Diabetes Mellitus Today

DIABETES MELLITUS TODAY DIANA W. GUTHRIE RN, PhD 2006

DEFINITION & THE PROBLEM • • • • • •

CRITERIA FOR DIAGNOSIS DEFINITION PATHOPHYSIOLOGY PREVALENCE OBESITY METABOLIC SYNDROME

Glucose Tolerance Categories mg/d L 100 and <126

<100

FP G Diabetes Mellitus

Prediabet Glucos e es Norm al

mg/d L 140 and

< 140

2-hr PG on OGTT Diabetes Mellitus

Prediabet Toleranc e es Norm al

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2002;25(suppl):S5

Etiologic Classification of Diabetes Mellitus lack of

insulin

Type 1 -cell destruction with insulin Type 2 Insulin resistance with deficiency

Other specific Genetic defects in -cell Types exocrine pancreas diseases,

Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-

Diabetes Trends* Among Adults in the U.S., (Includes Gestational Diabetes) 19 90

19 95

20 01

Source: Mokdad et al., Diabetes Care 2000;23:1278-83; J Am Med Assoc 2001;286:10.

Prevalence of Diabetes in Adults

<4%  

      4–6%            

Obesity Trends* Among U.S. Adults BRFSS, 1991-2002 (*BMI ≥30, or ~ 30 lbs overweight for 5’ 4”

1

1

2

No Data

<10%

10%–14%

15%–19%

20%–24%

DNPA DNPA Graphics: Graphics:

Diabetes Trends* Among Adults in the U.S., (Includes Gestational Diabetes)

Source: Mokdad et al., J Am Med Assoc 2001;286:10.

Obesity Trends* Among U.S. Adults BRFSS, 2002 (*BMI(*BMI ≥30, oror~ 30lbs lbs overweight 5’ 4” 30, ~ 30 overweight for 5’4” for person)

No Data

<10%

10%–14%

15%–19%

20%–24%

Source: Behavioral Risk Factor Surveillance System, CDC

GLOBAL  PROJECTIONS FOR THE  DIABETES EPIDEMIC: 2003­2025 (millions)

World 2003 = 194 million

2025 = 333 million Increase 72%

Diabetes Today: An Epidemic

• 20.8 million Americans have diabetes • 1.5 million new cases in 2005 more than 3500 each day • Complications of diabetes are a major cause of mortality and morbidity (2002 statistics) 90% of patients with diabetes are treated by primary care physicians

ADA National Diabetes Fact Sheet. Available at: http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2005.pdf. Accessed April 11, 2005; ADA Diabetes Statistics. Available at http://www.diabetes.org/utils/printthispage.jsp?PageID=STATISTICS_233181. December 29, 2005.

Total Cost of Diabetes in the US, 2002 Total Cost $132 billion

Outpatient care/ home health & medications $37.1 billion

Nursing home & hospice $14.4 billion

Mortality $21.5 billion

Disability $18.3 billion

Inpatient care $40.3 billion

Health Care Expenditures $91.8 billion American Diabetes Association. Diabetes Care. 2003;26(3):917-932.

Indirect Costs $39.8 billion

The Problem

Modern Life Has Both Conveniences

Illustration taken from: Lambert C, Bing C. The Way We Eat Now. Harvard Magazine. May-June, 2004;50.

METABOLIC SYNDROME • • • • • • •

Obesity- high waist to hip ratio Hyperlipidemia Hyperinsulinemia Hypertension Hyperglycemia Acanthosis Nigricans PCOS

ACANTHOSIS NIGRICANS

ACANTHOSIS NIGRICANS

ACANTHOSIS NIGRICANS

Waist/Hip Ratio An Index of Abdominal Versus

High WHR ( 

Low WHR (  American Diabetes Association

Visceral Fat Distribution Normal vs Type 2 Diabetes

Normal

Type 2 Diabetes

Courtesy of Wilfred Y. Fujimoto, MD.

And America Continues to Enjoy Strong Economic Growth……………………………..

