DIABETES MELLLITUS Strategies for Achieving Control in an Office Setting.

DIABETES MELLLITUS

Strategies for Achieving Control in an Office Setting

Type 2 Diabetes

Global Prevalence of Diabetes Projectedto More Than Double by 2030

Diabetes Reduces Lifespan

Risk Reduction for Key Endpoints with Intensive Therapy (UKPDS)

Tight Glycemic Control Reduces Incidence of Microvascular Complications

Intensive Glycemic Control in Type 2 Diabetes Reduces Risk of Complications (UKPDS)

Tight Glycemic Control Reduces Long-Term Cardiovascular Risk (DCCT/EDIC Study)

Current Treatment Goalsfor Glycemic Control

Glycemic Goals Are Not Being Met

Most Patients with Type 2 Diabetes Also Do Not Achieve Risk-Factor Control

Mechanism of Postprandial Hyperglycemia: Glucose Production

Mitrakou A, et al. N Engl J Med. 1992;326:22-29.

4.0

6.0

8.0

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12.0

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Time (min)

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IGT

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pm

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Glucose Glucagon

Impaired Glucagon Suppression in IGT

Mitrakou A, et al. N Engl J Med. 1992;326:22-29.

Insulin Glucagon

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Impaired Glucagon Suppression in IGT

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Impaired Glucagon Suppression in Type 2 Diabetes

Müller WA, et al. N Engl J Med. 1970;283:109-115.

Glucose Glucagon

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Impaired Glucagon Suppression in Type 2 Diabetes

Müller WA, et al. N Engl J Med. 1970;283:109-115.

Insulin Glucagon

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Time (min)

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T2DM

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TYPE 1 DIABETES

• 15% of the total

• INSULIN DEPENDENCE v REQUIRING

• GLUCAGON SUPPRESSION

TYPE 2 DIABETES

• INVOLVES 2 PRIMARY PATHOGENETIC MECHANISMS– PROGRESSIVE DECLINE IN BETA CELL

MASS AND FUNCTION• ASSOCIATED WITH THE LACK OF GLUCAGON

SUPPRESSION

– THE PRESENCE OF A RESISTANCE TO INSULIN ACTION AT THE TISSUE LEVEL

ISSUES TO DEAL WITH

• AWARENESS

• EDUCATION

• IMPLEMENTATION OF TREATMENT

TREATMENT OPTIONS

• FOOD • EXERCISE• ORAL• PARENTERAL

• BETA CELL FUNCTION

• GLUCAGON SUPPRESSION

• INSULIN RESISTANCE

TREATMENT OPTIONS

• ORAL– SECRETAGOGUES

• SULFONYLUREAS• NONSULFONYLUREAS

– INSULIN RESISTANCE• THIAZOLIDINEDIONES (TZD)• METFORMIN

– GLUCAGON SUPPRESSION• INCRETINS (INtestinal SECRETION of Insulin)

– JANUVIA

– STARCH BLOCKERS• ACARBOSE

TREATMENT OPTIONS

PARENTERAL– SUBCUTANEOUS

• INCRETIN MIMETICS• INSULIN

– TRANSPULMONARY

TREATMENT OPTIONS


• SULFONYLUREAS• NONSULFONYLUREAS

– INSULIN RESISTANCE• THIAZOLIDINEDIONES (TZD)• METFORMIN

– GLUCAGON SUPPRESSION• INCRETINS (INtestinal SECRETION of Insulin)

– JANUVIA

– STARCH BLOCKERS• ACARBOSE

TREATMENT OPTIONS ORAL


• SULFONYLUREAS– GLYBURIDE– GLIPIZIDE– GLIMEPIRIDE (LONG ACTING)

• NONSULFONYLUREAS– NATEGLINIDE (STARLIX)– REPAGLINIDE (PRANDIN)


• ORAL– INSULIN RESISTANCE

• THIAZOLIDINEDIONES (TZD)– PIOGLITAZONE (ACTOS)– ROSIGLITAZONE (AVANDIA)

• METFORMIN


• ORAL– GLUCAGON

SUPPRESSION• INCRETINS (GLP-1)

– SECRETED BY THE L-CELLS OF THE DISTAL ILEUM

– CIRCULATES TO THE PANCREAS

– STIMULATES INSULIN SECRETION

– INHIBITS GLUCAGON SECRETION

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• GLUCAGON SUPPRESSION– INCRETINS (GLP-1)---”GLIP-ONE”

• THERE ARE NO ORAL INCRETINS– BUT THERE IS AN ORAL WAY TO HELP

NATURALLY OCCURRING INCRETINS• GLIPTINS (DPP-4 INHIBITORS)

– SITAGLIPTIN (JANUVIA)– VILDAGLIPTIN (GALVUS -not yet released)

