ac meals H qhs N (bolus 60%, basal 40%)

• ac meals H UL q12h (bolus 50%, basal 50%)

Insulin Regimens

acB acL acD qhs

Bedtime NPH (+/-bids) N

NPH bid N N

30/70 bid 30/70 30/70

MDI (3 injections) H + N H N

MDI (>4 injections) H (+/-N) H H N

MDI (>4 injections) H + UL H H UL

CSII (Insulin Pump)

NEJM 347:1342-9

acB acL acD qhs Rx

22

(5R)

9 3.1

(O.J.)

15 acB N20 R10

acD R5

qhs N10

20 15 7 8 acB N20 R10

acD R5

qhs N10

22 17(RN calls)

acB N20 R10

Surgeon: ?Internal Medicine: ?Endocrinologist: ?

acB acL acD qhs Rx

22

(5R)

9 3.1

(O.J.)

15 acB N20 R10

acD R5

qhs N10

20 15 7 8 acB N20 R10

acD R5

qhs N10

22 17(RN calls)

acB N20 R10

Surgeon: Give 5 U Regular SC now

Internist: ?

Endocrine: ?

acB acL acD qhs Rx

22

(5R)

9 3.1

(O.J.)

15 acB N20 R10

acD R5

qhs N10

20 15 7 8 acB N20 R10

acD R5

qhs N10

22 17(RN calls)

acB N20 R10

Surgeon: Give 5 U Regular SC now

Internist: Increase qhs N to 12 tonight and acB R to 12 tomorrow

Endocrine: ?

acB acL acD qhs Rx

22

(5R)

9 3.1

(O.J.)

15 acB N20 R10

acD R5

qhs N10

20 15 7 8 acB N20 R10

acD R5

qhs N10

22 17(RN calls)

acB N20 R10

Surgeon: Give 5 U Regular SC now

Internist: Increase qhs N to 12 tonight and acB R to 12 tomorrow

Endocrine: Increase qhs N to 12 start tonightDecrease acB N15 R7 starting tomorrow AMCheck 3AM BS tonight

Guideline for Insulin Adjustments

1. Adjust the insulin that accounts for the high or low reading.

2. Always compare an abnormal BS reading with the one previous.

3. If insulin dose is:• Less than 8U, adjust by 1U

• 8-20U, adjust by 2U

• > 20 U, adjust by 10% (increase), 20% (decrease)

4. Don’t forget to compensate for a successful adjustment

SC Insulin Supplemental Scale

CBG Action

< 4.0 Call MD

4.1-10.0 nil

10.1-12.0 Humalog 2 U SC

12.1-14.0 Humalog 4 U SC

14.1-16.0 Humalog 6 U SC

16.1-18.0 Humalog 8 U SC

18.1-20.0 Humalog 10 U SC

> 20.0 Call MD

DM Inpatient Management

1. Eating

2. NPO: temporary (for a test)

3. NPO: prolonged

NPO for a test: T2DM on Diet Rx or OHA

• Schedule test for the AM

• Hold OHAs on AM of test

• CBG @ 7AM:

< 3.0 Consider postpone test

3.1-4.0 IV D5W gtt @ 75-100 cc/h

4.1-11.0 Proceed with test, no Rx necessary

> 11.1 Insulin R or analogue SC supplemental

or

IV insulin gtt & IV D5W gtt @ 75-100 cc/h

> 20.0 Check urine ketones, consider postpone test

Insulin IV gtt

• Add 50 U of Human regular insulin (Humulin R or Novolin Toronto) to 500cc D5W (1U/10cc).

• Flush & discard first 50cc.• Infuse insulin solution by IVAC (intravenous

infusion pump), piggybacked into D5W running at 100cc/h.

• Start insulin @ 0.9 U/h (9cc/h) or start at a rate dependent on patient’s insulin dose: IV insulin gtt rate = ( ½ TDD ) / 24

Insulin IV gtt

CPG q1h x 2, then q2h:

Adjust Insulin IV infusion rate as per scale below:

< 4.0 Call MD

4.1-6.0 0.5 U/h (5cc/h)

6.1-8.0 1.0 U/h (10cc/h)

8.1-10.0 1.5 U/h (15cc/h)

10.1-12.0 2.0 U/h (20cc/h)

12.1-15.0 2.5 U/h (25cc/h)

15.1-18.1 3.0 U/h (30cc/h)

18.1-22.0 3.5 U/h (35cc/h)

> 22.1 Call MD

NPO for a test: T1/T2DM on Insulin

• Schedule the test for the AM

• Hold AM Insulin on day of test

• CBG @ 7AM:

< 3.0 Consider postpone test

3.1-11.0 Give ½ of total AM insulin dose as NPH SC

IV D5W gtt @ 75-100 cc/h

> 11.1 IV insulin gtt & IV D5W gtt @ 75-100 cc/h

> 20.0 Check urine ketones, consider postpone test

DM Inpatient Management

1. Eating

2. NPO: temporary (for a test)

3. NPO: prolonged• Patient put on D5W if not on feeds or TPN

• IV insulin gtt

• SC NPH or UL q12h (+/- supplemental scale)» Starting dose 0.2 U/Kg q12h