2011acp insulin for internist

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American College of Physicians

Internal Medicine 2011

Insulin for the Internist

MTP 013 A

MTP 013 B

Faculty

Professor: Irl B. Hirsch, MD, FACP

Disclosure: Research Grants/Contracts: Novo Nordisk; Consultantship:

Roche, Bayer, Abbott, Animas;

1.How does one decide when and how (for example, which type of insulin regimen) to initiate insulin?

2.What self-management tools should most patients understand (mealtime dosing and correction-dose

insulin)?

3.How does one decide when adjustments in insulin dosing are appropriate and what tools can be used to

make these decisions?

4.Describe how to interpret downloaded glucose levels and translate them into insulin adjustments.

Clinical questions to be addressed:

©2011 American College of Physicians. All rights reserved. Reproduction of Internal Medicine 2011 presentations, or print or electronic material

associated with presentations, is prohibited without written permission from the ACP.

Posted Date: March 8, 2011



3/3/20

INSULIN FOR THE INTERNIST

Irl B. Hirsch, MD

University of Washington School of

Medicine

Irl B. Hirsch, MDFACULTY DISCLOSURE DECLARATION

FINANCIAL OR OTHER RELATIONSHIP(S)DISCLOSURE:

r. rsc as n ca e a e as a nanc a orother relationships with commercial interests withinthe past 12 months as follows:

Consulting/Speaking/Teaching: Roche, J&J, Bayer,Abbott, Boehinger Ingelheim

Grant/Research Support: Novo Nordisk, MannkindCorp, Halozyme

Impact of Intensive Therapy in DiabetesImpact of Intensive Therapy in Diabetes

Summary of Major Clinical TrialsSummary of Major Clinical Trials

StudyStudy Microvascular Microvascular CVDCVD MortalityMortality

DCCT/EDICDCCT/EDIC ↓↓ ↓↓ ↔↔ ↓↓ ↔↔ ↔↔

UKPDSUKPDS ↓↓ ↓↓ ↔↔ ↓↓ ↔↔ ↓↓

ACCORDACCORD ↓↓ ↔↔ ↑↑

ADVANCEADVANCE ↓↓ ↔↔ ↔↔

VADTVADT ↓↓ ↔↔ ↔↔

Long Term FollowLong Term Follow--upup

Initial TrialInitial Trial

Individualized Targets

The available evidence, albeit limited, suggests

that in younger patients with relatively recent onset

of T2DM and little, if any, micro- and macrovascular

complications, near-normal glycemic targets

should be the standard. Here, the aim is to help

prevent complications over the many years of life.

In older individuals with longstanding T2DM and

evidence of CVD (or multiple CVD risk factors),

somewhat higher targets should be considered.

Ann Intern Med, 2011, in press

Teaching Point 1, Case 1

After 1 year of attempted weight loss andrising A1C levels since his diagnosis, Mr.Henry, 51 years-old agrees it is time to start

insulin. His BMI is 28 kg/m2

, his weight is 80kg, his A1C is 8.8%, and he is currentlyreceiving metformin, glipizide, and sitagliptin.

Decision point 1- WHICH INSULIN/INSULINREGIMEN DO YOU START?

8

9

8.6 8.6

7.5 7.4

Glargine NPH

Mean A1c

%

Treat-to-Target TrialChange of A1c with systematic titration of basal insulin

6

7

0 4 8 12 16 20 24

Weeks of treatment

7.1 7.16.9 6.9 6.9 6.9

58% ≤ 7%

Riddle MC et al. Diabetes Care 2003;26: 3080-86



3/3/20

Consistent results using the Treat-to-Target

method with glargine as basal insulin

Baseline Study end

8.0

8.5

9.09.5

% )

8.6 8.6 8.7 8.78.8

∆ -1.6 ∆ -1.6 ∆ -1.7 ∆ -2.0 ∆ -1.7Teaching Point 1: Most people

1 . R id dl e M et al. Diabetes Care 2003;26:30802. Gerstein HCet al. Diabetes Med 2006;23:7363 . B re tz el R Get al. Lancet 2008;371:1073

4. Yki -Järvinen H et al. Diabetes Care 2007;30:13645 S ch re ib er SA et al. Diabetes Obes Metab 2007;9:31

5.5

6.0

6.5

7.0

7.5

T-T-T1

n = 367INSIGHT2

n = 206

APOLLO3

n = 174INITIATE4

n = 58

Schreiber 5

n = 12,216

H b A 1 C

(

7.0 7.0 7.0 6.8 7.0can reac an < w

basal insulin alone with baseline A1C levels in the mid-8s

A1c change from baseline % of patients attaining <7% A1c

Baseline A1c affects results of basal insulin Rx

2193 patients with 24 weeks systematically titrated glargine added to OAD

75

Riddle MC et al. Diabetes 2009;58(Suppl 1): A125

-0.963

5647

34

-1.4-1.6

-2.0

-2.6

<8.08.0-8.4

8.5-8.99.0-9.4

≥9.5<8.0

8.0-8.48.5-8.9

9.0-9.4≥9.5

75% of participants with baseline A1c <8% attained 7%

A1C (with basal insulin) is

dependent on baseline A1C!