Synthesis, Secretion, and Metabolismof GLP-1 and GIP

DPP-4 Degrades GLP-1

TREATMENT OPTIONS PARENTERAL

• INCRETIN MIMETICS– DIRECT STIMULATION OF INSULIN– DIRECT INHIBITION OF GLUCAGON

• Exenatide (BYETTA)• Amylin (SYMLIN)

– NOT DEGRADED BY DPP-4• LONG-ACTING

TREATMENT OPTIONS

PARENTERAL– SUBCUTANEOUS

• INCRETIN MIMETICS• INSULIN

– TRANSPULMONARY• INSULIN

INSULIN THERAPY

• LONG ACTING ANALOGUES– LANTUS– LEVEMIR

• RAPID ACTING ANALOGUES– HUMALOG– NOVOLOG– APIDRA

INSULIN THERAPY

• MIXTURES– 75/25 HUMALOG MIX– 70/30 NOVOLOG MIX

INSULIN THERAPY

• IS INSULIN INEVITABLE ?

b-Cell Function Declines Regardless of Intervention in Type 2 Diabetes

AVAILABLE INSULINS

AVAILABLE INSULINS

INSULIN ONSET PEAK DURATION

HUMALOG < 30 minutes 30-90 minute < 90 minutes

AVAILABLE INSULINS



NOVOLOG < 15 minutes 1-3 hours 3-5 hours

AVAILABLE INSULINS




REGULAR 30-60 min 2-4 hours 6-12 hours

AVAILABLE INSULINS





NPH 1-2 hours 4-14 hours 10-24 hours

AVAILABLE INSULINS






LENTE 1-3 hours 6-16 hours 12-24 hours

AVAILABLE INSULINS






LENTE 1-3 hours 6-16 hours 12-24 hours

ULRALENTE 4-8 hours 10-30 hours 18-36 hours

NEWER INSULINS


NOVOLOG MIX 70/30

< 15 min 1-4 hours 12-24 hours

HUMALOG MIX 75/25

<30 min 2-4 hours 6-12 hours

LANTUS 1 hour NONE 24 hours

LEVEMIR 1 hour NONE 24 hours

NEWER INSULINS

INSULINS ONSET PEAK DURATION

APIDRA <15 minutes 1-2 hour 3-4 hours

THERAPEUTIC GOALS

HbA1C as low as possibleREDUCE BASAL HYPERGLYCEMIA

Provide a basal amount of insulin

REDUCE POSPRANDIAL EXCURSIONSSupplemental insulin with the meal

REDUCING BASAL HYPERGLYCEMIA

NPH bid LANTUS qd LEVEMIR qd INSULIN PUMP w

HUMALOGNOVOLOGAPIDRA

• METFORMIN• AMARYL• BYETTA• JANUVIA• TZD

REDUCE POSTPRANDIAL GLUCOSE

• HUMALOG• NOVOLOG• APIDRA• BYETTA

• STARLIX• PRANDIN• JANUVIA

TREATMENT STRATEGIES

• FOR SIGNIFICANTLY ELEVATED HbA1C– GET THE FBS DOWN FIRST

– AS THE HbA1C DECLINES • THE POST-PRANDIAL GLUCOSES PLAY A

GREATER ROLE

TREATMENT STRATEGIES FOR FASTING GLUCOSE

NPH bid LANTUS q HS LEVEMIR q HS

• METFORMIN• AMARYL• BYETTA• JANUVIA

TREATMENT STRATEGIES FOR POST PRANDIAL GLUCOSES

• APPROACH WITH RAPID ACTING INSULIN– TWO ISSUES DETERMINE THE PPG

• CARB CONTENT OF THE MEAL• PRE-MEAL GLUCOSE LEVEL


• CARB CONTENT CORRECTION– 1 unit for every (15 grams) carbs consumed

• 1:15 carb ratio

• PRE MEAL GLUCOSE CORRECTION• 1 Unit drops FS 50 mg%


• CHOOSE A TARGET FOR CORRECTION

• e.g., 100 mg%• FORMULA combines CORRECTION + CARBS

FS CORRECTION + CARB RATIO = TOTAL

(FS-target)/50 + 1:15 = TOTAL

SAMPLE COMPUTATION

• Patient has a 60 gm CHO meal– Uses 1 unit for 15 gm

• 4 units

• Patient has a target of 120 mg%– Correction factor = 40 (1 unit drops 40mg%)

• Current FS is 240– Will need 3 units

• (FS-target)/40 + 4 units for carbs• (240-120) = 120/4 =3 units for FS

SUMMARY

– TYPE 2 DIABETES IS MULTIFACTORIAL– GO AFTER FBS FIRST

• METFORMIN• GLIMEPIRIDE hs• LEVEMIR or LANTUS

– MEALTIME CONTROL• NATEGLINIDE or REPAGLINIDE• EXENATIDE• JANUVIA• RAPID ACTING INSULIN ANALOGUES

SUMMARY

• DIET and EXERCISE– Cannot be emphasized more

DIABETES MELLLITUS Strategies for Achieving Control in an Office Setting.

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