Course of Type 2 Diabetes 350 – 300

Glucos e (mg/dL

Relativ e Functio n

Obesit y

I FG

Uncontrolled Hyperglyce mia

Diabet es Postmeal Glucose

– 250 – 200

Fasting Glucose

– 150 – 100 – 50 – 250 – 200 – 150 – 100 – 50 – 0 –

Insulin Resistance

-cell Failure

-1 0 5 1 1 2 2 3 0 5 0 5 0 5 0 Years of Diabetes *IFG=impaired fasting glucose. Burger HG, Loriaux DL, Marshall JC, Melmed S, Odell WD, Potts JT, Jr., Rubenstein AH. 2001. Diabetes Mellitus, Carbohydrate Metabolism, and Lipid Disorders. Chap. in Endocrinology. 4th ed. Edited by Leslie J. DeGroot and J. Larry Jameson. Vol. 1. Philadelphia: W.B. Saunders Co. Originally published in Type 2 Diabetes BASICS. (Minneapolis, International Diabetes Center, 2000).

Factors That May Drive the Progressive Decline of Beta-cell Hyperglycemia (glucose toxicity)

 cell

Insulin Resistanc e

“Lipotoxicity” (elevated FFA*, TG*)

*FFA=free fatty acids; TG=triglycerides. Adapted from: Kahn SE. J Clin Endocrinol Metab. 2001;86(9):4047-4058. Adapted from: Ludwig DS. JAMA. 2002;287(18):2414-2423.

Progression to Type 2 Diabetes Insulin resistance

Genetic Factors

Hyperinsuline mia

Acquired: •Obesity •Sedentary lifestyle •Aging

Compensated insulin resistance Normal glucose tolerance

ß-cell decompensation Impaired glucose tolerance

Genetic Factors Kruszynska Y, Olefsky JM. J Invest Med. Med. 1996;44:413-428. Weyer C, et al. J Clin Invest. 1999;104:787-794.

ß-cell “failure”

Type 2 diabetes

Glucose and/or fat toxicity

The Importance of Targeting Insulin Resistance Over 90% of type 2 diabetics are Insulin Resistant Complex Dyslipidem ia  TG, sdLDL Disordere d Fibrinolys

Hypertensi on

Endothelia l Dysfuncti

Insulin Resistance

2 of the American Adapted from the Consensus Development Type Conference Diabetes Association. Diabetes Diabetes Care. 1998;21(2):310-314.

Systemic Inflammati on

Atheroscleros is Viscer al Obesit

ETIOLOGY OF T1DM

DQ*

D

C

B

A

SHORT ARM # 6 CHROMOSOME

IMPORTANCE OF GLUCOSE CONTROL • • • •

DCCT KUMAMOTO UKPDS IN-PATIENT CONTROL

Complications of Diabetes Macrovascul ar

Brain Cerebrovascular disease • Transient ischemic attack • Cerebrovascular accident • Cognitive impairment Heart Coronary artery disease • Coronary syndrome • Myocardial infarction • Congestive heart failure Extremities Peripheral vascular disease • Ulceration • Gangrene • Amputation

Microvascul ar Eye Retinopathy Cataracts Glaucoma

Kidney Nephropathy • Microalbuminuria • Gross albuminuria • Kidney failure

Nerves Neuropathy • Peripheral • Autonomic

Good Glycemic Control (Lower HbA1c) Reduces Incidence of DCCT

Kumamoto

UKPDS

HbA1c







Retinopathy Nephropathy Neuropathy Macrovascular disease

63% 54% 60% 41%*

69% 70% – –

17-21% 24-33% – 16%*

* not statistically significant Diabetes Control and Complications Trial (DCCT) Research Group. N Engl J Med. Med. 1993;329:977-986. Ohkubo Y et al. Diabetes Res Clin Pract. Pract. 1995;28:103-117. UK Prospective Diabetes Study Group (UKPDS) 33: Lancet. Lancet. 1998;352:837-853.

29

Glycemic Goals For Diabetes

IN-HOSPITAL MANAGEMENT • • • • •

PREVALENCE SURGERY MI INFECTION ICU

Consensus: Glycemic Targets in the Hospital

• Intensive care unit

– 110 mg/dL (6.1 mmol/L)

• Medical/surgical floors – 110 mg/dL (6.1 mmol/L) preprandial – 140 mg/dL (7.78 mmo/L) maximal glucose Values above 180 mg/dL (10 mmol/L) are an indication to monitor glucose levels more frequently to determine the direction of any glucose trend and the need for more intensive intervention. Achieving these targets may require consultation with an endocrinologist or diabetes specialist. American Association of Clinical Endocrinologists. Available at: http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.