Hypoglycemiaconfirmed <3.9 mmol/L

Hypoglycemiarequiring assistance

Baseline A1c does not affect hypoglycemia risk

2193 patients with 24 weeks systematically titrated glargine added to OAD

50%

Riddle MC et al. Diabetes 2009;58(Suppl 1): A125

<8.08.0-8.4

8.5-8.99.0-9.4

≥9.5 <8.08.0-8.4

8.5-8.99.0-9.4

≥9.5

Titration of insulin was stopped at appropriate levels of risk

1.5%

Back to Mr. Henry

15 units of insulin glargine is started, and over thenext 4 months his dose was titrated to 80 units daily

The metformin, glipizide, and sitagliptin remainedunchanged; on glargine he has gained 3 kg

After bein on the 80 unit dose for 8 weeks 5 months after starting the insulin, his A1C is 7.3%.Fasting glucose levels are generally in the 130-140mg/dL (7.2-7.8 mM) range.

What now? A) Bump glargine to 90 u; B) Splitglargine to 40 u BID; C) SMBG to determine prandialinsulin needs; D) add pioglitazone; E) wait another 4weeks to recheck the A1C

What About Dose Response to Insulin

Glargine in Obese Patients?

20 subjects with type 2 diabetes (A1C 8.3%,

BMI 36 kg/m2) injected single injections ofinsulin glargine into abdomen at 0, 0.5, 1.0,

1.5, and 2.0 units/kg body weight 26-hour euglycemic clamp studies, so

conclusions longer than this time period were

not possible

Wang Z. Diabetes Care . 2010;33:1555-1560.

Glucose Infusion Rates (GIRs) for Different

Glargine Doses Injected into Abdomen

1.5units/kg

2.0 units/kg0.5 units/kg

1.0, 1.5, and 2.0 units/kg > GIRthan 0.5 units/kg, but not thaneach other!

1.0 units/kg

TEACHING POINT 3: although it is

possible duration of insulin action is

rolon ed with increasin doses of

placebo

glargine, there is no difference is insulin

action the 24 h after injection once dose

is > 1.0 u/kg



3/3/20

NOW WHAT?

What to do with the glargine?

What to do with prandial insulin?

What to do with metformin, glipizide, and

sitagliptin?

What’s Next?

Glargine is reduced to 70 units q HS

Insulin aspart is started at dinner, 10 units(10-15 min prior to dinner)

Correction dose for an re-meal BG: ISF 30

above 150

150-180 +1 unit 241-270 +4 units

181-210 +2 units 271-300 + 5 units

211-240 + 3 units 301-330 + 6 units

Sitagliptin is stopped!

NOW WHAT TO SUGGEST?

B’FAST LUNCH DINNER HS 0300

MON 116 162

10+1

221

70G

TUE 125 142

10

207

70G

WED 107 196

10+2

238

70G

THU 158 185

10+2

224

70G

How Has Our Ability To Capture Home

Glucose Data Changed Over The Past

Why the Interest In Glycemic

Variability?

Experimental data suggests an increase in

oxidative stress and activation of

inflammation

vascular complications

For those on insulin high variability predicts

severe hypoglycemia

A marker of insulin deficiency and poor

matching of prandial insulin to carbohydrate

load

Which Patient Has More Variable

Fasting Glucose Data?

60 54

148 286

70 203

Joe: HbA1c = 6.5%; on

liraglutide

Mary: HbA1c = 6.5%; on

metformin

= =165 112

110 69

185 68

210 138

144 192

75 114

138 52

SD = 51 SD = 77



3/3/20

Standard Deviation

Our clinically available measurement ofglycemic variability

Many other statistical analysis areavailable but correlation will be with CGM and outcomes, not SMBG

Can determine both overall and timespecific SD

Need sufficient data points

Minimum 5 but prefer 10

Calculation To Determine SD Target

SD X 2 < MEAN (T1DM)SD X 2 < MEAN (T1DM)

Significance of a High SD

Insulin deficiency (especially good with fasting bloodglucose)

Poor matching of calories (especially carbohydrates)with insulin

v ng mea t me nsu n ate or m ssng s otscompletely)

Erratic snacking

Poor matching of basal insulin, need for CSII?CGM?