Diabetes in Hospitalized Patients

• Fourth most common co-morbid condition among hospitalized patients • 10–12% of all hospital discharges • 29% of all cardiac surgery patients • 1–3 days longer hospital stay Hogan P, et al. Diabetes Care. 2003;26:917–932. American Association of Clinical Endocrinologists. Available at: http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.

Hyperglycemia in Patients With Undiagnosed Diabetes

• Hyperglycemia occurred in 38% of patients admitted to the hospital – 26% had known history of diabetes – 12% had no history of diabetes

• Newly discovered hyperglycemia was associated with: – Higher in-hospital mortality rate (16%) compared with patients with a history of diabetes (3%) and patients with normoglycemia (1.7%; both P < 0.01) – Longer hospital stays; higher admission rates to Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978– 982.

Higher Costs: Diabetes in Hospitalized • • • • • •

Higher rate of hospitalization Longer stays More procedures, meds. Chronic complications More arteriosclerotic diseaseMore infection

Hyperglycemia Is an Independent Marker of Inpatient Mortality in Patients With P < 0.01 P < 0.01

In-hospital Mortality Rate (%)

Patients With Normoglycemia

Patients With History of Diabetes

Newly Discovered Hyperglycemia

Adapted from Umpierrez GE, et al. J Clin Endocrinol Metab. 2002;87:978– 982.

Hospital Mortality Rate and Mean Glucose Levels in

Mortality Rate (%)

Mean Glucose Value (mg/dL) Retrospective review of 1,826 consecutive intensive care unit patients at The Stamford Hospital in Stamford, Connecticut. Krinsley JS. Mayo Clin Proc. 2003;78:1471–1478.

Intensive Insulin Therapy in Critically Ill Surgical Patients 100

Intensive treatment

96

Survival in ICU (%)

92 Conventional treatment 88 84 80 0

0

20

40

60

80

100 120 140 160

Days After Admission Conventional: insulin when blood glucose > 215 mg/dL. Intensive: insulin when glucose > 110 mg/dL and maintained at 80–110 mg/dL. van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367. Copyright ©2001 Massachusetts Medical Society. All rights reserved.

Intensive Insulin Therapy in Critically Ill Surgical Patients: Morbidity and • Intensive therapy to achieve blood glucose levels of 80– 110 mg/dL reduced mortality (-34%), sepsis (-46%), dialysis (-41%), blood transfusion (-50%), and polyneuropathy (-44%) Blood Mortality

Sepsis

Dialysis Transfusion

neuropathy

Reduction (%) 34% 41% 46%

van den Berghe G, et al. N Engl J Med. 2001;345:1359–1367.

44% 50%

Hyperglycemia and Risk of Infection in General Surgery • Glucose > 220 mg/dL on postoperative day 1 is – A sensitive predictor of nosocomial infection – Associated with • 2.7 times higher rate of infection • 5.9 times higher rate of severe infection

Pomposelli JJ, et al. J Parenter Enteral Nutr. 1998;22:77– 81.

Portland Diabetic Project: Rate of Deep Sternal Wound Infection 2.0% Rates With Different Insulin Protocols P = 0.01

Deep Wound Infection Rate (%)

SQI = subcutaneous insulin; CII = continuous insulin infusion. Anthony Furnary MD 1999 CCNM Furnary AP, et al. Ann Thorac Surg. 1999;67:352–362.

0.8%

Glucose Control Lowers Risk of Wound Infection 67% P = 0.002

Deep Wound Infection Rate (%)

25% 13%

16%

Day 1 Blood Glucose (mg/dL) Reprinted from Zerr KJ, et al. Ann Thorac Surg. 1997;63:356–361 with permission from Society of Thoracic Surgeons.

Portland Diabetic Project: Incidence of DSWI and Impact of Implementation of Insulin Infusion 4.0 CII

3.0

DSWI (%)

Patients with diabetes

2.0

Patients without diabetes

1.0

0.0 87

88

89

90

91

92

93

94

95

96

Year DSWI = deep sternal wound infection; CII = continuous insulin infusion. Reprinted from Furnary AP, et al. Ann Thorac Surg. 1999;67:352–362 with permission from Society of Thoracic Surgeons.

97

Cost-Effectiveness in First DIGAMI For every 9 patients treated with intensive insulin regimen, one life was saved

DIGAMI = Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction. Almbrand B, et al. Eur Heart J. 2000;21:733–739.

Indications for Intravenous Insulin Therapy: Summary • Diabetic ketoacidosis • Nonketotic hyperosmolar state • Critical care illness (surgical, medical) • Postcardiac surgery • Myocardial infarction or cardiogenic shock • NPO status in Type 1 diabetes

• Labor and delivery • Glucose exacerbated by high-dose glucocorticoid therapy • Perioperative period • After organ transplant • Total parenteral

American Association of Clinical Endocrinologists. Available at: http://www.aace.com/pub/ICC/inpatientStatement.php. Accessed March 17, 2004.

Yale Insulin Infusion Protocol Insulin infusion: Mix 1 U regular human insulin per 1 mL 0.9% NaCl Administer via infusion pump in increments of 0.5 U/h START INSULIN AT O.O5 U/KG/HR Subsequent rate adjustments: Changes in infusion rate are determined by the current infusion rate and the hourly rate of change from the prior BG level; see table for instructions OR ORDER-TITRATE TO KEEP BG 70-140 MG/DL

Goldberg PA, et al. Diabetes Care. 2004;27:461– 467.

Insulin Requirements in Health and Illness Correction Nutritional Prandial Basal

Units

Healthy

Sick/Eatin g

Sick/NPO

Copyright © 2004 American Diabetes Association. From Clement S, et al. Diabetes Care. 2004;27:553–591. Reprinted with permission.

TREATMENT OF DIABETES • • • •

IV INSULIN THERAPY ORAL HYPOGLYCMIC AGENTS INSULINS NEW AGENTS – SYMLIN – BYETTA – DPP-IV INHIBITORS – ALPHA-GAMMA TZD

Timeline for Utilization of Therapies Metformin, TZD, AGI SU Meglitini de Post Meal Glucose

Lifestyle

Glucos e

Relative Function

35 0 30 0 25 0 20 0 15 0 10 05 0 25

Insulin

Fasting Glucose

0 20 0 15 0 10 05

00

Insulin Resistance At risk for Diabetes -1 0

5

Insulin Level

Beta cell failure 0

5

1

1

5 Years of0 Diabetes

© International Diabetes Center. From Kendall D, Bergenstal R.

2 0

2 5

3 0

Oral Agents Drug Class

Examples

Glimepiride Sulfonylureas Glipizide Glyburide

Principal Mode of Action Stimulate insulin secretion from pancreatic ß-cells

Key Issues Hypoglycemia Weight gain

Stimulate insulin Hypoglycemia Repaglinide secretion from Weight gain Meglitol pancreatic ß-cells Meglitinides

Oral Agents •

Drug Class Examples

• •

Biguanides

•

Metformin

• •

TZD

•

Rosiglitazone Pioglitazone

Principal Mode of Key Issues Action Decreases hepatic GI upset glucose Renal dis. Improve peripheral Liver enzymes Weight gain insulin sensitivity

•

AlphaAcarbose glucosidase Miglitol •

Delay carbohydrate Flatulence

Mimicking Nature With Insulin Basal/Bolus Concept

Insulin (µU/mL)

Physiologic Insulin Secretion 24-hr

5 0 2 5 0

Basal insulin

Glucose (mg/dL)

B 15 0 10 0 5 0 0

L

D

§ Suppresses glucose production between meals and overnight § Nearly constant levels § 50% of daily needs

Basal glucose

7 8 9 1 11 1 1 2 3 4 5 6 7 8 9 A0 2 Time of Day P

M M Adapted with permission from Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology.