Caveats of the SD

Need sufficient SMBG data

Low or high averages makes the 2XSD<mean

Other Tricks To Reduce GV

Enough testing

Don’t over-treat the lows!

Reduce carbs Pramlintide

Lag times

Timing of Rapid-Acting Analog Insulin Injection

Alters PPG in Type 1 Diabetes Mellitus

L )

288

252

216

–30 m –15 m

0 m

+15 m

Injection-Meal Interval(minutes)

Insulin Lispro

L )

288

252

216

–20 m0 m

+20 m

Insulin Glulisine Injection-Meal Interval(minutes)

300

Rassam AG, et al. Diabetes Care . 1999;22:133-136.Cobry E, et al. Diabetes Technol Ther . 2010;12:173-177.

8.6 kcal/kg breakfast

Minutes

B G L e v e l ( m g /

180

144

108

72

36

0-30 0 30 60 24090 270120 150 180 210 300

Standardized breakfast

Minutes

B G L e v e l ( m g /

180

144

108

72

36

0-30 0 30 60 24090 270120 150 180 210



3/3/20

Now…Back to Mr. Henry

He is currently taking insulin glargine, 50 u q

HS with premeal insulin aspart, 2-5 u acbreakfast, 10-15 units ac lunch and dinner

corrects 25 mg/dL) above 150 before meals,

200 at HS.

A1C = 6.7%

What does the meter download suggest?

Mr. Henry’s Download Statistics

Summary (30 days)Frequency of testing = 3.2X/day

Fasting mean/SD: 114 + 24AC lunch mean/SD: 122 + 42AC dinner mean/SD 140 + 49HS mean/SD: 179 + 88Overall: 135 + 42

Conclusions:

1. Still too much basal insulin

2. Needs help with dosing at dinner (missing doses?)

3. Still making lots of insulin!

4. Need to look at downloaded “logbook” to understand specifics (insulin not yet

downloadable) and if ISF is correct

Teaching Point 4

Downloading of glucose data isextremely helpful to see patterns nototherwise noted for those checkinmore than 2X/day. These downloadswill become more accessible over the

next few years with the use of tabletsand smartphones

Mr. Jay Hawk

A 56 year-old mildly mentally retarded Caucasian manpresents with a random blood glucose found to be 435mg/dL. There is no family history of diabetes.

He lives with his brother who mentions nocturia and 10pound weight loss over the past month. The patient’sonly complaint is erectile dysfunction.

Exam is significant for a BMI of 32 kg/m2, BP 155/95,HR 88, mild acanthosis nigricans, normal fundi andvibratory sensation on his great toes.

Mr. Jay Hawk, cont

Glucose 435 mg/dL (24.1mM), all otherelectrolytes WNL except sodium of 133.

HbA1C 14.0% (normal 4-6%)

r ne e ones: nega ve

What would you suggest at this time?

A) Begin combination glipizide/pioglitazoneB) Begin basal-bolus insulin

C) Begin basal insulin alone

D) Begin twice daily NPH/regular

Ms. O. Duck

Ms. Duck is a 54 year-old woman who will be having a

pancreatectomy . What will you tell her she will

require for insulin therapy after his surgery?

A.Basal insulin alone

B.Pre-mix insulin, 0.5 u/kg

C.Basal-bolus insulin, 0.7 u/kg

D.Basal-bolus insulin, 0.25 u/kg

E. GLP-1 receptor agonist



3/3/20

Mr. CO Interest

Mr. Interest, also called COI, is an 81 year-old nursing

home patient. He has a known 10 year history of type 2diabetes and suffers from Alzheimer’s Disease andheart failure from a previous MI

pounds.

For his diabetes he receives glyburide 10 mg BID

His A1C is 10.4%. BID glucose testing shows all levelsbetween 220 and 280 mg/dL

Other lab: creatinine 1.4, BUN 25, LDL-C 59

COI (cont)

What to do now?

A) Nothing

B) Add a GLP-1 agonist

C) Add a thiazolidinedione

D) Add basal insulin

E) Begin basal-bolus insulin therap;y

Mrs. PIA

You receive a call at 5pm on a Friday from

Mrs Pia that she needs a new prescription

for insulin syringes. She takes 60 units of

uses a short insulin needle

What kind of insulin syringe to you call for

her?

2011acp insulin for internist

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