Comparison of Human Insulins Onset of Insulin Preparations Action

Peak

Duration of Action

Lispro,Asparte,Apidra 5 to 15 min 1 to 2 hr 4 to 6 hr Human Regular

30 to 60 min 2 to 4 hr 6 to 10 hr

Human NPH

1 to 2 hr

4 to 6 hr 10 to 16 hr

Glargine

2 hr

none

22 to 24 hr

Detimir

2 hr

none

8 to 24 hr

* The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered as general guidelines only.

Mimicking Nature: Endogenous insulin Bolus insulin Basal

Insulin Effect

insulin

B

L

D

H S

Adapted with permission from McCall A. In: Insulin Therapy. Leahy J, Cefalu W, eds. New York, NY: Marcel Dekker, Inc; 2002:193

Short-Acting Insulin Analogs: Lispro and Aspart Insulin aspart Aspartate at position B28 instead of proline

Human Insulin

 

1

S 5 Cy Cy

1

2 Cy

S 1

1 Cy

S

S

5

Pr

S Cy

S

1 1

3 Ly

2

Cy 2

Insulin lispro Adapted with permission from Barnett A, Owens D. Lancet. 1997;349:47 Bolli G et al. Diabetologia. 1999;42:1151

Positions of proline and lysine reversed at B28 and B29

GLULISINE-APIDRA

GLULISINE-APIDRA VS REGULAR

APIDRA VS HUMALOG VS REGULAR

Dissociation & Absorption of NovoLog Insulin Aspart (NovoLog  )

Regula r Human

Subcutaneous Tissue

Peak Time = 40-50

Peak Time = 80-120

Capillary Membra ne

Glucose Response to a High Caloric Meal in Patients with Type 1 Diabetes

Blood Glucos e (mg/dL)

25 0 20 0 15 0 10 0 5 0 0

Injectio

Regular insulin (n=10) Insulin lispro (n=10)

Mean + SE

-6 0

0.2 mU/min/kg insulin infusion 6 12 18 24 30 0 0 0 0 0 Me 0 Time al (minutes)

36 0

42 0

48 0

Insulin Glargine A-

S

S

Gl Il y e

Va Gl Gi Cy Cy Th Se r r l u n s s

1 2

3 4 5

6 7

8 9

Il Cy Se Le Ty Gi Le Gl As Ty Cy e s r u r n u u n r s

Gl y

As n

1 11 1 13 1 15 16 17 18 1 20 21

S S S

S

Ph V As Gi Hi Le Cy Gl Se Hi Le Va Gl Al Le Ty Le Va Cy Gl Gl Ar Gl Ph Ph Ty Th Pr Ly Th Ar Ar r o s r g g e al n n s u s y r s u l u a u r u l s y u g y e e r

1 2

3 4

5

6 7 8 9

1 11 1 13 1 15 1 17 1 19 2 21 22 2 24 25 2

2 28 29 3 31 32

BProduced by recombinant DNA technology; 2 modifications in amino acid sequence of insulin molecule create stable molecule Bolli GB, Owens DR. Lancet. 2000;356:443

Mechanism of Action Clear solution pH 4.0

Dissolutio n

pH 7.4

Injection acidicofsolution (pH 4.0) Microprecipitati on

Microprecipitation of glargine in SC insulin (pH tissue 7.4) Slow dissolution stabilized into aggregates

Capillary membrane

Insulin in blood

Protracted action

Seipke G et al. Diabetologia. 1992;35:A4; Hilgenfeld R et al. Diabetologia. 1992;35:A193

INSULIN TACTICS

Glargine vs NPH Insulin in Type 1 Diabetes Glucose Utilization Rate (mg/kg/h)

6 5 4

NP H

3 2

Glargin e

1 0

0

1 0 (h) After SC Time Injection

Lepore, et al. Diabetes. 1999;48(suppl 1):A97.

2 0 End of observation period

3 0

Insulin detemir LysB29(N-tetradecanoyl)des(B30)human insulin C14  f (My atty ac rist i ic a d cha in cid )

Lys

Thr Lys A 1

Pro

Thr

Ph

A2 1

B2 9

Gl

Tyr

Ph

Asn

Gl

Cy

Arg

Glu

Gl

Cys Val Leu

Tyr Asn

Tyr

Ile

Glu

Leu

Val

Leu

Ala

Gln

Glu

Glu Gln Cys

Tyr Cy

Se

Thr

Ile

Cy

Se

Val

Leu

Leu His Gl

B 1

Ph

Val

Asn Gln

His

Leu

Cy

Se

INSULIN IN DIABETES • INSULIN REQUIREMENTS – 1-2 UNITS/KG/DAY FOR CHILDREN-1/21UNITS/KG/DAY FOR ADULTS DEPENDING ON DEGREE OF KETOSIS &/OR GROWTH RATE – DISTRIBUTION FOR INJECTABLE INSULIN • • • •

BREAKFAST 20% OF TOTAL AS FAST ACTING LUNCH 13% OF TOTAL AS FAST ACTING SUPPER 17% OF TOTAL AS FAST ACTING BEDTIME 50% OF TOTAL AS LONG ACTING

EXAMPLE – 24 Units/day

CASE K.M.

EXUBERA INHALABLE INSULIN

Photograph reproduced with permission of

Continuous Glucose Monitoring System (CGMS) Physician Diagnostic System

Interstitial Fluid Measurement ✦

Interstitia l fluid glucose (G2) is ? comparab le with blood

Amylin the Hormone • Reported in 1987 • 37-amino acid peptide • Co-located and co-secreted with insulin from pancreatic β-cells • Neuroendocrine hormone • Deficient in diabetes T

A

T

N

C

T

A

Q

R

L

A

N

F

L

V

H

C

Amide

Y

S

K T

N S G

V N

S S T

L

I

Adapted from Unger RH, Foster DW. Williams Textbook of Endo (8th edition) 1992; 1273-1275

A

G

F

S N

N

SYMLIN Reduces Glucose Fluctuations Baseline (Insulin Only) 6 Months (Insulin + 120 mcg SYMLIN)

Glucose (mg/dL)

220 200 180 160 140

*

*

*

*

*

*

*

120 dt be e

im

r ne

in -d st po

r

ne in -d

e pr

ch un

t-l

s po

h nc -lu

e pr t

s fa ak

re t-b

s po

st fa

ak re -b

e pr

n = 166 at baseline; observed cases; Mean (SE); *P-values for all data points <0.05 Data on file, Amylin Pharmaceuticals, Inc. See safety information with Boxed Warning in this presentation and the accompanying Prescribing Information

GILA MONSTER-ORIGINAL SOURCE OF EXENATIDE

GLP-1 Effects in Natural Role of Incretins GLP-1 secreted upon the ingestion of food

 Beta-cell

workload

Promotes satiety and reduces appetite

Alpha cells:

 Beta-cell

response

 Postprandial glucagon secretion

Liver:

Beta cells:

Enhances glucose-dependent insulin secretion

 Glucagon reduces hepatic glucose output

Stomach:

Helps regulate

Adapted Adapted Adapted Adapted

from from from from

Flint A, et al. J Clin Invest. 1998;101:515-520 Larsson H, et al. Acta Physiol Scand. 1997;160:413-422 Nauck MA, et al. Diabetologia. 1996;39:1546-1553 Drucker DJ. Diabetes. 1998;47:159-169

Prescribing Consideration BYETTA Dosing

• 2 fixed-dose prefilled pens

– 60 doses per pen (30-day supply) – Ready to use, easy to teach

See Important Safety Information included in this presentation

Summary • The evidence is overwhelming that good control does count • Morbidity and mortality can be reduced • There is nothing inevitable about the complications of diabetes

Summary (cont) • The cost of diabetes is in its complications • Any expense paid up front in better management will pay off handsomely in the long run • The tools for good diabetes care already exist • No tool is more important than the services of a certified diabetes educator

Summary (cont) • Assessment tools include Self Monitoring of Blood Glucose and HbA1C • Targets should be established for each of these for each patients within the national guidelines • When targets are not reached the help of a specialist should be sought • Christopher D. Saudek MD. Pres. ADA 2002

Summary Insulin administration should mimic nature Natures way is basal insulin 24 hrs. a day And bolus insulin with every feeding Insulin lispro, asparte or glulisine can supply bolus • Insulin glargine or detemir can supply the basal with one injection per day • Control of blood sugar will prevent the complications of diabetes • • • •